Hypertension affects over 1.2 billion individuals worldwide and has become the most critical and expensive public health problem. Hypertension is a multifactorial disease involving environmental and ...genetic factors together with risk-conferring behaviors. The cause of the disease is identified in ∼10% of the cases (secondary hypertension), but in 90% of the cases no etiology is found (primary or essential hypertension). For this reason, a better understanding of the mechanisms controlling blood pressure in normal and hypertensive patients is the aim of very active experimental and clinical research. In this article, we review the importance of the renin-angiotensin-aldosterone system (RAAS) for the control of blood pressure, focusing on the evolution of the system and its critical importance for adaptation of vertebrates to a terrestrial and dry environment. The evolution of blood pressure control during the evolution of primates, hominins, and humans is discussed, together with the role of common genetic factors and the possible causes of the current hypertension pandemic in the light of evolutionary medicine.
Unhealthy behaviors and their social patterning have been frequently proposed as factors mediating socioeconomic differences in health. However, a clear quantification of the contribution of health ...behaviors to the socioeconomic gradient in health is lacking. This study systematically reviews the role of health behaviors in explaining socioeconomic inequalities in health.
Published studies were identified by a systematic review of PubMed, Embase and Web-of-Science. Four health behaviors were considered: smoking, alcohol consumption, physical activity and diet. We restricted health outcomes to cardiometabolic disorders and mortality. To allow comparison between studies, the contribution of health behaviors, or the part of the socioeconomic gradient in health that is explained by health behaviors, was recalculated in all studies according to the absolute scale difference method.
We identified 114 articles on socioeconomic position, health behaviors and cardiometabolic disorders or mortality from electronic databases and articles reference lists. Lower socioeconomic position was associated with an increased risk of all-cause mortality and cardiometabolic disorders, this gradient was explained by health behaviors to varying degrees (minimum contribution −43%; maximum contribution 261%).
Health behaviors explained a larger proportion of the SEP-health gradient in studies conducted in North America and Northern Europe, in studies examining all-cause mortality and cardiovascular disease, among men, in younger individuals, and in longitudinal studies, when compared to other settings. Of the four behaviors examined, smoking contributed the most to social inequalities in health, with a median contribution of 19%.
Health behaviors contribute to the socioeconomic gradient in cardiometabolic disease and mortality, but this contribution varies according to population and study characteristics. Nevertheless, our results should encourage the implementation of interventions targeting health behaviors, as they may reduce socioeconomic inequalities in health and increase population health.
•Health behaviors are key contributors to the socioeconomic gradient in health.•Multiple health behaviors contribute more than individual health behaviors.•Smoking contributes more than alcohol, physical activity, or dietary patterns.•The contribution of health behaviors varies according to multiple factors.
The effect of particulate matter (PM) on health increases with exposure duration but the change from short to longer term is not well studied. We examined the exposure to PM smaller 10 μm (PM
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) ...from short to longer duration and their associations with levels of inflammatory markers in the population-based CoLaus cohort in Lausanne, Switzerland. Baseline and follow-up CoLaus data were used to study the associations between PM
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exposure and inflammatory markers, including the high-sensitivity C-reactive protein (CRP), as well as interleukin 1-beta (IL-1β), interleukin 6 (IL-6), and tumor-necrosis-factor alpha (TNF-α) using mixed models. Exposure was determined for each participant’s home address from hourly air quality simulations at a 5-m resolution. Short-term exposure intervals were 1 day, 1 week, and 1 month prior to the hospital visit (blood withdrawal); long-term exposure intervals were 3 and 6 months prior to the visit. In most time windows, IL-6, IL-1β, and TNF-α were positively associated with PM
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. No significant associations were identified for CRP. Adjusted associations with long-term exposures were stronger and more significant than those for short-term exposures. In stratified models, gender, age, smoking status, and hypertension only led to small modifications in effect estimates, though a few of the estimates for IL-6 and TNF-α became non-significant. In this general adult cohort exposed to relatively low average PM
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levels, clear associations with markers of systemic inflammation were observed. Longer duration of elevated exposure was associated with an exacerbated inflammatory response. This may partially explain the elevated disease risk observed with chronic PM
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exposure. It also suggests that reducing prolonged episodes of high PM exposure may be a strategy to reduce inflammatory risk.
Chronic inflammation has been proposed as having a prominent role in the construction of social inequalities in health. Disentangling the effects of early life and adulthood social disadvantage on ...inflammation is key in elucidating biological mechanisms underlying socioeconomic disparities. Here we explore the relationship between socioeconomic position (SEP) across the life course and inflammation (as measured by CRP levels) in up to 23,008 participants from six European cohort studies from three countries conducted between 1958 and 2013. We find a consistent inverse association between SEP and CRP across cohorts, where participants with a less advantaged SEP have higher levels of inflammation. Educational attainment is most strongly related to inflammation, after adjusting for health behaviours, body mass index and later-in-life SEP. These findings suggest socioeconomic disadvantage in young adulthood is independently associated with later life inflammation calling for further studies of the pathways operating through educational processes.
Approximately 3% of the world population is chronically infected with the hepatitis C virus (HCV), with potential development of cirrhosis and hepatocellular carcinoma. Despite the availability of ...new antiviral agents, treatment remains suboptimal. Genome-wide association studies (GWAS) identified rs12979860, a polymorphism nearby IL28B, as an important predictor of HCV clearance. We report the identification of a novel TT/-G polymorphism in the CpG region upstream of IL28B, which is a better predictor of HCV clearance than rs12979860. By using peripheral blood mononuclear cells (PBMCs) from individuals carrying different allelic combinations of the TT/-G and rs12979860 polymorphisms, we show that induction of IL28B and IFN-γ-inducible protein 10 (IP-10) mRNA relies on TT/-G, but not rs12979860, making TT/-G the only functional variant identified so far. This novel step in understanding the genetic regulation of IL28B may have important implications for clinical practice, as the use of TT/G genotyping instead of rs12979860 would improve patient management.
Low birth weight is associated with increased rates of obesity, insulin resistance and type 2 diabetes, but the precise mechanisms for this association remain unclear. We aimed to assess the ...relationships between birth weight and markers of glucose homeostasis or obesity in adults.
Cross-sectional population-based study on 1458 women and 1088 men aged 35-75 years living in Lausanne, Switzerland. Birth weight was self-reported and categorized into ≤ 2.5, 2.6-3.5, 3.6-4.0 and >4.0 kg. Body composition was assessed by bioimpedance. Leptin and adiponectin levels were measured by ELISA.
Women with low birth weight (≤ 2.5 kg) had higher levels of fasting plasma glucose, insulin, HOMA, diabetes and metabolic syndrome; a non significant similar trend was seen in men. In both genders, height increased with birth weight, whereas a U-shaped association was found between birth weight and body mass index, waist circumference and body fat percentage. After adjusting for age, smoking status, physical activity and fat mass, an inverse association was found between leptin and birth weight categories: adjusted mean ± standard error 17.3 ± 0.7, 16.2 ± 0.3, 15.6 ± 0.5 and 14.0 ± 0.8 ng/dL for birth weight categories ≤ 2.5, 2.6-3.5, 3.6-4.0 and >4.0 kg, respectively, in women (p < 0.05) and 9.8 ± 0.8, 9.1 ± 03, 7.8 ± 0.4 and 7.7 ± 0.5 ng/dL in men (p < 0.05). An inverse association was also found between reported birth weight and leptin to fat mass ratio: mean ± standard error 0.77 ± 0.04, 0.73 ± 0.02, 0.69 ± 0.03 and 0.62 ± 0.04 in women (p < 0.05); 0.46 ± 0.05, 0.45 ± 0.02, 0.39 ± 0.02 and 0.38 ± 0.03 in men (p < 0.05). No differences in adiponectin levels were found between birth weight groups.
Middle-aged adults born with a low weight present a higher prevalence of diabetes and obesity and also higher leptin levels and leptin to fat mass ratio than adults born with a normal weight. The higher leptin levels and leptin to fat mass ratio among adults born with a low weight might be related to nutritional factors during childhood or to the development of leptin resistance and/or higher leptin production by body fat unit. Subjects born with a low weight should be counselled regarding the risks of developing diabetes and/or cardiovascular disease.
High sodium intake is a cause of elevated blood pressure in adults. In children and adolescents, less evidence is available and findings are equivocal. We systematically reviewed the evidence from ...experimental and observational studies on the association between sodium intake and blood pressure in children and adolescents.
A systematic search of the Medline, Embase, CINAHL and CENTRAL databases up to March 2017 was conducted and supplemented by a manual search of bibliographies and unpublished studies. Experimental and observational studies involving children or adolescents between 0 and 18 years of age were included. Random-effects meta-analyses were performed by pooling data across all studies, separately for experimental and observational studies, and restricting to studies with sodium intake and blood pressure measurement methods of high quality. Subgroup meta-analyses, sensitivity analyses and meta-regressions were conducted to investigate sources of heterogeneity and confounding. The dose-response relationship was also investigated.
Of the 6572 publications identified, 85 studies (14 experimental; 71 observational, including 60 cross-sectional, 6 cohort and 5 case-control studies) with 58 531 participants were included. In experimental studies, sodium reduction interventions decreased systolic blood pressure by 0.6 mm Hg 95% confidence interval (CI): 0.5, 0.8 and diastolic blood pressure by 1.2 mm Hg (95% CI: 0.4, 1.9). The meta-analysis of 18 experimental and observational studies (including 3406 participants) with sodium intake and blood pressure measurement methods of high quality showed that, for every additional gram of sodium intake per day, systolic blood pressure increased by 0.8 mm Hg (95% CI: 0.4, 1.3) and diastolic blood pressure by 0.7 mm Hg (95% CI: 0.0, 1.4). The association was stronger among children with overweight and with low potassium intake. A quasi-linear relationship was found between sodium intake and blood pressure.
Sodium intake is positively associated with blood pressure in children and adolescents, with consistent findings in experimental and observational studies. Since blood pressure tracks across the life course, our findings support the reduction of sodium intake during childhood and adolescence to lower blood pressure and prevent the development of hypertension.
As a powerful phenotyping technology, metabolomics provides new opportunities in biomarker discovery through metabolome-wide association studies (MWAS) and the identification of metabolites having a ...regulatory effect in various biological processes. While mass spectrometry-based (MS) metabolomics assays are endowed with high throughput and sensitivity, MWAS are doomed to long-term data acquisition generating an overtime-analytical signal drift that can hinder the uncovering of real biologically relevant changes. We developed "dbnorm", a package in the R environment, which allows for an easy comparison of the model performance of advanced statistical tools commonly used in metabolomics to remove batch effects from large metabolomics datasets. "dbnorm" integrates advanced statistical tools to inspect the dataset structure not only at the macroscopic (sample batches) scale, but also at the microscopic (metabolic features) level. To compare the model performance on data correction, "dbnorm" assigns a score that help users identify the best fitting model for each dataset. In this study, we applied "dbnorm" to two large-scale metabolomics datasets as a proof of concept. We demonstrate that "dbnorm" allows for the accurate selection of the most appropriate statistical tool to efficiently remove the overtime signal drift and to focus on the relevant biological components of complex datasets.
Background Obesity and African American ethnicity are established independent risk factors for the development of chronic kidney disease. No data exist about the association between obesity and renal ...hemodynamics in the African region. Study Design Cross-sectional study. Setting & Participants 301 nondiabetic participants (97 lean, 108 overweight, and 96 obese) of African descent with a positive family history of hypertension from the Seychelles islands. Predictor Body mass index (BMI). Outcomes Glomerular hyperfiltration, glomerular filtration rate (GFR), effective renal plasma flow (ERPF), and filtration fraction. Measurements GFR and ERPF were measured using inulin and para -aminohippurate clearances, respectively. Participants' baseline demographics, laboratory data, and blood pressure were measured using standard techniques. Results The prevalence of glomerular hyperfiltration (defined as GFR ≥140 mL/min) increased across BMI categories (7.2%, 14.8%, and 27.1% for lean, overweight, and obese participants, respectively; P < 0.001). Higher BMI was associated with higher median GFR (99, 110, and 117 mL/min for lean, overweight, and obese participants, respectively; P < 0.001), ERPF (424, 462, and 477 mL/min, respectively; P = 0.01), and filtration fraction (0.23, 0.24, and 0.25; P < 0.001). Multivariate analyses adjusting for age, sex, blood pressure, fasting glucose level, and urinary sodium excretion and accounting for familial correlations confirmed the associations between high BMI (>25 kg/m2 ) and increased GFR, ERPF, and filtration fraction. No association between BMI categories and GFR was found with adjustment for body surface area. Limitations Participants had a positive family history of hypertension. Conclusion Overweight and obesity are associated with increased GFR, ERPF, and filtration fraction and a high prevalence of glomerular hyperfiltration in nondiabetic individuals of African descent. The absence of associations between BMI categories and GFR indexed for body surface area raises questions regarding the appropriateness of indexing GFR for body surface area in overweight populations.
AbstractObjectiveTo assess the association of low socioeconomic status and risk factors for non-communicable diseases (diabetes, high alcohol intake, high blood pressure, obesity, physical ...inactivity, smoking) with loss of physical functioning at older ages.DesignMulti-cohort population based study.Setting37 cohort studies from 24 countries in Europe, the United States, Latin America, Africa, and Asia, 1990-2017.Participants109 107 men and women aged 45-90 years.Main outcome measurePhysical functioning assessed using the walking speed test, a valid index of overall functional capacity. Years of functioning lost was computed as a metric to quantify the difference in walking speed between those exposed and unexposed to low socioeconomic status and risk factors.ResultsAccording to mixed model estimations, men aged 60 and of low socioeconomic status had the same walking speed as men aged 66.6 of high socioeconomic status (years of functioning lost 6.6 years, 95% confidence interval 5.0 to 9.4). The years of functioning lost for women were 4.6 (3.6 to 6.2). In men and women, respectively, 5.7 (4.4 to 8.1) and 5.4 (4.3 to 7.3) years of functioning were lost by age 60 due to insufficient physical activity, 5.1 (3.9 to 7.0) and 7.5 (6.1 to 9.5) due to obesity, 2.3 (1.6 to 3.4) and 3.0 (2.3 to 4.0) due to hypertension, 5.6 (4.2 to 8.0) and 6.3 (4.9 to 8.4) due to diabetes, and 3.0 (2.2 to 4.3) and 0.7 (0.1 to 1.5) due to tobacco use. In analyses restricted to high income countries, the number of years of functioning lost attributable to low socioeconomic status by age 60 was 8.0 (5.7 to 13.1) for men and 5.4 (4.0 to 8.0) for women, whereas in low and middle income countries it was 2.6 (0.2 to 6.8) for men and 2.7 (1.0 to 5.5) for women. Within high income countries, the number of years of functioning lost attributable to low socioeconomic status by age 60 was greater in the United States than in Europe. Physical functioning continued to decline as a function of unfavourable risk factors between ages 60 and 85. Years of functioning lost were greater than years of life lost due to low socioeconomic status and non-communicable disease risk factors.ConclusionsThe independent association between socioeconomic status and physical functioning in old age is comparable in strength and consistency with those for established non-communicable disease risk factors. The results of this study suggest that tackling all these risk factors might substantially increase life years spent in good physical functioning.
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