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Blue light exposure decreases systolic blood pressure, arterial stiffness, and improves endothelial function in humans
Abstract
Aims:
Previous studies have shown that ultraviolet light can lead to the release of nitric oxide from the skin and decrease blood pressure. In contrast to visible light the local application of ultraviolet light bears a cancerogenic risk. Here, we investigated whether whole body exposure to visible blue light can also decrease blood pressure and increase endothelial function in healthy subjects.
Methods:
In a randomised crossover study, 14 healthy male subjects were exposed on 2 days to monochromatic blue light or blue light with a filter foil (control light) over 30 minutes. We measured blood pressure (primary endpoint), heart rate, forearm vascular resistance, forearm blood flow, endothelial function (flow-mediated dilation), pulse wave velocity and plasma nitric oxide species, nitrite and nitroso compounds (secondary endpoints) during and up to 2 hours after exposure.
Results:
Blue light exposure significantly decreased systolic blood pressure and increased heart rate as compared to control. In parallel, blue light significantly increased forearm blood flow, flow-mediated dilation, circulating nitric oxide species and nitroso compounds while it decreased forearm vascular resistance and pulse wave velocity.
Conclusion:
Whole body irradiation with visible blue light at real world doses improves blood pressure, endothelial function and arterial stiffness by nitric oxide released from photolabile intracutanous nitric oxide metabolites into circulating blood.
Supplementary resource (1)
Data
September 2018
... Light therapy in the visible range spectrum can affect photosensitive molecules, such as ATP, superoxide dismutase, or cytochrome C oxidase, which then affect the redox balance in the cells [11][12][13]. Current studies suggest that light therapy leads to an increase in mitochondrial activity, ROS production, as well as NO and, therefore, in vasodilation [11,[34][35][36]. We did not find that light therapy had any significant effects on systolic blood pressure (SBP) or diastolic blood pressure (DPB). ...
... To support the light therapy findings above, Heiss and colleagues, in a randomized crossover study that included 14 healthy male subjects, investigated the 2-day effect of monochromatic blue light or blue light with a filter foil (control light) on cardiovascular health. One light session took 30 min [36]. They saw that monochromatic blue light causes a decrease in SBP and arterial stiffness, and improves endothelial function [36]. ...
... One light session took 30 min [36]. They saw that monochromatic blue light causes a decrease in SBP and arterial stiffness, and improves endothelial function [36]. Moreover, they also observed increased blood flows and increased levels of nitric oxide species as clear signs of vasodilatation, which is in contrast with the present study. ...
(1) Background: Studies have reported the effectiveness of light therapy in various medical conditions. Our pilot study aimed to assess the effect of Maharishi light therapy (MLT) on physiological parameters, such as the heart rate (HR), HR variability (HRV), blood pressure (BP), BP variability (BPV), and the retinal microvasculature of healthy participants; (2) Methodology: Thirty (14 males and 16 females) healthy, non-smoking participants between 23 and 71 years old (46 ± 18 years) were included in this randomized crossover study. Each participant was tested with a placebo (using LED light) and gem lights, 24 h apart. Hemodynamic parameters were recorded during the session, and 24 h heart rate and BP levels were assessed via mobile devices. Retinal vascular responses were captured with fundus images and the subsequent analysis of retinal vessel widths. A linear model, using repeated measures ANOVA, was used to compare the responses across the sexes and to assess the effect of the MLT; (3) Results: Changes in the central retinal artery equivalent (CRAE) (p < 0.001) and central retinal vein equivalent (CRVE) (p = 0.002) parameters were observed. CRAE and CRVE decreased under MLT and increased under the placebo condition from before to after. However, the baseline values of the participants already differed significantly before the application of any therapy, and the variation in the retinal vessel diameters was already large in the baseline measurements. This suggests that the observed effect results may only reflect naturally occurring fluctuations in the microcirculation and not the effect of MLT. Furthermore, no significant effects were observed in any other investigated parameters; (4) Conclusion: Our study with healthy participants finds significant changes in retinal parameters, but the biological variation in the baseline measurements was large to begin with. This suggests that the observed effect results only reflect naturally occurring fluctuations in the microcirculation and not the effect of MLT. However, in the future, larger studies in which MLT is applied for longer periods and/or in patients with different diseases could discover the physiological impacts of this type of therapy.
... This NO was the product of photodecomposition of photo-labile NO derivates. In the case of whole body exposure of healthy volunteers to UVA or blue light the enhanced cutaneous formation of non-enzymatic NO resulted in significantly augmented systemic concentrations of bioactive NO derivates as well as in markedly increased systemic NO-mediated physiological effects, i. e. reduced blood pressure [9,11]. ...
... This study was designed as a 2 arm randomized, controlled, cross over study, exactly as shown recently [11]. The 14 healthy male volunteers were exposed in random order to monochromatic blue light (450 nm) and control light (filter foil covering the volunteers) each on a different day separated by one week of wash-out delivered by the same irradiation device. ...
... As shown in Fig. 5B, which contains measured values obtained in the context of a very recently published study describing the impact of blue light on blood pressure of healthy volunteers [11], whole body ...
β-Endorphin exerts a broad spectrum of physiological activity on mood, immune functions, pain management, reward effects, and behavioral stability. β-Endorphin is produced in certain neurons within the central and peripheral nervous system but also in the skin, especially in response to ultraviolet radiation. In the present study we have investigated the impact of visible blue light at λ = 453 nm (BL) on β-endorphin production of primary human skin keratinocytes (hKC) in-vitro as well as on systemic β-endorphin formation of whole-body exposed subjects in-vivo. We found that BL irradiation significantly enhanced both keratinocytic β-endorphin production of hKC cultures as well as systemic β-endorphin concentrations in light exposed healthy subjects. Interestingly, in hKC cultures elevated β-endorphin formation was paralleled by significantly increased levels of non-enzymatically generated nitric oxide (NO), whereas elevated systemic β-endorphin values of BL-exposed subjects were accompanied by enhanced systemic concentration of bioactive NO-derivates. These findings point to a pivotal role of NO in the molecular mechanism of the observed BL-induced effects, and indeed, exogenously applied NO was able to significantly enhance β-endorphin production in hKC cultures. Thus, our finding of BL-induced increases in systemic β-endorphin concentration in-vivo can be plausibly explained by an event sequence comprising 1.) BL-driven non-enzymatic formation of NO in the exposed skin tissue, 2.) systemic distribution of cutaneously produced NO, 3.) a subsequent NO-dependent induction of β-endorphin synthesis in epidermal keratinocytes, and 4.) probably also a NO-dependent modulation of β-endorphin synthesis in specialized neurons within the central and peripheral nervous system.
... More recently, UV-free blue light has been shown to release NO, providing cardiovascular benefits by releasing NO from photolabile intracutaneous NO metabolites [17][18][19]. These studies indicate that blue light can release NO from the skin non-enzymatically, both in vitro and clinically. ...
... These studies indicate that blue light can release NO from the skin non-enzymatically, both in vitro and clinically. A proposed mechanism is a catalytic effect of Cu 1+ with blue light that seems to increase intradermal free NO levels, leading to NO release, translocation into underlying tissue, and increased local blood flow [17][18][19]. Another study found that blue LED light (453 nm) releases NO from nitrosated proteins, with UVA light (360 nm) also causing a decrease in nitrosation, while red light (659 nm) had no effect [20]. ...
Significance: This study investigates the therapeutic potential of photobiomodulation (PBM) using visible and
near-infrared (NIR) light on nitric oxide (NO) release from intact human skin. Given NO’s critical role in
physiological processes such as wound healing, inflammation control, and vasodilation, this research could lead
to innovative non-invasive treatments.
Aim: The primary aim was to explore how PBM at different wavelengths affects NO release from human skin.
Custom-built airtight sleeves equipped with gas ports were used to measure NO levels, assessing the impact of
three specific wavelengths of light (455 nm, 660 nm, and 850 nm).
Approach: Eighteen healthy participants had their forearms enclosed in airtight sleeves. The skin was irradiated
with the specified wavelengths at a fluence of 45 J/cm2 and an irradiance of 50 mW/cm2 for 15 min. NO
levels were quantified after irradiation using chemiluminescence detection (CLD), which measures the chemiluminescent
reaction of NO with ozone (O3) for real-time analysis.
Results: Significant differences in NO release were observed among the wavelengths tested, indicating that
PBM stimulates NO release from intact human skin.
Conclusions: The study provides strong evidence that PBM using visible and NIR light can enhance NO release
from human skin, suggesting potential therapeutic applications for conditions involving NO. Further research is
needed to understand the mechanisms behind PBM-induced NO release and its clinical implications.
... Notably, it has been associated with the generation of ROS [10], direct damage to photoreceptors [11], and the activation of speci c genes such as Cryptochrome (Cry) [12,13], which in turn activates Calcium and Integrin Binding 1 (CIB1) and AKT [14,15]. Intriguingly, brief exposure to blue light has been shown to release nitric oxide (NO) [16,17], resulting in decreased blood pressure in humans [17]. Such ndings were reinforced by clinical studies revealing that blue light exposure enhanced blood pressure, endothelial function, and reduced arterial stiffness due to nitric oxide being released from intracutaneous nitric oxide metabolites into the bloodstream [11]. ...
... Notably, it has been associated with the generation of ROS [10], direct damage to photoreceptors [11], and the activation of speci c genes such as Cryptochrome (Cry) [12,13], which in turn activates Calcium and Integrin Binding 1 (CIB1) and AKT [14,15]. Intriguingly, brief exposure to blue light has been shown to release nitric oxide (NO) [16,17], resulting in decreased blood pressure in humans [17]. Such ndings were reinforced by clinical studies revealing that blue light exposure enhanced blood pressure, endothelial function, and reduced arterial stiffness due to nitric oxide being released from intracutaneous nitric oxide metabolites into the bloodstream [11]. ...
Nitric oxide (NO) is a short-lived free-radical molecule implicated in the pathophysiology of various eye diseases. The regulatory imbalance of NO, either its overproduction or under-production, is a key factor in oxidative stress-related ocular disorders. Given the increasing concern regarding blue-light-induced oxidative stress leading to retinopathy, we postulate that maintaining consistent NO levels through sustained release could be beneficial. To achieve this, we developed and synthesized nano-NO-releasing systems (NORS), with a hydrodynamic size of approximately 130 nm and a surface charge of -10 mV, respectively. Our findings reveal that blue-light irradiation can trigger NO release from NORS in a light-intensity-dependent manner. Furthermore, NORS can be internalized by retinal pigment epithelial (RPE) cells without exhibiting cytotoxic effects at concentrations up to 100 µM. In RPE cells damaged by blue light, NORS effectively counteracted the upregulation of several antioxidant responses at both the protein and gene levels. These include the Nrf-2/Keap-1 and heme oxygenase-1 (HO-1) protein and the glutathione S-transferase (GST) genes (a1-1, a1-2, a1-5). In the C57BL/6 mice model of blue-light-induced retinopathy, chronic low-intensity blue light exposure (300 Lux, 12 hours/day for 28 days) resulted in photoreceptor dysfunction, vascular leakage, and an increase in mean blood flow rate (MBFR), without affecting the thickness of the retina. However, treatment with NORS mitigated the detrimental effects of blue light on the retina, as evidenced by reduced fluorescence leakages and a reversal of the electroretinographic alterations induced by photoreceptor dysfunction. In conclusion, our data suggested that NORS can effectively enable prolonged NO delivery both in vitro and in vivo. This protective effect appears to be accomplished by restoring normal antioxidant responses and improving vascular homeostasis.
... 65 Cutaneous NO stores are significant, particularly in the epidermis, where it modulates local cytomodulatory effects and presumably many remote systemic effects like lowering blood pressure. 79 PBM visual overview. ...
... The skin is also the interface for light-induced NO release, especially after large surface exposure leading to systemic hemodynamic effects. 79 NO stored in a pool of compounds is easily converted to N, via photolytic or enzymatic effects, after skin exposure to UVA/blue light. The innovation is that 65 ). ...
Objective: To describe current knowledge regarding established and putative cell signaling pathways involved in skin photobiomodulation.
Background: The skin is the largest and most accessible organ of the body. It is the first line of defense against the external environment, including solar radiation. Among solar rays, visible and infrared non-ionizing photons may reach human skin and trigger a cascade of non-thermal cell signaling pathways called photobiomodulation (PBM). The use of PBM using artificial light sources has been known for more than 50 years, but it has not yet been widely accepted due to uncertainty about the cellular mechanisms of action. However, much knowledge has been gained in this field in recent years, which will be summarized in this review.
Methods: An extensive literature review was performed using Medline, Embase, and Google Scholar as research databases to acquire relevant publications in this particular field.
Results: A comprehensive description of chromophores, primary and secondary effectors is provided in addition to a visual representation of known and putative cell signaling mechanisms involved in such complex light-skin interactions. Also, a summary of clinical indications of skin PBM, key light parameters, and promising skin applications (local and systemic) are mentioned.
Conclusions: In PBM, skin cells are the first to absorb photons, triggering specific cell-signaling pathways through primary and secondary effectors, leading to enhanced cell repair and survival, notably in hypoxic or stressed cells. A better understanding of the mechanisms of action will help us optimize known indications and discover new ones.
... The results showed that 30 min after the end of irradiation, the levels of nitric oxide species increased in circulation. In particular, the levels of RXNOs were significantly elevated by 30-50% [87]. ...
... Thus, elevated dermal NOD levels obtained also, for example, by a nitrite/nitraterich diet or inflammation, should be affected by UV/VIS, possibly leading to more dermal/circulatory RSNO/RXNO concentrations with consequent NO-induced effects on blood pressure and microcirculation [87]. ...
The generation of nitric oxide (NO) in the skin plays a critical role in wound healing and the response to several stimuli, such as UV exposure, heat, infection, and inflammation. Furthermore, in the human body, NO is involved in vascular homeostasis and the regulation of blood pressure. Physiologically, a family of enzymes termed nitric oxide synthases (NOS) generates NO. In addition, there are many methods of non-enzymatic/NOS-independent NO generation, e.g., the reduction of NO derivates (NODs) such as nitrite, nitrate, and nitrosylated proteins under certain conditions. The skin is the largest and heaviest human organ and contains a comparatively high concentration of these NODs; therefore, it represents a promising target for many therapeutic strategies for NO-dependent pathological conditions. In this review, we give an overview of how the cutaneous NOD stores can be targeted and modulated, leading to a further accumulation of NO-related compounds and/or the local and systemic release of bioactive NO, and eventually, NO-related physiological effects with a potential therapeutical use for diseases such as hypertension, disturbed microcirculation, impaired wound healing, and skin infections.
... More recently, blue light has been shown to release NO [18,19] in the blood circulation from photolabile intracutaneous NO metabolites with corresponding cardiovascular benefits [20]. ...
... Despite established ultraviolet radiation (UVR) and blue light photolytic release of NO in the skin [15,24], light exposure in the red/NIR spectrum is a promising alternative using safer non-ionizing photons [21,25]. NO stores are prominent and mostly located in the epidermis, modulating local and remote systemic effects [20]. Finding new methods to mobilize such a substantial NO reservoir in the skin have broad implications in photomedicine. ...
Nitric oxide (NO) is omnipresent in the body and synthesized by 3 isoenzymes (nNOS, eNOS and iNOS), all detected in human skin. NO can be stored in a pool of compounds readily converted to NO following skin irradiation by UVR and blue light. This non-enzymatic (without NOS involvement) photolytic reaction mobilizes cutaneous stores of NO derivatives to the bloodstream, lowering blood pressure. However, with the likelihood of skin deleterious effects caused by UVR/blue light, safer wavelengths in the red/near-infrared (NIR) spectrum are becoming potential contenders to release cutaneous NO, possibly via NOS temperature-dependent effects. The use of red/NIR light to mobilize NO stores from the body's largest organ (the skin) is auspicious. This review focuses on UVR, blue, red, and NIR spectra and their capacity to release NO in human skin. PubMed and Google Scholar were used as article databases to find relevant publications related to this particular field.
... NO is released as part of thermoregulation, an adaptive process that tightly regulates body heat to prevent heat stress, which can be fatal [80]. Sunlight and artificial light also increase systemic NO levels [72,[81][82][83][84][85][86][87] while decreasing blood pressure and vascular resistance [71,72,82,85,87]. Because high NO and NO-metabolite levels are found in people with histories of suicide attempts [88][89][90], heat and/or light-induced NO increases could increase risk for suicide. ...
... NO is released as part of thermoregulation, an adaptive process that tightly regulates body heat to prevent heat stress, which can be fatal [80]. Sunlight and artificial light also increase systemic NO levels [72,[81][82][83][84][85][86][87] while decreasing blood pressure and vascular resistance [71,72,82,85,87]. Because high NO and NO-metabolite levels are found in people with histories of suicide attempts [88][89][90], heat and/or light-induced NO increases could increase risk for suicide. ...
Background
Nearly 800,000 suicides occur worldwide annually and suicide rates are increasing faster than population growth. Unfortunately, the pathophysiology of suicide remains poorly understood, which has hindered suicide prevention efforts. However, mechanistic clues may be found by studying effects of seasonality on suicide and other mortality causes. Suicides tend to peak in spring-summer periods and nadir in fall-winter periods while circulatory system disease-related mortality tends to exhibit the opposite temporal trends. This study aimed to determine for the first time whether monthly temporal cross-correlations exist between suicide and circulatory system disease-related mortality at the population level. If so and if common biological factors moderate risks for both mortality types, such factors may be discoverable and utilized to improve suicide prevention.
Methods
We conducted time series analyses of monthly mortality data from northern (England and Wales, South Korea, United States) and southern (Australia, Brazil) hemisphere countries during the period 2009–2018 ( N = 41.8 million all-cause mortality cases). We used a Poisson regression variant of the standard cosinor model to determine peak months of mortality. We also estimated cross-correlations between monthly mortality counts from suicide and from circulatory system diseases.
Results
Suicide and circulatory disease-related mortality temporal patterns were negatively correlated in Australia (− 0.32), Brazil (− 0.57), South Korea (− 0.32), and in the United States (− 0.66), but no temporal correlation was discernable in England and Wales.
Conclusions
The negative temporal cross-correlations between these mortality types we found in 4 of 5 countries studied suggest that seasonal factors broadly and inversely moderate risks for circulatory disease-related mortality and suicide, but not in all regions, indicating that the effect is not uniform. Since the seasonal factors of temperature and light exert opposite effects on suicide and circulatory disease-related mortality in several countries, we propose that physiologically-adaptive circulatory system responses to heat and light may increase risk for suicide and should be studied to determine whether they affect suicide risk. For example, heat and light increase production and release of the bioactive gas nitric oxide and reduce circulatory system disease by relaxing blood vessel tone, while elevated nitric oxide levels are associated with suicidal behavior, inverse effects that parallel the inverse temporal mortality patterns we detected.
... NO is released as part of thermoregulation, an adaptive process that tightly regulates body heat to prevent heat stress, which can be fatal [76]. Sunlight and arti cial light also increase systemic NO levels [66,[77][78][79][80][81][82][83] while decreasing blood pressure and vascular resistance [66,68,[77][78][79][80][81][82][83]. Because high NO and NO-metabolite levels are found in people with histories of suicide attempts [84][85][86], heat and/or light-induced NO increases could increase risk for suicide. ...
... NO is released as part of thermoregulation, an adaptive process that tightly regulates body heat to prevent heat stress, which can be fatal [76]. Sunlight and arti cial light also increase systemic NO levels [66,[77][78][79][80][81][82][83] while decreasing blood pressure and vascular resistance [66,68,[77][78][79][80][81][82][83]. Because high NO and NO-metabolite levels are found in people with histories of suicide attempts [84][85][86], heat and/or light-induced NO increases could increase risk for suicide. ...
Background Nearly 800,000 suicides occur worldwide annually and suicide rates are increasing faster than population growth. Unfortunately, the pathophysiology of suicide remains poorly understood, which has hindered suicide prevention efforts. However, mechanistic clues may be found by studying effects of seasonality on suicide and other mortality causes. Suicides tend to peak in spring-summer periods and nadir in fall-winter periods while circulatory system disease-related mortality tends to exhibit the opposite temporal trends. This study aimed to determine for the first time whether monthly temporal cross-correlations exist between suicide and circulatory system disease-related mortality at the population level. If so and if common biological factors moderate risks for both mortality types, such factors may be discoverable and utilized to improve suicide prevention.
Methods We conducted time series analyses of monthly mortality data from northern (England and Wales, South Korea, United States) and southern (Australia, Brazil) hemisphere countries during the period 2009-2018 (N=41.8 million all-cause mortality cases). We used a Poisson regression variant of the standard cosinor model to determine cross-correlations between monthly mortality rates from suicide and from circulatory system diseases.
Results Suicide and circulatory disease-related mortality temporal patterns were negatively correlated in Australia (-0.32), Brazil (-0.57), South Korea (-0.32), and in the United States (-0.66), but no temporal correlation was discernable in England and Wales.
Conclusions The negative temporal cross-correlations between these mortality types we found in 4 of 5 countries studied suggest that seasonal factors broadly and inversely moderate risks for circulatory disease-related mortality and suicide. Since the seasonal factors of temperature and light exert opposite effects on suicide and circulatory disease-related mortality in several countries, we propose that physiologically-adaptive circulatory system responses to heat and light may increase risk for suicide and should be studied to determine whether they affect suicide risk. For example, heat and light increase production and release of the bioactive gas nitric oxide and reduce circulatory system disease by relaxing blood vessel tone, while elevated nitric oxide levels are associated with suicidal behavior, inverse effects that parallel the inverse temporal mortality patterns we detected.
... Sikka et al. [73] showed that blood vessels express melanopsin and display vasorelaxation under blue light, and in a recent study, Stern et al. [74] measured a decrease of systolic blood pressure minutes after a full-body blue-light shower, with no changes in a control group. While the evidence for this effect is still limited, it is worth discussing it in the context of the present study. ...
... We cannot rule out the occurrence, or interaction, of blood-vessel mediated melanopic effects with retina-mediated melanopic effects, since the participants' skin was partly exposed to the room lighting, but we find it rather unlikely. Firstly, when compared to Stern et al. [74], the exposed skin areas of our participants were small, with only face and hands exposed by all participants, plus neck and arms by some. Secondly, irradiance levels were only one thousandth of those in that study. ...
Melanopic stimuli trigger diverse non-image-forming effects. However, evidence of a melanopic contribution to acute effects on alertness and performance is inconclusive, especially under common lighting situations. Effects on cognitive performance are likely mediated by effort-related physiological changes. We assessed the acute effects of lighting in three scenarios, at two times of day, on effort-related changes to cardiac contraction as indexed by the cardiac pre-ejection period (PEP). In a within-subject design, twenty-seven participants performed a cognitive task thrice during a morning and a late-afternoon session. We set the lighting at 500 lux in all three lighting scenarios, measured horizontally at the desk level, but with 54 lux, 128 lux, or 241 lux melanopic equivalent daylight illuminance at the eye level. Impedance cardiography and electrocardiography measurements were used to calculate PEP, for the baseline and task period. A shorter PEP during the task represents a sympathetic heart activation and therefore increased effort. Data were analysed with linear mixed-effect models. PEP changes depended on both the light scene and time of day (p = 0.01 and p = 0.002, respectively). The highest change (sympathetic activation) occurred for the medium one of the three stimuli (128 lux) during the late-afternoon session. However, effect sizes for the singular effects were small, and only for the combined effect of light and time of day middle-sized. Performance scores or self-reported scores on alertness and task demand did not change with the light scene. In conclusion, participants reached the same performance most efficiently at both the highest and lowest melanopic setting, and during the morning session. The resulting U-shaped relation between melanopic stimulus intensity and PEP is likely not dependent solely on intrinsic ipRGC stimuli, and might be moderated by extrinsic cone input. Since lighting situations were modelled according to current integrative lighting strategies and real-life indoor light intensities, the result has implications for artificial lighting in a work environment.
... Blue light consistently induced the highest NO release across all the keratinocyte populations. These results reinforce the well-established role of blue light in promoting NO production in the skin, as documented in previous research [10,[19][20][21]. ...
NO is a crucial signaling molecule involved in skin health, the immune response, and the protection against environmental stressors. This study explores how different wavelengths of light, namely blue (455 nm), red (660 nm), and near infrared (NIR, 850 nm), affect nitric oxide (NO) production in skin cells. Primary keratinocytes and fibroblasts from three donors were exposed to these wavelengths, and NO production was quantified using a DAF-FM fluorescent probe. The results demonstrated that all three wavelengths stimulated NO release, with blue light showing the most pronounced effect. Specifically, blue light induced a 1.7-fold increase in NO in keratinocytes compared to red and NIR light and a 2.3-fold increase in fibroblasts compared to red light. Notably, fibroblasts exposed to NIR light produced 1.5 times more NO than those exposed to red light, while keratinocytes consistently responded more robustly across all wavelengths. In conclusion, blue light significantly boosts NO production in both keratinocytes and fibroblasts, making it the most effective wavelength. Red and NIR light, while less potent, also promote NO production and could serve as complementary therapeutic options, particularly for minimizing potential photoaging effects.
... At the same time, a certain correction of the spectral composition of light radiation in medical institutions and workplaces has a positive effect on human health [9]. At the same time, lighting control can use the data of personal sensor devices that determine the human condition [10]. ...
The difference in the spectral composition of artificial and natural lighting can negatively affect health, as well as lead to a distorted perception of the color of surrounding objects. At the same time, a certain correction of the spectral composition of visible radiation in medical institutions and workplaces has a positive effect on human health, while can be carried lighting control out taking into account the data of personal sensor devices that determine the human condition. The purpose of the research was to select criteria for comparing natural and LED optical and visible radiation by spectral composition and by the visibility of color differences in natural and LED lighting. The effectiveness of the application of known and developed criteria for assessing the difference in the spectral composition of optical and visible radiation from natural and LED sources was investigated, as well as for the visibility of color differences in natural and LED lighting. To minimize the values of criteria are proposed additive and subtractive methods for calculating LED parameters. Their comparison allowed us to conclude that a more complex calculation algorithm, but higher performance for an additive technique than for a subtractive one with the same minimization results.
It was found that to simulate the spectral composition of natural radiation using LEDs, it is most effective to use the criteria "standard deviations of the relative differences between the optical and visible spectral components of natural and LED radiation". A comparison of the criteria for the visibility of color differences in natural and LED lighting showed approximately the same effectiveness of using the criteria "small color differences" and "standard deviation by photoreceptors" at the present stage and the prospects for applying the second criterion, provided that its acceptable values are established.
... Moreover, the blood pressure results are in line with previous research [31], where patients who listened to BBM before surgery experienced significant reductions in blood pressure and anxiety levels. These findings further validate the effectiveness of artificial light exposure in reducing blood pressure in healthy individuals [32]. Hence, the combination of BBM and rhythmic photic stimulation may assist individuals with moderate anxiety in alleviating their anxiety by enhancing HRV and lowering blood pressure. ...
This study investigated the efficacy of combining binaural beat music (BBM) with rhythmical photic stimulation at the α frequency in alleviating anxiety among daycare staff and explored its impacts on daycare staff with different anxiety levels. A quasi-experimental research design was adopted, which included three interventions: BBM, BBM integrated with rhythmical photic stimulation, and relaxation music (control group). Participants completed a questionnaire prior to the first intervention, which included personal demographic information and the Beck Anxiety Inventory. The effects of these interventions on anxiety relief among daycare staff were evaluated through heart rate variability (HRV), brain waves, and blood pressure before and after the interventions. Statistical analysis primarily employed the Friedman test to analyze the differences in changes in HRV, brain waves, and blood pressure before and after the interventions. A total of 40 individuals participated in this study (16 males and 24 females), with an average age of 31.73 ± 8.83 years. The results showed that, compared to BBM alone, BBM integrated with rhythmical photic stimulation significantly reduced the normalized low/high frequency (nLF/nHF) ratio in participants with moderate anxiety (p<0.05). The results suggest that BBM integrated with rhythmical photic stimulation may serve as an intervention for the prevention and relief of anxiety by regulating an individual’s autonomic nervous system. However, further research is required to confirm these findings.
... These photons interact with chromophores resulting in photophysical and photochemical changes that impact biological function at molecular, cellular, and tissue levels. Light-mediated changes in the intricate physiological processes of infected or injured tissues can expedite tissue regeneration and wound healing, improve circulation, minimize acute inflammation, alleviate acute and chronic pain, and aid in reestablishing normal cell function [9][10][11][12]. ...
Blue light–mediated photobiomodulation (PBM) is a promising approach to promote osteogenesis. However, the underlying mechanisms of PBM in osteogenesis are poorly understood. In this study, a human osteosarcoma cell line (i.e., Saos-2 cells) was subjected to intermittent blue light exposure (2500 µM/m²/s, 70 mW/cm², 4.2 J/cm², once every 48 h) and the effects on Saos-2 cell viability, metabolic activity, differentiation, and mineralization were investigated. In addition, this study addressed a possible role of blue light induced cellular oxidative stress as a mechanism for enhanced osteoblast differentiation and mineralization. Results showed that Saos-2 cell viability and metabolic activity were maintained upon blue light exposure compared to unilluminated controls, indicating no negative effects. To the contrary, blue light exposure significantly increased (p < 0.05) alkaline phosphatase activity and Saos-2 cell mediated mineralization. High-performance liquid chromatography (HPLC) assay was used for measurement of reactive oxygen species (ROS) activity and showed a significant increase (p < 0.05) in superoxide (O2•−) and hydrogen peroxide (H2O2) formed after blue light exposure. Together, these results suggest that the beneficial effects of blue light–mediated PBM on osteogenesis may be induced by controlled release of ROS.
... It was shown that light may influence blood pressure depending on time and mechanisms of action. Daytime blue light exposure decreased blood pressure, possibly by modulating endothelial function and arterial stiffness by release of nitric oxide from photolabile intracutaneous nitric oxide metabolites into the circulation (Stern et al. 2018). Also, light therapy improved diurnal blood pressure control in night shift workers (Hannemann et al. 2021), while nocturnal light increased blood pressure, possibly by suppressing melatonin production (Gubin et al. 2017. ...
This study relates answers to the Munich Chronotype Questionnaire (MCTQ) and Pittsburgh Sleep Quality Index (PSQI) from Arctic Sojourn Workers (ASW) of Yamburg Settlement, 68° Latitude North, 75° Longitude East (n = 180; mean age ± SD; range: 49.2 ± 7.8; 25-66 y; 45% women) to Arctic Sojourn Work Experience (ASWE), age and health status. Chronotype, Mid Sleep on Free Days sleep corrected (MSFsc) and sleep characteristics of ASW were compared to those of age-matched Tyumen Residents (TR, n = 270; mean age ± SD; range: 48.4 ± 8.4; 25-69 y; 48% women), 57° Latitude North, 65° Longitude East. ASW have earlier MSFsc than TR (70 min in men, p < 0.0001, and 45 min in women, p < 0.0001). Unlike TR, their MSFsc was not associated with age (r = 0.037; p = 0.627) and was linked to a larger Social Jet Lag (+21 min in men; p = 0.003, and +18 min in women; p = 0.003). These differences were not due to outdoor light exposure (OLE): OLE on work (OLEw) or free (OLEf) days was not significantly different between ASW and TR in men and was significantly less in ASW than in TR women (OLEw: −31 min; p < 0.001; OLEf: −24 min; p = 0.036). ASWE, but not age, was associated with compromised lipid metabolism in men. After accounting for multiple testing, when corrected for age and sex, higher triglycerides to high-density lipoprotein ratio, TG/HDL correlated with ASWE (r = 0.271, p < 0.05). In men, greater SJL was associated with lower HDL (r =-0.204; p = 0.043). Worse proxies of metabolic health were related to unfavorable components of the Pittsburgh Sleep Quality Index in ASW. Higher OLE on free days was associated with lower systolic (b =-0.210; p < 0.05) and diastolic (b =-0.240; p < 0.05) blood pressure.
... Pulse wave velocity and pulse wave analysis using SphygmoCor (AtCor Medical, Sydney, Australia) were performed to non-invasively assess arterial vascular stiffness. This device is invasively validated for this application and is used in several clinical trials (Weber et al., 2015;Stern et al., 2018). ...
Background:
Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) effectively decrease low-density lipoprotein cholesterol (LDL-C) and reduce cardiovascular events in patients at very high cardiovascular risk. Recent short-term studies suggest a partially LDL-C independent beneficial effect of PCSK9 inhibitor (PCSK9i) therapy on endothelial function and arterial stiffness, whereas it is unknown if this effect persists and what the effect is on microcirculation.
Objective:
To investigate the effects of PCSK9i therapy on vascular parameters beyond its lipid lowering effect.
Methods:
In this prospective trial, 32 patients at very high cardiovascular risk and indication for PCSK9i therapy were included. Measurements were performed at baseline and after 6 months of PCSK9i treatment. Endothelial function was assessed as flow-mediated dilation (FMD). Arterial stiffness was measured as pulse wave velocity (PWV) and aortic augmentation index (AIx). Peripheral tissue oxygenation (StO2) as a marker of microvascular function was assessed at the distal extremities using near-infrared spectroscopy camera.
Results:
Six months of PCSK9i therapy decreased LDL-C levels from 141 ± 54 to 60 ± 30 mg/dl (-56 ± 21 %, p < 0.001), FMD significantly increased from 5.4 ± 1.7 % to 6.4 ± 1.9 % (+19 ± 10 %, p < 0.001), PWV decreased in male patients significantly from 8.9 ± 2.1 to 7.9 ± 1.5 m/s (-12 ± 9 %, p = 0.025). AIx decreased from 27.1 ± 10.4 % to 23.0 ± 9.7 % (-16 ± 14 %, p < 0.001), StO2 significantly increased from 67 ± 12 % to 71 ± 11 % (+7 ± 6 %, p = 0.012). Brachial and aortic blood pressure showed no significant changes after six months. There was no correlation between LDL-C reduction and changes in vascular parameters.
Conclusions:
Chronic PCSK9i therapy is associated with sustained improvements in endothelial function, arterial stiffness, and microvascular function independent from lipid lowering.
... nm laser increased NO due to photodissociation of nitrosyl hemoglobin (HbNO) [118]. Stern et al. demonstrated in human volunteers that whole-body irradiation with 445-455 nm blue light increased plasma NOx (nitrite, nitrate, and RXNOs) and blood flow and decreased systolic blood pressure [119], suggesting NO release from photolabile NO metabolites into circulation. ...
Nitric oxide (NO) is a well-known gaseous mediator that maintains vascular homeostasis. Extensive evidence supports that a hallmark of endothelial dysfunction, which leads to cardiovascular diseases, is endothelial NO deficiency. Thus, restoring endothelial NO represents a promising approach to treating cardiovascular complications. Despite many therapeutic agents having been shown to augment NO bioavailability under various pathological conditions, success in resulting clinical trials has remained elusive. There is solid evidence of diverse beneficial effects of the treatment with low-power near-infrared (NIR) light, defined as photobiomodulation (PBM). Although the precise mechanisms of action of PBM are still elusive, recent studies consistently report that PBM improves endothelial dysfunction via increasing bioavailable NO in a dose-dependent manner and open a feasible path to the use of PBM for treating cardiovascular diseases via NO elevation. In particular, the use of NIR light in the NIR-II window (1000–1700 nm) for PBM, which has reduced scattering and minimal tissue absorption with the largest penetration depth, is emerging as a promising therapy. In this review, we update recent findings on PBM and NO.
... Earlier studies have shown that resting HR is affected by the day/night cycle and light levels [22][23][24]. It is known that exposure to light of different colors (wavelengths) and intensities affects HR variability through various mechanisms, including the modulation of sympathovagal balance, the renin-angiotensin-aldosterone system, the endocrine system acting through anterior and posterior hypothalamic stimulation, etc. [25]. ...
Artificial light is characterized by certain features of its impact on the body in terms of its spectral distribution of power, duration of exposure and intensity. Short waves, perceived as blue light, are the strongest synchronizing agent for the circadian system. In the present work, we investigated the features of the circadian rhythms of blood pressure (BP), heart rate (HR), the excretion of electrolytes and the secretion of melatonin in normotensive (Wistar–Kyoto) and hypertensive (SHR) rats under the action of monochromatic blue light in the daytime period. It was found that the exposure of Wistar–Kyoto rats to monochromatic blue light was accompanied by a significant decrease in nighttime and 24h systolic BP. The most remarkable changes are characteristic of the HR in SHR rats under monochromatic light. A significant decrease in HR in each time period was found, but the predominance of nighttime over daytime values remained in SHR animals. There was also a significant increase in the mesor of the HR in SHR rats. Additionally, the amplitude of diastolic BP and HR, as well as the range of oscillations in HR, were significantly increased compared with the standard light pattern. In contrast to SHR rats, the regulation of the circadian rhythms in Wistar–Kyoto rats was more flexible and presented more changes, which may be aimed at the adaptation of the body to environmental conditions. For Wistar–Kyoto rats, an increase in the level of excreted electrolytes was observed under the action of monochromatic light, but no similar changes were found in SHR rats. For Wistar–Kyoto rats, a significant decrease in the urine concentration of aMT6s in the daytime and nighttime periods is characteristic, which results in the loss of the circadian rhythm. In SHR rats, there was a significant decrease in the nighttime content of aMT6s in the urine, while the daytime concentration, on the contrary, increased. The obtained data demonstrate that prolonged exposure to monochromatic blue light in the daytime period affects the circadian structure of the rhythms of the cardiovascular system, the rhythm of electrolyte excretion and the production of epiphyseal melatonin in wild-type and hypertensive animals. In SHR rats, the rhythms of BP and HR exhibit a more rigid pattern.
... This is a key point as such changes may have a systemic impact. Evidence for a systemic effect comes from Stern et al. [25]. They exposed the human body to 450 nm for 30 minutes resulting in significantly elevated heart rate and reduced blood pressure during exposure, but this returned to a normal range relatively rapidly after blue light was removed. ...
Blue light (~400-470nm) is considered potentially detrimental to the retina but is present in natural environmental light. Mitochondrial density is highest in the retina, and they exhibit a prominent optical absorption around 420nm arising from the Soret band of their porphyrins, including in cytochrome-c-oxidase in their respiratory chain. We examine the impact of continuous 420nm at environmental energy levels on retinal mitochondrial metabolism and haemodynamics in vivo in real time using broadband near-infrared spectroscopy. 1h environmental exposure to 420nm induces significant metabolic instability in retinal mitochondria and blood signals, which continues for up to 1h post blue exposure. Porphyrins are important in mitochondrial adenosine triphosphate (ATP) production and cytochrome-c-oxidase is a key part of the electron transport chain through which this is achieved. Hence, environmental 420nm likely restricts respiration and ATP production that may impact on retinal function.
This article is protected by copyright. All rights reserved.
... In this context it may be relevant that blue light exposure to the human body results in decreasing systolic blood pressure and increasing heart rate. It also increases blood flow [42]. ...
Increased blue light exposure has become a matter of concern as it has a range of detrimental effects, but the mechanisms remain unclear. Mitochondria absorb short wavelength light but have a specific absorbance at 420nm at the lower end of the human visual range. This 420nm absorption is probably due to the presence of porphyrin. We examine the impact of 420nm exposure on drosophila melanogaster mitochondria and its impact on fly mobility. Daily 15 mins exposures for a week significantly reduced mitochondrial complex activities and increased mitochondrial inner membrane permeability, which is a key metric of mitochondrial health. Adenosine triphosphate (ATP) levels were not significantly reduced and mobility was unchanged. There are multiple options for energy/time exposure combinations, but we then applied single 420nm exposure of 3h to increase the probability of an effect on ATP and mobility, and both were significantly reduced. ATP and mitochondrial membrane permeability recovered and over corrected at 72h post exposure. However, despite this, normal mobility did not return. Hence, the effect of short wavelengths on mitochondrial function is to reduce complex activity and increasing membrane permeability, but light exposure to reduce ATP and to translate into reduced mobility needs to be sustained.
... For example, in rats, the wound healing of the abdominal flap was accelerated by a blue light stimulus with 50 mW/cm 2 × 10 min/per day (470 nm) by enhancing the local angiogenesis [11]. Furthermore, a recent clinical study showed that 30 min of blue light (453 nm, 42 mW/cm 2 ) treatment decreased the blood pressure by increasing NO releasing into circulating blood in healthy volunteers [12]. Several other studies have also focused on the role of nitric oxide production (NO) under blue light illumination, as NO plays a vital role in maintaining vascular homeostasis [33,34]. ...
Blue light regulates biological function in various cells, such as proliferation, oxidative stress, and cell death. We employed blue light illumination on human umbilical vein endothelial cells utilizing a LED device at 453 nm wavelength and revealed a novel biphasic response on human umbilical vein endothelial cells (HUVECs). The results showed that low fluence blue light irradiation promoted the fundamental cell activities, including cell viability, migration and angiogenesis by activating the angiogenic pathways such as the VEGF signaling pathway. In contrast, high fluence illumination caused the opposite effect on those activities by upregulating pro-apoptotic signaling cascades like ferroptosis, necroptosis and the p53 signaling pathways. Our results provide an underlying insight into photobiomodulation by blue light and may help to implement potential treatment strategies for treating angiogenesis-dependent diseases.
... Failure to consider these wavelengths may have negative consequences for wellbeing and health. For instance, recent studies have shown that high blood pressure can be actively lowered in the presence of UV radiation [1,2]. On the other hand, however, it is a fact that too much ultraviolet radiation can be very harmful and may cause skin cancer or eye damage. ...
The spectral composition of light has a significant influence on human wellbeing, emotion and health. Natural sunlight is often considered as the ideal light source in this regard. Therefore, artificial lighting solutions that mimic natural sunlight are a central research topic in the lighting industry. Another global trend is the monitoring and evaluation of the vital parameters of human beings to improve their health status and their personal lifestyle. Here, we present VitaLight, a laboratory sample for a smart lighting system that aims to interconnect these global trends and consists of VitaWatch, a wristband with functionally integrated sensors that is comfortable to wear on the body, and VitaLUMI, a lighting unit with access to the internet.
... Blue light also produces other non-visual effects, such as the inhibition of pineal melatonin production, an increase in heart rate and the stimulation of cortisol secretion [6][7][8]. Since blue light acts as a neurophysiological stimulant, several therapeutic effects have been described, from depression [9] to a reduction of blood pressure [10]. Besides the positive influence, some studies have indicated negative effects on the balance of circadian cycles and on the quality of sleep after long exposures to blue light, mainly from mobile phones [11]. ...
Over recent years, a technological revolution has taken place in which conventional lighting has been replaced by light emitting diodes (LEDs). Some studies have shown the possibility that blue light from these artificial sources could have deleterious effects on the retina. Considering that people spend a non-negligible time in front of screens from computers and mobile phones, the eyes receive blue light of different intensities depending on the source. Nevertheless, any study about the visual and non-visual effects of blue light must consider precise measurements taken from actual artificial sources. For this reason, we have analyzed the spectral emission of 10 different electronic devices and weighted them according to the hazard caused by blue light to the eyes, comparing the results with solar radiation simulated with a radiative transfer model. The maximum spectral irradiance of the measured electronic devices at 10 cm from the detector was located between 440 nm and 460 nm. The irradiance for blue light hazard ranged from 0.008 to 0.230 Wm−2 depending on the particular characteristics of each electronic device. In contrast, the solar radiances in the same spectral range are larger both under clear and cloudy conditions.
... Because all subjects worked in the fab of a TFT-LCD manufacturing factory, the temperature and humidity was rigorously controlled at a constant range to avoid the generation of particles that would not produce the difference between groups or subjects. Short-term exposure to blue light has been reported to decrease SBP in healthy subjects [23]. In contrast, exposure to high CO 2 levels was reported to be associated with elevated DBP [24]. ...
This cross-sectional study aimed to determine the concentration of indoor volatile organic compounds (VOCs) and to investigate the association between indoor VOCs exposure and the prevalence of hypertension among thin film transistor liquid crystal display (TFT-LCD) workers. A total of 20 canisters were used to collect VOCs samples in the array, cell and module areas over 12 hours and VOCs concentrations were analyzed by the gas chromatography with mass spectrum. Individual information of health examination and lifestyles by self-administrated questionnaire were provided by 155 volunteers. The multivariate regression models were used to evaluate the associations between VOCs exposure, blood pressure and the prevalence of hypertension. The four dominant VOCs were ethanol (1870.8 ± 1754.0 ppb), acetone (689.9 ± 587.4 ppb), isopropyl alcohol (177.1 ± 202.3 ppb) and propylene glycol monomethyl ether acetate (98.2 ± 100.8 ppb), which were identified with the highest level in the module area for ethanol and acetone and in the array area for the others. Subjects exposed to a total level of ethanol, cyclohexanone and toluene ≥ 2500 ppb had an increased systolic blood pressure of 5.95 mmHg (95% confidence interval: 0.20–11.71; p = 0.043) compared with those exposed to <2500 ppb. Exposure to mixed VOCs in the indoor environment might be associated with elevated blood pressure among TFT-LCD workers.
... In addition, especially blue light wavelengths seem to increase the circulating β-endorphin concentration and decrease the systolic blood pressure in humans via nitric oxide related mechanisms in the skin (Albers et al., 2019;Stern et al., 2018). A body of preclinical evidence also suggests that low doses of blue light might have photobiomodulation-like effects in cells as well as in animals, though higher doses might lead to unfavourable outcomes (Serrage et al., 2019). ...
Both sun exposure and serum vitamin D levels have been associated with lower risks of all-cause mortality and chronic age-related diseases, e.g., cancer, diabetes and cardiovascular disease, in epidemiological studies. These associations have mainly been ascribed to beneficial effects of vitamin D. However, a vast body of randomized controlled trials (RCTs) and Mendelian randomization studies have failed to confirm any major health benefits from vitamin D supplementation.
In this review, we present tentative evidence showing that red and near-infrared light, both being present in sunlight, could explain the associations between sunlight exposure and better health status. Body irradiation with red and near-infrared light, usually termed as photobiomodulation (PBM), has demonstrated beneficial effects in animal models of chronic diseases. Beyond this, preliminary evidence from RCTs suggest potential clinical benefit from PBM for chronic diseases. PBM is currently being investigated in many pre-registered clinical trials, results of which will eventually clarify the role of red and near-infrared light in the prevention and treatment of common age-related chronic diseases.
... Свет* -модулирует АД в зависимости от време-ни и характера воздействия (через кожу или через орган зрения). Ультрафиолет и солнечный свет при воздействии на все тело в дневное время -снижение АД за счет модуляции уровня NO ( Stern et al., 2018;Johnson et al., 2016), либо витамина D ( Rostand et al., 2016); Синий свет при воздействии через орган зре-ния в ночное время -повышение АД ( Gubin et al., 2017; Губин и др., 2018), вероятно за счет угнетения продукции эндогенного мелатонина ( Gubin et al., 2019). ...
Многие врачи до сих пор считают, что однократное измерение артериального давления дает достоверную
информацию для принятия диагностического решения и, соответственно, назначения лечения. Однако уже 40
лет назад, задолго до того, как амбулаторный мониторинг артериального давления стал рутинной практи-
кой, было признано, что такая стратегия по сути эквивалента подбрасыванию монеты и приводит к более
чем 40% ложных диагностических заключений (Management Committee, Australian National Blood Pressure Study,
1980). Сегодня мы знаем гораздо больше о природе вариабельности АД и о множестве факторов, которые суще-
ственно влияют на то, какие значения АД высвечиваются на экране (независимо от того, какое устройство
врач или пациент будут использовать для измерения АД). Значительную роль играет как время суток (фаза
суточного ритма), так и циклы ряда других частот, в частности 12-часовой и недельный. Кроме того, времен-
ной фактор сказывается не только на величине АД, но и на производных параметрах его вариабельности. Це-
лью настоящего мини-обзора является схематичное, но емкое представление, почему единичные измерения АД
не только мало-информативны, но и нередко обманчивы. Представленная информация должна быть исполь-
зована прежде всего клиницистами широкого профиля, кардиологами, а также специалистами, вовлеченными
в развитие технологий телемедицины и концепции персонализированной медицины.
Many physicians still believe that single blood pressure (BP) measurements provide reliable information for diagnostic purposes and treatment decisions. However, already 40 years ago, long before ambulatory BP monitoring became available, it was recognized that such strategy is nearly equal to flipping a coin and may end up in over 40% of false diagnostic conclusions (Management Committee, Australian National Blood Pressure Study, 1980). Today we know much more about BP variability (BPV). Plenty of factors heavily influence BP (irrespective of the device doctors or patients are using to measure BP). Not only are BP values influenced at the time of measurement, BPV and circadian characteristics of BP have also been shown to be affected. A significant role is played not just by time of the day (circadian phase and amplitude) but also by rhythms of some other frequencies, for example, 12-hour and about-week. In addition, timing determines not only how high or low blood pressure is at this very moment, but also the derivative parameters of its variability. The purpose of this mini review is to give a schematic but dense idea of why single measurements of blood pressure are not only informative, but often misleading. The presented information should be used primarily by general clinicians, cardiologists, as well as specialists involved in the development of telemedicine technologies and the concept of personalized medicine.
... Blinding participants using a plastic covering to block UVR 4 is possible, but difficult to achieve within logistical and space constraints of dermatology clinics and could be noticed by participants (thus removing blinding). Alternatively, a 'placebo' visible light therapy could be used; however, blue light (within the visible spectrum) may have beneficial effects on related outcomes (specifically blood pressure and endothelial function), 45 and other visible light wavelengths may have unexpected effects (as described above for green light 43 ), and so may not be suitable for placebo controls. ...
Emerging findings suggest that exposure to ultraviolet wavelengths of sunlight modulates metabolic function. Here we review the metabolic effects of exposure to ultraviolet radiation (UVR), focusing on the effects of phototherapies (that administer UVR), and advice to increase sun exposure in individuals enrolled in clinical trials and intervention studies. We identified 25 studies in which the effects of UVR on metabolic outcomes were examined, including: narrowband ultraviolet B phototherapy (nbUVB, n = 12); psoralen ultraviolet A phototherapy (n = 4); other types of UVR phototherapy (n = 5); and sun exposure advice (n = 5). Most studies recruited a small number of participants (≤100), who were middle-aged individuals undergoing treatment for psoriasis flare, with phototherapy or sun exposure advice administered for ≤12 weeks. Data obtained at baseline were usually compared with an endpoint following treatment with UVR, for a limited number of outcomes. There were few studies in which markers of glucose metabolism were assessed, with some beneficial effects of sun exposure (but not phototherapy) reported. LDL-cholesterol levels were lower in individuals receiving sun exposure advice, while treatment with nbUVB reduced blood concentrations of inflammatory markers (C-reactive protein and interleukin-6). Future studies should focus on determining whether the effects of these interventions change with time, and if they are dependent on the source of UVR (i.e. phototherapy or sun exposure) and wavelength(s) of light administered. Furthermore, studies need to measure a variety of (clinical) markers of glucose metabolism, adiposity and inflammation, control for factors such as skin type and sex, and stratify participants for metabolic disease diagnosis.
Objective
Hypertension affects approximately 1.28 billion adults worldwide, driving the search for integrative therapeutic approaches alongside conventional treatments. While chromotherapy, particularly blue light exposure, has historical roots in traditional medicine and its specific impact on blood pressure regulation remains understudied . So, the present study aims to investigate the immediate impact of exposure to blue glass through sunlight on blood pressure in hypertensive individuals.
Methods
This randomized controlled trial was carried out with a sample of 60 hypertensive patients, who were divided into two groups: a study group that received blue glass exposure for 20 min and a control group that received exposure to colourless glass. The primary outcome measures were systolic and diastolic blood pressure, pulse rate, and oxygen saturation levels.
Results
The results of the study revealed statistically significant differences in systolic blood pressure (p=0.006) and pulse rate (p=0.005) after the intervention in the study group and no such changes were noted in the control group.
Conclusions
The findings of this study suggest that blue glass exposure has a significant impact on reducing blood pressure and pulse rate in hypertensive patients, indicating its potential use as a integrative treatment in the management of hypertension.
Mitochondria absorb short wavelengths around 420nm. This is associated with reduced ATP and restricted mobility. The 420-450nm range is a significant element of LED lighting and computer monitors. Here we expose freely moving mice to 420nm or 450nm lighting and show rapidly weight gain within a week. This may be due to reduced mitochondrial demand for circulating carbohydrates. Both groups displayed marked shifts in serum cytokines. Open field mobility was examined. The distance travelled was similar between both experimental groups and their controls. However, both experimental groups showed avoidance of central regions consistent with anxiety-like behaviours. This was significant in the 420nm group whose wavelength exposure is closer to peak mitochondrial absorbance. These data demonstrate the potential hazards of exposure to specific short wavelengths in the visual range now common in the built environment. Data are consistent with a wider literature on systemic problems arising from exposure to short wavelength light.
Cutaneous diseases (such as atopic dermatitis, acne, psoriasis, alopecia and chronic wounds) rank as the fourth most prevalent human disease, affecting nearly one-third of the world’s population. Skin diseases contribute to significant non-fatal disability globally, impacting individuals, partners, and society at large. Recent evidence suggests that specific microbes colonising our skin and its appendages are often overrepresented in disease. Therefore, manipulating interactions of the microbiome in a non-invasive and safe way presents an attractive approach for management of skin and hair follicle conditions. Due to its proven anti-microbial and anti-inflammatory effects, blue light (380 – 495nm) has received considerable attention as a possible ‘magic bullet’ for management of skin dysbiosis. As humans, we have evolved under the influence of sun exposure, which comprise a significant portion of blue light. A growing body of evidence indicates that our resident skin microbiome possesses the ability to detect and respond to blue light through expression of chromophores. This can modulate physiological responses, ranging from cytotoxicity to proliferation. In this review we first present evidence of the diverse blue light-sensitive chromophores expressed by members of the skin microbiome. Subsequently, we discuss how blue light may impact the dialog between the host and its skin microbiome in prevalent skin and hair follicle conditions. Finally, we examine the constraints of this non-invasive treatment strategy and outline prospective avenues for further research. Collectively, these findings present a comprehensive body of evidence regarding the potential utility of blue light as a restorative tool for managing prevalent skin conditions. Furthermore, they underscore the critical unmet need for a whole systems approach to comprehend the ramifications of blue light on both host and microbial behaviour.
Raynaud’s phenomenon (RP) is a condition that causes decreased blood flow to areas perfused by small blood vessels (e.g., fingers, toes). In severe cases, ulceration, gangrene, and loss of fingers may occur. Most treatments focus on inducing vasorelaxation in affected areas by the way of pharmaceuticals. Recently, animal studies have shown that vasorelaxation can be induced by non-coherent blue light (wavelength ~ 430–460 nm) through the actions of melanopsin, a photoreceptive opsin protein encoded by the OPN4 gene. To study this effect in humans, a reliable phototherapy device (PTD) is needed. We outline the construction of a PTD to be used in studying blue light effects on Raynaud’s patients. Our design addresses user safety, calibration, electromagnetic compatibility/interference (EMC/EMI), and techniques for measuring physiological responses (temperature sensors, laser Doppler flow sensors, infrared thermal imaging of the hands). We tested our device to ensure (1) safe operating conditions, (2) predictable, user-controlled irradiance output levels, (3) an ability for measuring physiological responses, and (4) features necessary to enable a double-blinded crossover study for a clinical trial. We also include in the Methods an approved research protocol utilizing our device that may serve as a starting point for clinical study. We introduced a reliable PTD for studying the effects of blue light therapy for patients suffering from Raynaud’s phenomenon and showed that our device is safe and reliable and includes the required measurement vectors for tracking treatment effects throughout the duration of a clinical study.
Mitochondria regulate metabolism, but
solar light influences its rate. Photobiomodulation (PBM) with red light (670 nm)
increases mitochondrial membrane potentials and adenosine triphosphate production
and may increase glucose demand. Here we
show, with a glucose tolerance test, that
PBM of normal subjects significantly reduces
blood sugar levels. A 15 min exposure to
670 nm light reduced the degree of blood
glucose elevation following glucose intake by 27.7%, integrated over 2 h after the
glucose challenge. Maximum glucose spiking was reduced by 7.5%. Consequently,
PBM with 670 nm light can be used to reduce blood glucose spikes following meals.
This intervention may reduce damaging fluctuations of blood glucose on the body.
A series of experimental trials over the past two centuries has put forth Photobiomodulation (PBM) as a treatment modality that utilizes colored lights for various conditions. While in its cradle, PBM was used for treating simple conditions such as burns and wounds, advancements in recent years have extended the use of PBM for treating complex neurodegenerative diseases (NDDs). PBM has exhibited the potential to curb several symptoms and signs associated with NDDs. While several of the currently used therapeutics cause adverse side effects alongside being highly invasive, PBM on the contrary, seems to be broad-acting, less toxic, and non-invasive. Despite being projected as an ideal therapeutic for NDDs, PBM still isn't considered a mainstream treatment modality due to some of the challenges and knowledge gaps associated with it. Here, we review the advantages of PBM summarized above with an emphasis on the common mechanisms that underlie major NDDs and how PBM helps tackle them. We also discuss important questions such as whether PBM should be considered a mainstay treatment modality for these conditions and if PBM's properties can be harnessed to develop prophylactic therapies for high-risk individuals and also highlight important animal studies that underscore the importance of PBM and the challenges associated with it. Overall, this review is intended to bring the major advances made in the field to the spotlight alongside addressing the practicalities and caveats to develop PBM as a major therapeutic for NDDs.
Circadian rhythms are crucial for maintaining vascular function and disruption of these rhythms are associated with negative health outcomes including cardiovascular disease and hypertension. Circadian rhythms are regulated by the central clock within the suprachiasmatic nucleus of the hypothalamus and peripheral clocks located in nearly every cell type in the body, including cells within the heart and vasculature. In this review, we summarize the most recent preclinical and clinical research linking circadian disruption, with a focus on molecular circadian clock mechanisms, in atherosclerosis and hypertension. Furthermore, we provide insight into potential future chrono-therapeutics for hypertension and vascular disease. A better understanding of the influence of daily rhythms in behavior, such as sleep/wake cycles, feeding, and physical activity, as well as the endogenous circadian system on cardiovascular risk will help pave the way for targeted approaches in atherosclerosis and hypertension treatment/prevention.
In Bangladesh, accidents are happening frequently at the railway crossing due to the use of typical manual railway crossing systems/ boom gates. The main reasons are likely having these accidents in the railway crossings due to not possible to stop the train engine mechanism system automatically or instantly such as cars and other vehicles as well as for fewer safety measures in the railway crossing. Currently, there are very few automatic railway crossing systems (without any obstacle detector, just runs with the schedule of the trains crossing) are available, however, all of them are dependent on the national power grid that has no backup plan for any emergency cases. As Bangladesh is running a bit behind in the power generation of its consumption, hence it is not possible to have a continuous power supply at all times. This paper aims to design and develop a railway crossing system with a smart obstacle detector to prevent very common types of accidents in the railway crossing points in Bangladesh. In the railway system, time consumption is the biggest issue that leads to having most of the accidents in the railway crossings. In this research, we design to use two infrared (IR) sensors for opening and closing the railway crossing systems/ gates and the whole system to be controlled by the Arduino. To run the process without having any interruption, we propose to use renewable energy i.e., mainly the solar photovoltaic (PV) power systems which are economic friendly and apply under the national green energy policy towards achieving the sustainable goal.
Systemic glucose levels can be modulated with specific solar wavelengths that influence mitochondrial metabolism. Mitochondrial respiration can be modulated using light that shifts ATP production with exceptional conservation of effect across species, from insects to humans. Known wavelengths have opposing effects of photobiomodulation, with longer wavelengths (660–900 nm red/infrared) increasing ATP production, and 420 nm (blue) light suppressing metabolism. Increasing mitochondrial respiration should result in a greater demand for glucose, and a decrease should result in a reduced demand for glucose. Here we have tested the hypothesis that these wavelengths alter circulating glucose concentration. We first established an oral glucose tolerance test curve in a bumblebee model, which showed sustained increase in systemic glucose beyond that seen in mammals, with a gradual normalisation over eight hours. This extended period of increased systemic glucose provided a stable model for glucose manipulation. Bees were starved overnight and given a glucose load in the morning. In the first group glucose levels were examined at hourly intervals. In the second group, bees were additionally exposed to either 670 nm or 420 nm light and their blood glucose examined. Increasing mitochondrial activity with 670 nm light at the peak of circulating glucose, resulted in a significant 50% reduction in concentration measured. Exposure to 420nm light that retards mitochondrial respiration elevated systemic glucose levels by over 50%. The impact of 670 nm and 420 nm on mitochondria is highly conserved. Hence, different wavelengths of visible light may be used to modulate systemic metabolism bidirectionally and may prove an effective agent in mammals.
The efficacy of blue light therapy in dermatology relies on numerous clinical studies. The safety remains to be a topic of controversy, where potentially deleterious effects were derived from in vitro rather than in vivo experiments. The objectives of this work were 1) to highlight the nuances behind ‘colors’ of blue light, light propagation in tissue and the plurality of modes of action; and 2) to rigorously analyze studies on humans reporting both clinical and histological data from skin biopsies with focus on DNA damage, proliferation, apoptosis, oxidative stress, impact on collagen, elastin, immune cells, and pigmentation. We conclude that blue light therapy is safe for human skin. It induces intriguing skin pigmentation, in part mediated by photoreceptor Opsin‐3, which might have a photoprotective effect against ultraviolet irradiation. Future research needs to unravel photochemical reactions and the most effective and safe parameters of blue light in dermatology. This article is protected by copyright. All rights reserved.
Understanding the compartment fire behavior has a vital importance for fire protection
engineers. For design purposes, whether to use a prescriptive code or performance based on design, life safety and property protection issues are required to be assessed. The use of design fires in computer modelling is the general method to determine fire safety. However, these computer models are generally limited to the input of one design fire, with consideration of the complex interaction between fuel packages and the compartment environment being simplified. Of particular interest is the Heat Release Rate, HRR, as this is the commonly prescribed design parameter for fire modelling. If the HRR is not accurate then it can be subsequently argued that the design scenario may be flawed. Therefore, the selection of the most appropriate fire design scenario is critical, and an increased level of understanding of compartment behavior is an invaluable aid to fire engineering assumptions. This thesis studies 3 types of pool fire geometry to enhance the understanding of the impact and interaction that the size and location of pool fires within an enclosure have upon the compartment fire behavior, also Ethanol pool fires were used. In this present work, we have carried out to analysis the effect of water to extinguish the fire and it and it's tested in 4 different ways with and without water. Also in the result, we can see the effect of water to visibility and also the concentration
of air.
Transcranial photobiomodulation therapy (PBMT) also known as low-level laser therapy (LLLT) relies on the use of red/NIR light to stimulate, preserve and regenerate cells and tissues. In this review, we will present the most important laser types and sources used in the treatment of the brain, required energy densities to provide treatment, and laser delivery techniques to the brain through the cranium, eye, internal ear, and nostril. Various forms of light therapy have been practiced all over the world for many years. Among them, laser therapy has flourished in recent years. More and more laser equipment is being used in this area. The use of PBMT for neuronal stimulation has been studied in various animal and human models and has been shown to improve cerebral metabolic activity and blood flow and provide neuroprotection through anti-inflammatory and antioxidant pathways. In recent years, the concept of thermotherapy for the treatment of brain tumors has become more widespread. Traditionally, heat therapy is divided into hyperthermia, with a moderate increase in the temperature of the treated tissue above the physiological baseline level, and heat ablation, in which even higher temperatures are reached. Recently, intranasal light therapy, light delivery to the brain through the ear and other channels have become attractive and potential treatments for brain diseases. Here we summarize the various methods of delivering light through the nostrils and ear canals using lasers or light-emitting diodes (LEDs), which can be used alone or in combination with transcranial devices or (applied directly to the scalp) to treat a wide range of brain conditions such as the lungs cognitive impairment, Alzheimer's disease, Parkinson's disease, cerebrovascular disease, depression and anxiety, and insomnia. Evidence shows that low-intensity laser therapy improves blood rheology and cerebral blood flow, so there is no need to pierce blood vessels.
Phototherapy has been tried for treating cardiovascular diseases. In particular, ultraviolet and blue visible lights were suggested to be useful due to their nitric oxide (NO)-production ability in the skin. However, the effects of blue light on the arterial contractility is controversial. Here, we hypothesized that appropriate protocol of blue laser can induce selective vasorelaxation by activating vasodilating signaling molecules in arteries. Using organ chamber arterial mechanics, NO assay, Matrigel assay, and microarray, we showed that a 200-Hz, 300-μs, 445-nm pulsed-laser (total energy of 600 mJ; spot size 4 mm) induced selective vasorelaxation, without vasocontraction in rat mesenteric arteries. The laser stimulation increased NO production in the cord blood-endothelial progenitor cells (CB-EPCs). Both the laser-induced vasorelaxation and NO production were inhibited by a non-selective, pan-NO synthase inhibitor, L-NG-Nitro arginine methyl ester. Microarray study in CB-EPCs suggested up-regulation of cryptochrome (CRY)2 as well as NO synthase (NOS)1 and NOSTRIN (NOS trafficking) by the laser. In conclusion, this study suggests that the 445-nm blue puled-laser can induce vasorelaxation possibly via the CRY photoreceptors and NOSs activation. The blue laser-therapy would be useful for treating systemic hypertension as well as improving local blood flow depending on the area of irradiation.
Humans are exposed to varying amounts of ultraviolet radiation (UVR) through sunlight. UVR penetrates into human skin leading to release of neuropeptides, neurotransmitters and neuroendocrine hormones. These messengers released from local sensory nerves, keratinocytes, Langerhans cells (LCs), mast cells, melanocytes and endothelial cells (ECs) modulate local and systemic immune responses, mediate inflammation and promote differing cell biologic effects. In this review, we will focus on both animal and human studies that elucidate the roles of calcitonin gene‐related peptide (CGRP), substance P (SP), nerve growth factor (NGF), nitric oxide and proopiomelanocortin (POMC) derivatives in mediating immune and inflammatory effects of exposure to UVR as well as other cell biologic effects of UVR exposure.
Objectives:
Night shift work is associated with high rates of hypertension and cardiometabolic disease, which are linked to disrupted circadian rhythms. We hypothesized that timed light therapy might improve disrupted circadian rhythms and stabilize diurnal control of blood pressure and glucose in night shift workers.
Methods:
We randomized 24 rotating night shift workers (mean age, 36 ± 13 years, 7 men) who had spent a median of 6 years on rotating night shifts (median, six night shifts per month) to 12 weeks of light therapy or no intervention and compared them with 12 daytime workers (37 ± 11 years, 6 men). We measured oral glucose tolerance (OGTT), 24-h blood pressure and arterial stiffness, and the circadian profiles of melatonin, cortisol, metanephrine and nor-metanephrine at baseline, after 12 weeks of intervention, and 12 weeks after the end of intervention.
Results:
At baseline, fewer night shift workers showed dipper status as compared with daytime workers (29 vs. 58%; P < 0.001). After 12 weeks of light therapy, there was a highly significant increase in the proportion of dippers (to 58%; P < 0.0001). We also observed a significant decrease in serum glucose during OGTT in the light therapy group (-22%; P < 0.05) with no change in serum insulin. Whilst circadian profiles of melatonin and cortisol were unchanged, plasma metanephrine and nor-metanephrine levels were significantly reduced in the light therapy group (P < 0.01).
Conclusion:
Timed light therapy improves diurnal blood pressure control and glucose tolerance in rotating night shift workers. This effect is unrelated to melatonin and cortisol but is paralleled by reduced catecholamine levels.
The first ever venous thrombotic condition associated with spaceflight, an internal jugular vein thrombus requiring anticoagulation, has recently been reported. Systematic investigation of space travel-associated thrombotic risk has not been conducted. Cellular, animal, and human studies performed in ground-based models and in actual weightlessness revealed influences of weightlessness and gravity on the blood coagulation system. However, human study populations were small and limited to highly selected participants. Evidence in individuals with medical conditions and older persons is lacking. Evidence for thrombotic risk in spaceflight is unsatisfactory. This issue deserves further study in heterogeneous, high risk populations to find prevention strategies and to enable safe governmental and touristic human spaceflight.
The application of photobiomodulation therapy (PBMT) for neuronal stimulation has been studied in different animal models and in humans, and has been shown to improve cerebral metabolic activity and blood flow, and provide neuroprotection via anti-inflammatory and antioxidant pathways. Recently, intranasal PBMT (i-PBMT) has become an attractive and potential method for the treatment of brain conditions. Herein, we provide a summary of different intranasal light delivery approaches including a nostril-based portable method and implanted deep-nasal methods for the effective systemic or direct irradiation of the brain. Nostril-based i-PBMT devices are available, using either lasers or LEDs, and can be applied either alone or in combination to transcranial devices (the latter applied directly to the scalp) to treat a wide range of brain conditions such as mild cognitive impairment, Alzheimer’s disease, Parkinson’s disease, cerebrovascular diseases, depression and anxiety as well as insomnia. Evidence shows that nostril-based i-PBMT improves blood rheology and cerebral blood flow, so that, without needing to puncture blood vessels, i-PBMT may have equivalent results to a peripheral intravenous laser irradiation procedure. Up to now, no studies have been conducted to implant PBMT light sources deep within the nose in a clinical setting, but simulation studies suggest that deep-nasal PBMT via cribriform plate and sphenoid sinus might be an effective method to deliver light to the ventromedial part of the prefrontal and orbitofrontal cortex. Home-based i-PBMT, using inexpensive LED applicators, has potential as a novel approach for neurorehabilitation; comparative studies also testing sham and transcranial PBMT are warranted.
Background:
The most appropriate targets for systolic blood pressure to reduce cardiovascular morbidity and mortality among persons without diabetes remain uncertain.
Methods:
We randomly assigned 9361 persons with a systolic blood pressure of 130 mm Hg or higher and an increased cardiovascular risk, but without diabetes, to a systolic blood-pressure target of less than 120 mm Hg (intensive treatment) or a target of less than 140 mm Hg (standard treatment). The primary composite outcome was myocardial infarction, other acute coronary syndromes, stroke, heart failure, or death from cardiovascular causes.
Results:
At 1 year, the mean systolic blood pressure was 121.4 mm Hg in the intensive-treatment group and 136.2 mm Hg in the standard-treatment group. The intervention was stopped early after a median follow-up of 3.26 years owing to a significantly lower rate of the primary composite outcome in the intensive-treatment group than in the standard-treatment group (1.65% per year vs. 2.19% per year; hazard ratio with intensive treatment, 0.75; 95% confidence interval [CI], 0.64 to 0.89; P<0.001). All-cause mortality was also significantly lower in the intensive-treatment group (hazard ratio, 0.73; 95% CI, 0.60 to 0.90; P=0.003). Rates of serious adverse events of hypotension, syncope, electrolyte abnormalities, and acute kidney injury or failure, but not of injurious falls, were higher in the intensive-treatment group than in the standard-treatment group.
Conclusions:
Among patients at high risk for cardiovascular events but without diabetes, targeting a systolic blood pressure of less than 120 mm Hg, as compared with less than 140 mm Hg, resulted in lower rates of fatal and nonfatal major cardiovascular events and death from any cause, although significantly higher rates of some adverse events were observed in the intensive-treatment group. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT01206062.).
The role of vitamin D in curtailing the development of obesity and comorbidities such as the metabolic syndrome (MetS) and type 2 diabetes has received much attention recently. However, clinical trials have failed to conclusively demonstrate the benefits of vitamin D supplementation. In most studies, serum 25-hydroxyvitamin D [25(OH)D] decreases with increasing BMI above normal weight. These low 25(OH)D levels may also be a proxy for reduced exposure to sunlight-derived ultraviolet radiation (UVR). Here we investigate whether UVR and/or vitamin D supplementation modifies the development of obesity and type 2 diabetes in a murine model of obesity. Long-term suberythemal and erythemal UVR significantly suppressed weight gain, glucose intolerance, insulin resistance, nonalcoholic fatty liver disease measures; and serum levels of fasting insulin, glucose, and cholesterol in C57BL/6 male mice fed a high-fat diet. However, many of the benefits of UVR were not reproduced by vitamin D supplementation. In further mechanistic studies, skin induction of the UVR-induced mediator nitric oxide (NO) reproduced many of the effects of UVR. These studies suggest that UVR (sunlight exposure) may be an effective means of suppressing the development of obesity and MetS, through mechanisms that are independent of vitamin D but dependent on other UVR-induced mediators such as NO.
We conducted a systematic review of evidence from randomized controlled trials to answer the following research question: What are the relative effects of different classes of antihypertensive drugs in reducing the incidence of cardiovascular disease outcomes for healthy people at risk of cardiovascular disease?
We searched MEDLINE, EMBASE, AMED (up to February 2011) and CENTRAL (up to May 2009), and reference lists in recent systematic reviews. Titles and abstracts were assessed for relevance and those potentially fulfilling our inclusion criteria were then assessed in full text. Two reviewers made independent assessments at each step. We selected the following main outcomes: total mortality, myocardial infarction and stroke. We also report on angina, heart failure and incidence of diabetes. We conducted a multiple treatments meta-analysis using random-effects models. We assessed the quality of the evidence using the GRADE-instrument.
We included 25 trials. Overall, the results were mixed, with few significant differences, and with no drug-class standing out as superior across multiple outcomes. The only significant finding for total mortality based on moderate to high quality evidence was that beta-blockers (atenolol) were inferior to angiotensin receptor blockers (ARB) (relative risk (RR) 1.14; 95% credibility interval (CrI) 1.02 to 1.28). Angiotensin converting enzyme (ACE)-inhibitors came out inferior to calcium-channel blockers (CCB) regarding stroke-risk (RR 1.19; 1.03 to 1.38), but superior regarding risk of heart failure (RR 0.82; 0.69 to 0.94), both based on moderate quality evidence. Diuretics reduced the risk of myocardial infarction compared to beta-blockers (RR 0.82; 0.68 to 0.98), and lowered the risk of heart failure compared to CCB (RR 0.73; 0.62 to 0.84), beta-blockers (RR 0.73; 0.54 to 0.96), and alpha-blockers (RR 0.51; 0.40 to 0.64). The risk of diabetes increased with diuretics compared to ACE-inhibitors (RR 1.43; 1.12 to 1.83) and CCB (RR 1.27; 1.05 to 1.57).
Based on the available evidence, there seems to be little or no difference between commonly used blood pressure lowering medications for primary prevention of cardiovascular disease. Beta-blockers (atenolol) and alpha-blockers may not be first-choice drugs as they were the only drug-classes that were not significantly superior to any other, for any outcomes. Review registration: CRD database ("PROSPERO") CRD42011001066.
Ecological studies have reported possible effects of sunlight on the risk of several diseases. Little evidence is available on the association between mortality and solar and artificial UV exposure by individual level from prospective studies.
The Swedish Women's Lifestyle and Health cohort study included women aged 30 to 49 years in 1991-1992. Participants completed a questionnaire and were followed-up through linkages to national registries until the end of 2006. Cox models were used to estimate adjusted HRs and 95% CIs for all-cause mortality and for cancer and cardiovascular disease (CVD) mortality.
During 15 years of follow-up, among the 38,472 women included in the present study, 754 deaths occurred: 457 due to cancer and 100 due to CVD. When combining the information on sun exposure from age 10 to 39 years, women who got sunburned twice or more per year during adolescence had a reduced all-cause mortality, compared with women who had been sunburned once or less. A reduced risk for all-cause and CVD mortality was observed in women who went on sunbathing vacations more than once a year over three decades. Solarium use once or more per month for at least one decade increased the risk of all-cause mortality, when compared with women who never used a solarium.
Solar UV exposure was associated with reduced overall and CVD mortality, whereas artificial UV exposure was associated with increased overall and cancer mortality among Swedish women.
Moderate sun exposure may protect against cause-specific mortality.
Sunlight influences the physiology of the human skin in beneficial as well as harmful ways, as has been shown for UV light. However, little is known about the effects of other wavelengths of solar irradiation. In this study we irradiated human keratinocytes and skin-derived endothelial cells with light-emitting-diode devices of distinct wavelengths to study the effects on cell physiology. We found that light at wavelengths of 632-940 nm has no effect, but irradiation with blue light at 412-426 nm exerts toxic effects at high fluences. Light at 453 nm is nontoxic up to a fluence of 500 J/cm(2). At nontoxic fluences, blue light reduces proliferation dose dependently by up to 50%, which is attributable to differentiation induction as shown by an increase of differentiation markers. Experiments with BSA demonstrate that blue-light irradiation up to 453 nm photolytically generates nitric oxide (NO) from nitrosated proteins, which is known to initiate differentiation in skin cells. Our data provide evidence for a molecular mechanism by which blue light may be effective in treating hyperproliferative skin conditions by reducing proliferation due to the induction of differentiation. We observed a photolytic release of NO from nitrosated proteins, indicating that they are light acceptors and signal transducers up to a wavelength of 453 nm.
Although hitherto considered as a strictly locally acting vasodilator, results from recent clinical studies with inhaled nitric oxide (NO) indicate that NO can exert effects beyond the pulmonary circulation. We therefore sought to investigate potential remote vascular effects of intra-arterially applied aqueous NO solution and to identify the mechanisms involved. On bolus application of NO into the brachial artery of 32 healthy volunteers, both diameter of the downstream radial artery and forearm blood flow increased in a dose-dependent manner. Maximum dilator responses were comparable to those after stimulation of endogenous NO formation with acetylcholine and bradykinin. Response kinetics and pattern of NO decomposition suggested that despite the presence of hemoglobin-containing erythrocytes, a significant portion of NO was transported in its unbound form. Infusion of NO (36 micromol/min) into the brachial artery increased levels of plasma nitroso species, nitrite, and nitrate in the draining antecubital vein (by < 2-fold, 30-fold, and 4-fold, respectively), indicative of oxidative and nitrosative chemistry. Infused N-oxides were inactive as vasodilators whereas S-nitrosoglutathione dilated conduit and resistance arteries. Our results suggest that NO can be transported in bioactive form for significant distances along the vascular bed. Both free NO and plasma nitroso species contribute to the dilation of the downstream vasculature.
It has recently been shown that nitrosyl complexes of hemoglobin (NO-Hb) are sensitive to low-level blue laser irradiation, suggesting that laser irradiation can facilitate the release of biologically active nitric oxide (NO), which can affect tissue perfusion. The aim of this study was to evaluate the therapeutic value of blue laser irradiation for local tissue perfusion after surgical intervention. Blood was withdrawn from a rat, exposed to NO and infused back to the same rat or used for in vitro experiments. In vitro, an increase of NO-Hb levels (electron paramagnetic resonance spectroscopy) up to 15 microM in rat blood did not result in the release of detectable amounts of NO (NO selective electrode). Blue laser irradiation of NO-Hb in blood caused decomposition of NO-Hb complexes and release of free NO. Systemic infusion of NO-Hb in rats affected neither systemic circulation (mean arterial pressure) nor local tissue perfusion (Doppler blood flow imaging system). In contrast, a clear enhancement of local tissue perfusion was observed in epigastric flap when elevated NO-Hb levels in blood were combined with local He-Cd laser irradiation focused on the left epigastric artery. The enhancement of regional tissue perfusion was not accompanied by any detectable changes in systemic circulation. This study demonstrates that blue laser irradiation improves local tissue perfusion in a controlled manner stimulating NO release from NO-Hb complexes.
Background
Only a few studies have investigated the relationship between neck circumference and cardiometabolic risk. The aim of this study was to assess the relationships between neck circumference, waist circumference, metabolic variables and arterial stiffness in a group of overweight and obese subjects evaluating a possible independent role of neck circumference in determining arterial stiffness.
Methods and results
We studied 95 subjects (53 women) with an age range of 20–77 years and body mass index range from 25.69 to 47.04 kg/m2. In each subject we evaluated body mass index, waist, hip and neck circumference, systolic and diastolic blood pressure, insulin, fasting glucose, cholesterol, low-density lipoprotein and high-density lipoprotein cholesterol and triglycerides. Arterial stiffness was assessed by carotid-femoral pulse wave velocity (PWVcf) and carotid-radial pulse wave velocity (PWVcr). Both PWVcf and PWVcr were higher in subjects with high values of neck circumference compared with subjects with normal values of neck circumference. Subjects with high values of neck circumference and abdominal obesity presented higher values of mean arterial pressure, PWVcr and homeostasis model assessment (HOMA) index and lower values of high-density lipoprotein than subjects with only abdominal obesity. Two models of stepwise multiple regression were performed in order to evaluate the combined effect of independent variables on arterial stiffness. In the first model PWVcf was considered a dependent variable, and age, gender, systolic blood pressure, triglycerides, high-density lipoprotein cholesterol, waist circumference, neck circumference, HOMA index and the use of anti-hypertensive medications were considered independent variables. Age, systolic blood pressure, triglycerides and waist circumference were significant predictors of PWVcf, explaining 65% of its variance. In the second model, in which PWVcr was considered a dependent variable, neck circumference and gender were significant predictors of PWVcr, explaining 24% of its variance.
Conclusions
These findings emphasise the need to measure not only waist but even neck circumference to better stratify and identify individuals at increased cardiometabolic risk, as upper-body subcutaneous fat is a novel, easily measured fat depot.
With observational epidemiological studies it has been possible in the 1950-60 s to identify what has been called cardiovascular risk factors. The multifactorial origin of atherothrombotic cardiovascular disease has been elucidated and in multifactorial intervention trials it was demonstrated that lifestyle changes related to smoking, diet and exercise can prevent the incidence of premature cardiovascular events. The application of that knowledge at the level of the community has resulted in a reversal of the cardiovascular disease epidemic. More investment is needed in the prevention of the development of cardiovascular risk from childhood onwards. More studies are needed to examine the long-term effects of low-intensity exposure to environmental factors on the cardiovascular system using the most appropriate study design and biosensors. More epidemiological studies are needed to evaluate societal changes on cardiovascular disease. Given the actual knowledge on how to prevent cardiovascular disease there is a need for a shift from aetiological epidemiological research into preventive research.
Background:
We assessed the long-term effects of a Mediterranean diet on circulating levels of endothelial progenitor cells (EPCs) and the carotid intima-media thickness (CIMT) in patients with type 2 diabetes.
Design:
This was a parallel, two-arm, single-centre trial.
Methods:
Two hundred and fifteen men and women with newly diagnosed type 2 diabetes were randomized to a Mediterranean diet (n = 108) or a low-fat diet (n = 107). The primary outcome measures were changes in the EPC count and the CIMT of the common carotid artery after the treatment period defined as the end of trial (EOT).
Results:
At the EOT, both the CD34(+)KDR(+) and CD34(+)KDR(+)CD133(+) counts had increased with the Mediterranean diet compared with the low-fat diet (p < 0.05 for both). At the EOT evaluation, there was a significant (p = 0.024) difference of -0.025 mm in the CIMT favouring the Mediterranean diet. Compared with the low-fat diet, the rate of regression in the CIMT was higher in the Mediterranean diet group (51 vs. 26%), whereas the rate of progression was lower (25 vs. 50%) (p = 0.032 for both). Changes in the CIMT were inversely correlated with the changes in EPC levels (CD34(+)KDR(+), r = -0.24, p = 0.020; CD34(+)KDR(+)CD133(+), r = -0.28, p = 0.014). At the EOT, changes in levels of HbA1c, HOMA, total cholesterol, high-density lipoprotein cholesterol and systolic blood pressure were significantly greater with the Mediterranean diet than with the low-fat diet.
Conclusion:
Compared with a low-fat diet, a long-term trial with Mediterranean diet was associated with an increase in circulating EPCs levels and prevention of the progression of subclinical atherosclerosis in patients with newly diagnosed type 2 diabetes.
Objective:
Women with active sunlight exposure habits experience a lower mortality rate than women who avoid sun exposure; however, they are at an increased risk of skin cancer. We aimed to explore the differences in main causes of death according to sun exposure.
Methods:
We assessed the differences in sun exposure as a risk factor for all-cause mortality in a competing risk scenario for 29 518 Swedish women in a prospective 20-year follow-up of the Melanoma in Southern Sweden (MISS) cohort. Women were recruited from 1990 to 1992 (aged 25-64 years at the start of the study). We obtained detailed information at baseline on sun exposure habits and potential confounders. The data were analysed using modern survival statistics.
Results:
Women with active sun exposure habits were mainly at a lower risk of cardiovascular disease (CVD) and noncancer/non-CVD death as compared to those who avoided sun exposure. As a result of their increased survival, the relative contribution of cancer death increased in these women. Nonsmokers who avoided sun exposure had a life expectancy similar to smokers in the highest sun exposure group, indicating that avoidance of sun exposure is a risk factor for death of a similar magnitude as smoking. Compared to the highest sun exposure group, life expectancy of avoiders of sun exposure was reduced by 0.6-2.1 years.
Conclusion:
The longer life expectancy amongst women with active sun exposure habits was related to a decrease in CVD and noncancer/non-CVD mortality, causing the relative contribution of death due to cancer to increase.
The age-specific relevance of blood pressure to cause-specific mortality is best assessed by collaborative meta-analysis of individual participant data from the separate prospective studies. Methods Information was obtained on each of one million adults with no previous vascular disease recorded at baseline in 61 prospective observational studies of blood pressure and mortality. During 12.7 million person-years at risk, there were about 56 000 vascular deaths (12 000 stroke, 34000 ischaemic heart disease [IHD], 10000 other vascular) and 66 000 other deaths at ages 40-89 years. Meta-analyses, involving "time-dependent" correction for regression dilution, related mortality during each decade of age at death to the estimated usual blood pressure at the start of that decade. Findings Within each decade of age at death, the proportional difference in the risk of vascular death associated with a given absolute difference in usual blood pressure is about the same down to at least 115 mm Hg usual systolic blood pressure (SBP) and 75 mm Hg usual diastolic blood pressure (DBP), below which there is little evidence. At ages 40-69 years, each difference of 20 mm Hg usual SBP (or, approximately equivalently, 10 mm Hg usual DBP) is associated with more than a twofold difference in the stroke death rate, and with twofold differences in the death rates from IHD and from other vascular causes. All of these proportional differences in vascular mortality are about half as extreme at ages 80-89 years as at,ages 40-49 years, but the annual absolute differences in risk are greater in old age. The age-specific associations are similar for men and women, and for cerebral haemorrhage and cerebral ischaemia. For predicting vascular mortality from a single blood pressure measurement, the average of SBP and DBP is slightly more informative than either alone, and pulse pressure is much less informative. Interpretation Throughout middle and old age, usual blood pressure is strongly and directly related to vascular (and overall) mortality, without any evidence of a threshold down to at least 115/75 mm Hg.
Background and aims:
To investigate if frequency of outdoor recreational activity (ORA) predicts cardiovascular disease (CVD) mortality, independent of serum 25(OH)D concentration.
Methods and results:
Baseline data on ORA and serum 25(OH)D, collected from 11,746 participants aged 30-90 years in the Third National Health and Nutrition Examination Survey during 1988-1994, were linked to the National Death Index for assessment of CVD deaths from baseline through December 2006. CVD mortality as a primary cause of death was assessed during a mean follow up of 12.9 (SD, 4.2) years. There were 1519 CVD deaths during follow up. A strong positive association was observed between frequency of ORA in the last month and serum 25(OH)D (p < 0.001). Compared to participants who did no ORA in the last month, the hazard ratio (HR) of CVD mortality was 0.72 (95% confidence interval 0.58-0.90) for those doing ORA 1-4 times, 0.64 (0.47-0.89) for 5-12 times, 0.70 (0.56-0.89) for 13-30 times and 0.63 (0.47-0.84) for ≥30 times (p-trend < 0.001), in a Cox proportional hazards regression model which included 25(OH)D and CVD risk factors. Serum 25(OH)D was inversely associated with CVD mortality (p-trend, 0.01) in this same model.
Conclusions:
An inverse association between ORA and CVD mortality was observed independent of 25(OH)D. The underlying mechanism for this association may not involve 25(OH)D hence, further studies are warranted to confirm and investigate the underlying mechanism.
Background The benefits of reducing blood pressure on the risks of major cardiovascular disease are well established, but uncertainty remains about the comparative effects of different blood-pressure-lowering regimens. We aimed to estimate effects of strategies based on different drug classes (angiotensin-converting-enzyme [ACE] inhibitors, calcium antagonists, angiotensin-receptor blockers [ARBs], and diuretics or P blockers) or those targeting different blood pressure goals, on the risks of major cardiovascular events and death. Methods We did seven sets of prospectively-designed overviews with data from 29 randomised trials (n=162 341). The trial eligibility criteria, primary outcomes, and main hypotheses were specified before the result of any contributing trial was known. Findings In placebo-controlled trials the relative risks of total major cardiovascular events were reduced by regimens based on ACE inhibitors (22%; 95% Cl 17-27) or calcium antagonists (18%; 5-29). Greater risk reductions were produced by regimens that targeted lower blood pressure goals (15%; 5-24). ARB-based regimens reduced the risks of total major cardiovascular events (10%; 4-17) compared with control regimens. There were no significant differences in total major cardiovascular events between regimens based on ACE inhibitors, calcium antagonists, or diuretics or P blockers, although ACE-inhibitor-based regimens reduced blood pressure less. There was evidence of some differences between active regimens in their effects on cause-specific outcomes. For every outcome other than heart failure, the difference between randomised groups in achieved blood pressure reduction was directly related to the observed difference in risk. Interpretation Treatment with any commonly-used regimen reduces the risk of total major cardiovascular events, and larger reductions in blood pressure produce larger reductions in risk.
The benefits of reducing blood pressure on the risks of major cardiovascular disease are well established, but uncertainty remains about the comparative effects of different blood-pressure-lowering regimens. We aimed to estimate effects of strategies based on different drug classes (angiotensin-converting-enzyme [ACE] inhibitors, calcium antagonists, angiotensin-receptor blockers [ARBs], and diuretics or β blockers) or those targeting different blood pressure goals, on the risks of major cardiovascular events and death.
Human skin contains photo-labile nitric oxide (NO) derivates like nitrite and S-nitrosothiols, which upon UVA radiation decompose under high-output NO formation and exert NO-specific biological responses like increased local blood flow or reduced blood pressure.
In order to avoid the injurious effects of UVA radiation, we here investigated the mechanism and biological relevance of blue light (420 - 453 nm)-induced non-enzymatic NO generation from photo-labile nitric oxide derivates in human skin in vitro and in vivo.
As quantified by chemiluminescence detection (CLD), at phyisiological pH-values blue light at 420 or 453 nm induced a significant NO formation from S-nitroso albumin and also from aqueous nitrite solutions by a to date not entirely identified Cu(1+)-dependent mechanism. As detected by electron paramagnetic resonance (EPR) spectrometry in vitro with human skin specimens, blue light irradiation significantly increased the intradermal levels of free NO. As detected by CLD in vivo in healthy volunteers, irradiation of human skin with blue light induced a significant emanation of NO from the irradiated skin area as well as a significant translocation of NO from the skin surface into the underlying tissue. In parallel, blue light irradiation caused a rapid and significant rise in local cutaneous blood flow as detected non-invasively by using microlightguide spectrophotometry.
Irradiation of human skin with moderate doses of blue light caused a significant increase in enzyme-independent cutaneous NO formation as well as NO-dependent local biological responses, i.e. increased blood flow. The effects were attributed to blue light-induced release of NO from cutaneous photo-labile NO derivates. Thus, in contrast to UVA, blue light-induced NO generation might be therapeutically used in the treatment of systemic and local hemodynamic disorders that are based on impaired physiological NO production or bio-availability.
— The reduced pyridine coenzymes NADPH and NADH produced superoxide anion(“CK”) from ground state molecular oxygen when irradiated by ultraviolet (UV) radiation extending from 290 to 405 nm as detected by cytochrome c reduction. Superoxide dismutase (SOD), but not catalase or heat-inactivated SOD, decreased the amount of cytochrome c reduced, indicating that O2− was responsible for the reduction of cytochrome c. Decreased oxygen tension during irradiation also inhibited production of O2−. Quantum yields for the production of the anion were in the region of 10−7 to 10−9 mol per photon. These data indicate that NADH and NADPH can act as type II photosensitizers of both far-and near-UV radiation, and that the deleterious biological effects of exposure to these radiations such as erythema and dermal carcinogenesis may be mediated at least in part through the generation of O2−.
Background:
Flow-mediated dilation (FMD) is an accepted technique to quantify endothelial function and has shown to have prognostic value for future cardiovascular disease (CVD). The predictive strength of FMD in CVD patients compared to populations not diagnosed for CVD warrants further investigation. We systematically reviewed prospective studies that investigated the association between brachial FMD and future cardiovascular events, with particular focus on the role of underlying health status.
Methods:
To obtain eligible studies, several literature databases were systematically searched through March 2011. Pooled overall risk estimates were calculated separately for continuous risk estimates for CVD (per 1% higher FMD) and for categorical risk estimates for CVD (having high vs. low FMD), based on random-effects models.
Results:
A total of 23 studies including 14,753 subjects were eligible for inclusion in the meta-analysis. For studies reporting continuous risk estimates, the pooled overall CVD risk was 0.92 (95%CI: 0.88; 0.95) per 1% higher FMD. The observed association seemed stronger (P-value<0.01) in diseased populations than in asymptomatic populations (0.87 (95%CI: 0.83; 0.92) and 0.96 (95%CI: 0.92; 1.00) per 1% higher FMD, respectively). For studies reporting categorical risk estimates, the pooled overall CVD risk for high vs. low FMD was similar in both types of populations, on average 0.49 (95%CI: 0.39; 0.62).
Conclusions:
Our findings show that brachial FMD is inversely associated with future CVD events, with some indications for a stronger relation in diseased populations. Endothelial dysfunction may be considered relevant for classifying subjects in terms of CVD risk.
In patients with coronary artery disease (CAD) medically managed according to currently accepted guidelines, we tested whether a 1-month dietary intervention with flavanol-containing cocoa leads to an improvement of endothelial dysfunction and whether this is associated with an enhanced number and function of circulating angiogenic cells (CACs).
Dietary flavanols can improve endothelial dysfunction. The CACs, also termed endothelial progenitor cells, are critical for vascular repair and maintenance of endothelial function.
In a randomized, controlled, double-masked, cross-over trial, 16 CAD patients (64+/-3 years of age) received a dietary high-flavanol intervention (HiFI [375 mg]) and a macronutrient- and micronutrient-matched low-flavanol intervention (LoFI [9 mg]) twice daily in random order over 30 days.
Endothelium-dependent vasomotor function, as measured by flow-mediated vasodilation of the brachial artery, improved by 47% in the HiFI period compared with the LoFI period. After HiFI, the number of CD34+/KDR+-CACs, as measured by flow cytometry, increased 2.2-fold as compared with after LoFI. The CAC functions, as measured by the capacity to survive, differentiate, proliferate, and to migrate were not different between the groups. The HiFI led to a decrease in systolic blood pressure (mean change over LoFI: -4.2+/-2.7 mm Hg), and increase in plasma nitrite level (mean change over LoFI: 74+/-32 nM). Applying a mixed-effects linear regression model, the results demonstrated a significant increase in flow-mediated vasodilation and a decrease in systolic blood pressure with increasing levels of CD34+/KDR+-CACs.
Sustained improvements in endothelial dysfunction by regular dietary intake of flavanols are associated with mobilization of functional CACs. (Effect of Cocoa Flavanols on Vascular Function in Optimally Treated Coronary Artery Disease Patients: Interaction Between Endothelial Progenitor Cells, Reactivity of Micro- and Macrocirculation; NCT00553774).
Human skin contains photolabile nitric oxide derivates like nitrite and S-nitroso thiols, which after UVA irradiation, decompose and lead to the formation of vasoactive NO.
Here, we investigated whether whole body UVA irradiation influences the blood pressure of healthy volunteers because of cutaneous nonenzymatic NO formation.
As detected by chemoluminescence detection or by electron paramagnetic resonance spectroscopy in vitro with human skin specimens, UVA illumination (25 J/cm(2)) significantly increased the intradermal levels of free NO. In addition, UVA enhanced dermal S-nitrosothiols 2.3-fold, and the subfraction of dermal S-nitrosoalbumin 2.9-fold. In vivo, in healthy volunteers creamed with a skin cream containing isotopically labeled (15)N-nitrite, whole body UVA irradiation (20 J/cm(2)) induced significant levels of (15)N-labeled S-nitrosothiols in the blood plasma of light exposed subjects, as detected by cavity leak out spectroscopy. Furthermore, whole body UVA irradiation caused a rapid, significant decrease, lasting up to 60 minutes, in systolic and diastolic blood pressure of healthy volunteers by 11+/-2% at 30 minutes after UVA exposure. The decrease in blood pressure strongly correlated (R(2)=0.74) with enhanced plasma concentration of nitrosated species, as detected by a chemiluminescence assay, with increased forearm blood flow (+26+/-7%), with increased flow mediated vasodilation of the brachial artery (+68+/-22%), and with decreased forearm vascular resistance (-28+/-7%).
UVA irradiation of human skin caused a significant drop in blood pressure even at moderate UVA doses. The effects were attributed to UVA induced release of NO from cutaneous photolabile NO derivates.
— Hemolysis induced by irradiation with ultraviolet (UV) light at 254 nm showed a pronounced oxygen effect: under irradiation in vacuum, the rate of hemolysis was decreased by an order of magnitude. Irradiation at 254 nm in air but not under vacuum caused the peroxidation of erythrocyte membrane lipids. These results suggest that membrane lipid photoperoxidation is one of the causative factors of UV hemolysis. Irradiation at different wavelengths showed that UV-induced lipid photoperoxidation in erythrocyte membranes developed while the antioxidant α-tocopherol was directly photooxidized. It is shown that the process of lipid photolysis in erythrocyte membranes involves sensitization, possibly by protoporphyrin, whose presence in liposomes accelerates the photoperoxidation at 254 and 365 nm of unsaturated fatty acid residues in lecithin. Possible mechanisms of photochemical damage to erythrocyte membranes are discussed.
The initial yields of DNA-to-protein crosslinks (dpc) caused by ionizing and nonionizing radiations were compared, with emphasis upon values within the biological dose ranges (D0). Induction of dpc in cold (0-0.5 degrees C) human P3 teratocarcinoma cells was measured by using alkaline elution techniques after exposure to monochromatic UVC (254 nm), UVB (313 nm), UVA (365 and 405 nm), and blue light (434 nm). UVC and UVB light induced detectable numbers (about 100 dpc per cell per D0). Monochromatic UVA radiations produced yields about 8 times higher than UVC or UVB (for 365 nm, about 1500 dpc per cell per D0) Similar results at low doses were obtained for measurements of single-strand breaks induced by the different radiations. The action spectra for dpc were closely similar. The biological significance of these relatively high numbers of DNA lesions caused by environmental nonionizing radiation that readily penetrates into human skin is not understood.
Blood pressure measurements recorded during the medical Research Council's treatment trial for mild hypertension have been analysed according to the calendar month in which the readings were made. For each age, sex, and treatment group systolic and diastolic pressures were higher in winter than in summer. The seasonal variation in blood pressure was greater in older than in younger subjects and was highly significantly related to maximum and minimum daily air temperature measurements but not to rainfall.
Previous studies have suggested that there is an increase in cardiac events in the morning. Fewer data relate cardiac events to months of the year and season.
We analyzed all monthly death certificate data from Los Angeles County, California, for death caused by coronary artery disease from 1985 through 1996 (n=222 265). The mean number of deaths was highest in December at 1808 and January at 1925; the lowest rates were in June, July, August, and September at 1402, 1424, 1418, and 1371, respectively. December and January had significantly higher rates than would be expected from a uniform distribution of monthly deaths (P=0.00001). The percent of yearly coronary deaths was defined by the quadratic U-shaped equation [percent=13.1198-1.5238(month)+0. 0952(month(2)), where January=1, February=2, etc]. When monthly deaths were plotted by year, there was a decrease from 1985 through 1996. Monthly mortality correlated inversely with temperature. During the months with the highest frequency of death (December, January), however, there was an increase in deaths that peaked around the holiday season and then fell, which could not be explained solely on the basis of the daily temperature change.
Even in the mild climate of Los Angeles County, there are seasonal variations in the development of coronary artery death, with approximately 33% more deaths occurring in December and January than in June through September. Although cooler temperatures may play a role, other factors such as overindulgence or the stress of the holidays might also contribute to excess deaths during these peak times.
Many lifestyle-related risk factors for coronary heart disease have been identified, but little is known about their effect on the risk of disease when they are considered together.
We followed 84,129 women participating in the Nurses' Health Study who were free of diagnosed cardiovascular disease, cancer, and diabetes at base line in 1980. Information on diet and lifestyle was updated periodically. During 14 years of follow-up, we documented 1128 major coronary events (296 deaths from coronary heart disease and 832 nonfatal infarctions). We defined subjects at low risk as those who were not currently smoking, had a body-mass index (the weight in kilograms divided by the square of the height in meters) under 25, consumed an average of at least half a drink of an alcoholic beverage per day, engaged in moderate-to-vigorous physical activity (which could include brisk walking) for at least half an hour per day, on average, and scored in the highest 40 percent of the cohort for consumption of a diet high in cereal fiber, marine n-3 fatty acids, and folate, with a high ratio of polyunsaturated to saturated fat, and low in trans fat and glycemic load, which reflects the extent to which diet raises blood glucose levels.
Many of the factors were correlated, but each independently and significantly predicted risk, even after further adjustment for age, family history, presence or absence of diagnosed hypertension or diagnosed high cholesterol level, and menopausal status. Women in the low-risk category (who made up 3 percent of the population) had a relative risk of coronary events of 0.17 (95 percent confidence interval, 0.07 to 0.41) as compared with all the other women. Eighty-two percent of coronary events in the study cohort (95 percent confidence interval, 58 to 93 percent) could be attributed to lack of adherence to this low-risk pattern.
Among women, adherence to lifestyle guidelines involving diet, exercise, and abstinence from smoking is associated with a very low risk of coronary heart disease.
There is persuasive evidence that each of the three main types of skin cancer, basal cell carcinoma (BCC), squamous cell carcinoma (SCC) and melanoma, is caused by sun exposure. The incidence rate of each is higher in fairer skinned, sun-sensitive rather than darker skinned, less sun-sensitive people; risk increases with increasing ambient solar radiation; the highest densities are on the most sun exposed parts of the body and the lowest on the least exposed; and they are associated in individuals with total (mainly SCC), occupational (mainly SCC) and non-occupational or recreational sun exposure (mainly melanoma and BCC) and a history of sunburn and presence of benign sun damage in the skin. That UV radiation specifically causes these skin cancers depends on indirect inferences from the action spectrum of solar radiation for skin cancer from studies in animals and the action spectrum for dipyrimidine dimers and evidence that presumed causative mutations for skin cancer arise most commonly at dipyrimidine sites. Sun protection is essential if skin cancer incidence is to be reduced. The epidemiological data suggest that in implementing sun protection an increase in intermittency of exposure should be avoided, that sun protection will have the greatest impact if achieved as early as possible in life and that it will probably have an impact later in life, especially in those who had high childhood exposure to solar radiation.
The age-specific relevance of blood pressure to cause-specific mortality is best assessed by collaborative meta-analysis of individual participant data from the separate prospective studies.
Information was obtained on each of one million adults with no previous vascular disease recorded at baseline in 61 prospective observational studies of blood pressure and mortality. During 12.7 million person-years at risk, there were about 56000 vascular deaths (12000 stroke, 34000 ischaemic heart disease [IHD], 10000 other vascular) and 66000 other deaths at ages 40-89 years. Meta-analyses, involving "time-dependent" correction for regression dilution, related mortality during each decade of age at death to the estimated usual blood pressure at the start of that decade.
Within each decade of age at death, the proportional difference in the risk of vascular death associated with a given absolute difference in usual blood pressure is about the same down to at least 115 mm Hg usual systolic blood pressure (SBP) and 75 mm Hg usual diastolic blood pressure (DBP), below which there is little evidence. At ages 40-69 years, each difference of 20 mm Hg usual SBP (or, approximately equivalently, 10 mm Hg usual DBP) is associated with more than a twofold difference in the stroke death rate, and with twofold differences in the death rates from IHD and from other vascular causes. All of these proportional differences in vascular mortality are about half as extreme at ages 80-89 years as at ages 40-49 years, but the annual absolute differences in risk are greater in old ag