Predicting longer-term mortality risk requires collection of clinical data, which is often cumbersome. Therefore, we use a well-standardized metabolomics platform to identify metabolic predictors of ...long-term mortality in the circulation of 44,168 individuals (age at baseline 18-109), of whom 5512 died during follow-up. We apply a stepwise (forward-backward) procedure based on meta-analysis results and identify 14 circulating biomarkers independently associating with all-cause mortality. Overall, these associations are similar in men and women and across different age strata. We subsequently show that the prediction accuracy of 5- and 10-year mortality based on a model containing the identified biomarkers and sex (C-statistic = 0.837 and 0.830, respectively) is better than that of a model containing conventional risk factors for mortality (C-statistic = 0.772 and 0.790, respectively). The use of the identified metabolic profile as a predictor of mortality or surrogate endpoint in clinical studies needs further investigation.
Studies on the association between traffic noise and cardiovascular diseases have rarely considered air pollution as a covariate in the analyses. Isolated systolic hypertension has not yet been in ...the focus of epidemiological noise research.
The association between traffic noise (road and rail) and the prevalence of hypertension was assessed in two study populations with a total of 4,166 participants 25-74 years of age. Traffic noise (weighted day-night average noise level; LDN) at the facade of the dwellings was derived from noise maps. Annual average PM2.5 mass concentrations at residential addresses were estimated by land-use regression. Hypertension was assessed by blood pressure readings, self-reported doctor-diagnosed hypertension, and antihypertensive drug intake.
In the Greater Augsburg, Germany, study population, traffic noise and air pollution were not associated with hypertension. In the City of Augsburg population (n = 1,893), where the exposure assessment was more detailed, the adjusted odds ratio (OR) for a 10-dB(A) increase in noise was 1.16 (95% CI: 1.00, 1.35), and 1.11 (95% CI: 0.94, 1.30) after additional adjustment for PM2.5. The adjusted OR for a 1-μg/m3 increase in PM2.5 was 1.15 (95% CI: 1.02, 1.30), and 1.11 (95% CI: 0.98, 1.27) after additional adjustment for noise. For isolated systolic hypertension, the fully adjusted OR for noise was 1.43 (95% CI: 1.10, 1.86) and for PM2.5 was 1.08 (95% CI: 0.87, 1.34).
Traffic noise and PM2.5 were both associated with a higher prevalence of hypertension. Mutually adjusted associations with hypertension were positive but no longer statistically significant.
Lifestyle, obesity, and the gut microbiome are important risk factors for metabolic disorders. We demonstrate in 1,976 subjects of a German population cohort (KORA) that specific microbiota members ...show 24-h oscillations in their relative abundance and identified 13 taxa with disrupted rhythmicity in type 2 diabetes (T2D). Cross-validated prediction models based on this signature similarly classified T2D. In an independent cohort (FoCus), disruption of microbial oscillation and the model for T2D classification was confirmed in 1,363 subjects. This arrhythmic risk signature was able to predict T2D in 699 KORA subjects 5 years after initial sampling, being most effective in combination with BMI. Shotgun metagenomic analysis functionally linked 26 metabolic pathways to the diurnal oscillation of gut bacteria. Thus, a cohort-specific risk pattern of arrhythmic taxa enables classification and prediction of T2D, suggesting a functional link between circadian rhythms and the microbiome in metabolic diseases.
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•Human gut microbiome exhibits diurnal rhythmicity across populations and individuals•Obese and T2D individuals show disrupted circadian rhythms in the gut microbiome•Arrhytmic bacterial signatures contribute to risk classification and prediction of T2D•These risk signatures show regional differences in applicability across three cohorts
Reitmeier et al. show that specific gut microbes exhibit rhythmic oscillations in relative abundance and identified taxa with disrupted rhythmicity in individuals with type 2 diabetes (T2D). This arrhythmic signature contributed to the classification and prediction of T2D, suggesting functional links between circadian rhythmicity and the microbiome in metabolic diseases.
To investigate the causal role of high-density lipoprotein cholesterol (HDL-C) and triglycerides in coronary heart disease (CHD) using multiple instrumental variables for Mendelian randomization.
We ...developed weighted allele scores based on single nucleotide polymorphisms (SNPs) with established associations with HDL-C, triglycerides, and low-density lipoprotein cholesterol (LDL-C). For each trait, we constructed two scores. The first was unrestricted, including all independent SNPs associated with the lipid trait identified from a prior meta-analysis (threshold P < 2 × 10(-6)); and the second a restricted score, filtered to remove any SNPs also associated with either of the other two lipid traits at P ≤ 0.01. Mendelian randomization meta-analyses were conducted in 17 studies including 62,199 participants and 12,099 CHD events. Both the unrestricted and restricted allele scores for LDL-C (42 and 19 SNPs, respectively) associated with CHD. For HDL-C, the unrestricted allele score (48 SNPs) was associated with CHD (OR: 0.53; 95% CI: 0.40, 0.70), per 1 mmol/L higher HDL-C, but neither the restricted allele score (19 SNPs; OR: 0.91; 95% CI: 0.42, 1.98) nor the unrestricted HDL-C allele score adjusted for triglycerides, LDL-C, or statin use (OR: 0.81; 95% CI: 0.44, 1.46) showed a robust association. For triglycerides, the unrestricted allele score (67 SNPs) and the restricted allele score (27 SNPs) were both associated with CHD (OR: 1.62; 95% CI: 1.24, 2.11 and 1.61; 95% CI: 1.00, 2.59, respectively) per 1-log unit increment. However, the unrestricted triglyceride score adjusted for HDL-C, LDL-C, and statin use gave an OR for CHD of 1.01 (95% CI: 0.59, 1.75).
The genetic findings support a causal effect of triglycerides on CHD risk, but a causal role for HDL-C, though possible, remains less certain.
Abstract
Background
Hypertension remains a significant modifiable risk factor for cardiovascular diseases and a major determinant of morbidity and mortality. We aimed to describe sex-stratified ...age-standardized estimates of prevalence, awareness, treatment and control of hypertension, and their associated factors in older adults.
Methods
The KORA-Age1 is a population-based cross-sectional survey carried out in 2008/2009 on individuals aged 65–94 years in Augsburg region, Germany. Blood pressure measurements were available for 1052 out of 1079 persons who participated in the physical examination. Factors associated with prevalence, awareness and control of hypertension were investigated by multivariable logistic regression.
Results
The overall prevalence of hypertension (≥140/90 mmHg) was 73.8% 95% confidence interval (CI), 69.3–77.9, representing 74.8% (95% CI, 68.4–80.2) in men and 73.5% (95% CI, 66.8–79.3) in women. Among those with hypertension, 80.2% (95% CI, 75.3–84.4) were aware of their hypertensive condition and 74.4% (95% CI, 69.2–79.1) were on treatment for hypertension. Among those aware of their hypertension status, 92.8% (95% CI, 88.8–95.6) were on treatment and 53.7% (95% CI, 47.0–60.1) had their blood pressure controlled. Hypertension was more frequent in individuals who were older, obese, or had diabetes. Higher education attainment or presence of comorbidities was associated with higher level of hypertension awareness. Individuals taking three antihypertensive drug classes were more likely to have controlled hypertension compared with those taking one antihypertensive drug class, odds ratio (OR), 1.85 (95% CI, 1.14–2.99).
Conclusion
Our findings identified high prevalence of hypertension and relevant health gaps on awareness, treatment and suboptimal control of hypertension in older adults in Germany. Screening for hypertension should especially target older adults with low educational attainment and ‘healthy’ elderly with less contact to physicians.
Estimates of biological age based on DNA methylation patterns, often referred to as "epigenetic age", "DNAm age", have been shown to be robust biomarkers of age in humans. We previously demonstrated ...that independent of chronological age, epigenetic age assessed in blood predicted all-cause mortality in four human cohorts. Here, we expanded our original observation to 13 different cohorts for a total sample size of 13,089 individuals, including three racial/ethnic groups. In addition, we examined whether incorporating information on blood cell composition into the epigenetic age metrics improves their predictive power for mortality. All considered measures of epigenetic age acceleration were predictive of mortality (p≤8.2x10
, independent of chronological age, even after adjusting for additional risk factors (p<5.4x10
, and within the racial/ethnic groups that we examined (non-Hispanic whites, Hispanics, African Americans). Epigenetic age estimates that incorporated information on blood cell composition led to the smallest p-values for time to death (p=7.5x10
). Overall, this study a) strengthens the evidence that epigenetic age predicts all-cause mortality above and beyond chronological age and traditional risk factors, and b) demonstrates that epigenetic age estimates that incorporate information on blood cell counts lead to highly significant associations with all-cause mortality.
•Multi-city study with highly standardized particle size distribution measurements.•We applied a novel multilevel model to meta-analyze site-specific results.•No clear associations for ultrafine ...particles (UFP) and cause-specific hospital admissions.•Consistent effects for larger particle size fractions and fine particles (PM2.5).•Higher respiratory hospital admission risk for children, and in the cold season.
Numerous studies have shown associations between daily concentrations of fine particles (e.g., particulate matter with an aerodynamic diameter ≤2.5 µm; PM2.5) and morbidity. However, evidence for ultrafine particles (UFP; particles with an aerodynamic diameter of 10–100 nm) remains conflicting. Therefore, we aimed to examine the short-term associations of UFP with five cause-specific hospital admission endpoints for Leipzig, Dresden, and Augsburg, Germany.
We obtained daily counts of (cause-specific) cardiorespiratory hospital admissions between 2010 and 2017. Daily average concentrations of UFP, total particle number (PNC; 10–800 nm), and black carbon (BC) were measured at six sites; PM2.5 and nitrogen dioxide (NO2) were obtained from monitoring networks. We assessed immediate (lag 0–1), delayed (lag 2–4, lag 5–7), and cumulative (lag 0–7) effects by applying station-specific confounder-adjusted Poisson regression models. We then used a novel multi-level meta-analytical method to obtain pooled risk estimates. Finally, we performed two-pollutant models to investigate interdependencies between pollutants and examined possible effect modification by age, sex, and season.
UFP showed a delayed (lag 2–4) increase in respiratory hospital admissions of 0.69% 95% confidence interval (CI): −0.28%; 1.67%. For other hospital admission endpoints, we found only suggestive results. Larger particle size fractions, such as accumulation mode particles (particles with an aerodynamic diameter of 100–800 nm), generally showed stronger effects (respiratory hospital admissions & lag 2–4: 1.55% 95% CI: 0.86%; 2.25%). PM2.5 showed the most consistent associations for (cardio-)respiratory hospital admissions, whereas NO2 did not show any associations. Two-pollutant models showed independent effects of PM2.5 and BC. Moreover, higher risks have been observed for children.
We observed clear associations with PM2.5 but UFP or PNC did not show a clear association across different exposure windows and cause-specific hospital admissions. Further multi-center studies are needed using harmonized UFP measurements to draw definite conclusions on the health effects of UFP.
Epidemiological studies have reported associations between particulate matter (PM) concentrations and cancer and respiratory and cardiovascular diseases. DNA methylation has been identified as a ...possible link but so far it has only been analyzed in candidate sites.
We studied the association between DNA methylation and short- and mid-term air pollution exposure using genome-wide data and identified potential biological pathways for additional investigation.
We collected whole blood samples from three independent studies-KORA F3 (2004-2005) and F4 (2006-2008) in Germany, and the Normative Aging Study (1999-2007) in the United States-and measured genome-wide DNA methylation proportions with the Illumina 450k BeadChip. PM concentration was measured daily at fixed monitoring stations and three different trailing averages were considered and regressed against DNA methylation: 2-day, 7-day and 28-day. Meta-analysis was performed to pool the study-specific results.
Random-effect meta-analysis revealed 12 CpG (cytosine-guanine dinucleotide) sites as associated with PM concentration (1 for 2-day average, 1 for 7-day, and 10 for 28-day) at a genome-wide Bonferroni significance level (p ≤ 7.5E-8); 9 out of these 12 sites expressed increased methylation. Through estimation of I2 for homogeneity assessment across the studies, 4 of these sites (annotated in NSMAF, C1orf212, MSGN1, NXN) showed p > 0.05 and I2 < 0.5: the site from the 7-day average results and 3 for the 28-day average. Applying false discovery rate, p-value < 0.05 was observed in 8 and 1,819 additional CpGs at 7- and 28-day average PM2.5 exposure respectively.
The PM-related CpG sites found in our study suggest novel plausible systemic pathways linking ambient PM exposure to adverse health effect through variations in DNA methylation.
Panni T, Mehta AJ, Schwartz JD, Baccarelli AA, Just AC, Wolf K, Wahl S, Cyrys J, Kunze S, Strauch K, Waldenberger M, Peters A. 2016. A genome-wide analysis of DNA methylation and fine particulate matter air pollution in three study populations: KORA F3, KORA F4, and the Normative Aging Study. Environ Health Perspect 124:983-990; http://dx.doi.org/10.1289/ehp.1509966.
Fat mass and fat-free mass may play independent roles in mortality risk but available studies on body composition have yielded inconsistent results.
The aim was to determine the relations of body fat ...mass and fat-free mass to risk of mortality.
In pooled data from 7 prospective cohorts encompassing 16,155 individuals aged 20 to 93 y (median, 44 y), we used Cox regression and restricted cubic splines to estimate HRs and 95% CIs for the relation of body composition, measured by bioelectrical impedance analysis, to total mortality. We adjusted for age, study, sex, ethnicity, history of diabetes mellitus, education, smoking, physical activity, and alcohol consumption.
During a median follow-up period of 14 y (range, 3–21 y), 1347 deaths were identified. After mutual adjustment for fat mass and fat-free mass, fat mass showed a J-shaped association with mortality (overall P value < 0.001; P for nonlinearity = 0.003). Using a fat mass index of 7.3 kg/m2 as the reference, a high fat mass index of 13.0 kg/m2 was associated with an HR of 1.56 (95% CI: 1.30, 1.87). In contrast, fat-free mass showed an inverse association with mortality (overall P value < 0.001; P for nonlinearity = 0.001). Compared with a low fat-free mass index of 16.1 kg/m2, a high fat-free mass of 21.9 kg/m2 was associated with an HR of 0.70 (95% CI: 0.56, 0.87).
Fat mass and fat-free mass show opposing associations with mortality. Excess fat mass is related to increased mortality risk, whereas fat-free mass protects against risk of mortality. These findings suggest that body composition provides important prognostic information on an individual’s mortality risk not provided by traditional proxies of adiposity such as BMI.
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The clinical significance of isolated systolic hypertension in young adults (ISHY) remains a topic of debate due to evidence ISHY could be a spurious condition resulting from exageratted pulse ...pressure amplification in "young tall men with elastic arteries". Hence, we aimed to investigate whether ISHY is associated with an increased risk of cardivascular (CVD) mortality in a sample of 5597 young adults (49.8% men, 50.2% women) between 25 and 45 years old from the prospective population-based MONICA/KORA cohort. ISHY was prevalent in 5.2% of the population, affecting mostly men (73.1%), and associated with increased smoking, obesity, and hypercholesterolemia in comparison to participants with normal blood pressure (BP). Within a follow-up period of 25.3 years (SD ± 5.2; 141,768 person-years), 133(2.4%) CVD mortality cases were observed. Participants with ISHY had a hazard ratio (HR) of 1.89(1.01-3.53, p < 0.05) times higher risk of CVD mortality than participants with normal BP, even following adjustment for CVD risk factors. However, adjustment for antihypertensive medication (HR 0.46; 0.26-0.81, p < 0.001) and increasing height (HR 0.96; 0.93-0.99, p < 0.05) revealed independently protective effects against CVD mortality, suggesting that although ISHY is associated with an increased risk of CVD mortality, the protective effects of increasing height or antihypertensive medication should be considered in treatment rationale.
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