Homocysteine (Hcy) is a heritable biomarker for CVD, peripheral artery disease, stroke, and dementia. Little is known about genetic associations with Hcy in individuals of African ancestry. We ...performed a genome-wide association study for Hcy in 4927 AAs from the Jackson Heart Study (JHS), the Multi-Ethnic Study of Atherosclerosis (MESA), and the Coronary Artery Risk in Young Adults (CARDIA) study. Analyses were stratified by sex and results were meta-analyzed within and across sex. In the sex-combined meta-analysis, we observed genome-wide significant evidence (p < 5.0 × 10
) for the NOX4 locus (lead variant rs2289125, β = -0.15, p = 5.3 × 10
). While the NOX4 locus was previously reported as associated with Hcy in European-American populations, rs2289125 remained genome-wide significant when conditioned on the previously reported lead variants. Previously reported genome-wide significant associations at NOX4, MTR, CBS, and MMACHC were also nominally (p < 0.050) replicated in AAs. Associations at the CPS1 locus, previously reported in females only, also was replicated specifically in females in this analysis, supporting sex-specific effects for this locus. These results suggest that there may be a combination of cross-population and population-specific genetic effects, as well as differences in genetic effects between males and females, in the regulation of Hcy levels.
•POPs in young adults were associated with blood lipids measured up to 23y later.•There were positive associations between PCBs and most lipid components.•Non-dioxin-like PCBs had stronger ...associations than dioxin-like PCBs.•PBB-153 had positive curvilinear associations with most lipid outcomes.•OCPs were likely not associated with blood lipids.
Some evidence in humans suggests that persistent organic pollutants (POPs), including organochlorine pesticides (OCPs) and polychlorinated biphenyls (PCBs), may alter the blood lipid composition. This study analyzed associations between serum POPs concentrations in young adulthood with blood lipid levels up to 23 years later.
Serum POPs were measured in year 2 of follow-up (n = 180 men and women, ages: 20-32y), and plasma lipids in follow-up years 2, 7, 10, 15, 20 and 25. 32 POPs were detectable in ≥75% of participants (23 PCBs, 8 OCPs and PBB-153). We created summary scores for PCBs and OCPs for both wet-weight, and lipid standardized (LP) concentrations. We used repeated measures regression adjusting for demographic factors, BMI, smoking, diabetes status, among others.
We observed positive associations of the 23 LP-PCB score with total cholesterol (βper SD increase 95%CI: 5.0 mg/dL 0.7, 9.2), triglycerides (7.8 mg/dL -0.9, 16.5), LDL (4.2 mg/dL 0.2, 8.2), oxidized LDL 3.4 U/L (-0.05, 6.8), and cholesterol/HDL ratio (0.2 0.02, 0.3). The associations for triglycerides (14.7 mg/dL 0.4, 20.1), cholesterol/HDL (0.33 0.09, 0.56) and, to some extent, LDL (4.7 md/dL -1.6, 10.9) were only observed among participants in the upper 50th percentile of BMI. Non-dioxin-like PCBs had stronger associations that dioxin-like PCBs. OCPs and PBB-s had positive associations with most outcomes.
PCBs and PBB-153 measured in young adulthood were positively associated with prospective alterations in most blood lipid components, with evidence of effect modification by BMI. Further longitudinal studies with multiple measures of POPs overtime are needed.
Background: Epidemiologic studies have found whole-grain intake to be inversely associated with the risk of type 2 diabetes and heart disease. Objective: We tested the hypothesis that whole-grain ...consumption improves insulin sensitivity in overweight and obese adults. Design: This controlled experiment compared insulin sensitivity between diets (55% carbohydrate, 30% fat) including 6-10 servings/d of breakfast cereal, bread, rice, pasta, muffins, cookies, and snacks of either whole or refined grains. Total energy needs were estimated to maintain body weight. Eleven overweight or obese body mass index (in kg/m2): 27-36 hyperinsulinemic adults aged 25-56 y participated in a randomized crossover design. At the end of each 6-wk diet period, the subjects consumed 355 mL (12 oz) of a liquid mixed meal, and blood samples were taken over 2 h. The next day a euglycemic hyperinsulinemic clamp test was administered. Results: Fasting insulin was 10% lower during consumption of the whole-grain than during consumption of the refined-grain diet (mean difference: -15 +/- 5.5 pmol/L; P = 0.03). After the whole-grain diet, the area under the 2-h insulin curve tended to be lower (-8832 pmol·min/L; 95% CI: -18720, 1062) than after the refined-grain diet. The rate of glucose infusion during the final 30 min of the clamp test was higher after the whole-grain diet (0.07 × 10(-4) mmol·kg−1·min-1 per pmol/L; 95% CI: 0.003 × 10(-4), 0.144 × 10(-4). Conclusion: Insulin sensitivity may be an important mechanism whereby whole-grain foods reduce the risk of type 2 diabetes and heart disease.
Adipose tissue produces adiponectin, an anti-inflammatory protein. Adiponectin deficiency in mice is associated with abnormal post-natal alveolar development.
We hypothesized that lower serum ...adiponectin concentrations are associated with lower lung function in humans, independent of obesity. We explored mediation of this association by insulin resistance and systemic inflammation.
Spirometry testing was conducted at years 10 and 20 follow-up evaluation visits in 2,056 eligible young adult participants in the Coronary Artery Risk Development in Young Adults (CARDIA) study. Body mass index, serum adiponectin, serum C-reactive protein (a marker of systemic inflammation), and insulin resistance were assessed at year 15.
After controlling for body mass index, years 10 and 20 forced vital capacity (FVC) were 81 ml and 82 ml lower respectively (p = 0.004 and 0.01 respectively) in the lowest vs. highest adiponectin quartiles. Similarly, years 10 and 20 forced expiratory volume in one second (FEV1) were 50 ml and 38 ml lower (p = 0.01 and 0.09, respectively) in the lowest vs. highest adiponectin quartiles. These associations were no longer significant after adjustment for insulin resistance and C-reactive protein. Serum adiponectin was not associated with FEV1/FVC or peak FEV1.
Independent of obesity, lower serum adiponectin concentrations are associated with lower lung function. The attenuation of this association after adjustment for insulin resistance and systemic inflammation suggests that these covariates are on a causal pathway linking adiponectin and lung function.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background The relationship between long-term cardiovascular health (CVH) patterns and elevated CRP (C-reactive protein) in late middle age has yet to be investigated. We aimed to assess this ...relationship. Methods and Results Individual CVH components were measured in 4405 Black and White men and women (aged 18-30 years at baseline) in the CARDIA (Coronary Artery Risk Development in Young Adults) study at 8 examinations over 25 years. CRP was measured at 4 examinations (years 7, 15, 20, and 25). Latent class modeling was used to identify individuals with similar trajectories in CVH from young adulthood to middle age. Multivariable Poisson regression models were used to assess the association between race-specific CVH trajectories and prevalence of elevated CRP levels (>3.0 mg/L) after 25 years of follow-up. Five distinct CVH trajectories were identified for each race. Lower and decreasing trajectories had higher prevalence of elevated CRP relative to the highest trajectory. Prevalence ratios for elevated CRP in lowest trajectory groups at year 25 were 2.58 (95% CI, 1.89-3.51) and 7.20 (95% CI, 5.09-10.18) among Black and White people, respectively. Prevalence ratios for chronically elevated CRP (elevated CRP at 3 or more of the examinations) in the lowest trajectory groups were 8.37 (95% CI, 4.37-16.00) and 15.89 (95% CI, 9.01-28.02) among Black and White people, respectively. Conclusions Lower and decreasing CVH trajectories are associated with higher prevalence of elevated CRP during the transition from young adulthood to middle age.
Serum carotenoid concentrations relate inversely to cardiovascular disease incidence. To clarify the effect of carotenoids on atherosclerotic risk factors, we examined the association of circulating ...carotenoids with inflammation, oxidative stress, endothelial dysfunction, and smoking.
Black and white men and women in the Coronary Artery Risk Development in Young Adults study, ages 18 to 30 years at recruitment (1985-1986) from 4 US cities, were investigated over 15 years. We included 2048 to 4580 participants in analyses of the sum of serum alpha-carotene, beta-carotene, zeaxanthin/lutein, and beta-cryptoxanthin concentrations and of lycopene at year 0 and at year 7.
The year 0 sum of 4 carotenoids was inversely associated (all P <0.05) with year 0 leukocyte count (slope per sum carotenoid SD, -0.17); year 7 fibrinogen (slope, -0.10); year 7 and year 15 C-reactive protein (slope, -0.12 and -0.09); and year 15 F(2)-isoprostanes (slope, -13.0), soluble P-selectin (slope, -0.48), and soluble intercellular adhesion molecule-1 (sICAM1; slope, -5.1). Leukocyte counts and sICAM1 and F(2)-isoprostane concentrations had stronger associations in smokers than in nonsmokers, and sICAM1 concentrations were higher in the highest carotenoid quartile in smokers than in the lowest carotenoid quartile in nonsmokers. Superoxide dismutase was positively associated with the sum of 4 carotenoids (slope, 0.12; P <0.01). Lycopene was inversely associated only with sICAM1. The year 7 carotenoid associations with these markers were mostly similar to those at year 0.
Circulating serum carotenoids were associated, some interactively with smoking, in apparently beneficial directions with markers of inflammation, oxidative stress, and endothelial dysfunction.
IMPORTANCE: Most primary care clinicians lack the skills and resources to offer effective lifestyle and medication (L&M) counseling to reduce coronary heart disease (CHD) risk. Thus, effective and ...feasible CHD prevention programs are needed for typical practice settings. OBJECTIVE: To assess the effectiveness, acceptability, and cost-effectiveness of a combined L&M intervention to reduce CHD risk offered in counselor-delivered and web-based formats. DESIGN, SETTING, AND PARTICIPANTS: A comparative effectiveness trial in 5 diverse family medicine practices in North Carolina. Participants were established patients, aged 35 to 79 years, with no known cardiovascular disease, and at moderate to high risk for CHD (10-year Framingham Risk Score FRS, ≥10%). INTERVENTIONS: Participants were randomized to counselor-delivered or web-based format, each including 4 intensive and 3 maintenance sessions. After randomization, both formats used a web-based decision aid showing potential CHD risk reduction associated with L&M risk-reducing strategies. Participants chose the risk-reducing strategies they wished to follow. MAIN OUTCOMES AND MEASURES: The primary outcome was within-group change in FRS at 4-month follow-up. Other measures included standardized assessments of blood pressure, blood lipid levels, lifestyle behaviors, and medication adherence. Acceptability and cost-effectiveness were also assessed. Outcomes were assessed at 4 and 12 months. RESULTS: Of 2274 screened patients, 385 were randomized (192 counselor; 193 web): mean age, 62 years; 24% African American; and mean FRS, 16.9%. Follow-up at 4 and 12 months included 91% and 87% of the randomized participants, respectively. There was a sustained reduction in FRS at both 4 months (primary outcome) and 12 months for both counselor-based (−2.3% 95% CI, −3.0% to −1.6% and −1.9% 95% CI, −2.8% to −1.1%, respectively) and web-based groups (−1.5% 95% CI, −2.2% to −0.9% and −1.7% 95% CI, −2.6% to −0.8% respectively). At 4 months, the adjusted difference in FRS between groups was −1.0% (95% CI, −1.8% to −0.1%) (P = .03), and at 12 months, it was −0.6% (95% CI, −1.7% to 0.5%) (P = .30). The 12-month costs from the payer perspective were $207 and $110 per person for the counselor- and web-based interventions, respectively. CONCLUSIONS AND RELEVANCE: Both intervention formats reduced CHD risk through 12-month follow-up. The web format was less expensive. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01245686
OBJECTIVE:Vascular remodeling associated with increased extracellular matrix (ECM) may precede hypertension. Procollagen type III N-terminal propeptide (PIIINP) and collagen type I carboxy-terminal ...telopeptide (ICTP) reflect collagen turnover and are important in ECM remodeling. PIIINP and ICTP are increased in cardiovascular diseases (CVD). We hypothesized that PIIINP and ICTP among normotensives predict incident hypertension.
METHODS:We included 1252 Multi-Ethnic Study of Atherosclerosis participants with mean age 58.1 ± 12.4 years, 48% men, free of overt CVD, having SBP and DBP less than 130/85 mmHg and not using any antihypertensive medication, and having plasma PIIINP and ICTP measurements, all assessed at baseline. We studied the association of baseline PIIINP and ICTP with the relative incidence density (RID) of incident hypertension, defined as SBP/DBP at least 140/90 mmHg, or antihypertensive therapy use during follow-up (four examinations over median 9.4 years).
RESULTS:Baseline mean SBP/DBP was 110.9 ± 14.0/67.9 ± 10.4 mmHg. Mean concentration of PIIINP was 5.39 ± 1.95 μg/l and ICTP was 3.18 ± 1.39 μg/l. During follow-up visits, 35.9% of the participants developed hypertension. After adjustment for age, race, and sex there was a significant RID for new onset of hypertension of 1.16 (1.06, 1.28), P = 0.0017 for PIIINP and 1.20 (1.08,1.33) for ICTP, P = 0.0008. After additional adjustment for renal function, CVD risk factors and inflammatory variables, RID for new onset hypertension was 1.28 (1.15,1.42), P < 0.001 for PIIINP and 1.29 (1.15,1.44) for ICTP, P < 0.0001.
CONCLUSION:Biomarkers of ECM remodeling predicted the development of hypertension in normotensive participants free of overt CVD.
Sustained remodeling of extracellular matrix can compromise organs and tissues. Procollagen type III N-terminal propeptide (PIIINP) and collagen type I carboxy-terminal telopeptide (ICTP) reflect ...collagen synthesis and degradation. We studied their predictive value for future death and disease.
A total of 3068 men and women in the Multi-Ethnic Study of Atherosclerosis who were free of cardiovascular disease (CVD) and in generally good health had a baseline blood sample taken for ICTP and PIIINP. Median follow-up was 13.0 years. Among 4 primary outcomes, CVD events (n = 697) were adjudicated, death (n = 571) was by death certificate, and chronic inflammatory-related severe hospitalization and death (ChrIRD, n = 726) and total cancer (n = 327) were classified using International Classification of Diseases codes. We used Poisson regression to study baseline ICTP and PIIINP relative to these outcomes.
Mean (SD) PIIINP was 5.47 (1.95) μg/L and ICTP was 3.37 (1.70) μg/L. PIIINP and ICTP were highly correlated with each other and with estimated glomerular filtration rate (eGFR). Adjustment for age and eGFR attenuated relative risks, remaining 20%-30% per SD of both PIIINP and ICTP in prediction for total death and ChrIRD, and of PIIINP for cancer, with little additional attenuation by adjusting for risk factors and inflammatory biomarkers. CVD outcome was generally unrelated to PIIINP but became marginally inversely related to ICTP in the most adjusted model.
The collagen biomarkers PIIINP and ICTP, in part through pathophysiologically parallel associations with renal function, predicted ChrIRD and total death. Moreover, PIIINP predicted future cancer. These collagen markers may help differentiate healthy from unhealthy aging.
OBJECTIVE:We studied associations of circulating collagen type I carboxy-terminal telopeptide (ICTP) and procollagen type III N-terminal propeptide (PIIINP) with long-term renal function decline.
...METHODS:In the Multi-Ethnic Study of Atherosclerosis, we included 2492 participants initially aged 45–84 years and free of clinical cardiovascular disease (CVD), excluding people with estimated glomerular filtration rate (eGFR) less than 60 ml/min per 1.73 m or urine albumin/creatinine (UAC) at least 30 mg/g. The primary outcome in median 9.4-year follow-up was renal function decline (≥30% decline in eGFR between any two exams or incident UAC ≥ 30 mg/g). The associations of baseline plasma ICTP and PIIINP with renal function decline were estimated using Poisson regression, adjusting for baseline variables race/ethnicity, sex, age, and continuous eGFR and UAC, with further adjustment for CVD risk factors and medications.
RESULTS:Baseline serum ICTP was 3.27 ± 1.43 μg/l and PIIINP was 5.43 ± 1.85 μg/l. Mean baseline eGFR was 91.5 ± 18.4 ml/min per 1.73 m. Renal function decline occurred in 19.5% during 9.4-year follow-up. The renal function decline outcome was positively associated with serum ICTP and PIIINPrelative incidence density (95% confidence interval) per SD 1.22 (1.11–1.33) and 1.27 (1.16–1.40), respectively. Additional adjustment for other risk factors did not greatly alter findings.
CONCLUSION:High collagen biomarker concentrations in serum were associated with future decline in renal function in people initially free of CVD and with normal eGFR, consistent with collagen production signaling renal decline. The continuous association observed for ICTP which, unlike PIIINP, is filtered by the kidney, may owe to its double status as a sensitive marker of glomerular function and collagen degradation.
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