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High-sensitivity C-reactive protein, adiposity, and blood pressure in the Yakut of Siberia
Abstract
C-reactive protein (CRP), an acute-phase reactant and marker of inflammatory response, is known to be an important predictor of future cardiovascular mortality, independent of other risk factors. The purpose of this research was to investigate the association between CRP, adiposity, and blood pressure in the Yakut, an indigenous Siberian population undergoing rapid cultural change. We conducted a cross-sectional study of 265 healthy Yakut adults in six villages in rural northeastern Siberia. Plasma CRP was measured by high-sensitivity immunoturbidimetric assay. The median CRP value was 0.85 mg/l, with values for the 25th, 50th, and 75th percentiles of 0.30, 0.85, and 2.28 mg/l, respectively. CRP was positively associated with age (r = 0.19; P = 0.002), but not plasma lipids or smoking status. CRP was associated with measures of central adiposity and characteristics of the metabolic syndrome, particularly in women. We found significantly higher CRP across quintiles (Q) of waist circumference for women (difference = 0.7 mg/l; P = 0.035), but not men (difference = 0.36 mg/l; P = 0.515). CRP was significantly associated with systolic blood pressure in men (difference, Q1 vs. Q5 = 1.1 mg/l; P = 0.044) but not women (difference, Q1 vs. Q5 = 0.03 mg/l; P = 0.713) after adjusting for age, waist circumference, and smoking status. CRP in the Yakut was considerably lower than was reported for other populations. The low CRP levels may be explained in part by a low prevalence of abdominal obesity. Among the Yakut, the high physical-activity demands of a traditional herding lifeway likely play a role through high energy expenditure and maintenance of negative energy balance. Our findings underscore the need for further research on the metabolic activity of adipose tissue, blood pressure, and inflammatory activation in non-Western populations.
... Research on health in post-Soviet Siberia has examined lifestyle change, diet and risk for cardiovascular disease , adiposity, blood pressure and inflammation (Sorensen et al., 2006), physical activity and energetics (Snodgrass, 2004;Leonard et al., 2005), risk for obesity (Snodgrass et al., 2006), high blood pressure (Snodgrass et al., 2008), and growth and nutritional status (Leonard et al., 2002). ...
... Research on health in post-Soviet Siberia has examined lifestyle change, diet and risk for cardiovascular disease , adiposity, blood pressure and inflammation (Sorensen et al., 2006), physical activity and energetics (Snodgrass, 2004;Leonard et al., 2005), risk for obesity (Snodgrass et al., 2006), high blood pressure (Snodgrass et al., 2008), and growth and nutritional status (Leonard et al., 2002). ...
... Current infection was assessed through analysis of CRP, a biomarker of infection and inflammation. CRP is part of the systemic response to injury or infection representing the body's initial response, and is a highly sensitive marker of systemic inflammation, infection, and tissue injury (Libby and Ridker, 1999;Mortensen, 2001;Sorensen et al., 2006). ...
The purpose of this study was to investigate the impact of economic and cultural change on immune function and psychosocial stress in an indigenous Siberian population. We examined Epstein-Barr virus antibodies (EBV), an indirect biomarker of cell-mediated immune function, in venous whole blood samples collected from 143 Yakut (Sakha) herders (45 men and 98 women) in six communities using a cross-sectional study design. We modeled economic change through the analysis of lifestyle incongruity (LI), calculated as the disparity between socioeconomic status and material lifestyle, computed with two orthogonal scales: market and subsistence lifestyle. EBV antibody level was significantly negatively associated with both a market and a subsistence lifestyle, indicating higher cell-mediated immune function associated with higher material lifestyle scores. In contrast, LI was significantly positively associated with EBV antibodies indicating lower immune function, and suggesting higher psychosocial stress, among individuals with economic status in excess of material lifestyle. Individuals with lower incongruity scores (i.e., economic status at parity with material resources, or with material resources in excess of economic status) had significantly lower EBV antibodies. The findings suggest significant health impacts of changes in material well-being and shifting status and prestige markers on health during the transition to a market economy in Siberia. The findings also suggest that relative, as opposed to absolute, level of economic status or material wealth is more strongly related to stress in the Siberian context.
... Most research on inflammation, particularly during pregnancy, has been conducted in high-income countries (Ross et al. 2019). Studies, including previous work in Cebu, demonstrate that inflammatory profiles differ markedly across social, cultural, and ecological contexts (Bernstein and Dominy 2013;Evans and Goedecke 2011;Heald et al. 2003;Hové et al. 2020;McDade 2012;McDade et al. 2009McDade et al. , 2012Minihane et al. 2015;Schutte et al. 2006;Sorensen et al. 2006). Evidence from the Philippines, Ecuador, Ghana, and Bolivia suggests the link between chronic inflammation and cardiovascular disease risk/ morbidity is weaker or absent in lower-income, rural, and/ or less industrialized settings (Gurven et al. 2009;Koopman et al. 2012;McDade et al. 2012McDade et al. , 2015. ...
Objectives:
Maternal socioeconomic status (SES) is an important predictor of adverse birth outcomes and postnatal health across global populations. Chronic inflammation is implicated in cardiometabolic disease risk in high‐income contexts and is a potential pathway linking maternal adversity to offspring health trajectories. To clarify how socioeconomic inequality shapes pregnancy inflammation in middle‐income settings, we investigated SES as a predictor of inflammatory cytokines in late gestation in a sample from the Cebu Longitudinal Health Nutrition Survey in Cebu, Philippines.
Methods:
We used multiple regression to evaluate maternal SES, reflected in household assets, as a predictor of general inflammation (C‐reactive protein), inflammatory cytokines (interleukin‐6, interleukin‐10), and inflammatory balance ( n = 407). Inflammatory markers were measured at 29.9 weeks gestation in dried blood spots, and a measure reflecting relative balance of IL6 and IL10 was calculated to capture pro‐ versus anti‐inflammatory skewed immune profiles.
Results:
Greater household assets significantly predicted lower IL6 concentration ( p < 0.001), with a trend toward lower IL6 relative to IL10 ( p = 0.084). C‐reactive protein and IL10 were not individually related to SES.
Conclusions:
The inverse relationship between SES and pregnancy inflammation in Cebu is consistent with results from high‐income settings. These findings further highlight the influence of socioeconomic conditions on immune regulation during pregnancy. Given the evidence that gestational inflammation impacts offspring fetal growth, our results suggest that social and economic effects on immune function may be an important pathway for the intergenerational transmission of health disparities.
... The dominant public health discourse concerning CRP is one of pathology and "chronic inflammation", yet for at least a decade human biologists working in non-Western populations have found lower CRP than expected, and more complicated relationships between CRP and metabolic disease [52][53]. We note that our CRP values are quite low in comparison to adult values from North America and Europe, though they are similar to those seen in other non-obese adolescent populations [54][55][56][57][58]. ...
Background and objectives:
The human immune system is an ever-changing composition of innumerable cells and proteins, continually ready to respond to pathogens or insults. The cost of maintaining this state of immunological readiness is rarely considered. In this paper we aim to discern a cost to non-acute immune function by investigating how low levels of C-reactive protein (CRP) relate to other energetic demands and resources in adolescent Gambian girls.
Methodology:
Data from a longitudinal study of 66 adolescent girls was used to test hypotheses around investment in immune function. Non-acute (under 2 mg/L) CRP was used as an index of immune function. Predictor variables include linear height velocity, adiposity, leptin, and measures of energy balance.
Results:
Non-acute log CRP was positively associated with adiposity (β = 0.16, p < 0.001, R(2) = 0.17) and levels of the adipokine leptin (β = 1.17, p = 0.006, R(2) = 0.09). CRP was also negatively associated with increased investment in growth, as measured by height velocity (β = -0.58, p < 0.001, R(2) = 0.13) and lean mass deposition β = -0.42, p = 0.005, R(2) = 0.08). Relationships between adiposity and growth explained some, but not all, of this association. We do not find that CRP was related to energy balance.
Conclusions and implications:
These data support a hypothesis that investment in non-acute immune function is facultative, and sensitive to energetic resources and demands. We also find support for an adaptive association between the immune system and adipose tissue.
... Using CRP, myriad studies have demonstrated a relationship between inflammation and degenerative disease in Western popu-lations (i.e., Danesh et al., 2000;Pradhan et al., 2001). This relationship has recently been investigated among a traditionally nonagricultural population as well: among the Yakut, Sorensen et al. (2006) demonstrate low CRP values (relative to Western populations), despite the presence of substantial CVD mortality, suggesting that subsistence activities may modify the relationship between inflammation and CVD. ...
... Diversos estudos em populações saudáveis [14][15][16][17][18][19][20][21][22] descreveram a associação entre a PCR e variáveis antropométricas. Em populações de indivíduos com doença cardíaca conhecida, esta relação não foi ainda sistematicamente analisada. ...
Obesity is a widespread and growing problem and one of metabolic syndrome (MS) components. In healthy populations, C reactive protein (CRP) is correlated with obesity measurements.To study in a population of patients with cardiac disease, if the correlation between CRP and MS variables is also maintained, and the relation between CRP and coronary artery disease (CAD).Study of 1231 patients admitted for an elective cardiac invasive procedure. We collected anthropometric measurements, CRP levels, as well as the other variables of MS. We compared groups according to body mass index distribution and correlation was performed between CRP and all other variables. Results: The overall frequency of MS was 59%. CRP was significantly higher in obese patients, compared to normal and overweight patients. CRP was significantly correlated with all risk factors. The best correlations were obtained for waist circumference, body mass index and number of metabolic syndrome components. The best cut-off value of CRP to predict MS is 0.38 mg/dL. Risk factors, including obesity measures can only explain 3.3 - 3.5% of CRP variance. Gender was the best correlate, followed by HDL-cholesterol. From the anthropometric variables, only body mass index contributed to the variance. No significant association was found between CRP, MS and the presence of CAD.In patients with cardiac disease, we found a significant association between CRP, anthropometric variables and MS, however not as significant as previously described in healthy patients. The number of MS components was also an important influence for CRP.
... The importance of obesity in the development of lowgrade inflammatory states becomes evident when assessing serum hs-CRP levels based on waist circumference values for both genders, where the analyses unveiled significantly greater concentrations in subjects included in the fourth quartile of waist circumference values, harmonizing with the results portrayed by Sorensen et al. in Siberian subjects (48). This highlights meaningfulness of visceral adipose tissue, typical of the abdominal region, in the systemic inflammation found in obesity (49). Notwithstanding the undisputed role of chronic inflammation in the development of obesity, and by consequence, of insulin resistance (50), population studies assessing these elements through hs-CRP and HOMA2-IR are scarce. ...
Objectives: High-sensitivity C-Reactive Protein (hs-CRP) is one of the most applied inflammation markers; therefore, the main objective of this research is to evaluate its epidemiological behavior in adult subjects of the Maracaibo City, Venezuela. Materials and Methods: A total of 1,422 subjects, 704 (49.5%) women and 718 (50.5%) men, were enrolled in the Maracaibo City Metabolic Syndrome Prevalence Study. The results were expressed as medians and interquartile ranges (p25-p75). Differences were determined through
the Mann-Whitney U-test and one-way ANOVA test with the Bonferroni adjustment. A multiple logistic regression model was designed for the analysis of the main factors associated with high serum hs-CRP levels. Results: Overall hs-CRP median was 0.372 mg/L (0.126-0.765 mg/L), 0,382 mg/L (0.122-0.829 mg/L) for women and 0.365 mg/L (0.133-0.712 mg/L) for men; p=0.616. An increasing pattern was observed in hs-CRP concentrations through age, BMI, waist circumference and HOMA2-IR categories. After adjusting for independent variables, a greater risk for elevated hs-CRP levels was observed with female gender, hypertriacylglyceridemia, obesity, diagnosis of metabolic syndrome and very large waist circumference values. Conclusions: Elevated hs-CRP levels are related to the metabolic syndrome but not with each of their separate components, being a greater waist circumference one of the more important risk factors, but only at values much higher than those proposed for our population.
... While a number of studies have reported that overweight and obesity raise baseline CRP levels among adults (e.g. Chambers et al., 2001;Lim et al., 2006;Sorensen et al., 2006), studies on the association between CRP and adiposity among children are mostly limited to Western populations, except for a study which showed that among 14-to 25-year-old males and females in North India there were positive associations between CRP and BMI and triceps skinfold thickness (Vikram et al., 2003). Research from the United States that used NHANES data suggested that even in children who are as young as 3-to 7-years old, there may be an association between CRP and BMI percentile (Ford, 2003). ...
Life history theory predicts a trade-off between immunostimulation and growth. Using a cross-sectional study design, this study aims to test the hypothesis that C-reactive protein (CRP) is negatively associated with height-for-age z-scores (HAZ scores) and BMI-for-age z-scores (BAZ scores) among 6- to 19-year olds (N = 426) residing in five Nepalese communities. Dried blood spot (DBS) samples were collected and assayed for CRP using an in-house enzyme immunoassay (EIA). Sex- and age-group-specific CRP quartiles were used to examine its association with growth in linear mixed-effects (LME) models. A significant difference was found in the proportion of elevated CRP (>2 mg/L, equivalent to ∼3.2 mg/L serum CRP) between 13- and 19-year-old boys (12%) and girls (4%). Concentrations of CRP were positively associated with HAZ score among adolescent (13-19 years) boys, which may indicate that individuals with greater energy resources have better growth and a better response to infections, thus eliminating the expected trade-off between body maintenance (immunostimulation) and growth. Adolescent boys with low BAZ and HAZ scores had low CRP values, suggesting that those who do not have enough energy for growth cannot increase their CRP level even when infected with pathogens. Among adolescent girls a positive association was observed between CRP and BAZ scores suggesting the possible effects of chronic low-grade inflammation due to body fat rather than infection. The association between CRP and growth was less evident among children (6-12 years) compared with adolescents, indicating that the elevated energy requirement needed for the adolescent growth spurt and puberty may play some role. Am J Phys Anthropol, 2014. © 2014 Wiley Periodicals, Inc.
... In this population, CRP can be markedly suppressed, independent of adiposity, with median CRP levels being less than half of the control median (Tomaszewski et al., 2003). The Yakut, a subsistence population in Siberia, have also been shown to have low Table 3 -Correlation coefficients for biomarker measure (Sorensen et al., 2006). In the Yakut, the median CRP is 0.76, compared to a median CRP of 0.70 in the MLSFH biomarker sample. ...
The collection of biomarker-based indicators of adult health and fitness is an important addition to socioeconomic surveys since these indicators provide valuable insights into the biological functions, and the complex causal pathways between socioeconomic environments and health of adult individuals. Other than select Demographic and Health Surveys (DHS), there are almost no population-based sources of biomarker-based indicators of adult health in sub-Saharan Africa (SSA), where most population-based biologic data are focused on HIV, other STDs, malaria, or nutritional status. While infectious diseases---such as HIV and malaria---attract the majority of research and NGOs attention in sub-Saharan Africa, there is an important need to understand the general determinants of adult health in SSA since the region will rapidly age in the next decades in ways that are significantly different from the aging patterns in other developing regions due to the AIDS epidemic, and chronic diseases will increasingly become relevant for understanding the health of sub-Saharan populations. Methods and Design: We document our protocol for the collection of biomarker-based health indicators as a pilot project within the Malawi Longitudinal Study of Families and Health (MLSFH), and we provide basic descriptive information about the study population and the collected biomarker-based indicators of adult health obtained from respondents in rural Malawi. LabAnywhere kits were used to obtain blood plasma from 980 adult men and women living in Balaka, the southern-most region in rural Malawi. The procedure allows for the non-invasive collection of blood plasma, but has not been been previously used in the context of a developing country. We collected biomarkers for inflammation and immunity, lipids, organ function, and metabolic processes. We specifically collected wide-range CRP, total cholesterol, LDL, HDL, total protein, urea, albumin, blood urea nitrogen, creatinine, random blood glucose and HbA1c assays. Overall, the mean values of the biomarkers are below the lower limits of clinical guidelines for adult populations in the U.S. and other developed countries, and only small proportions of the sample are above the upper limits of the normal clinical ranges as defined by U.S. standards. The correlationional patterns of the collected biomarkers are consistent with observations from developed countries, and the comparison with other low-income populations such as the Tsimane in Bolivia or the Yakuts in Siberia show remarkably similar age-specific patterns of the biomarkers despite differences in the mode of blood sampling. Discussion: The MLSFH biomarker sample makes a potentially important contribution to understanding the health of the adult populations in low income environments. The present study confirms that the collection of such biomarkers using the LabAnywhere system is feasible in rural sub-Saharan contexts: the refusal rate was very low in the MLSFH and following the procedures described above, only a small fraction of the biomarker samples could not be analyzed by LabAnywhere. The system therefore provides an attractive alternative to the collection of dried blood spots (DBS) and venous blood samples, providing a broader range of potential biomarkers than DBS and being logistically easier than the collection of venous blood.
... Possible confounding due to current infection was assessed through analysis of C-reactive protein (CRP), a non-specific marker of infection and inflammation. Creactive protein is an acute phase reactant, an innate nonspecific, systemic response to injury or infection representing the body's initial response to a pathogen, and is a highly sensitive marker of systemic inflammation, infection, and tissue injury (Libby and Ridker, 1999;Mortensen, 2001;Sorensen et al., 2006). Upon activation, it responds rapidly with up to a 10,000-fold increase and a 19 hour half life in plasma; plasma concentrations of CRP remain elevated for up to 7 days following an infectious episode. ...
... In a prior study describing the methodology of the data collection, we tested the validity of our measurement approach and showed that this distribution of the biomarkers is not an artifact of measurement issues or problems [39], but it is similar to patterns observed in other low-income populations such as the Tsimane in Bolivia [45][46][47] or the Yakuts in Siberia who are, for http://www.pophealthmetrics.com/content/11/1/4 instance, also characterized by very low CRP levels compared to the U.S. population samples [48,49]. The analysis of the age-gradient reveals that the distribution of cholesterol is shifted upward for older individuals (Table 2 and Figure 1); the same is the case for HDL (men only), Chol/HDL Ratio (women only), LDL, and creatinine (women only). ...
Background
The objective of these analyses is to document the relationship between biomarker-based indicators of health and socioeconomic status (SES) in a low-income African population where the cumulative effects of exposure to multiple stressors on physiological functions and health in general are expected to be highly detrimental for the well-being of individuals.
Methods
Biomarkers were collected subsequent to the 2008 round of the Malawi Longitudinal Study of Families and Health (MLSFH), a population-based study in rural Malawi, including blood lipids (total cholesterol, LDL, HDL, ratio of total cholesterol to HDL), biomarkers of renal and liver organ function (albumin and creatinine) and wide-range C-reactive protein (CRP) as a non-specific biomarker for inflammation. These biomarkers represent widely used indicators of health that are individually or cumulatively recognized as risk factors for age-related diseases among prime-aged and elderly individuals. Quantile regressions are used to estimate the age-gradient and the within-day variation of each biomarker distribution. Differences in biomarker levels by socioeconomic status are investigated using descriptive and multivariate statistics.
Results
Overall, the number of significant associations between the biomarkers and socioeconomic measures is very modest. None of the biomarkers significantly varies with schooling. Except for CRP where being married is weakly associated with lower risk of having an elevated CRP level, marriage is not associated with the biomarkers measured in the MLSFH. Similarly, being Muslim is associated with a lower risk of having elevated CRP but otherwise religion does not predict being in the high-risk quartiles of any of the MLSFH biomarkers. Wealth does not predict being in the high-risk quartile of any of the MLSFH biomarkers, with the exception of a weak effect on creatinine. Being overweight or obese is associated with increased likelihood of being in the high-risk quartile for cholesterol, Chol/HDL ratio, and LDL.
Conclusions
The results provide only weak evidence for variation of the biomarkers by socioeconomic indicators in a poor Malawian context. Our findings underscore the need for further research to understand the determinants of health outcomes in a poor low-income context such as rural Malawi.
... Among the Yakut, median serum equivalent CRP concentration was 0.79 mg/L in women and 0.86 mg/L among men (Table 3). These concentrations are similar to those we documented from venous whole blood samples among Yakut residents of six villages in the Sakha Republic (median CRP concentrations of 0.91 mg/L in women and 0.64 mg/L in men) (Sorensen et al., 2006). The slight difference between the two Yakut studies, with that of Sorensen and colleagues (2006) documenting higher CRP concentrations among women compared to men, may in part reflect the inclusion of fewer women with clinically elevated CRP concentrations (Ͼ10.0 mg/L) in the present study. ...
C-reactive protein (CRP) is an inflammatory marker, which at low-level elevations is associated with increased cardiovascular risk. Although CRP has been extensively investigated in North American and European settings, few studies have measured CRP among non-Western groups. The present study used dried whole blood spot samples to examine high-sensitivity CRP concentrations among the Yakut (Sakha) of Siberia (85 females, 56 males; 18-58 years old). Our goals were: (1) to compare Yakut CRP concentrations with other populations; (2) to investigate sex differences; and (3) to explore anthropometric correlates of CRP. Results indicate that serum equivalent CRP concentrations are similar to those from industrializing nations, lower than US and European values, and greater than Japanese concentrations. Yakut men and women display similar CRP concentrations; however, CRP was significantly higher among men after adjustment for body fat, age, and smoking. Positive associations were documented between CRP and BMI, body fat, and central adiposity.
... Using CRP, myriad studies have demonstrated a relationship between inflammation and degenerative disease in Western popu-lations (i.e., Danesh et al., 2000;Pradhan et al., 2001). This relationship has recently been investigated among a traditionally nonagricultural population as well: among the Yakut, Sorensen et al. (2006) demonstrate low CRP values (relative to Western populations), despite the presence of substantial CVD mortality, suggesting that subsistence activities may modify the relationship between inflammation and CVD. ...
C-reactive protein (CRP) is a widely used, sensitive biomarker of inflammation. Studies conducted among users of exogenous hormones suggest that estrogen increases CRP, whereas progesterone decreases CRP. Examinations of CRP in normally cycling women suggest the opposite: CRP is negatively associated with endogenous estrogen and positively associated with endogenous progesterone. This work evaluates the association between menstrual cycle-related hormone changes and events (menstruation and ovulation) and CRP. Eight female subjects gave urine and blood samples from twelve days across the menstrual cycle, for a total of eleven cycles. Blood samples were assayed for CRP; urine samples for beta-follicle stimulating hormone (betaFSH), pregnanediol 3-glucuronide (PDG), and estrone glucuronide (E1G). Ovulation day was estimated using hormone levels. Presence or absence of menses was reported by subjects. Analyses were conducted with random-effects linear regression. All cycles were ovulatory; day of ovulation was identified for nine cycles. A ten-fold increase in progesterone was associated with a 23% increase in CRP (P = 0.01), a ten-fold increase in estrogen was associated with a 29% decrease in CRP (P = 0.05), and menses was associated with a 17% increase in CRP (P = 0.18); no association between ovulation or FSH and CRP was found. Hormone changes across the menstrual cycle should be controlled for in future studies of inflammation in reproductive-age women.
... Among males, 82.7% of participants had suboptimal blood pressure, and the blood pressure mean was 133.1/82.6 mm Hg. The overall high blood pressure and hypertension prevalence rates documented here are consistent with findings from other studies conducted among native Siberian populations in the post-Soviet period (Kozlov et al., 2003; Sorensen, 2003; Sorensen et al., 2006), although a few relatively isolated coastal groups have somewhat lower blood pressure (Nikitin et al., 1981; Shephard and Rode, 1996). Taken together, blood pressure among indigenous Siberians is considerably higher than that documented in most traditionally living indigenous groups and isolated populations in developing nations; for both these groups, the prevalence of hypertension rarely exceeds 5% and they show at most a minimal age-related increase in blood pressure (Carvalho et al., 1989; Pavan et al., 1999; Cooper, 2003 ). ...
Hypertension is an important global health issue and is currently increasing at a rapid pace in most industrializing nations. Although a number of risk factors have been linked with the development of hypertension, including obesity, high dietary sodium, and chronic psychosocial stress, these factors cannot fully explain the variation in blood pressure and hypertension rates that occurs within and between populations. The present study uses data collected on adults from three indigenous Siberian populations (Evenki, Buryat, and Yakut [Sakha]) to test the hypothesis of Luke et al. (Hypertension 43 (2004) 555-560) that basal metabolic rate (BMR) and blood pressure are positively associated independent of body size. When adjusted for body size and composition, as well as potentially confounding variables such as age, smoking status, ethnicity, and degree of urbanization, BMR was positively correlated with systolic blood pressure (SBP; P < 0.01) and pulse pressure (PP; P < 0.01); BMR showed a trend with diastolic blood pressure (DBP; P = 0.08). Thus, higher BMR is associated with higher SBP and PP; this is opposite the well-documented inverse relationship between physical activity and blood pressure. If the influence of BMR on blood pressure is confirmed, the systematically elevated BMRs of indigenous Siberians may help explain the relatively high blood pressures and hypertension rates documented among native Siberians in the post-Soviet period. These findings underscore the importance of considering the influence of biological adaptation to regional environmental conditions in structuring health changes associated with economic development and lifestyle change.
The aim is to determine the ratio of low physical activity (PA) to a high sedentary behavior (SB) and to change it in the experiment. Methods and organization of the research. We carried out descriptive (n = 425) and cross-sectional (n = 36) experiments using the IPAQ-RU questionnaire for a random group of elderly people in Surgut. Research results. The research revealed that the proportion of inactive elderly people was 36% among men, 48% among women. The proportion of moderately active women was 29%, men – 55%. The duration of the SB was 6-12 hours per day. Conclusion. Optimization of the PA and SB ratio provided a moderately intense PA (140-150 minutes) in elderly women and a decrease in SB time from 6.0 to 3.8 hours per day due to Nordic walking.
synthetic cathinone, is a new class of designer drugs, with psychoactive
effect at the peak intoxication which can cause disorders psychotic level. The review
provides data about the chemical structure of synthetic cathinone’s, mechanisms of
addiction, social profile of the consumers, clinical aspects of use.
The objective of the study was to establish gender-specific characteristics of physical activity (PA) and sedentary behavior in elderly inhabitants of North Yugra. Two hundred and ninety-five residents of Surgut (102 men aged 62.9 ± 5.3 years, 35%; 193 women aged 61.9 ± 3.8 years, 65%) completed a IPAQ-RU questionnaire. The study revealed gender-specific differences in body length and mass, as well as in the bodymass and body-fat indices. It was found that more energy was spent on physical activity in work in the home or summer home (moderate-intensity physical activity for women and high-intensity for men). The data of the study showed no statistically significant gender-specific differences in general physical activity. Sedentary behavior is more common among men than women (2543 vs. 2441 min/week). An amount of 47% of lowactivity men and 56% of women reported that they spent 6–9 h/day sitting, while 42% reported 9–12 h/day. Special measures should be taken to increase physical activity, which is too low at the moment, and to decrease sedentary behavior, which is currently at a high level.
Background and objectives:
We examined a mechanism that may coordinate trade-offs between reproduction and immune response in healthy women, namely, changes in inflammation across the ovarian cycle.
Methodology:
We investigated C-reactive protein (CRP), an inflammation marker, across two consecutive ovarian cycles in 61 Bolivian women. Participants provided saliva samples every other day, and dried blood spots on 5-6 days spread across weeks 2-3 of each cycle. Cycles were characterized as ovulatory/anovulatory based on profiles of reproductive hormones. Participants also reported whether they were sexually partnered with a male or sexually abstinent during the study.
Results:
High early-cycle, but not late-cycle, CRP was associated with anovulation. High inflammation at the end of one cycle was not associated with anovulation in the subsequent cycle. Among ovulatory cycles, women with sexual partners had significantly lower CRP at midcycle, and higher CRP at follicular and luteal phases; in contrast, sexually abstinent women had little cycle-related change in CRP. In anovulatory cycles, partnership had no effect on CRP. CRP varied significantly with socioeconomic status (higher in better-off than in poorer women).
Conclusions and implications:
These findings suggest that the cycle-specific effect of inflammation on ovarian function may be a flexible, adaptive mechanism for managing trade-offs between reproduction and immunity. Sociosexual behavior may moderate changes in inflammation across the ovarian cycle, suggesting that these shifts represent evolved mechanisms to manage the trade-offs between reproduction and immunity. Clinically, these findings support considering both menstrual cycle phase and sexual activity in evaluations of pre-menopausal women's CRP concentrations.
In this paper we examine the distribution of a marker of immune system stimulation-C-reactive protein-in urban Brazil. Social relationships are associated with immunostimulation, and we argue that cultural dimensions of social support, assessed by cultural consonance, are important in this process. Cultural consonance is the degree to which individuals, in their own beliefs and behaviors, approximate shared cultural models. A measure of cultural consonance in social support, based on a cultural consensus analysis regarding sources and patterns of social support in Brazil, was developed. In a survey of 258 persons, the association of cultural consonance in social support and C-reactive protein was examined, controlling for age, sex, the body mass index, low-density lipoprotein cholesterol, depressive symptoms, and a social network index. Lower cultural consonance in social support was associated with higher C-reactive protein. Implications of these results for future research are discussed. This article is protected by copyright. All rights reserved.
This article is protected by copyright. All rights reserved.
Background:
Circumpolar regions are undergoing social and economic transition, which often corresponds to a behavioural transition. Yet, physical activity and sedentary behaviour are rarely objectively measured within these groups.
Aim:
This study aimed to characterize objectively measured physical activity and sedentary behaviour in a sample of indigenous Siberians.
Subjects and methods:
Yakut (Sakha) adults (n = 68, 32 men) underwent anthropometry, interviews and wore a triaxial accelerometer for two days. Time spent in moderate-to-vigorous physical activity (MVPA) or sedentary behaviour was calculated using a single axis and also all three axes.
Results:
Men spent significantly more time in MVPA than women, although no sex difference was found in sedentary behaviour. Participants were far more active and less sedentary when classified using all three axes (vector magnitude) than a single axis. Television viewing time significantly related to sedentary behaviour in men only.
Conclusion:
The Yakut have gender differences in amount and predictors of physical activity and sedentary behaviour. Triaxial accelerometry is more sensitive to daily physical activity in free living populations than single axis.
Background:
Inflammation may be an important mediator of the association between nutrition and cardiovascular diseases, but most studies have been conducted in Western populations with high rates of overweight and obesity and low levels of infectious disease.
Objectives:
This study sought to investigate the predictors of C-reactive protein (CRP) in young adults living in the Philippines and to examine patterns of association with adiposity compared with young adults in the United States.
Design:
Maximum likelihood logistic regression models were used to predict elevated high-sensitivity CRP (>3 mg/L) in relation to anthropometric measures of adiposity, symptoms of infectious disease, and proxy measures of pathogen exposure in men and women from the Philippines (n = 1648; age: 20-22 y). Comparative data were drawn from a nationally representative sample in the United States (National Health and Nutrition Examination Survey; n = 616; age: 19-24 y).
Results:
Median concentrations of CRP were substantially lower in the Philippines (0.2 mg/L) than in the United States (0.9 mg/L), and the likelihood of elevated CRP was lower in the Philippines than in the United States at the same level of waist circumference or skinfold thickness. In the Philippines, infectious symptoms and pathogen exposure predicted elevated CRP, independent of adiposity.
Conclusions:
Adiposity and infectious exposures are associated with elevated CRP in the Philippines; other populations undergoing comparable lifestyle and dietary changes associated with increasing rates of overweight and obesity are likely experiencing similar double burdens of inflammatory stimuli. Low concentrations of CRP in this Philippine sample raise the question of whether CRP cutoffs based on European or European-American reference populations are appropriate for predicting disease risk in populations undergoing the nutrition transition.
Obesity is a widespread and growing problem and one of metabolic syndrome (MS) components. In healthy populations, C reactive protein (CRP) is correlated with obesity measurements.
To study in a population of patients with cardiac disease, if the correlation between CRP and MS variables is also maintained, and the relation between CRP and coronary artery disease (CAD).
Study of 1231 patients admitted for an elective cardiac invasive procedure. We collected anthropometric measurements, CRP levels, as well as the other variables of MS. We compared groups according to body mass index distribution and correlation was performed between CRP and all other variables. Results: The overall frequency of MS was 59%. CRP was significantly higher in obese patients, compared to normal and overweight patients. CRP was significantly correlated with all risk factors. The best correlations were obtained for waist circumference, body mass index and number of metabolic syndrome components. The best cut-off value of CRP to predict MS is 0.38 mg/dL. Risk factors, including obesity measures can only explain 3.3 - 3.5% of CRP variance. Gender was the best correlate, followed by HDL-cholesterol. From the anthropometric variables, only body mass index contributed to the variance. No significant association was found between CRP, MS and the presence of CAD.
In patients with cardiac disease, we found a significant association between CRP, anthropometric variables and MS, however not as significant as previously described in healthy patients. The number of MS components was also an important influence for CRP.
The use of dried whole blood spot samples provides medical anthropological researchers-especially those working in remote, isolated communities-with several advantages over traditional methods. Anthropological research utilizing venous-drawn blood samples can create challenges in terms of phlebotomy training, personnel needs, storage and transportation requirements, and participant discomfort. Alternatively, research utilizing dried blood spot samples, via finger stick collection techniques, eliminates or reduces these problems greatly. While the use of dried blood spots is often the best sampling option for anthropologists or other population-level researchers, the method does have some limitations. Nevertheless, as the number of dried blood spot analyte protocols continues to increase, the logistical and participant advantages of dried blood spot methods assure their increased utility in biomedical anthropological research in the future.
Typescript. Thesis (M.A.)--DePaul University, 1996. Department of History. Includes bibliographical references (leaves [67-69]).
Human adipose tissue expresses and releases the proinflammatory cytokine interleukin 6, potentially inducing low-grade systemic inflammation in persons with excess body fat.
To test whether overweight and obesity are associated with low-grade systemic inflammation as measured by serum C-reactive protein (CRP) level.
The Third National Health and Nutrition Examination Survey, representative of the US population from 1988 to 1994.
A total of 16616 men and nonpregnant women aged 17 years or older.
Elevated CRP level of 0.22 mg/dL or more and a more stringent clinically raised CRP level of more than 1.00 mg/dL.
Elevated CRP levels and clinically raised CRP levels were present in 27.6% and 6.7% of the population, respectively. Both overweight (body mass index [BMI], 25-29.9 kg/m2) and obese (BMI, > or =30 kg/m2) persons were more likely to have elevated CRP levels than their normal-weight counterparts (BMI, <25 kg/m2). After adjustment for potential confounders, including smoking and health status, the odds ratio (OR) for elevated CRP was 2.13 (95% confidence interval [CI], 1.56-2.91) for obese men and 6.21 (95% CI, 4.94-7.81) for obese women. In addition, BMI was associated with clinically raised CRP levels in women, with an OR of 4.76 (95% CI, 3.42-6.61) for obese women. Waist-to-hip ratio was positively associated with both elevated and clinically raised CRP levels, independent of BMI. Restricting the analyses to young adults (aged 17-39 years) and excluding smokers, persons with inflammatory disease, cardiovascular disease, or diabetes mellitus and estrogen users did not change the main findings.
Higher BMI is associated with higher CRP concentrations, even among young adults aged 17 to 39 years. These findings suggest a state of low-grade systemic inflammation in overweight and obese persons.
The discovery of leptin has imparted great impetus to adipose tissue research by demonstrating a more active role for the adipocyte in energy regulation. Besides leptin, however, the adipose tissue also secretes a large number other signals. Cytokine signals, TNFalpha and IL-6, and components of the alternative pathway of complement influence peripheral fuel storage, mobilization and combustion, as well as energy homeostasis. In addition to the acute regulation of fuel metabolism, adipose tissue also influences steroid conversion and sexual maturation. In this way, adipose tissue is an active endocrine organ, influencing many aspects of fuel metabolism through a network of local and systemic signals, which interact with the established neuroendocrine regulators of adipose tissue. Thus, insulin, catecholamines and anterior pituitary endocrine axes interact at multiple levels with both cytokines and leptin. It may be proposed that the existence of this network of adipose tissue signalling pathways, arranged in an hierarchical fashion, constitutes a metabolic repertoire which enables the organism to adapt to a range of different metabolic challenges, including starvation, reproduction, times of physical activity, stress and infection, as well as short periods of gross energy excess. However, the occurrence of more prolonged periods of energy surplus, leading to obesity, is an unusual state in evolutionary terms, and the adipose tissue signalling repertoire, although sophisticated, adapts poorly to these conditions. Rather, the responses of the adipose tissue endocrine network to obesity are maladaptive, and lay the foundations of metabolic disease.
To assess associations between baseline values of four different circulating markers of inflammation and future risk of coronary heart disease, potential triggers of systemic inflammation (such as persistent infection), and other markers of inflammation.
Nested case-control comparisons in a prospective, population based cohort.
General practices in 18 towns in Britain.
506 men who died from coronary heart disease or had a non-fatal myocardial infarction and 1025 men who remained free of such disease until 1996 selected from 5661 men aged 40-59 years who provided blood samples in 1978-1980.
Plasma concentrations of C reactive protein, serum amyloid A protein, and serum albumin and leucocyte count. Information on fatal and non-fatal coronary heart disease was obtained from medical records and death certificates.
Compared with men in the bottom third of baseline measurements of C reactive protein, men in the top third had an odds ratio for coronary heart disease of 2.13 (95% confidence interval 1.38 to 3.28) after age, town, smoking, vascular risk factors, and indicators of socioeconomic status were adjusted for. Similar adjusted odds ratios were 1.65 (1.07 to 2.55) for serum amyloid A protein; 1.12 (0.71 to 1.77) for leucocyte count; and 0.67 (0.43 to 1.04) for albumin. No strong associations were observed of these factors with Helicobacter pylori seropositivity, Chlamydia pneumoniae IgG titres, or plasma total homocysteine concentrations. Baseline values of the acute phase reactants were significantly associated with one another (P<0.0001), although the association between low serum albumin concentration and leucocyte count was weaker (P=0.08).
In the context of results from other relevant studies these findings suggest that some inflammatory processes, unrelated to the chronic infections studied here, are likely to be involved in coronary heart disease.
The distribution of serum C-reactive protein (CRP) levels and their association with age, sex, and atherosclerotic risk factors were studied in a large Japanese population between 1992 and 1995. The subjects consisted of 2,275 males and 3,832 females aged 30 years and over. CRP was measured by nephelometry. The distribution of CRP was highly skewed toward a lower level than that of previous studies and seemed to be a combination of two separate distribution curves. The increase in CRP with age was statistically significant, and males had higher CRP levels than did females. Males who were current smokers had higher CRP levels than did nonsmokers. Age, systolic blood pressure, diastolic blood pressure, triglycerides, fibrinogen, and body mass index were all positively associated with CRP in both sexes, while total cholesterol and blood glucose were positively related in females only. High density lipoprotein cholesterol was inversely related in both sexes. Multiple logistic regression analysis showed that sex, age, systolic pressure, high density lipoprotein cholesterol, triglycerides, fibrinogen, and body mass index were significant independent variables. In conclusion, the distribution of CRP among the Japanese was quite different from that among Westerners, although CRP levels correlated with other atherosclerotic risk factors, similar to those in Westerners.
To investigate the association between circulating C-reactive protein (CRP) concentrations and indices of body fat distribution and the insulin resistance syndrome in South Asians and Europeans.
: Cross-sectional study.
A total of 113 healthy South Asian and European men and women in West London (age 40-55 y, body mass index (BMI) 17-34 kg/m(2)).
Fatness and fat distribution parameters (by anthropometry, dual-energy X-ray absorptiometry and abdominal CT scan); oral glucose tolerance test with insulin response; modified fat tolerance test; and CRP concentration by sensitive ELISA.
Median CRP level in South Asian women was nearly double that in European women (1.35 vs 0.70 mg/1, P=0.05). Measures of obesity and CRP concentration were significantly associated in both ethnic groups. The correlation to CRP was especially strong among South Asians (P<0.01) for measures of central obesity (waist girth and visceral fat area), whereas BMI and percentage fat were more significantly associated with CRP in Europeans (P<0.05). In South Asians the associations of CRP with visceral fat area and waist girth persisted after adjustment for either BMI or percent fat (all, P<0.05). In age-, sex- and smoking-adjusted regression analyses CRP concentrations were significantly associated with fasting and 2 h insulin and lipid levels in both ethnic groups (P<0.05). When further statistical adjustment was made for visceral fat area these associations were abolished (P>0.15).
We suggest that adiposity and in particular visceral adipose tissue is a key promoter of low-grade chronic inflammation. This observation may in part account for the association of CRP with markers of the metabolic syndrome. Future studies should confirm whether CRP concentrations are elevated in South Asians and whether losing weight by exercise or diet, or reduction in visceral fat mass, is associated with reduction in plasma CRP concentrations.
This is a comprehensive text on the methods—dietary, anthropometric, laboratory and clinical—of assessing the nutritional status of populations and of individuals in the hospital or the community. The second edition incorporates recent data from national nutritional surveys in the US and Europe; the flood of new information about iron, vitamin A and iodine; the role of folate in preventing neural tube defects; the use of HPLC techniques and enzyme assays; improvements in data handling; and many other developments since 1990.
Background: Prospective studies have shown that C-reactive protein (CRP) can be used to predict risk of future cardiovascular events. High-sensitivity methods for CRP (hs-CRP) measurement are needed for this purpose.
Methods: We compared the clinical efficacy of an automated and commercially available latex-enhanced assay (Latex) for hs-CRP (Dade Behring) to a validated in-house ELISA, previously shown to predict future peripheral arterial disease (PAD) in asymptomatic populations. Using a prospective, nested, case-control design, we measured baseline hs-CRP concentrations in 144 apparently healthy men who subsequently developed symptomatic PAD and 144 age- and smoking habit-matched controls who remained free of vascular disease over the follow-up period of 60 months.
Results: The two hs-CRP assays correlated highly (r = 0.95; P <0.001), and all but two participants were classified into concordant quartiles or varied by only one quartile. The median hs-CRP of the case group was significantly higher than that of controls when measured by either the ELISA (1.34 vs 0.99 mg/L; P = 0.034) or the Latex method (1.80 vs 1.20 mg/L; P = 0.042). Furthermore, for both ELISA and the Latex method, the calculated relative risks of developing PAD increased significantly with each increasing quartile of hs-CRP. The calculated interquartile increase in relative risk of PAD was 31% (95% confidence interval, 5.2–62.2%; P = 0.01) for ELISA and 34% (95% confidence interval, 8.2–66.1%; P = 0.007) for the Latex method.
Conclusions: Our findings indicate that the Latex method is equally as efficacious as the validated ELISA in classifying patients into cutoff points established by prospective studies for risk stratification for coronary and cerebrovascular disease.
Background: Increased values of C-reactive protein (CRP), the classical acute phase protein, within the range below 5 mg/L, previously considered to be within the reference interval, are strongly associated with increased risk of atherothrombotic events, and are clinically significant in osteoarthritis and neonatal infection.
Methods: A robust new polyclonal-monoclonal solid- phase IRMA for CRP was developed, with a range of 0.05–10.0 mg/L.
Results: Plasma CRP values in general adult populations from Augsburg, Germany (2291 males and 2203 females; ages, 25–74 years) and Glasgow, Scotland (604 males and 650 females; ages, 25–64 years) were very similar. The median CRP approximately doubled with age, from ∼1 mg/L in the youngest decade to ∼2 mg/L in the oldest, and tended to be higher in females.
Conclusion: This extensive data set, the largest such study of CRP, provides valuable reference information for future clinical and epidemiological investigations.
The National Cholesterol Education Program’s Adult Treatment Panel III report (ATP III)1 identified the metabolic syndrome as a multiplex risk factor for cardiovascular disease (CVD) that is deserving of more clinical attention. The cardiovascular community has responded with heightened awareness and interest. ATP III criteria for metabolic syndrome differ somewhat from those of other organizations. Consequently, the National Heart, Lung, and Blood Institute, in collaboration with the American Heart Association, convened a conference to examine scientific issues related to definition of the metabolic syndrome. The scientific evidence related to definition was reviewed and considered from several perspectives: (1) major clinical outcomes, (2) metabolic components, (3) pathogenesis, (4) clinical criteria for diagnosis, (5) risk for clinical outcomes, and (6) therapeutic interventions.
ATP III viewed CVD as the primary clinical outcome of metabolic syndrome. Most individuals who develop CVD have multiple risk factors. In 1988, Reaven2 noted that several risk factors (eg, dyslipidemia, hypertension, hyperglycemia) commonly cluster together. This clustering he called Syndrome X , and he recognized it as a multiplex risk factor for CVD. Reaven and subsequently others postulated that insulin resistance underlies Syndrome X (hence the commonly used term insulin resistance syndrome ). Other researchers use the term metabolic syndrome for this clustering of metabolic risk factors. ATP III used this alternative term. It avoids the implication that insulin resistance is the primary or only cause of associated risk factors. Although ATP III identified CVD as the primary clinical outcome of the metabolic syndrome, most people with this syndrome have insulin resistance, which confers increased risk for type 2 diabetes. When diabetes becomes clinically apparent, CVD risk rises sharply. Beyond CVD and type 2 diabetes, individuals with metabolic syndrome seemingly are susceptible to other conditions, notably polycystic ovary syndrome, fatty liver, cholesterol gallstones, asthma, sleep disturbances, and some …
Context The Third Report of the National Cholesterol Education Program Expert
Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in
Adults (ATP III) highlights the importance of treating patients with the metabolic
syndrome to prevent cardiovascular disease. Limited information is available
about the prevalence of the metabolic syndrome in the United States, however.Objective To estimate the prevalence of the metabolic syndrome in the United States
as defined by the ATP III report.Design, Setting, and Participants Analysis of data on 8814 men and women aged 20 years or older from the
Third National Health and Nutrition Examination Survey (1988-1994), a cross-sectional
health survey of a nationally representative sample of the noninstitutionalized
civilian US population.Main Outcome Measures Prevalence of the metabolic syndrome as defined by ATP III (≥3 of
the following abnormalities): waist circumference greater than 102 cm in men
and 88 cm in women; serum triglycerides level of at least 150 mg/dL (1.69
mmol/L); high-density lipoprotein cholesterol level of less than 40 mg/dL
(1.04 mmol/L) in men and 50 mg/dL (1.29 mmol/L) in women; blood pressure of
at least 130/85 mm Hg; or serum glucose level of at least 110 mg/dL (6.1 mmol/L).Results The unadjusted and age-adjusted prevalences of the metabolic syndrome
were 21.8% and 23.7%, respectively. The prevalence increased from 6.7% among
participants aged 20 through 29 years to 43.5% and 42.0% for participants
aged 60 through 69 years and aged at least 70 years, respectively. Mexican
Americans had the highest age-adjusted prevalence of the metabolic syndrome
(31.9%). The age-adjusted prevalence was similar for men (24.0%) and women
(23.4%). However, among African Americans, women had about a 57% higher prevalence
than men did and among Mexican Americans, women had about a 26% higher prevalence
than men did. Using 2000 census data, about 47 million US residents have the
metabolic syndrome.Conclusions These results from a representative sample of US adults show that the
metabolic syndrome is highly prevalent. The large numbers of US residents
with the metabolic syndrome may have important implications for the health
care sector.
Background: Both C-reactive protein and low-density lipoprotein (LDL) cholesterol levels are elevated in persons at risk for cardiovascular events. However, population-based data directly comparing these two biologic markers are not available. Methods: C-reactive protein and LDL cholesterol were measured at base line in 27,939 apparently healthy American women, who were then followed for a mean of eight years for the occurrence of myocardial infarction, ischemic stroke, coronary revascularization, or death from cardiovascular causes. We assessed the value of these two measurements in predicting the risk of cardiovascular events in the study population. Results: Although C-reactive protein and LDL cholesterol were minimally correlated (r=0.08), base-line levels of each had a strong linear relation with the incidence of cardiovascular events. After adjustment for age, smoking status, the presence or absence of diabetes mellitus, categorical levels of blood pressure, and use or nonuse of hormone-replacement therapy, the relative risks of first cardiovascular events according to increasing quartiles of C-reactive protein, as compared with the women in the lowest quintile, were 1.4, 1.6, 2.0, and 2.3 (P<0.001), whereas the corresponding relative risks in increasing quintiles of LDL cholesterol, as compared with the lowest, were 0.9, 1.1, 1.3, and 1.5 (P<0.001). Similar effects were observed in separate analyses of each component of the composite end point and among users and nonusers of hormone-replacement therapy. Overall, 77 percent of all events occurred among women with LDL cholesterol levels below 160 mg per deciliter (4.14 mmol per liter), and 46 percent occurred among those with LDL cholesterol levels below 130 mg per deciliter (3.36 mmol per liter). By contrast, because C-reactive protein and LDL cholesterol measurements tended to identify different high-risk groups, screening for both biologic markers provided better prognostic information than screening for either alone. Independent effects were also observed for C-reactive protein in analyses adjusted for all components of the Framingham risk score. Conclusions: These data suggest that the C-reactive protein level is a stronger predictor of cardiovascular events than the LDL cholesterol level and that it adds prognostic information to that conveyed by the Framingham risk score.
The advanced lesions of atherosclerosis represent the culmination of a specialized form of chronic inflammation followed by a fibroproliferative process that takes place within the intima of the affected artery. Proliferation of smooth muscle cells and generation of connective tissue occur. Proliferation results from interactions between arterial smooth muscle, monocyte-derived macrophages, T lymphocytes, and endothelium. The initial lesion of atherosclerosis, the fatty streak, begins as an accumulation of monocytederived macrophages and T lymphocytes, which adhere and migrate into the intima of the affected artery. Smooth muscle cells, which are present in the intima or which migrate into the intima from the media, then replicate. Monocyte-derived macrophages and T cells also replicate during lesion formation and progression due to the production of cytokines and growth-regulatory molecules. These molecules determine whether there is proliferation and lesion progression or inhibition of proliferation and lesion regression. Several growthregulatory molecules may play critical roles in this process, including platelet-derived growth factor (PGDF), transforming growth factor beta, fibroblast growth factor, heparinbinding epidermal growth factor-like growth factor, and others. PDGF may be one of the principal components in this process because protein containing the PDGF B-chain has been demonstrated within activated lesion macrophages during every phase of atherogenesis. The presence of this growth factor and its receptors on lesion smooth muscle cells creates opportunities for smooth muscle chemotaxis and replication. Smooth muscle proliferation depends upon a series of complex signals based upon cellular interactions in the local microenvironment of the artery. The intracellular signalling pathways for mitogenesis versus chemotaxis are being investigated for smooth muscle. The roles of the cytokines and growth-regulatory peptides involved in these cellular interactions represent critical points of departure for intervention and the development of new diagnostic methods. In addition, magnetic resonance imaging has been developed to demonstrate the fine structure of lesions of atherosclerosis in peripheral arteries not subject to cardiac motion. This noninvasive methodology holds great promise for the future of these approaches.
Previous research has suggested that arctic populations have ele-vated metabolic rates in response to their cold, marginal climate. Recent studies of indigenous Siberian groups have confirmed these earlier findings and have shed light on the mechanisms through which northern populations adapt to their environments. Indige-nous Siberians show significant elevations in basal metabolic rate compared with reference values. Total energy expenditure is variable across Siberian groups and is correlated with levels of acculturation. Siberian populations appear to have adapted to cold stress through both short-term acclimatization and genetic adaptations, with thy-roid hormones playing an important role in shaping metabolic re-sponses. Elevated metabolic rates also have important consequences for health and may contribute to the low serum lipid levels observed in Siberian groups. Further research is needed to elucidate the un-derlying mechanisms of metabolic adaptation and their implications for ongoing health changes among indigenous Siberians.
This study examines serum lipid levels (total, HDL and LDL cholesterol, and triglycerides) among the Evenki reindeer herders of Central Siberia. Cholesterol and triglyceride levels among the Evenki are low, even relative to other indigenous arctic and herding populations. Total and LDL cholesterol levels are higher in women, while HDL and triglyceride levels are comparable between the sexes. Additionally, residence location (i.e., herding brigade vs. central villages) has a significant influence on men's but not women's total and LDL cholesterol levels. Low lipid levels among the Evenki appear to reflect the maintenance of a traditional lifestyle with high levels of energy expenditure and relatively low levels of fat consumption. Sex differences in lipid levels may be partly attributable to differences in activity patterns, as women have significantly lower levels of energy expenditure than men. © 1994 Wiley-Liss, Inc.
This study examined the health consequences of economic development in the Yakut (Sakha), a high-latitude indigenous pastoral population from northeastern Siberia. The three main objectives were: (1) to investigate metabolic adaptation; (2) to explore health and energy balance within the context of economic modernization; and (3) to examine the intersection of biological adaptation and lifestyle change. Research was conducted in the Sakha Republic of Russia. Energetic (basal metabolic rate [BMR] and total energy expenditure [TEE]), anthropometric (body size and composition), and blood pressure data were obtained from Yakut adults. Extensive information on lifestyle, socioeconomic status, and diet was assessed by questionnaire. Yakut men and women had significantly elevated BMRs compared to reference norms, which were not attributable to body composition, diet, or anxiety. Further, no significant relationships were documented between lifestyle variables and BMR, suggesting a role for genetic and/or developmental factors. TEE and physical activity level (PAL; TEE/BMR) were measured over a 10-day period using the doubly labeled water (DLW) technique. Physical activity levels among the Yakut were relatively low compared to other subsistence populations, especially among women, and similar to individuals in industrialized nations. Individuals who participated in more subsistence activities and consumed fewer market foods had significantly higher activity levels. Obesity has emerged as a health problem for both Yakut men and women. However, there were significant sex differences in the relationship between lifestyle and body composition; affluence was positively associated with obesity among men, while the reverse was true for women. Hypertension was identified as a major health concern, especially among men. In both sexes, elevated blood pressure was associated with greater age and adiposity, and relatively lower income; among men it was also associated with prolonged television viewing. Blood pressure was also positively associated with BMR, independent of body size and composition. Overall, this study demonstrated that economic modernization exerted profound and variable effects on Yakut health, which were shaped by both lifestyle factors and by physiological adaptation to the circumpolar environment. These findings underscore the importance of examining how human adaptability influences health changes in response to economic modernization. Source: Dissertation Abstracts International, Volume: 65-12, Section: A, page: 4622. Adviser: William R. Leonard. Thesis (Ph.D.)--Northwestern University, 2004.
1. Skinfold thicknesses at four sites – biceps, triceps, subscapular and supra-iliac – and total body density (by underwater weighing) were measured on 209 males and 272 females aged from 16 to 72 years. The fat content varied from 5 to 50% of body-weight in the men and from 10 to 61% in the women.
2. When the results were plotted it was found necessary to use the logarithm of skinfold measurements in order to achieve a linear relationship with body density.
3. Linear regression equations were calculated for the estimation of body density, and hence body fat, using single skinfolds and all possible sums of two or more skinfolds. Separate equations for the different age-groupings are given. A table is derived where percentage body fat can be read off corresponding to differing values for the total of the four standard skinfolds. This table is subdivided for sex and for age.
4. The possible reasons for the altered position of the regression lines with sex and age, and the validation of the use of body density measurements, are discussed.
Recent experimental data suggest marked similarities between the effects of hypertension and hypercholesterolemia on the arterial intima. Both conditions also seem to exert proinflammatory effects on the artery, resulting in the recruitment of monocytes into the intima. These effects may be due to production of oxygen-free radicals, which in turn may stimulate genes involved in the recruitment of inflammatory cells into the arterial wall. Plaque rupture and acute myocardial infarction are related to local accumulation of inflammatory cells in vulnerable areas of the plaque. Recent clinical trials using cholesterol-lowering or antihypertensive therapies have shown a decrease in cardiovascular events that may have resulted from withdrawal of inflammatory effects on the arterial wall. Angiotensin-converting enzyme inhibitors decrease the rate of myocardial infarction in patients with overt congestive heart failure or left ventricular dysfunction. These drugs probably affect several mechanisms related to the inhibition of angiotensin production and the potentiation of bradykinin and resultant enhancement of nitric oxide and prostacyclin. The mechanisms could include reversing the proinflammatory effects of angiotensin and hypercholesterolemia on the arterial wall. Future therapeutic strategies of vascular protection in hypertension may include direct attacks on proinflammatory or pro-oxidant vascular mechanisms.
Arch Intern Med. 1996;156:1952-1956
We measured arterio-venous differences in concentrations of tumor necrosis factor-alpha (TNF alpha) and interleukin-6 (IL-6) across a sc adipose tissue bed in the postabsorptive state in 39 subjects [22 women and 17 men; median age, 36 yr (interquartile range, 26-48 yr); body mass index, 31.8 kg/m2 (range, 22.3- 38.7 kg/m2); percent body fat, 28.7% (range, 17.6-50.7%)]. A subgroup of 8 subjects had arteriovenous differences measured across forearm muscle. Thirty subjects were studied from late morning to early evening; 19 ate a high carbohydrate meal around 1300 h, and 11 continued to fast. We found a greater than 2-fold increase in IL-6 concentrations across the adipose tissue bed [arterial, 2.27 pg/mL (range, 1.42-3.53 pg/mL); venous, 6.71 pg/mL (range, 3.36-9.62 pg/mL); P < 0.001], but not across forearm muscle. Arterial plasma concentrations of IL-6 correlated significantly with body mass index (Spearman's r = 0.48; P < 0.01) and percent body fat (Spearman's r = 0.49; P < 0.01). Subcutaneous adipose tissue IL-6 production increased by the early evening (1800-1900 h) in both subjects who had extended their fasting and those who had eaten. Neither deep forearm nor sc adipose tissue consistently released TNF alpha [across adipose tissue: arterial, 1.83 pg/mL (range, 1.36-2.34 pg/mL); venous, 1.85 pg/mL (range, 1.44-2.53 pg/mL); P = NS: across forearm muscle: arterial, 1.22 pg/mL (range, 0.74-2.76 pg/mL); venous, 0.99 pg/mL (range, 0.69-1.70 pg/mL); P = NS]. Although both IL-6 and TNF alpha are expressed by adipose tissue, our results show that there are important differences in their systemic release. TNF alpha is not released by this sc depot. In contrast, IL-6 is released from the depot and is thereby able to signal systemically.
C-reactive protein (CRP) is a sensitive marker of inflammation, and elevated levels have been associated with future risk of myocardial infarction (MI). However, whether measurement of CRP adds to the predictive value of total cholesterol (TC) and HDL cholesterol (HDL-C) in determining risk is uncertain.
Among 14916 apparently healthy men participating in the Physicians' Health Study, baseline levels of CRP, TC, and HDL-C were measured among 245 study subjects who subsequently developed a first MI (cases) and among 372 subjects who remained free of cardiovascular disease during an average follow-up period of 9 years (controls). In univariate analyses, high baseline levels of CRP, TC, and TC:HDL-C ratio were each associated with significantly increased risks of future MI (all P values <0.001). In multivariate analyses, models incorporating CRP and lipid parameters provided a significantly better method to predict risk than did models using lipids alone (all likelihood ratio test P values <0.003). For example, relative risks of future MI among those with high levels of both CRP and TC (RR=5.0, P=0.0001) were greater than the product of the individual risks associated with isolated elevations of either CRP (RR=1.5) or TC (RR=2.3). In stratified analyses, baseline CRP level was predictive of risk for those with low as well as high levels of TC and the TC:HDL-C ratio. These findings were virtually identical in analyses limited to nonsmokers and after control for other cardiovascular risk factors.
In prospective data from a large cohort of apparently healthy men, baseline CRP level added to the predictive value of lipid parameters in determining risk of first MI.
Inflammatory reactions in coronary plaques play an important role in the pathogenesis of acute atherothrombotic events; inflammation elsewhere is also associated with both atherogenesis generally and its thrombotic complications. Recent studies indicate that systemic markers of inflammation can identify subjects at high risk of coronary events.
We used a sensitive immunoradiometric assay to examine the association of serum C-reactive protein (CRP) with the incidence of first major coronary heart disease (CHD) event in 936 men 45 to 64 years of age. The subjects, who were sampled at random from the general population, participated in the first MONICA Augsburg survey (1984 to 1985) and were followed for 8 years. There was a positive and statistically significant unadjusted relationship, which was linear on the log-hazards scale, between CRP values and the incidence of CHD events (n=53). The hazard rate ratio (HRR) of CHD events associated with a 1-SD increase in log-CRP level was 1.67 (95% CI, 1.29 to 2. 17). After adjustment for age, the HRR was 1.60 (95% CI, 1.23 to 2. 08). Adjusting further for smoking behavior, the only variable selected from a variety of potential confounders by a forward stepping process with a 5% change in the relative risk of CRP as the selection criterion, yielded an HRR of 1.50 (95% CI, 1.14 to 1.97).
These results confirm the prognostic relevance of CRP, a sensitive systemic marker of inflammation, to the risk of CHD in a large, randomly selected cohort of initially healthy middle-aged men. They suggest that low-grade inflammation is involved in pathogenesis of atherosclerosis, especially its thrombo-occlusive complications.
Interleukin-6 (IL-6) is a multifunctional cytokine expressed by angiotensin II (Ang II)-stimulated vascular smooth muscle cells (VSMCs) that functions as an autocrine growth factor. In this study, we analyze the mechanism for Ang II-inducible IL-6 expression in quiescent rat VSMCs. Stimulation with the Ang II agonist Sar1 Ang II (100 nmol/L) induced transcriptional expression of IL-6 mRNA transcripts of 1.8 and 2.4 kb. In transient transfection assays of IL-6 promoter/luciferase reporter plasmids, Sar1 Ang II treatment induced IL-6 transcription in a manner completely dependent on the nuclear factor-kappaB (NF-kappaB) motif. Sar1 Ang II induced cytoplasmic-to-nuclear translocation of the NF-kappaB subunits Rel A and NF-kappaB1 with parallel changes in DNA-binding activity in a biphasic manner, which produced an early peak at 15 minutes followed by a nadir 1 to 6 hours later and a later peak at 24 hours. The early phase of NF-kappaB translocation was dependent on weak simultaneous proteolysis of the IkappaBalpha and beta inhibitors, whereas later translocation was associated with enhanced processing of the p105 precursor into the mature 50-kDa NF-kappaB1 form. Pretreatment with a potent inhibitor of IkappaBalpha proteolysis, TPCK, completely blocked Sar1 Ang IIAng II-induced NF-kappaB activation and induction of endogenous IL-6 gene expression, which indicated the essential role of NF-kappaB in mediating IL-6 expression. We conclude that Ang II is a pleiotropic regulator of the NF-kappaB transcription factor family and may be responsible for activating the expression of cytokine gene networks in VSMCs.
C-reactive protein, a hepatic acute phase protein largely regulated by circulating levels of interleukin-6, predicts coronary heart disease incidence in healthy subjects. We have shown that subcutaneous adipose tissue secretes interleukin-6 in vivo. In this study we have sought associations of levels of C-reactive protein and interleukin-6 with measures of obesity and of chronic infection as their putative determinants. We have also related levels of C-reactive protein and interleukin-6 to markers of the insulin resistance syndrome and of endothelial dysfunction. We performed a cross-sectional study in 107 nondiabetic subjects: (1) Levels of C-reactive protein, and concentrations of the proinflammatory cytokines interleukin-6 and tumor necrosis factor-alpha, were related to all measures of obesity, but titers of antibodies to Helicobacter pylori were only weakly and those of Chlamydia pneumoniae and cytomegalovirus were not significantly correlated with levels of these molecules. Levels of C-reactive protein were significantly related to those of interleukin-6 (r=0.37, P<0.0005) and tumor necrosis factor-alpha (r=0.46, P<0.0001). (2) Concentrations of C-reactive protein were related to insulin resistance as calculated from the homoeostasis model assessment model, blood pressure, HDL, and triglyceride, and to markers of endothelial dysfunction (plasma levels of von Willebrand factor, tissue plasminogen activator, and cellular fibronectin). A mean standard deviation score of levels of acute phase markers correlated closely with a similar score of insulin resistance syndrome variables (r=0.59, P<0.00005), this relationship being weakened only marginally by removing measures of obesity from the insulin resistance score (r=0.53, P<0.00005). These data suggest that adipose tissue is an important determinant of a low level, chronic inflammatory state as reflected by levels of interleukin-6, tumor necrosis factor-alpha, and C-reactive protein, and that infection with H pylori, C pneumoniae, and cytomegalovirus is not. Moreover, our data support the concept that such a low-level, chronic inflammatory state may induce insulin resistance and endothelial dysfunction and thus link the latter phenomena with obesity and cardiovascular disease.
Circulating levels of C-reactive protein (CRP) may constitute an independent risk factor for cardiovascular disease. How CRP as a risk factor is involved in cardiovascular disease is still unclear.
By reviewing available studies, we discuss explanations for the associations between CRP and cardiovascular disease. CRP levels within the upper quartile/quintile of the normal range constitute an increased risk for cardiovascular events, both in apparently healthy persons and in persons with preexisting angina pectoris. High CRP responses after acute myocardial infarction indicate an unfavorable outcome, even after correction for other risk factors. This link between CRP and cardiovascular disease has been considered to reflect the response of the body to the inflammatory reactions in the atherosclerotic (coronary) vessels and adjacent myocardium. However, because CRP localizes in infarcted myocardium (with colocalization of activated complement), we hypothesize that CRP may directly interact with atherosclerotic vessels or ischemic myocardium by activation of the complement system, thereby promoting inflammation and thrombosis.
CRP constitutes an independent cardiovascular risk factor. Unraveling the molecular background of this association may provide new directions for prevention of cardiovascular events.
Multiple data suggest that the renin-angiotensin system contributes to the pathogenesis of atherosclerosis. The atherogenic effect of the renin-angiotensin system can only in part be explained by the influence of its effector angiotensin II on blood pressure, smooth muscle cell (SMC) growth, or antifibrinolytic activity. Because chronic inflammation of the vessel wall is a hallmark of atherosclerosis, we hypothesized that angiotensin II may elicit inflammatory signals in vascular SMCs. Human vascular SMCs were stimulated with angiotensin. Inflammatory activation was assessed by determination of interleukin-6 (IL-6) release into the culture medium, detection of IL-6 mRNA by RT-PCR, and demonstration of activation of nuclear factor-kappaB in electrophoretic mobility shift assays. Angiotensin II concentration-dependently (1 nmol/L to 1 micromol/L) stimulated IL-6 production by SMCs via activation of the angiotensin II type 1 receptor (demonstrated by the inhibitory action of the receptor antagonist losartan). Angiotensin I increased IL-6 production by SMCs, too. This effect was inhibited by captopril and ramiprilat, suggesting conversion of angiotensin I to angiotensin II by angiotensin-converting enzyme in SMCs. Steady-state mRNA for IL-6 was augmented after stimulation with angiotensin II, suggesting regulation of angiotensin-induced IL-6 release at the pretranslational level. Moreover, the proinflammatory transcription factor nuclear factor-kappaB, which is necessary for transcription of most cytokine genes, was also activated by angiotensin II. Pyrrolidine dithiocarbamate suppressed angiotensin II-induced IL-6 release, a finding compatible with involvement of reactive oxygen species as second messengers in cytokine production mediated by angiotensin. The data demonstrate the ability of angiotensin to elicit an inflammatory response in human vascular SMCs by stimulation of cytokine production and activation of nuclear factor-kappaB. Inflammatory activation of the vessel wall by a dysregulated renin-angiotensin system may contribute to the pathogenesis of atherosclerosis.
For practitioners committed to coronary risk reduction, recent clinical trial data pose a considerable challenge. Specifically, in the Air Force/Texas Coronary Atherosclerosis Prevention Study (AFCAPS/TexCAPS), a primary prevention trial,1 treatment with lovastatin among an apparently healthy group of individuals without traditional coronary risk factors resulted in significant reductions in future cardiovascular events. Application of the results of that trial and of the West of Scotland primary prevention trial of pravastatin2 suggests that tens of millions of Americans without manifest atherosclerosis could benefit from lipid-lowering therapy.
Such a blanket approach, however, may be unwise from medical as well as economic perspectives. Unnecessary exposure to pharmacological agents, even those as safe as the statins, will ultimately subject some asymptomatic and low-risk individuals to unwanted side effects. Furthermore, economic constraints dictate that primary prevention strategies with even modest cost must be limited to those individuals who are likely to gain the greatest benefit. Even when an inexpensive preventive therapy such as low-dose aspirin is proven effective,3 behavioral barriers on the parts of both physicians and patients must be overcome if long-term compliance is to be achieved. All of these considerations highlight the need for better methods to stratify risk of atherosclerotic events in apparently healthy populations.
Clinical strategies designed to improve risk prediction have taken several forms. Imaging techniques including carotid ultrasound, MRI, and electron beam computed tomography (EBCT) all hold promise for identifying “vulnerable plaques” and detecting silent atheroma. However, prospective studies demonstrating the clinical utility of these approaches are limited. For example, a recent study4 of coronary calcification detected by EBCT has shown that this method does not accurately predict future coronary events, even in high-risk patients. The cost of these noninvasive imaging modalities may also prohibit their application for widespread screening application.
Provocative testing of endothelium-dependent …
Thus the lesions of atherosclerosis represent a protective, inflammatory-fibroproliferative response against the different agents that can cause the disease. If the injury continues over a long period of time, it may become excessive, and in its excess it becomes the disease itself. It has been shown that this excessive, inflammatory, fibroproliferative response can be reversed given sufficient opportunity for the injurious factors to be modified. Approaches to modifying specific cellular interactions, growth- regulatory molecules, or intracellular signaling molecules may afford opportunities to modify these processes and lead to lesion prevention or regression.
Prospective studies have shown that C-reactive protein (CRP) can be used to predict risk of future cardiovascular events. High-sensitivity methods for CRP (hs-CRP) measurement are needed for this purpose.
We compared the clinical efficacy of an automated and commercially available latex-enhanced assay (Latex) for hs-CRP (Dade Behring) to a validated in-house ELISA, previously shown to predict future peripheral arterial disease (PAD) in asymptomatic populations. Using a prospective, nested, case-control design, we measured baseline hs-CRP concentrations in 144 apparently healthy men who subsequently developed symptomatic PAD and 144 age- and smoking habit-matched controls who remained free of vascular disease over the follow-up period of 60 months.
The two hs-CRP assays correlated highly (r = 0.95; P <0.001), and all but two participants were classified into concordant quartiles or varied by only one quartile. The median hs-CRP of the case group was significantly higher than that of controls when measured by either the ELISA (1.34 vs 0.99 mg/L; P = 0.034) or the Latex method (1.80 vs 1.20 mg/L; P = 0.042). Furthermore, for both ELISA and the Latex method, the calculated relative risks of developing PAD increased significantly with each increasing quartile of hs-CRP. The calculated interquartile increase in relative risk of PAD was 31% (95% confidence interval, 5.2-62.2%; P = 0.01) for ELISA and 34% (95% confidence interval, 8.2-66.1%; P = 0.007) for the Latex method.
Our findings indicate that the Latex method is equally as efficacious as the validated ELISA in classifying patients into cutoff points established by prospective studies for risk stratification for coronary and cerebrovascular disease.
The author examined the relationship between C-reactive protein and BMI and diabetes status among 16,573 participants aged > or = 20 years of the Third National Health and Nutrition Examination Survey (1988-1994).
The study had a cross-sectional design.
Geometric mean concentrations of C-reactive protein were lowest among individuals with a BMI < 18.5 kg/m2 and increased with increasing BMI categories. Restricting the analysis to participants without various medical conditions did not change the relation. After adjusting for age, sex, race or ethnicity, and education, using logistic regression analysis, odds ratios for an elevated C-reactive protein concentration (> or = 85th percentile of the sex-specific C-reactive protein concentration distribution) among participants with a BMI of 25 to < 30, 30 to < 35, 35 to < 40, and > or = 40 kg/m2 were 1.51 (95% CI 1.23-1.86), 3.19 (2.60-3.91), 6.11 (4.67-7.98), and 9.30 (6.43-13.46), respectively, compared with participants with a BMI < 25 kg/m2. C-reactive protein concentrations were lowest among those individuals without diabetes or with impaired fasting glucose and highest among those with newly or previously diagnosed diabetes. Compared with participants with a normal fasting glucose, participants with impaired fasting glucose, newly diagnosed diabetes, and previously diagnosed diabetes had 0.99 (0.72-1.37), 1.84 (1.25-2.71), and 1.59 (1.25-2.01) odds of having an elevated C-reactive protein concentration after adjustment for age, sex, race or ethnicity, education, and BMI.
These results confirm cross-sectional findings from previous studies that show elevated C-reactive protein concentrations among individuals who are obese or have diabetes. The implications of these findings, however, remain unclear.
Since inflammation is believed to have a role in the pathogenesis of cardiovascular events, measurement of markers of inflammation has been proposed as a method to improve the prediction of the risk of these events.
We conducted a prospective, nested case-control study among 28,263 apparently healthy postmenopausal women over a mean follow-up period of three years to assess the risk of cardiovascular events associated with base-line levels of markers of inflammation. The markers included high-sensitivity C-reactive protein (hs-CRP), serum amyloid A, interleukin-6, and soluble intercellular adhesion molecule type 1 (sICAM-1). We also studied homocysteine and a variety of lipid and lipoprotein measurements. Cardiovascular events were defined as death from coronary heart disease, nonfatal myocardial infarction or stroke, or the need for coronary-revascularization procedures.
Of the 12 markers measured, hs-CRP was the strongest univariate predictor of the risk of cardiovascular events; the relative risk of events for women in the highest as compared with the lowest quartile for this marker was 4.4 (95 percent confidence interval, 2.2 to 8.9). Other markers significantly associated with the risk of cardiovascular events were serum amyloid A (relative risk for the highest as compared with the lowest quartile, 3.0), sICAM-1 (2.6), interleukin-6 (2.2), homocysteine (2.0), total cholesterol (2.4), LDL cholesterol (2.4), apolipoprotein B-100 (3.4), HDL cholesterol (0.3), and the ratio of total cholesterol to HDL cholesterol (3.4). Prediction models that incorporated markers of inflammation in addition to lipids were significantly better at predicting risk than models based on lipid levels alone (P<0.001). The levels of hs-CRP and serum amyloid A were significant predictors of risk even in the subgroup of women with LDL cholesterol levels below 130 mg per deciliter (3.4 mmol per liter), the target for primary prevention established by the National Cholesterol Education Program. In multivariate analyses, the only plasma markers that independently predicted risk were hs-CRP (relative risk for the highest as compared with the lowest quartile, 1.5; 95 percent confidence interval, 1.1 to 2.1) and the ratio of total cholesterol to HDL cholesterol (relative risk, 1.4; 95 percent confidence interval, 1.1 to 1.9).
The addition of the measurement of C-reactive protein to screening based on lipid levels may provide an improved method of identifying persons at risk for cardiovascular events.
C-reactive protein (CRP) can provide prognostic information about the risk of developing atherosclerotic complications in apparently healthy patients. This new clinical application requires quantification of CRP concentrations below those traditionally measured in the clinical laboratory.
The Dade Behring BN II, the Abbott IMx, the Diagnostic Products Corporation IMMULITE, and the Beckman Coulter IMMAGE are four automated analyzers with high-sensitivity CRP (hs-CRP) methods. We evaluated these assays for precision, linearity, and comparability with samples from 322 apparently healthy blood donors.
The imprecision (CV) of the BN II, IMx, IMMULITE, and IMMAGE methods was < or = 7.6%, < or = 12%, < or = 9.8%, and < or = 9.7% at 3.5 mg/L, respectively. The BN II, IMx, IMMULITE, and IMMAGE methods were linear down to < or = 0.30, < or = 0.32, < or = 0.85, and 2.26 mg/L, respectively. CRP concentrations demarcating each quartile in a healthy population were method dependent. The IMx method gave results comparable to the BN II method for values in the reference interval. The IMMULITE method had a positive intercept compared with the BN II method. The IMMAGE method demonstrated more scatter and a positive intercept compared with the BN II method, which may reflect the fact that it is a less sensitive assay.
The four hs-CRP methods exhibited differences in results for a healthy population. Additional standardization efforts are required to ensure that hs-CRP results can be related to large-scale epidemiologic studies.
: Increased values of C-reactive protein (CRP), the classical acute phase protein, within the range below 5 mg/L, previously considered to be within the reference interval, are strongly associated with increased risk of atherothrombotic events, and are clinically significant in osteoarthritis and neonatal infection.
: A robust new polyclonal-monoclonal solid- phase IRMA for CRP was developed, with a range of 0.05-10.0 mg/L.
: Plasma CRP values in general adult populations from Augsburg, Germany (2291 males and 2203 females; ages, 25-74 years) and Glasgow, Scotland (604 males and 650 females; ages, 25-64 years) were very similar. The median CRP approximately doubled with age, from approximately 1 mg/L in the youngest decade to approximately 2 mg/L in the oldest, and tended to be higher in females.
: This extensive data set, the largest such study of CRP, provides valuable reference information for future clinical and epidemiological investigations.
The concentration of C-reactive protein (CRP) in otherwise healthy subjects has been shown to predict future risk of myocardial infarction and stroke. CRP is synthesized by the liver in response to interleukin-6, the serum concentration of which is subject to diurnal variation.
To examine the existence of a time-of-day effect for baseline CRP values, we determined CRP concentrations in hourly blood samples drawn from healthy subjects (10 males, 3 females; age range, 21-35 years) during a baseline day in a controlled environment (8 h of nighttime sleep).
Overall CRP concentrations were low, with only three subjects having CRP concentrations >2 mg/L. Comparison of raw data showed stability of CRP concentrations throughout the 24 h studied. When compared with cutoff values of CRP quintile derived from population-based studies, misclassification of greater than one quintile did not occur as a result of diurnal variation in any of the subjects studied. Nonparametric ANOVA comparing different time points showed no significant differences for both raw and z-transformed data. Analysis for rhythmic diurnal variation using a method fitting a cosine curve to the group data was negative.
Our data show that baseline CRP concentrations are not subject to time-of-day variation and thus help to explain why CRP concentrations are a better predictor of vascular risk than interleukin-6. Determination of CRP for cardiovascular risk prediction may be performed without concern for diurnal variation.
Inflammation plays a major role in atherothrombosis, and measurement of inflammatory markers such as high-sensitivity C-reactive protein (HSCRP) may provide a novel method for detecting individuals at high risk of plaque rupture. Several large-scale prospective studies demonstrate that HSCRP is a strong independent predictor of future myocardial infarction and stroke among apparently healthy men and women and that the addition of HSCRP to standard lipid screening may improve global risk prediction among those with high as well as low cholesterol levels. Because agents such as aspirin and statins seem to attenuate inflammatory risk, HSCRP may also have utility in targeting proven therapies for primary prevention. Inexpensive commercial assays for HSCRP are now available; they have shown variability and classification accuracy similar to that of cholesterol screening. Risk prediction algorithms using a simple quintile approach to HSCRP evaluation have been developed for outpatient use. Thus, although limitations inherent to inflammatory screening remain, available data suggest that HSCRP has the potential to play an important role as an adjunct for global risk assessment in the primary prevention of cardiovascular disease.
C-reactive protein (CRP), predicts coronary heart disease incidence in healthy subjects and has been associated with decreased endothelium-dependent relaxation, a potential risk factor for hypertension. However, the relationship between CRP and hypertension has not been studied.
To assess whether circulating levels of CRP are independently related to essential hypertension.
Cross-sectional population survey. We measured circulating levels of CRP, blood pressure and cardiovascular risk factors among participants. Binomial regression was used to calculate the adjusted effect of CRP on the prevalence of hypertension.
General community of Bucaramanga, Colombia.
A random sample of 300 subjects > or = 30 years old.
Arterial blood pressure.
Overall hypertension prevalence was 46.0%. The unadjusted prevalence of hypertension was 58.7% in the highest quartile of CRP, but only 34.7% in the lowest quartile. After adjustment for age, sex, body mass index, family history of hypertension, fasting glycemia, sedentary behaviour, and alcohol consumption, the prevalence of hypertension was 1.14 [95% confidence interval (CI), 0.82, 1.58; P= 0.442], 1.36 (95% CI, 0.99, 1.87; P= 0.057) and 1.56 (95% CI, 1.14, 2.13; P = 0.005) times higher in subjects in the second, third and fourth quartiles of CRP, as compared to subjects in the first quartile.
Our results suggest, for the first time, that CRP level may be an independent risk factor for the development of hypertension. However, because of the cross-sectional nature of our study, this finding should be confirmed in prospective cohort studies, aimed at elucidating the role of CRP in the prediction, diagnosis and management of hypertension.
C-reactive protein (CRP) has been recognized as a useful marker for coronary or cardiovascular risk in healthy subjects or patients with coronary heart disease (CHD) in industrialized societies. We assessed whether CRP could serve as a marker of prevalent CHD risk in a cross-sectional study of a population with low cholesterol levels (4.61 mmol/L in men and 4.82 mmol/L in women) but higher prevalence of other risk factors. In 1,046 participants of the Turkish Adult Risk Factor Survey in 2000, high-sensitivity CRP as well as other risk variables were evaluated, and CHD was diagnosed, based on clinical findings and Minnesota coding of electrocardiograms at rest. Almost an equal number of men and women > or = 30 years of age constituted the population sample of the western regions of Turkey. Geometric mean value of CRP was 1.9 mg/L (interquartile range 0.8 to 4.3), without revealing a significant difference in gender. CRP was correlated with many variables, notably those involving central obesity, fibrinogen, and apolipoprotein-B, but not with smoking status (regardless of age adjustment). In multiple regression models, blood fibrinogen, waist circumference, total cholesterol, and physical activity grade were independently associated with log CRP concentrations. Among many risk variables, CRP quartiles and systolic blood pressure were, besides age and gender, the only significant independent determinants of CHD. The age-adjusted odds ratio for CHD in the highest as opposed to the lowest quartile was 4.48 (p < 0.001). Even after adjustment for the 5 previously mentioned determinants of CRP, a 4.2-fold increased risk of CHD still persisted between the highest and lowest quartiles. Thus, the observed increased risk was not in large part due to the intermediary effects of fibrinogen, nor were some indicators of insulin resistance, but interaction appeared to be independent of these effects. Thus, CRP values serve as a marker of prevalent CHD risk in populations with low cholesterol levels. This association is independent of, or in addition to, the effects of conventional risk factors, suggesting that the contribution of chronic low-grade inflammation to the atherothrombotic process is present even in the setting of low cholesterol levels.
Inflammation plays an important role in the development of atherosclerosis, but the specific stimuli governing cytokine release in atherogenesis are unknown. We examined the hypothesis that hypertension may increase the risk of atherosclerosis via proinflammatory effects. In a cross-sectional study involving 508 apparently healthy men, we studied the association between blood pressure and baseline plasma concentrations of 2 inflammatory markers, intercellular adhesion molecule-1 (sICAM-1) and interleukin-6 (IL-6). Increase in systolic blood pressure (SBP) (P=0.003), pulse pressure (PP) (P=0.019), and mean arterial pressure (P=0.014) was significantly associated with levels of sICAM-1. All of these measures of blood pressure, as well as diastolic blood pressure (DBP), were significantly associated with levels of IL-6 (all, P</=0.001). In multiple linear regression models controlled for age and other cardiac risk factors, SBP (7.6 ng/mL per 10 mm Hg, P=0.016) and PP (8.13 ng/mL per 10 mm Hg, P=0.038) were significantly associated with sICAM-1 levels, whereas SBP (0.11 pg/mL per 10 mm Hg, P<0.001), DBP (0.11 pg/mL per 10 mm Hg, P=0.008), PP (0.10 pg/mL per 10 mm Hg, P=0.009), and mean arterial pressure (0.15 pg/mL per 10 mm Hg, P<0.001) had similar strong relationships with log-transformed IL-6 levels. Therefore, in apparently healthy men, we observed significant graded relationships between blood pressure and levels of sICAM-1 as well as IL-6. These data suggest that increased blood pressure may be a stimulus for inflammation and that this is a possible mechanism underlying the well-established role of hypertension as a risk factor for atherosclerotic disease.
The Third Report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (ATP III) highlights the importance of treating patients with the metabolic syndrome to prevent cardiovascular disease. Limited information is available about the prevalence of the metabolic syndrome in the United States, however.
To estimate the prevalence of the metabolic syndrome in the United States as defined by the ATP III report.
Analysis of data on 8814 men and women aged 20 years or older from the Third National Health and Nutrition Examination Survey (1988-1994), a cross-sectional health survey of a nationally representative sample of the noninstitutionalized civilian US population.
Prevalence of the metabolic syndrome as defined by ATP III (>/=3 of the following abnormalities): waist circumference greater than 102 cm in men and 88 cm in women; serum triglycerides level of at least 150 mg/dL (1.69 mmol/L); high-density lipoprotein cholesterol level of less than 40 mg/dL (1.04 mmol/L) in men and 50 mg/dL (1.29 mmol/L) in women; blood pressure of at least 130/85 mm Hg; or serum glucose level of at least 110 mg/dL (6.1 mmol/L).
The unadjusted and age-adjusted prevalences of the metabolic syndrome were 21.8% and 23.7%, respectively. The prevalence increased from 6.7% among participants aged 20 through 29 years to 43.5% and 42.0% for participants aged 60 through 69 years and aged at least 70 years, respectively. Mexican Americans had the highest age-adjusted prevalence of the metabolic syndrome (31.9%). The age-adjusted prevalence was similar for men (24.0%) and women (23.4%). However, among African Americans, women had about a 57% higher prevalence than men did and among Mexican Americans, women had about a 26% higher prevalence than men did. Using 2000 census data, about 47 million US residents have the metabolic syndrome.
These results from a representative sample of US adults show that the metabolic syndrome is highly prevalent. The large numbers of US residents with the metabolic syndrome may have important implications for the health care sector.
C-reactive protein (CRP) has been suggested to actively participate in the development of atherosclerosis. In the present study, we examined the role of the potent endothelium-derived vasoactive factor endothelin-1 (ET-1) and the inflammatory cytokine interleukin-6 (IL-6) as mediators of CRP-induced proatherogenic processes.
Saphenous vein endothelial cells (HSVECs) were incubated with human recombinant CRP (25 microg/mL, 24 hours) and the expression of vascular cell adhesion molecule (VCAM-1), intracellular adhesion molecule (ICAM-1), and monocyte chemoattractant chemokine-1 was determined. The effects of CRP on LDL uptake were assessed in macrophages using immunofluorescent labeling of CD32 and CD14. In each study, the effect of endothelin antagonism (bosentan) and IL-6 inhibition (monoclonal anti-IL-6 antibodies) was examined. The effects of CRP on the secretion of ET-1 and IL-6 from HSVECs were also evaluated. Incubation of HSVECs with recombinant human CRP resulted in a marked increase in ICAM-1 and VCAM-1 expression (P<0.001). Likewise, CRP caused a significant increase in monocyte chemoattractant chemokine-1 production, a key mediator of leukocyte transmigration (P<0.001). CRP caused a marked and sustained increase in native LDL uptake by macrophages (P<0.05). These proatherosclerotic effects of CRP were mediated, in part, via increased secretion of ET-1 and IL-6 (P<0.01) and were attenuated by both bosentan and IL-6 antagonism (P<0.01).
CRP actively promotes a proatherosclerotic and proinflammatory phenotype. These effects are mediated, in part, via the production of ET-1 and IL-6 and are attenuated by mixed ET(A/B) receptor antagonism and IL-6 inhibition. Bosentan may be useful in decreasing CRP-mediated vascular disease.