Article

Effects of aerobic interval training on arterial stiffness and microvascular function in patients with metabolic syndrome

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Abstract

The authors determined the effect of high-intensity aerobic interval training on arterial stiffness and microvascular dysfunction in patients with metabolic syndrome with hypertension. Applanation tonometry was used to measure arterial stiffness and laser Doppler flowmetry to assess microvascular dysfunction before and after 6 months of stationary cycling (training group; n = 23) in comparison to a group that remained sedentary (control group; n = 23). While no variable improved in controls, hypertension fell from 79% (59%-91%) to 41% (24%-61%) in the training group, resulting in lower systolic and diastolic pressures than controls (-12 ± 3 and -6 ± 2 mm Hg, P < .008). Arterial stiffness declined (-17% augmentation index, P = .048) and reactive hyperemia increased (20%, P = .028) posttreatment in the training group vs controls. Blood constituents associated with arterial stiffness and a prothrombotic state (high-sensitivity C-reactive protein, fibrinogen, platelets, and erythrocytes) remained unchanged in the training and control groups. In summary, 6 months of an intense aerobic exercise program reduced both arterial stiffness and microvascular dysfunction in patients with metabolic syndrome despite unchanged blood-borne cardiovascular risk factors. Training lowers blood flow resistance in central and peripheral vascular beds in a coordinated fashion, resulting in clinically relevant reductions in hypertension.

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... Although several studies examined the potential role of exercise on arterial stiffness in MetS to lower CVD risk [285][286][287][288][289]. An 8-week aerobic training program lowered carotid-femoral PWV in MetS [285]. ...
... An 8-week aerobic training program lowered carotid-femoral PWV in MetS [285]. A 6-month intense aerobic exercise program lowered both carotid-femoral PWV and microvascular dysfunction in MetS [286]. However, an 8-week progressive resistance exercise training did not decrease the carotid-femoral PWV in MetS or healthy controls [287]. ...
Chapter
Metabolic syndrome (MetS) is a global health challenge characterized as a group of risk factors for developing atherosclerotic cardiovascular disease. Although visceral adipose tissue, adipocyte dysfunction, chronic low-grade inflammation, and insulin resistance are fundamental to MetS, the exact biochemical mechanisms underlying this disease state remain unclear. Numerous biomarkers, however, have been proposed to improve our understanding of its complex pathophysiology and facilitate diagnosis. This review examines these biomarkers and clarifies their potential roles in the pathogenesis, diagnosis, prediction, progression, and severity of MetS and MetS-related disorders.
... Approaches to control high blood pressure include lifestyle changes like reducing salt intake, body weight, quitting smoking, and engaging in regular exercise [1]. A program of intense aerobic exercise lowers brachial blood pressure in patients with metabolic syndrome (MetS) [2,3] through lowering arterial stiffness [4,5] and enhancing the vasodilatory response of peripheral vasculature at least when tested using transient ischemia [5,6]. However, frequently, exercise programs are not effective enough for individuals with hypertension to withdrawn from the exercise program, and clinicians resort to prescribing antihypertensive medication. ...
... Approaches to control high blood pressure include lifestyle changes like reducing salt intake, body weight, quitting smoking, and engaging in regular exercise [1]. A program of intense aerobic exercise lowers brachial blood pressure in patients with metabolic syndrome (MetS) [2,3] through lowering arterial stiffness [4,5] and enhancing the vasodilatory response of peripheral vasculature at least when tested using transient ischemia [5,6]. However, frequently, exercise programs are not effective enough for individuals with hypertension to withdrawn from the exercise program, and clinicians resort to prescribing antihypertensive medication. ...
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Objective: There is a growing tendency for physicians to prescribe exercise in accordance with the 'exercise is medicine' global health initiative. However, the exercise-pharmacologic interactions for controlling blood pressure are not well described. Our purpose was to study whether angiotensin II receptor type 1 blocker (ARB) antihypertensive medicine enhances the blood pressure-lowering effects of intense exercise. Participants and methods: Fifteen hypertensive individuals with metabolic syndrome chronically medicated with ARB underwent two exercise trials in a blind randomized order. One trial was conducted after taking their habitual dose of ARB (ARB MED trial) and another after 48 h of placebo medicine (i.e. dextrose; PLAC trial). Results: After placebo medication, brachial systolic blood pressure increased by 5.5 mmHg [P=0.009; effect size (ES)=0.476] and diastolic by 2.5 mmHg (P=0.030; ES=0.373). Exercise reduced systolic and diastolic blood pressures to the same extent in ARB MED and PLAC trials (7 and 8 mmHg, respectively, for systolic and 5 and 4 mmHg, respectively, for diastolic, all P<0.05). Pulsatile measures of arterial stiffness did not reveal an interaction effect between exercise and medication. However, postocclusion reactive hyperemia increased after exercise only in the ARB MED trial (361±169 to 449±240% from baseline; P=0.033; ES=0.429). Conclusion: ARBs and a bout of intense exercise each have an independent effect on lowering blood pressure in hypertensive individuals, and these effects are additive.
... 14 A correlação entre HAS e hiperativação do sistema simpático na função vascular ainda não está plenamente elucidada; contudo, estudos que utilizam infusão de acetilcolina, nitroprussiato de sódio e fenilefedrina em protocolo de seis semanas de HIIT e repouso passivo demonstram não apenas redução da PAS e da PAD, mas também na resposta frente ao uso de medicações, e forte correlação entre o HIIT e a atividade da musculatura lisa vascular e seus receptores. 16 Ou seja, o HIIT apresenta ação no ganho da capacidade cardiovascular 1,8 e na redução de resistência vascular periférica, viscosidade sanguínea, 13,17 rigidez arterial, 18,19 controle glicêmico 20 e atividade simpática. 16,21 Existe também a comparação entre protocolos de treino com intensidade moderada (MICT) e HIIT em cicloergômetro, ou ainda exercícios com carga realizados em piscina, incluindo com o cicloergômetro em imersão. ...
... Em sedentários com síndrome metabólica, o HIIT realizado em cicloergômetro estacionário, comparado a grupo controle, identificou redução da pressão arterial e disfunção microvascular. 19 Na população com síndrome metabólica, os efeitos do HIIT aparentam otimizar o uso de medicação anti-hipertensiva e proporcionam efeito por aproximadamente 24 horas, assim como redução dos valores plasmáticos de renina ativada. [21][22][23][24] O que se pode perceber é que, apesar dos benefícios, ainda é importante definir qual o melhor protocolo para cada efeito a ser conquistado. ...
Article
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A hipertensão arterial sistêmica (HAS) é uma doença prevalente na população adulta e associada a alta morbidade e mortalidade cardiovascular. Uma das medidas que auxiliam no controle da doença é a prática de exercício físico. O exercício intervalado de alta intensidade high-intensity interval training, HIIT) é uma modalidade de atividade física que ganha destaque na atualidade, pois a prática exige menos tempo e oferece bons resultados. Apesar disso, há uma ampla variedade de protocolos na literatura, o que dificulta a análise da evidência de cada um deles. Objetivamos assim, apresentar resultados de estudos clínicos e revisões sistemáticas com metanálise disponíveis nos últimos cinco anos sobre o treino HIIT na HAS. Foi realizada uma busca sistematizada da literatura na base PubMed, com estratégia de busca previamente padronizada. Após a triagem, os artigos selecionados foram lidos na íntegra e tabulados para análise. Foram localizados 62 artigos com a inclusão de 15 (13 trabalhos clínicos e duas revisões com metanálise). Os resultados dos artigos selecionados que aplicaram o HIIT como protocolo de treinamento para hipertensos, mostra que a modalidade foi uma ferramenta efetiva para controle da pressão arterial em diferentes protocolos e populações. Os artigos fomentam esses achados com análise de sua ação em musculatura endotelial, angiogênese, hiperreatividade do sistema simpático e viscosidade sanguínea. O efeito sobre a fração de ejeção ventricular e o controle glicêmico atribui a este protocolo destaque na reabilitação da população hipertensa com comorbidade associada.
... Evidence from systematic reviews and experimental studies has demonstrated a positive effects of various exercise modalities (aerobic, resistance and combined training) on endothelial functions [7,29,31], but there are controversies regarding the effects of HIT on indices pertaining to arterial stiffness and wave reflection [7,31,35]. The mechanism by which HIT significantly reduces PWV more than MCT does could be associated with reduced exposure of the vasculature to reactive oxygen species that are often observed during high-volume exercise [36]. ...
... It is also possible that the higher volume of exercise in the HIT group may have resulted in the requirement of longer time for PWV recovery from repeated HIT bouts, thereby providing a more accurate representation of the cumulative effect of exercise intervention. These results may help identify the vascular wall that is more responsive and, conversely, the wall that is more resistant to the arterial stiffness-lowering effects of HIT [35]. ...
Article
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Background: Strong evidence shows that physical inactivity increases the risk of many adverse health conditions, including major non-communicable diseases, such as cardiovascular disease (CVD), metabolic syndrome, and breast and colon cancers, and shortens life expectancy. We aimed to determine the effects of moderate (MCT)- versus high-intensity interval training (HIT) on vascular function parameters in physically inactive adults. We hypothesized that individualized HIT prescription would improve the vascular function parameters more than the MCT in a greater proportion of individuals. Methods: Twenty inactive adults were randomly allocated to receive either MCT group (60-75% of their heart rate reserve, [HRR] or HIT group (4 min at 85-95% of peak HRR), three days a week for 12 weeks. Vascular function (brachial artery flow-mediated dilation, FMD [%], normalized brachial artery flow-mediated dilation, FMDn [%], aortic pulse wave velocity, PWV [m·s−1], AIx, augmentation index: aortic and brachial [%]), were measured at baseline and over 12 weeks of training. In order for a participant to be considered a responder to improvements in vascular function parameters (FMDn and PWV), the typical error was calculated in a favorable direction. Results: FMD changed by −1.0 % (SE 2.1, d=0.388) in the MCT group, and +1.8 % (SE 1.8, d=0.699) in the HIT group (no significant difference between groups: 2.9 % [95% CI, −3.0 to 8.8]. PWV changed by +0.1 m·s-1 (SE 0.2, d=0.087) in the MCT group but decreased by −0.4 m·s-1 in the HIT group (SE 0.2, d=0.497), with significant difference between groups: −0.4 [95% CI, −0.2 to −0.7]. There was not a significant difference in the prevalence of no-responder for FMD (%) between the MCT and HIT groups (66% versus 36%, P=0.157). Regarding PWV (m·s-1), an analysis showed that the prevalence of no-responder was 77% (7 cases) in the MCT group and 45% (5 cases) in the HIT group (P=0.114). Conclusions: Under the conditions of the present study, both groups experienced changed in endothelial function parameters. Compared to MCT group, HIT is more efficacious for improving FMD and decreasing PWV, in physically inactive adults.
... General recommendations for hypertension treatment include lifestyle modifications with aerobic exercise to reduce high blood pressure (BP). It is well established that an aerobic training program long enough ( > 10 weeks) leads to chronic reductions in systolic blood pressure [4][5][6]. Furthermore, one bout of aerobic exercise elicits BP reductions that remain during several hours, a phenomenon named post-exercise hypotension (i. e., PEH; [7]). ...
... Due to the short-and long-term effects on lowering blood pressure, continuous aerobic training at a moderate intensity is recommended in scientific hypertension guidelines [9]. However, since lack of time is one of the main reasons for not exercising, low volume high-intensity interval training (HIIT) has emerged as an option to fight hypertension [5]. Evidence is also accumulating to suggest that intense exercise could result in PEH greater in magnitude and/or duration than when using moderately-intense continuous exercise [6,10,11]. ...
Article
We studied the effects of supramaximal interval exercise (SIE) with or without antihypertensive medication (AHM) on 21-hr blood pressure (BP) response. Twelve hypertensive patients chronically medicated with AHM, underwent three trials in a randomized order: a) control trial without exercise and substituting their AHM with a placebo (PLAC); b) placebo medicine and a morning bout of SIE (PLAC+SIE), and c) combining AHM and exercise (AHM+SIE). Acute and ambulatory blood pressure responses were measured for 21-hr after treatment. 20 min after treatment, systolic blood pressure (SBP) readings were reduced, similar to readings after PLAC+SIE (−9.7±6.0 mmHg, P<0.001) and AHM+SIE (−10.4±7.9 mmHg, P=0.001). 21 h after treatment, SBP remained reduced after PLAC+SIE (125±12 mmHg, P=0.022) and AHM+SIE (122±12 mmHg, P=0.013) compared to PLAC (132±16 mmHg). The BP reduction in PLAC+SIE faded out at 4 a.m., while in AHM+SIE it continued overnight. At night, BP reduction was larger in AHM+SIE than PLAC+SIE (–5.6±4.0 mmHg, P=0.006). Our data shows that a bout of supramaximal aerobic interval exercise in combination with ARB medication in the morning elicits a sustained blood pressure reduction lasting at least 21-h. Thus, the combination of exercise and angiotensin receptor blocker medication seems superior to exercise alone for acutely decreasing blood pressure.
... Blood pressure was the MetS factor that better responded to the 4 months per year HIIT exercise program. We have recently reported that this type of training acts simultaneously reducing arterial stiffness while improving endothelial factors in the peripheral circulation in MetS individuals (42). However, general practitioners in charge of our participants_ health, did not reduce antihypertensive medicine in the TRAIN group (Table 2). ...
Article
Objective: To study if repeated yearly training programs consolidate the transient blood pressure (BP) improvements of one exercise program into durable adaptations. Methods: Obese middle-age individuals with metabolic syndrome (MetS) underwent high-intensity aerobic interval training during 16 weeks (November to mid-March) in 3 consecutive years [training group (TRAIN); N = 23]. Evolution of MetS components was compared with a matched-group that remained sedentary [control group (CONT); N = 26]. Results: At the end of the first training program (0-4 months), TRAIN lowered systolic arterial pressure, blood glucose, waist circumference and MetS Z-score below CONT (-8.5 ± 2.5 mmHg; -19.9 ± 2.6 mg/dl; -3.8 ± 0.1 cm and -0.3 ± 0.1, respectively, all P < 0.05). With detraining (month 4-12) TRAIN adaptations relapsed to the levels of baseline (month 0) except for BP. A second exercise program (month 12-16) lowered blood glucose and waist circumference below CONT (-19.0 ± 2.0 mg/dl; -4.1 ± 0.1 cm). After detraining (month 16-24) BP, blood glucose and Z-score started below CONT values (-6.8 ± 0.9 mmHg; -24.6 ± 2.5 mg/dl and -0.4 ± 0.05, respectively, all P < 0.05) and those differences enlarged with the last training program (month 24-28). Ten-year atherosclerotic cardiovascular disease risk estimation increased only in CONT (8.6 ± 1.1-10.1 ± 1.3%; year 2-3; P < 0.05). Conclusion: At least two consecutive years of 4-month aerobic interval training are required to chronically improve MetS (Z-score). The chronic effect is mediated by BP that does not fully return to pretraining values allowing a cumulative improvement. On the other hand, sedentarism in MetS patients during 3 years increases their predicted atherosclerotic diseases risk. CLINICALTRIALS. Gov identifier: NCT03019796.
... Also, two studies performed two type of HIIT. 39,63 In this meta-analysis, 18 studies employed HIIT intervention, [39][40][41][42]49,51,53,55,58,[64][65][66][67][68][69][70][71]73 10 employed SIT interventions 50,52,54,57,[59][60][61][62][63]72 and 1 employed both SIT and HIIT. 56 Of the 29 studies, 13 used running or walking, 39 55,57 Most studies used active recovery and only 1 used passive recovery 58 and 2 used both of active and passive recovery. ...
Article
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Introduction High‐intensity interval training (HIIT) is considered a time‐efficient strategy to improve metabolic health. We performed a systematic meta‐analysis to assess the effects of HIIT on inflammatory markers and adipo‐cytokines compared with control conditions (CON) or moderate‐intensity continuous training (MICT) in individuals with metabolic disorders. Methods Up to January 2020, electronic databases were searched for HIIT interventions based on populations with metabolic disorders including diabetes, metabolic syndrome, polycystic ovary syndrome, non‐alcoholic fatty liver disease or overweight/obesity, with outcome measurements that included IL‐6, TNF‐α, CRP, leptin or adiponectin and training ≥2 weeks. Random‐effects models were used to aggregate a mean effect size (ES), 95% confidence intervals (Cis), and potential moderators were explored. Results Twenty‐nine studies involving 841 participants were included in the meta‐analysis. HIIT improved circulating adiponectin (P = .02), leptin (P = .02), and TNF‐α (P = .003) when compared to CON. There were no differences between groups in IL‐6 and CRP. Intervention duration was a significant moderator for the effect of HIIT on IL‐6, and leptin (P < .05). Conclusion High‐intensity interval training improves circulating TNF‐α, leptin and adiponectin, thereby indicating that it may be an effective and time‐efficient intervention for controlling low‐grade inflammation in individuals with metabolic disorders.
... 5 We and others have already reported on the beneficial effects of moderate-intensity aerobic exercise on microvascular endothelial function both in animal [31][32][33] and in human studies. [34][35][36][37] In contrast, the present study showed that a 5-wk strenuous exercise training in a military setting, in young healthy individuals, induces a marked reduction of endotheliumdependent systemic microvascular reactivity. In fact, microvascular relaxation curves resulting from skin transdermal iontophoresis of acetylcholine showed a reduction of approximately 30% after training. ...
Article
Introduction The main aim of the present study is to evaluate the effects of strenuous exercise, related to special military training for riot control, on systemic microvascular endothelial function and skin capillary density. Materials and Methods Endothelium-dependent microvascular reactivity was evaluated in the forearm skin of healthy military trainees (age 23.4 ± 2.3 yr; n = 15) using laser speckle contrast imaging coupled with cutaneous acetylcholine (ACh) iontophoresis and post-occlusive reactive hyperemia (PORH). Functional capillary density was assessed using high-resolution, intra-vital color microscopy in the dorsum of the middle phalanx. Capillary recruitment (capillary reserve) was evaluated using PORH. Microcirculatory tests were performed before and after a 5-wk special military training for riot control. Results Microvascular endothelium-dependent vasodilatory responses were markedly and significantly reduced after training, compared with values obtained before training. The peak values of microvascular conductance obtained during iontophoresis of ACh or PORH before training (0.84 ± 0.22 and 0.94 ± 0.72 APU/mmHg, respectively) were markedly reduced after training (0.47 ± 0.11 and 0.71 ± 0.14 APU/mmHg; p < 0.0001 and p = 0.0037, respectively). Endothelium-dependent capillary recruitment was significantly reduced after training (before 101 ± 9 and after 95 ± 8 capillaries/mm²; p = 0.0007). Conclusions The present study showed that a 5-wk strenuous military training, performed in unfavorable climatic conditions, induces marked systemic microvascular dysfunction, mainly characterized by reduced endothelium-dependent microvascular vasodilation and blunted capillary recruitment.
... Following, in the trials with exercise (PLAC+EXER and AHM+EXER trial) subjects pedaled during 43 min alternating high (90% of HR PEAK ) and low intensities (70% HR PEAK ) since data supports the effectiveness of this exercise mode to lower BP in the short 10 and long term 24 . In the non-exercise trials (AHM and PLAC trials), subjects remained resting supine during those 43 min. ...
Article
We studied the blood pressure lowering effects of a bout of exercise and/or antihypertensive medicine with the goal of studying if exercise could substitute or enhance pharmacologic hypertension treatment. Twenty‐three hypertensive metabolic syndrome patients chronically medicated with angiotensin II receptor 1 blockade antihypertensive medicine underwent 24‐hr monitoring in four separated days in a randomized order; a) after taking their habitual dose of antihypertensive medicine (AHM trial), b) substituting their medicine by placebo medicine (PLAC trial), c) placebo medicine with a morning bout of intense aerobic exercise (PLAC+EXER trial) and d) combining the exercise and antihypertensive medicine (AHM+EXER trial). We found that in trials with AHM subjects had lower plasma aldosterone/renin activity ratio evidencing treatment compliance. Before exercise, the trials with AHM displayed lower systolic (130±16 vs 133±15 mmHg; P=0.018) and mean blood pressures (94±11 vs 96±10 mmHg; P=0.036) than trials with placebo medication. Acutely (i.e., 30 min after treatments) combining AHM+EXER lowered systolic blood pressure (SBP) below the effects of PLAC+EXER (‐8.1±1.6 vs ‐4.9±1.5 mmHg; P=0.015). Twenty‐four hour monitoring revealed no differences among trials in body motion. However, PLAC+EXER and AHM lowered SBP below PLAC during the first 10 hours, time at which PLAC+EXER effects faded out (i.e., at 19 PM). Adding exercise to medication (i.e., AHM+EXER) resulted in longer reductions in SBP than with exercise alone (PLAC+EXER). In summary, one bout of intense aerobic exercise in the morning cannot substitute the long‐lasting effects of antihypertensive medicine in lowering blood pressure, but their combination is superior to exercise alone. This article is protected by copyright. All rights reserved.
... Data from a Norwegian research group sustain that aerobic interval training (EXER) improves endothelial function along with VO 2MAX beyond an isocaloric program of continuous exercise [22]. We have also reported that a 16 weeks of EXER increases VO 2MAX while lowering arterial stiffness and improving microvascular vasodilation [23]. Therefore, a correlation between VO 2MAX gains with EXER and reductions in blood pressure in MetS individuals is supported by the literature [5,18,24]. ...
Article
Abstract Background and Aims To examine the relationship between changes in cardiorespiratory fitness (CRF; estimated by VO2max) and metabolic syndrome (MetS) after an exercise training intervention to confirm/contradict the high association found in cross-sectional observational studies. Methods and Results MetS individuals (54±8 yrs old; BMI of 32±5) were randomly allocated (6:1 ratio) to a group that exercised trained for 16-weeks (EXER; n=138) or a control sedentary group (CONT; n=22). At baseline, MetS components, body composition and exercise responses were similar between groups (all P>0.05). After 16 weeks of intervention, only EXER reduced body weight, waist circumference (-1.21±0.22 kg and -2.7±0.3 cm; P<0.001), mean arterial blood pressure and hence the composite MetS Z-score (-7.06±0.77 mmHg and -0.21±0.03 SD; P<0.001). In the EXER group, CRF increased by 16% (0.302±0.026, 95% CI 0.346 to 0.259 mLO2·min-1; P<0.001) but was not a significant predictor of MetS Z-score improvements (r = -0.231; β = -0.024; P = 0.788). Instead, body weight reductions predicted 25% of MetS Z-score changes (r = 0.508; β = 0.360; P = 0.001) Conclusions In MetS individuals, the exercise-training increases in CRF are not predictive of the improvements in their health risk factors. Instead, body weight loss (<2%) was a significant contributor to the improved MetS Z-score and thus should be emphasized in exercise training programs.
... Amongst various forms of resistance training, circuit resistance training (CRT) is reported to improve maximum oxygen consumption, functional capacity, and body composition and strength (Camargo et al., 2008;Bocalini et al., 2012). While CRT is suggested as a time-efficient training modality that can elicit health benefits in various healthy and clinical populations, including postmenopausal individuals (Brentano et al., 2008;Williams et al., 2013), most clinical investigations have utilized aerobic exercise training (i.e., treadmill and cycling) as a strategy to induce desired changes in body composition and metabolic syndrome markers (Pearsall et al., 2014;Wiklund et al., 2014;Guadalupe-Grau et al., 2018;Mora-Rodriguez et al., 2018). It is reported, for example, that aerobic exercise training, alone or combined with hypocaloric diet, improve symptoms of the metabolic syndromes, presumably through changing the levels of inflammatory adipokines (You and Nicklas, 2008). ...
Article
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We examined the effects of the independent and combined effects of Zataria multiflora supplementation and circuit resistance training (CRT) on selected adipokines among postmenopausal women. Forty-eight postmenopausal women were divided into 4 groups: Exercise (EG, n =12), Zataria multiflora (ZMG, n =12), exercise and Zataria multiflora (ZMEG, n =12), and control (CG, n=12). Participants in experimental groups either performed CRT (3 sessions per week with intensity at 55% of one-repetition maximum) or supplemented with Zataria Multiflora (500mg every day after breakfast with 100 ml of water), or their combination, for 8 weeks. Blood samples were collected at pre- and post-intervention for measuring selected adipokines, including visfatin, omentin-1, vaspin, FGF-21, adiponectin, leptin, and ghrelin. Our findings demonstrated that visfatin, vaspin, and leptin levels significantly decreased over the intervention period (all P < .05), with these values were lower in EG and ZMEG in comparison to CG at post-intervention (all P < .05). Visfatin and vaspin levels were also lower in ZMEG in comparison to EG at post-intervention (both P < .05). In contrast, omentin-1, gherlin, adiponectin, and FGF21 significantly increased in EG and EMG (all P < .05) after CRT. These findings suggest that Zataria Multiflora supplementation by itself has little effect on measured adipokines, however, its combination with CRT produced noticeable effects on circulating levels of these adipokines, even more than CRT alone. Consequently, the combination of CRT and Zataria Multiflora supplementation may represent a potentially beneficial non-pharmacologic intervention on some selected adipokines in postmenopausal women.
... 10,20 The destiffening effects of aerobic exercise have been observed in other modes of aerobic exercises including cycling. 21 In contrast to the findings in apparently healthy aging adults, the efficacy of regular walking exercise remains controversial in patient populations as a lack of effects on arterial stiffness has been reported in patients with hypertension and diabetes mellitus. [22][23][24] The appropriate prescription of exercise as a preventive and treatment strategy should include a choice of the suitable modality of exercise. ...
... In the included 20 RCTs (n ¼ 30 arms), the following three types of exercise were investigated: aerobic exercise (n ¼ 17 arms), resistance exercise (n ¼ 7 arms), and a combination of aerobic and resistance exercise (n ¼ 6 arms). Of the 20 included studies, two studies investigated women (El-Kader & Al-Dahr, 2016;Saghebjoo et al., 2018), five studies investigated men (Annibalini et al., 2017;Cooper et al., 2016;Dadrass et al., 2019;Donges et al., 2013;Nikseresht et al., 2016), and others (Balducci et al., 2010;Donley et al., 2014;El-Kader et al., 2015;Jorge et al., 2011;Kadoglou et al., 2007Kadoglou et al., , 2010Levinger et al., 2009;Mora-Rodriguez et al., 2018;Sang et al., 2015;Slivovskaja et al., 2018;Stefanov et al., 2013;Swift et al., 2012;Venojärvi et al., 2013) studied both genders ( Table 1). ...
Article
Background: Increments in inflammatory indicators and low levels of physical activity are correlated to the expansion of the metabolic syndrome (MetS). Objective: The purpose of this study was to establish if exercise training ameliorates inflammatory status in MetS patients. Data sources: PubMed, CINAHL, and Medline, Google Scholar, and Scopus databases and reference lists of included studies were searched. Study selection: Twenty randomized controlled trials (RCTs) of exercise-training impact on inflammatory markers (tumor necrosis factor (TNF) a, C-reactive protein (CRP), interleukin (IL) 6, IL-8, IL-10, and IL-18) with concurrent control groups were included in this analysis. Results: Results demonstrated an overall significant decrease in serum levels of TNF-a (mean difference (MD): 1.21 pg/ml; 95% confidence interval (CI): 1.77, 0.66), CRP (MD: 0.52 mg/l; 95% CI: 0.79, 0.25), IL-8 (MD: 1.31 pg/ml; 95% CI: 2.57, 0.06), and a significant increase in IL-10 (MD: 0.48 pg/ml; 95% CI: 0.10, 0.86). But exercise training did not change the level of IL-6 (MD: 0.69 pg/ml; 95% CI: 1.53, 0.14) and IL-18 (MD: 53.01 pg/ml; 95% CI: 166.64, 60.62). Conclusion: Exercise training improves TNF-a, CRP, IL-8, and IL-10 levels in patients with MetS. For some variables, isolated aerobic exercise, and combined aerobic and resistance exercise appears to be optimal. Future research is needed to clarify the mechanisms underlying exercise training’s effect on this population’s inflammatory markers. More studies are required to confirm these findings.
... 14,15,17 However, it is unclear if this additive effect of one bout of exercise on AHM actions remains when combining AHM with a full exercise training program. A 16-week aerobic interval training program reduced both arterial stiffness and microvascular dysfunction 18 and lowers systemic vascular resistances 19 in MetS individuals. However, it is unclear if those cardiovascular improvements of training positively interact with AHM target effects. ...
Article
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Pharmacological and non‐pharmacological therapies are simultaneously prescribed when treating hypertensive individuals with elevated cardiovascular risk (i.e., metabolic syndrome individuals). However, it is unknown if the interactions between antihypertensive medication (AHM) and lifestyle interventions (i.e., exercise training) may result in a better ambulatory blood pressure (ABP) control. To test this hypothesis, thirty‐six hypertensive individuals with metabolic syndrome (MetS) under long‐term prescription with AHM targeting the renin‐angiotensin‐aldosterone system (RAAS) were recruited. Before and after 4‐months of high‐intensity interval training (HIIT), participants completed two trials in a double‐blind, randomized order: a) placebo trial consisting of AHM withdrawal for 3‐days and b) AHM trial where individuals held their habitual dose of AHM. 24‐h mean arterial pressure (MAP) was monitored in each trial and considered the primary study outcome. Secondary outcomes included plasma renin activity (PRA) and aldosterone concentration to confirm withdrawal effects on RAAS, along with the analysis of urine albumin‐to‐creatinine ratio (UACR) to assess kidney function. The results showed main effects from AHM and HIIT reducing 24‐h MAP (‐5.7 mmHg, P<0.001 and ‐2.3 mmHg, P=0.007, respectively). However, there was not interaction between AHM and HIIT on 24‐h MAP (P=0.240). There was a main effect of AHM increasing PRA (P<0.001) but no effect on plasma aldosterone concentration (P=0.423). HIIT did not significantly improve RAAS hormones or the UACR. In conclusion, AHM and HIIT have independent and additive effects in lowering ABP. These findings support the combination of habitual AHM with exercise training with the goal to reduce ABP in hypertensive MetS individuals.
... Two other studies had duplicated data, 12 were not randomised controlled trials, 14 studies did not apply HIIT in their interventions, 10 did not include participants with METS, and 3 did not have enough data to calculate effect size. Finally, 10 studies that met the selection criteria were identified [44][45][46][47][48][49][50][51][52][53]. Figure 1 shows the flow chart of the selection process of studies. ...
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Background Despite the current debate about the effects of high intensity interval training (HIIT), HIIT elicits big morpho-physiological benefit on Metabolic Syndrome (MetS) treatment. However, no review or meta-analysis has compared the effects of HIIT to non-exercising controls in MetS variables. The aim of this study was to determine through a systematic review, the effectiveness of HIIT on MetS clinical variables in adults. Methods Studies had to be randomised controlled trials, lasting at least 3 weeks, and compare the effects of HIIT on at least one of the MetS clinical variables [fasting blood glucose (BG), high-density lipoprotein (HDL-C) triglyceride (TG), systolic (SBP) or diastolic blood pressure (DBP) and waist circumference (WC)] compared to a control group. The methodological quality of the studies selected was evaluated using the PEDro scale. Results Ten articles fulfilled the selection criteria, with a mean quality score on the PEDro scale of 6.7. Compared with controls, HIIT groups showed significant and relevant reductions in BG (− 0.11 mmol/L), SBP (− 4.44 mmHg), DBP (− 3.60 mmHg), and WC (− 2.26 cm). Otherwise, a slight increase was observed in HDL-C (+ 0.02 mmol/L). HIIT did not produce any significant changes in TG (− 1.29 mmol/L). Conclusions HIIT improves certain clinical aspects in people with MetS (BG, SBP, DBP and WC) compared to people with MetS who do not perform physical exercise. Plausible physiological changes of HIIT interventions might be related with large skeletal muscle mass implication, improvements in the vasomotor control, better baroreflex control, reduction of the total peripheral resistance, increases in excess post-exercise oxygen consumption, and changes in appetite and satiety mechanisms.
... Exercise test guidelines are limited to the Bruce treadmill or cycleergometers tests, performed to maximally stress and provoke the cardiovascular response during exercise (Pescatello et al., 2004;Fletcher et al., 2013). Earlier studies looking at the blood pressure (BP) response during human movement were predominantly focused on orthostatic tolerance tests (Goswami et al., 2015), aerobic exercise interventions (Mora-Rodriguez et al., 2018), or isolated submaximal lower-limb contractions (Lamotte et al., 2010;Massaferri et al., 2015;Trinity et al., 2018). A study by Lovell et al. (2011) observed a substantial increase in the BP during a classical squat-exercise in sedentary male seniors. ...
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Aims Physical exercise has been associated with a reduction in arterial stiffness, a subclinical process underlying cardiovascular disease. However, the effect of different types of exercise (aerobic, resistance, combined, interval training, stretching, or mind–body modalities) on arterial stiffness is unclear. This network meta-analysis aimed to examine the effectiveness of different types of exercise on arterial stiffness as measured by pulse wave velocity in adults. Methods and results We searched Cochrane Central Register of Controlled Trials, CINAHL, MEDLINE (via Pubmed), Embase, and Web of Science databases, for randomized clinical trials including at least a comparison group, from their inception to 30 June 2020. A frequentist network meta-analysis was performed to compare the effect of different types of physical exercise on arterial stiffness as measured by pulse wave velocity. Finally, 35 studies, with a total of 1125 participants for exercise intervention and 633 participants for the control group, were included. In the pairwise meta-analyses, the exercises that improved arterial stiffness were: interval training [effect size (ES) 0.37; 95% confidence interval (CI) 0.01–0.73], aerobic exercise (ES 0.30; 95% CI 0.13–0.48) and combined exercise (ES 0.22; 95% CI 0.04–0.40). Furthermore, the network meta-analysis showed that mind–body interventions were the most effective type of exercise to reduce the pulse wave velocity (ES 0.86; 95% CI 0.04–1.69). In addition, combined exercise (ES 0.35; 95% CI 0.08–0.62), aerobic exercise (ES 0.33; 95% CI 0.09–0.57), and interval training (ES 0.33; 95% CI 0.02–0.64) showed significant improvements. Conclusion Our findings showed that aerobic exercise, combined exercise, interval training, and mind–body exercises were the most effective exercise modalities for reducing arterial stiffness, assuming an important role in the prevention of cardiovascular diseases.
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Objectives This study aims to determine whether 1 year of high-intensity interval training (HIIT) and omega-3 fatty acid (n-3 FA) supplementation would improve fitness, cardiovascular structure/function, and body composition in obese middle-aged adults at high-risk of heart failure (HF) (stage A). Background It is unclear if intensive lifestyle interventions begun in stage A HF can improve key cardiovascular and metabolic risk factors. Methods High-risk obese adults (n = 80; age 40 to 55 years; N-terminal pro–B-type natriuretic peptide >40 pg/mL or high-sensitivity cardiac troponin T > 0.6 pg/mL; visceral fat > 2 kg) were randomized to 1 year of HIIT exercise or attention control, with n-3 FA (1.6 g/daily omega-3-acid ethyl esters) or placebo supplementation (olive oil 1.6 g daily). Outcome variables were exercise capacity quantified as peak oxygen uptake (V.O2), left ventricular (LV) mass, LV volume, myocardial triglyceride content (magnetic resonance spectroscopy), arterial stiffness/function (central pulsed-wave velocity; augmentation index), and body composition (dual x-ray absorptiometry scan). Results Fifty-six volunteers completed the intervention. There was no detectible effect of HIIT on visceral fat or myocardial triglyceride content despite a reduction in total adiposity (Δ: -2.63 kg, 95% CI: -4.08 to -0.46, P = 0.018). HIIT improved exercise capacity by ∼24% (ΔV.O2: 4.46 mL/kg per minute, 95% CI: 3.18 to 5.56; P < 0.0001), increased LV mass (Δ: 9.40 g, 95% CI: 4.36 to 14.44; P < 0.001), and volume (Δ: 12.33 mL, 95 % CI: 5.61 to 19.05; P < 0.001) and reduced augmentation index (Δ: -4.81%, 95% CI: -8.63 to -0.98; P = 0.009). There was no independent or interaction effect of n-3 FA on any outcome. Conclusions One-year HIIT improved exercise capacity, cardiovascular structure/function, and adiposity in stage A HF with no independent or additive effect of n-3 FA administration. (Improving Metabolic Health in Patients With Diastolic Dysfunction [MTG]; NCT03448185).
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Objective: The absence of nocturnal blood pressure (BP) reduction at night in hypertensive individuals is associated with an increased cardiovascular risk. The main purpose of the present study was to investigate the effects of an aerobic training intervention on nocturnal BP dipping in medicated hypertensive individuals. Methods: At baseline, hypertensive individuals under pharmacological treatment underwent 24-h ambulatory BP monitoring and a morning urine sample to analyze albumin creatinine ratio (UACR). Then, participants were divided into nocturnal dippers (N = 15; 59 ± 6 years) and nondippers (N = 20; 58 ± 5 years) according to a day-to-night BP reduction of >10% or <10%, respectively. Next, participants underwent a 3-weekly, 4-month aerobic interval training intervention. Results: Follow-up measurements revealed a reduction in daytime diastolic BP in dippers and nondippers (Ptime < 0.001), whereas nighttime systolic BP was reduced only in nondippers (P = 0.004). Regarding dipping pattern, nocturnal systolic BP dipping increased after training in nondippers (5 ± 3 to 9 ± 7%; P = 0.018), whereas in dippers, there was a decrease in nocturnal dipping after training (14 ± 4 to 10 ± 7%, P = 0.016). Nocturnal diastolic BP dipping did not change in nondippers (8 ± 5 to 10 ± 7%; P = 0.273) but decreased in dippers (17 ± 6 to 12 ± 8%; P = 0.004). In addition, UACR was significantly reduced in both groups after training (Ptime = 0.020). Conclusion: Aerobic exercise training is associated with nocturnal BP dipping as nighttime BP was lower than before the program in medicated hypertensive individuals with an initial nondipping phenotype. The lack of improvement in individuals with a dipping phenotype warrants further investigation to discern whether dipping phenotypes influence BP responses to exercise training.
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Purpose of review: Metabolic syndrome (MetS), a cluster of risk factors including central obesity, metabolic abnormalities, and arterial hypertension, is a well-known determinant of arterial wall remodeling and stiffening. The mechanisms whereby MetS promotes arterial stiffening include increased sympathetic activity with the associated fast heart rate, enhanced activity of the renin-angiotensin-aldosterone system, increased production of inflammatory cytokines and reactive oxygen species, and reduction of nitric oxide availability. These adverse effects can explain why aerobic physical activity can retard the age-related decline in arterial elasticity in subjects with MetS. Recent findings: A large number of studies have shown that in patients with MetS, exercise can reduce body weight and blood pressure and improve the metabolic profile. In addition, regular exercise training can counterbalance the detrimental effects of MetS by reducing sympathetic activity and improving endothelial function with a beneficial effect on arterial elasticity. Indeed, the majority of published data have shown a favorable effect of aerobic exercise on pulse wave velocity, augmentation index, central blood pressure, and small artery compliance. Special attention should be paid by clinicians to people with MetS in whom the adverse effect of metabolic disturbances on arterial structure and function can be offset by a program of physical training.
Chapter
Metabolic syndrome is a pathologic condition that has increasing prevalence in modern world and is a significant precursor of cardiovascular disease. One of the main mechanisms underlying metabolic syndrome and each of its components is the inflammatory state that favors the development of the atherosclerotic process leading to increased arterial stiffness. Indeed, a body of evidence has demonstrated a strict link between metabolic syndrome and its components with arterial stiffness. Regular physical activity represents a key strategy for antagonizing the adverse effects of metabolic syndrome including the impairment of arterial elasticity, thereby reducing the burden of cardiovascular disease. Thus, special attention should be paid by clinicians to people with metabolic syndrome in whom the untoward effects of metabolic disturbances on the arteries can be offset by a program of physical activity.KeywordsMetabolic syndromeArterial stiffnessPhysical activityExercise
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Specific clusters of metabolic syndrome (MetS) components impact differentially on arterial stiffness, indexed as pulse wave velocity (PWV). Of note, in several population-based studies participating in the MARE (Metabolic syndrome and Arteries REsearch) Consortium the occurrence of specific clusters of MetS differed markedly across Europe and the US. The aim of the present study was to investigate whether specific clusters of MetS are consistently associated with stiffer arteries in different populations. We studied 20,570 subjects from 9 cohorts representing 8 different European countries and the US participating in the MARE Consortium. MetS was defined in accordance with NCEP ATPIII criteria as the simultaneous alteration in ≥3 of the 5 components: abdominal obesity (W), high triglycerides (T), low HDL cholesterol (H), elevated blood pressure (B), and elevated fasting glucose (G). PWV measured in each cohort was "normalized" to account for different acquisition methods. MetS had an overall prevalence of 24.2% (4985 subjects). MetS accelerated the age-associated increase in PWV levels at any age, and similarly in men and women. MetS clusters TBW, GBW, and GTBW are consistently associated with significantly stiffer arteries to an extent similar or greater than observed in subjects with alteration in all the five MetS components - even after controlling for age, sex, smoking, cholesterol levels, and diabetes mellitus - in all the MARE cohorts. In conclusion, different component clusters of MetS showed varying associations with arterial stiffness (PWV).
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The metabolic syndrome (MetS) is associated with a 3-fold increase risk of cardiovascular disease (CVD) mortality partly due to increased arterial stiffening. We compared the effects of aerobic exercise training on arterial stiffening/mechanics in MetS without overt CVD or Type 2 Diabetes. MetS and healthy controls (Con) underwent 8 weeks of exercise training (ExT; 11 MetS and 11 Con) or remained inactive (NonT; 11 MetS and 10 Con). The following measures were performed pre and post intervention: radial pulse wave analysis (applanation tonometry) was used to measure augmentation pressure and index, central pressures, and an estimate of myocardial efficiency; arterial stiffness was assessed from carotid-femoral pulse wave velocity (cfPWV, applanation tonometry); carotid thickness was assessed from B-mode ultrasound; and peak aerobic capacity (gas exchange) was performed in the seated position. Plasma matrix metalloproteinases (MMP), and CVD risk (Framingham risk score) were also assessed. cfPWV was reduced (p<0.05) in MetS-ExT (7.9+0.6 to 7.2+0.4 m/s) and Con-ExT (6.6+1.8 to 5.6+1.6 m/s). Exercise training reduced (p<0.05) central systolic pressure (116+5 to 110+4, mmHg), augmentation pressure (9+1 to 7+1, mmHg), augmentation index (19+3 to 15+4%), and improved myocardial efficiency (155+8 to 168+9) but only in the MetS group. Aerobic capacity increased (p<0.05) in MetS-ExT (16.6±1.0 to 19.9±1.0) and Con-ExT (23.8±1.6 to 26.3±1.6). MMP-1 and 7 were correlated with cfPWV and both MMP-1 and 7 were reduced post-exercise training in MetS. These findings suggest that some of the pathophysiological changes associated with MetS can be improved after aerobic exercise training thereby lowering their CV risk.
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The metabolic syndrome (MetS) is associated with increased risk of type-2 diabetes and cardiovascular disease (CVD). We hypothesized that both small and large arteries may be impaired in subjects with the MetS, even in the absence of known CVD or diabetes. We compared both skin capillary density (CD) and pulse-wave velocity (PWV) in 36 cases with the MetS with those from 108 age- and gender-matched controls from the SU.VIM.AX-2 cohort. Compared with controls, MetS subjects demonstrated increased PWV (12.2±2.8 vs. 10.7±1.9 m s−1, P=0.005) and lower functional CD (83.1±15.7 vs. 89.4±14.2 capillaries per mm2, P=0.03). Functional CD was inversely related to fasting glucose, triglycerides (TGs) and HOMA-IR (all P<0.05). On the other hand, no association was found between CD and BP or with PWV. In multivariate models, the odds ratios (95% confidence interval) for one standard deviation change, for having an impaired PWV (12 m s−1, n=44), were: 1.65 (1.11–2.45) for systolic BP and 1.93 (1.25–2.99) for TG only. For impaired CD (80 capillaries per mm2), the odds ratios (95% confidence interval) were 1.45 (1.00–2.08) for TG and 1.65 (1.13–2.43) for fasting glucose, only. In conclusion, MetS subjects exhibited evidence of macro- and microcirculatory dysfunction, even in the absence of diabetes and CVD. The common mechanism linking MetS components to CVD risk through small- and large-artery dysfunctions may be mediated through metabolic factors related to insulin resistance, not to increased BP.Keywords: arterial stiffness; capillary density; metabolic syndrome; microcirculation
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Individuals with metabolic syndrome (MetS; i.e., three of five of the following risk factors (RFs): elevated blood pressure, waist circumference, triglycerides, blood glucose, or reduced HDL) are thought to be prone to serious cardiovascular disease and there is debate as to whether the disease begins in the peripheral vasculature or centrally. This study investigates hemodynamics, cardiac function/morphology, and mechanical properties of the central (heart, carotid artery) or peripheral [total peripheral resistance (TPR), forearm vascular bed] vasculature in individuals without (1-2 RFs: n = 28), or with (≥3 RFs: n = 46) MetS. After adjustments for statin and blood pressure medication use, those with MetS had lower mitral valve E/A ratios (<3 RFs: 1.24 ± 0.07; ≥3 RFs: 1.01 ± 0.04; P = 0.025), and higher TPR index (<3 RFs: 48 ± 2 mmHg/L/min/m(2); ≥3 RFs: 53 ± 2 mmHg/L/min/m(2); P = 0.04). There were no differences in heart size, carotid artery measurements, cardiovagal baroreflex, pulse-wave velocity, stroke volume index, or cardiac output index due to MetS after adjustments for statin and blood pressure medication use. The use of statins was associated with increased inertia in the brachial vascular bed, increased HbA1c and decreased LDL cholesterol. The independent use of anti-hypertensive medication was associated with decreased predicted [Formula: see text] triglycerides, diastolic blood pressure, interventricular septum thickness, calculated left ventricle mass, left ventricle posterior wall thickness, and left ventricle pre-ejection period, but increased carotid stiffness, HDL cholesterol, and heart rate. These data imply that both a central cardiac effect and a peripheral effect of vascular resistance are expressed in MetS. These data also indicate that variance in between-group responses due to pharmacological treatments are important factors to consider in studying cardiovascular changes in these individuals.
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Metabolic syndrome is characterized by central obesity, elevated blood pressure, high fasting glucose and triglyceride levels, and low HDL levels. Regular physical activity can improve the metabolic profile and reduce the risks of cardiovascular diseases and premature mortality. However, the optimal training regime to treat metabolic syndrome and its associated cardiovascular abnormalities remains undefined. Forty-three participants with metabolic syndrome were randomized to one of the following groups: aerobic interval training (AIT; n = 11), strength training (ST; n = 11), a combination of AIT and ST (COM; n = 10) 3 times/wk for 12 wk, or control (n = 11). Risk factors comprising metabolic syndrome were evaluated before and after the intervention. Waist circumference (in cm) was significantly reduced after AIT [95% confidence interval (CI): -2.5 to -0.04], COM (95% CI: -2.11 to -0.63), and ST (95% CI: -2.68 to -0.84), whereas the control group had an increase in waist circumference (95% CI: 0.37-2.9). The AIT and COM groups had 11% and 10% increases in peak O2 uptake, respectively. There were 45% and 31% increases in maximal strength after ST and COM, respectively. Endothelial function, measured as flow-mediated dilatation (in %), was improved after AIT (95% CI: 0.3-3), COM (95% CI: 0.3-3), and ST (95% CI: 1.5-4.5). There were no changes in body weight, fasting plasma glucose, or HDL levels within or between the groups. In conclusion, all three training regimes have beneficial effects on physiological abnormalities associated with metabolic syndrome.
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The Global Cardiometabolic Risk Profile in Patients with hypertension disease survey investigated the cardiometabolic risk profile in adult outpatients with hypertension in Europe according to the control of blood pressure (BP) as defined in the European Society of Hypertension and of the European Society of Cardiology (ESH/ESC) guidelines. Data on BP control and cardiometabolic risk factors were collected for 3370 patients with hypertension in 12 European countries. Prevalence was analyzed according to BP status and ATP III criteria for metabolic syndrome. BP was controlled (BP < 140/90 mmHg for nondiabetic patients; BP < 130/80 mmHg for diabetic patients) in 28.1% of patients. Patients with uncontrolled BP had significantly higher mean weight, BMI, waist circumference, fasting blood glucose, total cholesterol and triglycerides and high-density lipoprotein cholesterol levels were significantly lower (women only) compared with patients with controlled BP (P < 0.05). The prevalence of metabolic syndrome and type 2 diabetes was also significantly higher in patients with uncontrolled BP compared with controlled BP (P < 0.001) (metabolic syndrome: 66.5 versus 35.5%; diabetes 41.1 versus 9.8%, respectively). 95.3% of patients with both metabolic syndrome and type 2 diabetes had uncontrolled BP. In a multivariate analysis, diabetes and metabolic syndrome were found to be associated with a high risk of poor BP control: odds ratio, 2.56 (metabolic syndrome); 5.16 (diabetes). In this European study, fewer than one third of treated hypertensive patients had controlled BP. Metabolic syndrome and diabetes were important characteristics associated with poor BP control. Thus, more focus is needed on controlling hypertension in people with high cardiometabolic risk and diabetes.
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This summary corresponds to the translation into Spanish of the Special Communication published in the Journal of the American Medical Association in August 1996, along with the editorial published in the same issue 'How to report Randomized Controlled Trials. The Consort Statement'. It describes the Consolidated Standards for Preparation of Controlled Clinical Trials, prepared by a work group made up of members of the SORT Group and of the Asilomar Work Group, along with the director of a magazine and the author of the report on a clinical trial. The work was carried out by means of a Delphi process and the result was a check list and a process diagram. The check list is made up of 21 items that mainly refer to methods, results and discussions on the report of a controlled clinical trial, identifying the necessary information in order to be able to evaluate the internal and external value of the report, judging the improvement to be positive for the patient, the editors and the reviewers of the magazines.
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Data are limited regarding prevalence and prognostic significance of subclinical cardiovascular disease (CVD) in individuals with metabolic syndrome (MetS). We investigated prevalence of subclinical CVD in 1,945 Framingham Offspring Study participants (mean age 58 years; 59% women) using electrocardiography, echocardiography, carotid ultrasound, ankle-brachial blood pressure, and urinary albumin excretion. We prospectively evaluated the incidence of CVD associated with MetS and diabetes according to presence versus absence of subclinical disease. Cross-sectionally, 51% of 581 participants with MetS had subclinical disease in at least one test, a frequency higher than individuals without MetS (multivariable-adjusted odds ratio 2.06 [95% CI 1.67-2.55]; P < 0.0001). On follow-up (mean 7.2 years), 139 individuals developed overt CVD, including 59 with MetS (10.2%). Overall, MetS was associated with increased CVD risk (multivariable-adjusted hazards ratio [HR] 1.61 [95% CI 1.12-2.33]). Participants with MetS and subclinical disease experienced increased risk of overt CVD (2.67 [1.62-4.41] compared with those without MetS, diabetes, or subclinical disease), whereas the association of MetS with CVD risk was attenuated in absence of subclinical disease (HR 1.59 [95% CI 0.87-2.90]). A similar attenuation of CVD risk in absence of subclinical disease was observed also for diabetes. Subclinical disease was a significant predictor of overt CVD in participants without MetS or diabetes (1.93 [1.15-3.24]). In our community-based sample, individuals with MetS have a high prevalence of subclinical atherosclerosis that likely contributes to the increased risk of overt CVD associated with the condition.
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Obesity is an important risk factor for insulin resistance and hypertension and plays a central role in the metabolic syndrome. Insight into the pathophysiology of this syndrome may lead to new treatments. This paper has reviewed the evidence for an important role for the microcirculation as a possible link between obesity, insulin resistance and hypertension.
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Regular exercise training is recognized as a powerful tool to improve work capacity, endothelial function and the cardiovascular risk profile in obesity, but it is unknown which of high-intensity aerobic exercise, moderate-intensity aerobic exercise or strength training is the optimal mode of exercise. In the present study, a total of 40 subjects were randomized to high-intensity interval aerobic training, continuous moderate-intensity aerobic training or maximal strength training programmes for 12 weeks, three times/week. The high-intensity group performed aerobic interval walking/running at 85-95 % of maximal heart rate, whereas the moderate-intensity group exercised continuously at 60-70% of maximal heart rate; protocols were isocaloric. The strength training group performed 'high-intensity' leg press, abdominal and back strength training. Maximal oxygen uptake and endothelial function improved in all groups; the greatest improvement was observed after high-intensity training, and an equal improvement was observed after moderate-intensity aerobic training and strength training. High-intensity aerobic training and strength training were associated with increased PGC-α (peroxisome-proliferator-activated receptor γ co-activator I α) levels and improved Ca2+ transport in the skeletal muscle, whereas only strength training improved antioxidant status. Both strength training and moderate-intensity aerobic training decreased oxidized LDL (low-density lipoprotein) levels. Only aerobic training decreased body weight and diastolic blood pressure. In conclusion, high-intensity aerobic interval training was better than moderate-intensity aerobic training in improving aerobic work capacity and endothelial function. An important contribution towards improved aerobic work capacity, endothelial function and cardiovascular health originates from strength training, which may serve as a substitute when whole-body aerobic exercise is contra-indicated or difficult to perform.
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Individuals with the metabolic syndrome are 3 times more likely to die of heart disease than healthy counterparts. Exercise training reduces several of the symptoms of the syndrome, but the exercise intensity that yields the maximal beneficial adaptations is in dispute. We compared moderate and high exercise intensity with regard to variables associated with cardiovascular function and prognosis in patients with the metabolic syndrome. Thirty-two metabolic syndrome patients (age, 52.3+/-3.7 years; maximal oxygen uptake [o(2)max], 34 mL x kg(-1) x min(-1)) were randomized to equal volumes of either moderate continuous moderate exercise (CME; 70% of highest measured heart rate [Hfmax]) or aerobic interval training (AIT; 90% of Hfmax) 3 times a week for 16 weeks or to a control group. o(2)max increased more after AIT than CME (35% versus 16%; P<0.01) and was associated with removal of more risk factors that constitute the metabolic syndrome (number of factors: AIT, 5.9 before versus 4.0 after; P<0.01; CME, 5.7 before versus 5.0 after; group difference, P<0.05). AIT was superior to CME in enhancing endothelial function (9% versus 5%; P<0.001), insulin signaling in fat and skeletal muscle, skeletal muscle biogenesis, and excitation-contraction coupling and in reducing blood glucose and lipogenesis in adipose tissue. The 2 exercise programs were equally effective at lowering mean arterial blood pressure and reducing body weight (-2.3 and -3.6 kg in AIT and CME, respectively) and fat. Exercise intensity was an important factor for improving aerobic capacity and reversing the risk factors of the metabolic syndrome. These findings may have important implications for exercise training in rehabilitation programs and future studies.
Article
Our purpose in this study was to investigate efficient and sustainable combinations of exercise and diet-induced weight loss (DIET), in order to combat obesity in metabolic syndrome (MetS) patients. We examined the impact of aerobic interval training (AIT), followed by or concurrent to a DIET on MetS components. 36 MetS patients (54±9 years old; 33±4 BMI; 27 males and 9 females) underwent 16 weeks of AIT followed by another 16 weeks without exercise from the fall of 2013 to the spring of 2014. Participants were randomized to AIT without DIET (E CON, n=12), AIT followed by DIET (E-then-D, n=12) or AIT concurrent with DIET (E+D, n=12) groups. Body weight decreased below E CON similarly in the E-then-D and E+D groups (~5%). Training improved blood pressure and cardiorespiratory fitness (VO2peak) in all groups with no additional effect of concurrent weight loss. However, E+D improved insulin sensitivity (HOMA) and lowered plasma triglycerides and blood cholesterol below E CON and E-then-D (all P<0.05). Weight loss in E-then-D in the 16 weeks without exercise lowered HOMA to the E+D levels and maintained blood pressure at trained levels. Our data suggest that a new lifestyle combination consisting of aerobic interval training followed by weight loss diet is similar, or even more effective on improving metabolic syndrome factors than concurrent exercise plus diet. © Georg Thieme Verlag KG Stuttgart · New York.
Article
Background: Weight loss appears to be an effective method for primary prevention of hypertension. However, the long-term effects of weight loss on blood pressure have not been extensively studied. Objective: To present detailed results from the weight loss arm of Trials of Hypertension Prevention (TOHP) II. Design: Multicenter, randomized clinical trial testing the efficacy of lifestyle interventions for reducing blood pressure over 3 to 4 years. Participants in TOHP II were randomly assigned to one of four groups. This report focuses only on participants assigned to the weight loss (n = 595) and usual care control (n = 596) groups. Patients: Men and women 30 to 54 years of age who had nonmedicated diastolic blood pressure of 83 to 89 mm Hg and systolic blood pressure less than 140 mm Hg and were 110% to 165% of their ideal body weight at baseline. Intervention: The weight loss intervention included a 3-year program of group meetings and individual counseling focused on dietary change, physical activity, and social support. Measurements: Weight and blood pressure data were collected every 6 months by staff who were blinded to treatment assignment Results: Mean weight change from baseline in the intervention group was -4.4 kg at 6 months, -2.0 kg at 18 months, and -0.2 kg at 36 months. Mean weight change in the control group at the same time points was 0.1, 0.7, and 1.8 kg. Blood pressure was significantly lower in the intervention group than in the control group at 6, 18, and 36 months. The risk ratio for hypertension in the intervention group was 0.58 (95% Cl, 0.36 to 0.94) at 6 months, 0.78 (Cl, 0.62 to 1.00) at 18 months, and 0.81 (Cl, 0.70 to 0.95) at 36 months. In subgroup analyses, intervention participants who lost at least 4.5 kg at 6 months and maintained this weight reduction for the next 30 months had the greatest reduction in blood pressure and a relative risk for hypertension of 0.35 (Cl, 0.20 to 0.59). Conclusions: Clinically significant long-term reductions in blood pressure and reduced risk for hypertension can be achieved with even modest weight loss.
Article
Sedentary lifestyle is a risk factor and a strong predictor for chronic disease and premature death. Low-grade inflammation has been proved a key player in the pathogenesis of cardiovascular disease. Inflammatory processes have been also involved in maintaining the balance between coagulation and fibrinolysis. In addition, an inverse linear dose-response relation between physical activity and mortality risks has also been reported. However, the favorable effects of structured exercise programs and the independent contribution of physical activity to cardiovascular risk are still under investigation.
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Controversy exists as to whether aerobic exercise training decreases arterial stiffness in obese subjects. The aim of this study was to systematically review and quantify the effect of aerobic exercise training on arterial stiffness in obese populations. MEDLINE, Cochrane, Scopus, and Web of Science were searched up until May 2013 for trials assessing the effect of aerobic training interventions lasting 8 weeks or more on arterial stiffness in obese populations (body mass index ≥30 kg/m(2)). Standardized mean difference (SMD) in arterial stiffness parameters (augmentation index, β-stiffness, distensibility, pulse wave velocity, arterial waveforms) was calculated using a random-effects model. Subgroup and meta-regression analyses were used to study potential moderating factors. Eight trials, comprising a total of 235 subjects with an age range of 49-70 years, met the inclusion criteria. Arterial stiffness was not significantly reduced by aerobic training (SMD -0.17; 95 % confidence interval (CI) -0.39, 0.06, P = 0.14). Similarly, post-intervention arterial stiffness was similar between the aerobic-trained and control obese groups (SMD 0.02; 95 % CI -0.28, 0.32, P = 0.88). Neither heterogeneity nor publication bias were detected in these analyses. In subgroup analyses, arterial stiffness was significantly reduced in aerobic-trained subgroups having below median values in post- minus pre-intervention systolic blood pressure (SBP) (P < 0.01), exercise intensity rating score (P < 0.01), and methodological quality score (P < 0.01). Equivalent results were obtained in meta-regression analyses. Based on current published trials, arterial stiffness is generally not reduced in middle-aged and older obese populations in response to aerobic training. However, in studies using low-intensity aerobic training and yielding a decrease in SBP, arterial stiffness may decrease. Long-term studies are needed to assess the prognostic value of these findings.
Article
Background and Aims Exercise training can improve health of patients with metabolic syndrome (MetS). However, which MetS factors are most responsive to exercise training remains unclear. We studied the time-course of changes in MetS factors in response to training and detraining. Methods and Results Forty eight MetS patients (52±8.8 yrs old; 33±4 BMI) underwent 4 months (3 days/week) of supervised aerobic interval training (AIT) program. After 1 month of training, there were progressive increases in high density lipoprotein cholesterol (HDL-c) and reductions in waist circumference and blood pressure (12±3%, -3.9±0.4, and -12±1, respectively after 4 months; all P<0.05). However, fasting plasma concentration of triglycerides and glucose were not reduced by training. Insulin sensitivity (HOMA), cardiorespiratory fitness (VO2peak) and exercise maximal fat oxidation (FOMAX) also progressively improved with training (-17±5; 21±2 and 31±8%, respectively, after 4 months; all P<0.05). Vastus lateralis samples from seven subjects revealed that mitochondrial O2 flux was markedly increased with training (71±11%) due to increased mitochondrial content. After 1 month of detraining, the training-induced improvements in waist circumference and blood pressure were maintained. HDL-c and VO2peak returned to the values found after 1-2 months of training while HOMA and FOMAX returned to pre-training values. Conclusions The health related variables most responsive to aerobic interval training in MetS patients are waist circumference, blood pressure and the muscle and systemic adaptations to consume oxygen and fat. However, the latter reverse with detraining while blood pressure and waist circumference are persistent to one month of detraining.
Article
Metabolic syndrome (MetS), an important component of insulin resistance and cardiovascular (CV) risk, is defined by 3 or more of the following characteristics: abdominal obesity, hyperglycemia, hypertension, hypertriglyceridemia, and hypo-high-density lipoprotein cholesterolemia. Based on the previously published age- and sex-mediated DESIR (Data from an Epidemiological Study on the Insulin Resistance Syndrome) cohort and parallel central hemodynamic measurements, our goal was to evaluate the effects of MetS on brachial central pulse pressure (PP), PP amplification, aortic stiffness, and wave reflections. These data were then compared with those of patients with essential hypertension but without MetS for the same mean arterial pressure. Increased aortic stiffness, a major mechanical factor predicting CV risk, has been well identified as playing a role in MetS. Its age progression is proportional to the number of risk factors involved in MetS and is responsible for increased systolic blood pressure and decreased diastolic blood pressure with increasing age, the principal hallmarks of hypertension in the elderly. Beyond brachial pressure measurements, central hemodynamic parameters involve increased aortic stiffness, reduced wave reflections, and increased PP amplification, a parameter commonly associated with increased heart rate. With the exception of arterial stiffness, all these findings are opposite in direction to those observed in essential hypertension, in which MetS is absent. A divergent behavior of wave reflections and PP amplification, but not of arterial stiffness, is observed when hypertension is studied alone or when compared with MetS for the same mean arterial pressure. This pulsatile hemodynamic abnormality contributes independently to increase age- and sex-mediated CV risk, justifying new research regarding Framingham scores and drug treatment.
Article
• Arterial stiffness is an important determinant of cardiovascular risk. Augmentation index (AIx) is a measure of systemic arterial stiffness derived from the ascending aortic pressure waveform. The aim of the present study was to assess the effect of heart rate on AIx. We elected to use cardiac pacing rather than chronotropic drugs to minimize confounding effects on the systemic circulation and myocardial contractility. • Twenty-two subjects (13 male) with a mean age of 63 years and permanent cardiac pacemakers in situ were studied. Pulse wave analysis was used to determine central arterial pressure waveforms, non-invasively, during incremental pacing (from 60 to 110 beats min−1), from which AIx and central blood pressure were calculated. Peripheral blood pressure was recorded non-invasively from the brachial artery. • There was a significant, inverse, linear relationship between AIx and heart rate (r=−0.76; P −1 increment, AIx fell by around 4 %. Ejection duration and heart rate were also inversely related (r=−0.51; P • Peripheral systolic, diastolic and mean arterial pressure increased significantly during incremental pacing. Although central diastolic pressure increased significantly with pacing, central systolic pressure did not. There was a significant increase in the ratio of peripheral to central pulse pressure ( P • These results demonstrate an inverse, linear relationship between AIx and heart rate. This is likely to be due to alterations in the timing of the reflected pressure wave, produced by changes in the absolute duration of systole. Consideration of wave reflection and aortic pressure augmentation may explain the lack of rise in central systolic pressure during incremental pacing despite an increase in peripheral pressure.
Article
Cardiovascular disease is characterized by decreased endothelial function. Chronic exercise training improves endothelial function in individuals with cardiovascular diseases; however, the acute endothelial responses to a single bout of exercise are not consistent in the literature. This study investigated whether a single bout of moderate-intensity endurance exercise (END) and low-volume high-intensity interval exercise (HIT) on a cycle ergometer resulted in similar acute changes in endothelial function. Ten individuals (66 ± 11 yr) with coronary artery disease (CAD) participated in two exercise sessions (END and HIT). Endothelial-dependent function was assessed using brachial artery flow-mediated dilation (FMD) preexercise and 60 min postexercise. Brachial artery diameters and velocities were determined using Doppler ultrasound before and after a 5 min ischemic period at all time points. Endothelial-independent function was assessed using a 0.4-mg sublingual dose of nitroglycerin. The total work performed was higher in END (166 ± 52 kJ) compared with HIT (93 ± 28 kJ) exercise (P < 0.001). Endothelial-dependent function improved (P = 0.01) after END (absolute FMD preexercise, 0.24 ± 0.18 mm; postexercise, 0.31 ± 0.24 mm) and HIT (absolute FMD preexercise, 0.25 ± 0.13 mm; postexercise, 0.29 ± 0.13 mm), with no differences between exercise conditions. A time effect for FMD normalized to the shear rate area under the curve was also observed (P = 0.02) after END (preexercise, 0.005 ± 0.004; postexercise, 0.010 ± 0.011) and HIT (preexercise, 0.005 ± 0.004; postexercise, 0.009 ± 0.011). Endothelial-independent function responses were unchanged after END and HIT (P > 0.05). HIT and END resulted in similar acute increases in brachial artery endothelial-dependent function in a population with dysfunction at rest, despite the difference in exercise intensities.
Article
In cardiovascular and metabolic diseases, small resistance arteries may show the presence of structural alterations. In particular, in essential hypertension, an increased media-to-lumen ratio of subcutaneous small arteries with no change in the total amount of vascular wall tissue (eutrophic remodelling) has already been described several years ago. Similar alterations have been demonstrated also in patients with diabetes mellitus and obesity; in this case, however, a more evident contribution of vascular smooth muscle cell growth (hypertrophic remodelling) is present. This review addresses the effects of obesity on small resistance artery structure. Similar to diabetic patients, obese patients show an increased media-to-lumen ratio of subcutaneous small arteries, which appears associated with hypertrophic remodelling, as demonstrated by an increase in media cross-sectional area. Endothelial dysfunction evaluated as vasodilator response to acetylcholine has also been observed. Several studies have shown that increased media-to-lumen ratio of subcutaneous small resistance arteries possesses a prognostic significance in relation to cardiovascular outcome. Appropriate antihypertensive treatment may improve microvascular alterations both in essential hypertension and in type 2 diabetes mellitus. In obesity, a pronounced weight loss may improve microvascular structure. However, further studies are needed to elucidate the effects of other pharmacological and non-pharmacological interventions in obesity.
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Please cite this paper as: Roustit and Cracowski (2012). Non-invasive Assessment of Skin Microvascular Function in Humans: An Insight Into Methods. Microcirculation 19(1), 47–64. For more than two decades, methods for the non-invasive exploration of cutaneous microcirculation have been mainly based on optical microscopy and laser Doppler techniques. In this review, we discuss the advantages and drawbacks of these techniques. Although optical microscopy-derived techniques, such as nailfold videocapillaroscopy, have found clinical applications, they mainly provide morphological information about the microvessels. Laser Doppler techniques coupled with reactivity tests are widespread in the field of microvascular function research, but many technical issues need to be taken into account when performing these tests. Post-occlusive reactive hyperemia and local thermal hyperemia have been shown to be reliable tests, although their underlying mechanisms are not yet fully understood. Acetylcholine and sodium nitroprusside iontophoresis, despite their wide use as specific tests of endothelium-dependent and -independent function, respectively, show limitations. The influence of the skin site, recording conditions, and the way of expressing data are also reviewed. Finally, we focus on promising tools such as laser speckle contrast imaging.
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Microcirculatory dysfunction contributes to morbidity and mortality in vascular diseases. Here, we aimed at establishing a sensitive and valid method to measure microvascular reactivity during post-occlusive reactive hyperemia (PORH) using scanning laser Doppler perfusion imaging (LDPI) of the forearm. In a first series, LDPI was methodologically evaluated on the volar forearm of healthy volunteers (n = 10) before and after one to five minutes of upper arm occlusion. In a second series, readings were performed in 20 healthy subjects and 20 patients with coronary artery disease (CAD). Three minutes of forearm occlusion were sufficient to induce maximal vasodilation during PORH as indicated by maximal increase in perfusion unit (PU) amplitude that did not further increase after five-minute occlusion. Five-minute occlusion led to a significant prolongation of PORH with greater area under curve (AUC) suggesting longer lasting vasodilation of microvessels. The five-minute occlusion was associated with lower variability as compared with three minutes (intraindividual variability: 9-17% vs. 12-21%; interindividual variability: 13-24% vs. 14-26%). CAD patients exhibited significantly reduced amplitude (105 +/- 49 vs. 164 +/- 35 PU; p < 0.001), ratio (4.7 +/- 1.8 vs. 7.1 +/- 1.8; p < 0.001), and AUC (1656 +/- 1070 vs. 2723 +/- 864 PU x minutes; p = 0.001). Scanning LDPI is a feasible and reproducible method for non-invasive assessment of the cutaneous microcirculatory response during PORH.
Article
Patients with the metabolic syndrome are at increased cardiovascular risk and display an augmented wall stiffness of the large-sized and medium-sized arteries, coupled with an endothelial dysfunction. Whether this is the case also for the small resistance arteries is unknown, however. It is also unknown whether and to what extent the hypothesized microvascular alterations are greater for magnitude than the ones characterizing obesity, that is the most common component of the metabolic syndrome. In 14 lean healthy controls (age 48.7 +/- 2.4 years, mean +/- SEM), 13 obese participants and 12 individuals with the metabolic syndrome (Adult Treatment Panel III criteria), all age-matched with healthy controls, we assessed the small resistance arteries dissected from the abdominal subcutaneous tissue on a pressurized myograph. The media thickness, media cross-sectional area (CSA) and media-to-lumen ratio (M/L) of the small resistance arteries were markedly and significantly greater in metabolic syndrome than in controls (media thickness: 28.3 +/- 0.7 vs. 17.5 +/- 0.3 microm; CSA: 24 760.8 +/- 1459 vs. 16 170.7 +/- 843.6 microm and M/L: 0.12 +/- 0.01 vs. 0.064 +/- 0.002 a.u., respectively, P < 0.01 for all). Acetylcholine-induced relaxation was impaired in the vessels from metabolic syndrome participants compared with the lean healthy individuals (-48.8%, P < 0.01), whereas endothelium-independent vasorelaxation was similar in the two groups. The structural and functional microvascular alterations seen in metabolic syndrome were slightly, although not significantly, greater than the ones seen in uncomplicated obese participants. Stiffness of small arteries, as assessed by the stress/strain relationship, was also similar in the three groups of participants. Thus, metabolic syndrome is characterized by marked alterations in the structural and functional patterns of the small resistance arteries. These alterations, which are only slightly greater than the ones seen in obesity, may be responsible for the increased incidence of coronary and cerebrovascular events reported in metabolic syndrome.
Article
A cluster of risk factors for cardiovascular disease and type 2 diabetes mellitus, which occur together more often than by chance alone, have become known as the metabolic syndrome. The risk factors include raised blood pressure, dyslipidemia (raised triglycerides and lowered high-density lipoprotein cholesterol), raised fasting glucose, and central obesity. Various diagnostic criteria have been proposed by different organizations over the past decade. Most recently, these have come from the International Diabetes Federation and the American Heart Association/National Heart, Lung, and Blood Institute. The main difference concerns the measure for central obesity, with this being an obligatory component in the International Diabetes Federation definition, lower than in the American Heart Association/National Heart, Lung, and Blood Institute criteria, and ethnic specific. The present article represents the outcome of a meeting between several major organizations in an attempt to unify criteria. It was agreed that there should not be an obligatory component, but that waist measurement would continue to be a useful preliminary screening tool. Three abnormal findings out of 5 would qualify a person for the metabolic syndrome. A single set of cut points would be used for all components except waist circumference, for which further work is required. In the interim, national or regional cut points for waist circumference can be used.
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Over the past decade, numerous studies have shown that increased aortic stiffness is associated with major cardiovascular disease end points, including heart disease, stroke, and kidney disease. Cardiac abnormalities and enhanced atherogenesis in the setting of increased pulsatile load on heart and arteries have been well described. However, recent studies have shown a further association between excessive pressure pulsatility and a number of afflictions of aging that share a predominant microvascular etiology, including many forms of kidney disease and cognitive impairment. In these disorders, microvascular remodeling and impaired regulation of local blood flow, which are related to large artery stiffness and pressure pulsatility, are associated with evidence of diffuse microscopic tissue damage. This brief review will summarize age-related changes in aortic and peripheral vascular function and will discuss potential mechanisms leading from changes in properties of large arteries to excessive pressure pulsatility, abnormal microvascular structure and function, and end-organ dysfunction and damage.
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A method for estimating the cholesterol content of the serum low-density lipoprotein fraction (Sf- 0.20)is presented. The method involves measure- ments of fasting plasma total cholesterol, tri- glyceride, and high-density lipoprotein cholesterol concentrations, none of which requires the use of the preparative ultracentrifuge. Cornparison of this suggested procedure with the more direct procedure, in which the ultracentrifuge is used, yielded correlation coefficients of .94 to .99, de- pending on the patient population compared. Additional Keyph rases hyperlipoproteinemia classifi- cation #{149} determination of plasma total cholesterol, tri- glyceride, high-density lipoprotein cholesterol #{149} beta lipo proteins
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It has been well established that arterial stiffness, manifest as an increase in arterial pulse wave velocity or late systolic amplification of the carotid artery pressure pulse, increases with age. However, the populations studied in prior investigations were not rigorously screened to exclude clinical hypertension, occult coronary disease, or diabetes. Furthermore, it is unknown whether exercise capacity or chronic physical endurance training affects the age-associated increase in arterial stiffness. Carotid arterial pressure pulse augmentation index (AGI), using applanation tonometry, and aortic pulse wave velocity (APWV) were measured in 146 male and female volunteers 21 to 96 years old from the Baltimore Longitudinal Study of Aging, who were rigorously screened to exclude clinical and occult cardiovascular disease. Aerobic capacity was determined in all individuals by measurement of maximal oxygen consumption (VO2max) during treadmill exercise. In this healthy, largely sedentary cohort, the arterial stiffness indexes AGI and APWV increased approximately fivefold and twofold, respectively, across the age span in both men and women, despite only a 14% increase in systolic blood pressure (SBP). These age-associated increases in AGI and APWV were of a similar magnitude to those in prior studies of less rigorously screened populations. Both AGI and APWV varied inversely with VO2max, and this relationship, at least for AGI, was independent of age. In endurance trained male athletes, 54 to 75 years old (VO2max = 44 +/- 3 mL.kg-1.min-1), the arterial stiffness indexes were significantly reduced relative to their sedentary age peers (AGI, 36% lower; APWV, 26% lower) despite similar blood pressures. Even in normotensive, rigorously screened volunteers in whom SBP increased an average of only 14% between ages 20 and 90 years, major age-associated increases of arterial stiffness occur. Higher physical conditioning status, indexed by VO2max, was associated with reduced arterial stiffness, both within this predominantly sedentary population and in endurance trained older men relative to their less active age peers. These findings suggest that interventions to improve aerobic capacity may mitigate the stiffening of the arterial tree that accompanies normative aging.
Article
Our objective was to validate a carotid artery tonometry-derived augmentation index as a means to estimate augmentation index (AI) of ascending aortic pressure under various physiological conditions. A total of 66 patients (50 men, 16 women; mean age, 55 years; range, 21 to 78 years; 44 in Taiwan and 22 in the United States) undergoing diagnostic catheterization were studied. Arterial pressure contours were obtained simultaneously from the right common carotid artery by applanation tonometry with an external micromanometer-tipped probe and from the ascending aorta by a micromanometer-tipped catheter at baseline (n = 62), after handgrip (n = 36), or after sublingual nitroglycerin administration (n = 17). The AI (expressed as percentage values) was calculated as the ratio of amplitude of the pressure wave above its systolic shoulder to the total pulse pressure. The carotid AI was consistently lower than the aortic AI, but the two were highly correlated at baseline and after both handgrip and nitroglycerin. Mean +/- SD and correlation coefficients were baseline (14 +/- 16, 28(+) +/- 17, .77), handgrip (18 +/- 19, 32(+) +/- 15, .86), and nitroglycerin (7 +/- 12, 18(+) +/- 13, .52). In addition, after adjusting for age, sex, height, blood pressure, heart rate, and study site, the changes of both AIs from baseline values with handgrip or nitroglycerin were highly associated such that the aortic AI could be approximated from the carotid AI with appropriate regression equations. The high correlations and predictable changes after interventions between the central AI and those estimated from noninvasive carotid tonometry suggest that this technique may have wide applicability for many cardiovascular studies.
Article
A strong but presently unexplained inverse association between blood pressure and insulin sensitivity has been reported. Microvascular vasodilator capacity may be a common antecedent linking insulin sensitivity to blood pressure. To test this hypothesis, we studied 18 normotensive and glucose-tolerant subjects showing a wide range in insulin sensitivity as assessed with the hyperinsulinemic, euglycemic clamp technique. Blood pressure was measured by 24-hour ambulatory blood pressure monitoring. Videomicroscopy was used to measure skin capillary density and capillary recruitment after arterial occlusion. Skin blood flow responses after iontophoresis of acetylcholine and sodium nitroprusside were evaluated by laser Doppler flowmetry. Insulin sensitivity correlated with 24-hour systolic blood pressure (24-hour SBP; r=-0.50, P<0.05). Capillary recruitment and acetylcholine-mediated vasodilatation were strongly and positively related to insulin sensitivity (r=0.84, P<0.001; r=0.78, P<0.001, respectively), and capillary recruitment was inversely related to 24-hour SBP (r=-0.53, P<0.05). Waist-to-hip ratio showed strong associations with insulin sensitivity, blood pressure, and the measures of microvascular function but did not confound the associations between these variables. Subsequent regression analysis showed that the association between insulin sensitivity and blood pressure was not independent of the estimates of microvascular function, and part of the variation in both blood pressure (R2=38%) and insulin sensitivity (R2=71%) could be explained by microvascular function. Insulin sensitivity and blood pressure are associated well within the physiological range. Microvascular function strongly relates to both, consistent with a central role in linking these variables.
Article
Weight loss appears to be an effective method for primary prevention of hypertension. However, the long-term effects of weight loss on blood pressure have not been extensively studied. To present detailed results from the weight loss arm of Trials of Hypertension Prevention (TOHP) II. Multicenter, randomized dinical trial testing the efficacy of lifestyle interventions for reducing blood pressure over 3 to 4 years. Participants in TOHP II were randomly assigned to one of four groups. This report focuses only on participants assigned to the weight loss (n = 595) and usual care control (n = 596) groups. Men and women 30 to 54 years of age who had nonmedicated diastolic blood pressure of 83 to 89 mm Hg and systolic blood pressure less than 140 mm Hg and were 110% to 165% of their ideal body weight at baseline. The weight loss intervention included a 3-year program of group meetings and individual counseling focused on dietary change, physical activity, and social support Weight and blood pressure data were collected every 6 months by staff who were blinded to treatment assignment Mean weight change from baseline in the intervention group was -4.4 kg at 6 months, -2.0 kg at 18 months, and -0.2 kg at 36 months. Mean weight change in the control group at the same time points was 0.1, 0.7, and 1.8 kg. Blood pressure was significantly lower in the intervention group than in the control group at 6, 18, and 36 months. The risk ratio for hypertension in the intervention group was 0.58 (95% CI, 0.36 to 0.94) at 6 months, 0.78 (CI, 0.62 to 1.00) at 18 months, and 0.81 (CI, 0.70 to 0.95) at 36 months. In subgroup analyses, intervention participants who lost at least 4.5 kg at 6 months and maintained this weight reduction for the next 30 months had the greatest reduction in blood pressure and a relative risk for hypertension of 0.35 (CI, 0.20 to 0.59). Clinically significant long-term reductions in blood pressure and reduced risk for hypertension can be achieved with even modest weight loss.
Article
Prior studies suggest that acute elevations in plasma triglycerides alter vascular tone and impair endothelial function. To investigate the relation between acute hypertriglyceridemia and vascular function, we examined the effects of high- and low-fat meals on brachial artery reactivity in 14 healthy volunteers. Flow-mediated dilation declined from 14.7 +/- 8.3% to 10.6 +/- 6.2% after the high-fat meal only (p <0.001), and this decline was associated with a 6% increase in baseline brachial artery diameter (3.50 +/- 0.74 mm to 3.70 +/- 0.81 mm, p <0.001), but not a decrease in the arterial diameter during hyperemia. The high-fat meal increased serum triglycerides and insulin by 94% and 438%, respectively. To investigate the effects of triglyceride elevation in isolation from hyperinsulinemia, we examined vascular responses to an intravenous infusion of a triglyceride emulsion in 28 subjects. Triglyceride emulsion increased serum triglycerides 197% but had no effect on serum insulin. Brachial artery diameter increased 4%, from 3.68 +/- 0.51 mm to 3.81 +/- 0.56 mm (p <0.05), and forearm flow increased 36%, reflecting vasodilation of forearm resistance vessels. Flow-mediated dilation and nitroglycerin-mediated dilation were unaffected. The triglyceride emulsion had no direct dilator effect on rabbit aortic tissue in vitro. In conclusion, acute hypertriglyceridemia is associated with vasodilation of conduit and resistance vessels in the arm and does not impair endothelial vasodilator function per se. The dilator effect is not insulin-dependent and does not appear to be a direct effect of triglycerides on vascular tissue.
Article
The present study aims to investigate whether laser Doppler flowmetry can be used to monitor improvements in vascular function during statin therapy. Endothelial dysfunction is an early feature of atherosclerosis in hypercholesterolemic patients and can be improved by statins. There are several methods to assess endothelial function in vivo, none of them being feasible in everyday practice. Skin perfusion, measured by laser Doppler flowmetry, was assessed at rest and during reactive hyperemia. Nineteen hypercholesterolemic patients (age 42 to 73 years, total cholesterol 5.4 to 9.6 mmol/l) were studied before and during statin therapy. To further investigate the mechanisms, postischemic skin hyperemia was measured before and after intradermal injection of the nitric oxide synthase inhibitor L-NAME and its inactive isoform D-NAME (0.5 micromol/10 microl each). On a separate day, the healthy volunteers were reexamined before and 2 h after 1,000 mg aspirin. Postischemic skin blood flow was markedly reduced in hypercholesterolemic patients (45 +/- 11%) compared with healthy controls (238 +/- 20%, p < 0.0001) and improved after statin therapy (113 +/- 15%, p = 0.0005 vs. pre-treatment). In the healthy volunteers, the hyperemic responses were not significantly different after L-NAME and D-NAME. Aspirin reduced hyperemia from 274 +/- 49% to 197 +/- 40% (p = 0.025). Reactive hyperemia of the skin microcirculation can be easily and reproducibly assessed by laser Doppler flowmetry. Vasodilator prostaglandins are the major mediators of postischemic skin hyperemia, which is impaired in hypercholesterolemic patients and can be enhanced by cholesterol-lowering therapy. Thus, laser Doppler flowmetry may represent a tool to assess and monitor vascular function during therapy in everyday practice.
Article
The National Cholesterol Education Program (NCEP) recently proposed a simple definition for metabolic syndrome. Information on the prospective association of this definition for coronary heart disease (CHD) and type 2 diabetes is currently limited. We used a modified NCEP definition with body mass index in place of waist circumference. Baseline assessments in the West of Scotland Coronary Prevention Study were available for 6447 men to predict CHD risk and for 5974 men to predict incident diabetes over 4.9 years of follow-up. Mean LDL cholesterol was similar but C-reactive protein was higher (P<0.0001) in the 26% of men with the syndrome compared with those without. Metabolic syndrome increased the risk for a CHD event [univariate hazard ratio (HR)=1.76 (95% CI, 1.44 to 2.15)] and for diabetes [univariate HR=3.50 (95% CI 2.51 to 4.90)]. Metabolic syndrome continued to predict CHD events (HR=1.30, 95% CI, 1.00 to 1.67, P=0.045) in a multivariate model incorporating conventional risk factors. Men with 4 or 5 features of the syndrome had a 3.7-fold increase in risk for CHD and a 24.5-fold increase for diabetes compared with men with none (both P<0.0001). C-reactive protein enhanced prognostic information for both outcomes. With pravastatin, men with the syndrome had similar risk reduction for CHD as compared with those without (HR, 0.73 and 0.69; pravastatin versus placebo). A modified NCEP metabolic syndrome definition predicts CHD events, and, more strikingly, new-onset diabetes, and thus helps identify individuals who may receive particular benefit from lifestyle measures to prevent these diseases.
Article
Endothelium-dependent flow-mediated dilation is a homeostatic response to short-term increases in local shear stress. Flow-mediated dilation of the brachial artery in response to postischemic reactive hyperemia is impaired in patients with cardiovascular disease risk factors and may reflect local endothelial dysfunction in the brachial artery. However, previous studies have largely neglected the effect of risk factors on evoked shear stress, which is the stimulus for dilation. We evaluated brachial artery percent dilation and evoked diastolic shear stress during reactive hyperemia using high-resolution ultrasound and Doppler in 2045 participants (1107 women, mean age 61 years) in the Framingham Offspring Study. In age- and sex-adjusted models, baseline and hyperemic shear stress were related to brachial artery percent dilation. In stepwise multivariable analyses examining clinical correlates of percent dilation (without shear stress in the model), age, sex, mean arterial pressure, pulse pressure, heart rate, body mass index, lipid medication use, and hormone replacement therapy were related to percent dilation (R2=0.189; P<0.001). When hyperemic shear stress was incorporated, the overall R2 improved (R2=0.335; P<0.001), but relationships between risk factors and percent dilation were attenuated (age and mean arterial pressure) or no longer significant (all others). In contrast, risk factors were related to baseline and hyperemic shear stress in multivariable analyses. Evoked hyperemic shear stress is a major correlate of brachial artery flow-mediated dilation. The associations between many risk factors and brachial artery flow-mediated dilation may be attributable to reduced stimulus for dilation rather than impaired local conduit artery response during hyperemia.
Postocclusive reactive hyperemia in forearm skin is a commonly used model for studying microvascular reactivity function, particularly in the assessment of vascular effect of topically applied pharmacological substances. In this study, we investigated the reproducibility of several different laser-Doppler-derived parameters in the measurement of postocclusive reactive hyperemia at forearm skin in healthy subjects. Eighteen young healthy male volunteers were recruited and studied in a supine position while fasted. Forearm blood flow was occluded at suprasystolic pressure for 3 min. Microvascular perfusion was measured continuously using laser Doppler fluximetry. Parameters studied were maximum increase in hyperemia perfusion (PORHmax), time-to-peak (Tp), amplitude of peak perfusion (PORHpeak), percentage of hyperemic response (PORH%) and mean velocity of the hyperemia increase (PORHmax/Tp). Measurement was performed twice within each study day for 2 study days. Coefficient of variation and intraclass correlation coefficient (ICC; with 95% confidence interval) were calculated for each parameter. An ICC value above 0.75 was interpreted as "excellent reproducibility". ICC analysis showed that all studied parameters, except for PORH%, demonstrated excellent reproducibility for both within- and between-day measurements. Satisfactory intraday and interday coefficients of variation (<10%) were also obtained for these parameters. Laser-Doppler-derived PORHmax, Tp, PORHpeak and PORHmax/Tp were highly reproducible parameters for measuring microvascular reactivity during reactive hyperemia, with PORHmax shown as the most reproducible index. PORH% is, however, less reproducible. These findings have implications for the use of laser Doppler fluximetry coupled with 3-min-occlusion PORHmax as a useful and reliable noninvasive clinical measurement index of microvascular function.
Article
Aortic stiffness and small-artery structure and function share various risk factors; however, relations between these 2 measures of vascular function are complex and incompletely understood. We examined hyperemic forearm blood flow, an indicator of microvascular structure and function, and aortic stiffness in 2045 participants (1107 women, mean age 61+/-9 years) in the Framingham Heart Study offspring cohort. Using arterial tonometry, we evaluated 3 measures of aortic stiffness: brachial pulse pressure; carotid-femoral pulse wave velocity (CFPWV), which is related directly to aortic wall stiffness; and forward pressure wave amplitude (Pf), which is related directly to aortic wall stiffness and inversely to aortic diameter. Using high-resolution ultrasound and Doppler, we evaluated brachial artery diameter, blood flow, and forearm vascular resistance (FVR) at baseline and during reactive hyperemia after 5 minutes of forearm ischemia. In multivariable models that adjusted for cardiovascular disease risk factors, local brachial pulse pressure, CFPWV, and Pf, considered separately, were associated with increased baseline and hyperemic FVR (P<0.001). In models that further adjusted for mean arterial pressure, each measure of aortic stiffness was associated with reduced hyperemic flow (P<0.001). In risk factor-adjusted models that simultaneously considered CFPWV and Pf, both were associated with increased FVR at baseline (P<0.01) and during hyperemia (P<0.001). Our findings indicate that abnormal aortic stiffness and increased pressure pulsatility are associated with blunted microvascular reactivity to ischemic stress that is in excess of changes attributable to conventional cardiovascular disease risk factors alone, including mean arterial pressure.
Article
Unlabelled: Aortic stiffness measured from pulse wave velocity (PWV) was studied during a six-year period in a population of subjects with zero to three and more cardiovascular (CV) factors involving hypertension, body mass index, dyslipidemia, hypertriglyceridemia, and hyperglycemia. During the follow-up, the increase in PWV was significantly higher in subjects with three and more CV risk factors (i.e., in subjects with metabolic syndrome) than in subjects with zero, one, or two factors, even after adjustments for confounding factors. Metabolic syndrome involves an increased progression of arterial stiffness with age and, thus, favors premature senescence. Objectives: The purpose of the study was to evaluate whether a clustering of metabolic risk factors might accelerate the progression of arterial stiffness with age in subjects with metabolic syndrome (MS). Background: Arterial stiffness is increased in MS, but the genetic and environmental factors that might influence its progression are unknown. Methods: Four hundred seventy-six subjects were classified at baseline according to their number of cardiovascular (CV) risk factors (from zero to three and more), after adjustment for smoking habits. The CV risk factors were: hypertension, body mass index, dyslipidemia, hypertriglyceridemia, and hyperglycemia, classified according to traditional criterions. Subjects were followed for six years and had, at the beginning and end of the survey, determinations of blood pressure (BP), heart rate (HR), and aortic pulse wave velocity (PWV). Results: At baseline, BP, HR, plasma creatinine, and PWV were significantly higher (p < 0.001) in the group with three and more CV risk factors than in groups with zero to two risk factors. During the follow-up, the increase in PWV, but not in pulse pressure, was significantly higher (p < 0.01) in the group with three and more risk factors (i.e., metabolic syndrome) than in other groups. Results were unmodified after adjustments for age, gender, baseline values, drug treatment, smoking habits, and mean arterial pressure. Conclusions: Metabolic syndrome is associated with an increased progression of aortic stiffness with age, supporting premature senescence in these patients.
Article
In general, pulse pressure (PP), augmentation index (AIx), and pulse wave velocity (PWV) are directly and positively associated with cardiovascular risk. However, in patients with systolic heart failure, the opposite (ie, an association between a lower PP and a worse outcome) has been reported as well. We assessed central PP and AIx, using applanation tonometry (SphygmoCor, AtCor Medical) in 63 patients with cardiomyopathy (CMP) and 126 controls, matched for age, gender, and brachial blood pressure (BP). All patients underwent coronary angiography for suspected coronary artery disease. In a subgroup (21 patients, 42 controls), we additionally measured aortic PWV invasively during catheter pullback. Mean age was 63.9 versus 64.1 years and ejection fraction (EF) was 29.9 versus 72.2% in patients versus controls, respectively. Calculated aortic systolic BP as well as invasively measured systolic BP was lower in patients versus controls. Central (but not peripheral) PP (33.8 versus 37.8 mm Hg, P = .01) and AIx (17.5 versus 23.3, P = .002) were lower and ejection duration was shorter (265 versus 314 ms, P < .00001) in patients as compared with controls. When we subdivided the CMP patients with respect to AIx, those with values below and equal to the median (median AIx = 17) had more advanced systolic dysfunction. In multiple regression analysis, EF was an independent predictor of AIx. PVW did not differ between CMP patients and controls (8.6 versus 8.2 m/s in patients versus controls, P = .43). Within the group of CMP patients, however, we observed a strong, positive correlation (r = 0.62, P = .003) between PWV and EF. Central PP, AIx, but also aortic PWV, key measures of arterial function, are susceptible to left ventricular performance.
Article
This study sought to evaluate whether pulse wave velocity (PWV), a noninvasive index of arterial stiffness, is a predictor of the longitudinal changes in systolic blood pressure (SBP) and of incident hypertension. Although arterial stiffness is believed to underlie, in part, the age-associated changes in SBP, particularly at older ages, few longitudinal studies in humans have examined the relationship between arterial stiffness and blood pressure. Pulse wave velocity was measured at baseline in 449 normotensive or untreated hypertensive volunteers (age 53 +/- 17 years). Repeated measurements of blood pressure were performed during an average follow-up of 4.9 +/- 2.5 years. After adjusting for covariates including age, body mass index, and mean arterial pressure, linear mixed effects regression models showed that PWV was an independent determinant of the longitudinal increase in SBP (p = 0.003 for the interaction term with time). In a subset of 306 subjects who were normotensive at baseline, hypertension developed in 105 (34%) during a median follow-up of 4.3 years (range 2 to 12 years). By stepwise Cox proportional hazards models, PWV was an independent predictor of incident hypertension (hazard ratio 1.10 per 1 m/s increase in PWV, 95% confidence interval 1.00 to 1.30, p = 0.03) in individuals with a follow-up duration greater than the median. Pulse wave velocity is an independent predictor of the longitudinal increase in SBP and of incident hypertension. This suggests that PWV could help identify normotensive individuals who should be targeted for the implementation of interventions aimed at preventing or delaying the progression of subclinical arterial stiffening and the onset of hypertension.
  • Friedewald WT
  • Levy RI
  • Fredrickson DS
  • M E Safar
  • M F O'rourke
Safar ME, O'Rourke MF. Arterial Stiffness in Hypertension. Vol 23. Edinburgh, United Kingdom: Elsevier; 2006.
Arterial stiffness, central blood pressures, and wave reflections in cardiomyopathyimplications for risk stratification
  • T Weber
  • J Auer
  • G Lamm
  • O Rourke
  • Mf Eber
Weber T, Auer J, Lamm G, O'Rourke MF, Eber B. Arterial stiffness, central blood pressures, and wave reflections in cardiomyopathyimplications for risk stratification. J Card Fail. 2007;13:353-359.
and International Association for the Study of Obesity
and International Association for the Study of Obesity. Circulation. 2009;120:1640-1645.