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3.
J Thromb Haemost ; 2019 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-31680443

RESUMO

BACKGROUND: Rare coding mutations underlying deficiencies of antithrombin and proteins C and S contribute to familial venous thromboembolism (VTE). It is uncertain whether rare variants play a role in the etiology of VTE in the general population. OBJECTIVES: We conducted a deep whole-exome sequencing (WES) study to investigate the associations between rare coding variants and the risk of VTE in two population-based prospective cohorts. PATIENTS/METHODS: WES was performed in the Longitudinal Investigation of Thromboembolism Etiology (LITE), which combines the ARIC study (316 incident VTE events among 3,159 African Americans (AAs) and 458 incident VTEs among 7,772 European Americans (EAs)) and the CHS study (60 incident VTEs among 1,751 EAs). We performed gene-based tests of rare variants (allele frequency <1%, exome-wide significance p<1.47x10-6 ) separately in each study and ancestry group, and meta-analyzed the results for the EAs in ARIC and CHS. RESULTS: In the meta-analysis of EAs, we identified one gene, PROC, in which the burden of rare, coding variants was significantly associated with increased risk of VTE (HR=5.42 [3.11, 9.42] for carriers versus non-carriers, p=2.27 x 10-9 ). In ARIC EAs, carriers of the PROC rare variants had on average 0.75 SD lower concentrations of plasma protein C and 0.28 SD higher D-dimer (p<0.05) than non-carriers. Adjustment for low protein C status did not eliminate the association of PROC burden with VTE. In AAs, rare coding PROC variants were not associated with VTE. CONCLUSIONS: Rare coding variants in PROC contribute to increased VTE risk in EAs in this general population sample.

4.
Am J Clin Nutr ; 2019 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-31622458

RESUMO

BACKGROUND: Low serum magnesium (Mg) concentrations have been associated with higher coronary artery disease (CAD) risk. A previous Atherosclerosis Risk in Communities (ARIC) Study article that evaluated the Mg-CAD association, based on 319 events occurring over 4-7 y, identified a sex-interaction whereby the inverse Mg-CAD association was much stronger among women than men. More than 1700 additional ARIC CAD events have since accrued. OBJECTIVE: We aimed to test our hypothesis that serum Mg is inversely and independently associated with long-term CAD risk in ARIC and in a meta-analysis with other prospective studies. METHODS: A total of 14,446 ARIC study participants (baseline mean ± SD age: 54 ± 6 y, 57% women, 27% African American) were followed for incident CAD through 2017. CAD events were defined by myocardial infarction or CAD mortality. Serum Mg was modeled as quintiles based on mean visit 1 (1987-1989) and visit 2 (1990-1992) concentrations. Cox regression models were used. We also conducted a random-effects meta-analysis incorporating these contemporary ARIC findings. RESULTS: Over a median follow-up of 27 y, 2131 incident CAD cases accrued. Overall, low serum Mg was associated with higher CAD risk after adjustment for demographics, lifestyle factors, and other CAD risk factors than was higher serum Mg (HR Q1 compared with Q5: 1.28; 95% CI: 1.11, 1.47; P-linear trend <0.001). The association was stronger among women (HR Q1 compared with Q5: 1.53; 95% CI: 1.22, 1.92) than men (HR: 1.11; 95% CI: 0.92, 1.34) (P-interaction = 0.05). In the meta-analysis including 5 studies, the pooled RR (95% CI) for CAD in the lowest compared with the highest circulating Mg category was 1.18 (1.06, 1.31) (I2 = 22%, P-heterogeneity = 0.27). CONCLUSIONS: In this large community-based cohort and updated meta-analysis, low circulating Mg was associated with higher CAD risk than was higher Mg. Whether increasing Mg concentrations within healthy limits is a useful strategy for CAD prevention remains to be seen.

5.
Lancet Respir Med ; 2019 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-31606435

RESUMO

BACKGROUND: Former smokers now outnumber current smokers in many developed countries, and current smokers are smoking fewer cigarettes per day. Some data suggest that lung function decline normalises with smoking cessation; however, mechanistic studies suggest that lung function decline could continue. We hypothesised that former smokers and low-intensity current smokers have accelerated lung function decline compared with never-smokers, including among those without prevalent lung disease. METHODS: We used data on six US population-based cohorts included in the NHLBI Pooled Cohort Study. We restricted the sample to participants with valid spirometry at two or more exams. Two cohorts recruited younger adults (≥17 years), two recruited middle-aged and older adults (≥45 years), and two recruited only elderly adults (≥65 years) with examinations done between 1983 and 2014. FEV1 decline in sustained former smokers and current smokers was compared to that of never-smokers by use of mixed models adjusted for sociodemographic and anthropometric factors. Differential FEV1 decline was also evaluated according to duration of smoking cessation and cumulative (number of pack-years) and current (number of cigarettes per day) cigarette consumption. FINDINGS: 25 352 participants (ages 17-93 years) completed 70 228 valid spirometry exams. Over a median follow-up of 7 years (IQR 3-20), FEV1 decline at the median age (57 years) was 31·01 mL per year (95% CI 30·66-31·37) in sustained never-smokers, 34·97 mL per year (34·36-35·57) in former smokers, and 39·92 mL per year (38·92-40·92) in current smokers. With adjustment, former smokers showed an accelerated FEV1 decline of 1·82 mL per year (95% CI 1·24-2·40) compared to never-smokers, which was approximately 20% of the effect estimate for current smokers (9·21 mL per year; 95% CI 8·35-10·08). Compared to never-smokers, accelerated FEV1 decline was observed in former smokers for decades after smoking cessation and in current smokers with low cumulative cigarette consumption (<10 pack-years). With respect to current cigarette consumption, the effect estimate for FEV1 decline in current smokers consuming less than five cigarettes per day (7·65 mL per year; 95% CI 6·21-9·09) was 68% of that in current smokers consuming 30 or more cigarettes per day (11·24 mL per year; 9·86-12·62), and around five times greater than in former smokers (1·57 mL per year; 1·00-2·14). Among participants without prevalent lung disease, associations were attenuated but were consistent with the main results. INTERPRETATION: Former smokers and low-intensity current smokers have accelerated lung function decline compared with never-smokers. These results suggest that all levels of smoking exposure are likely to be associated with lasting and progressive lung damage. FUNDING: National Institutes of Health, National Heart Lung and Blood Institute, and US Environmental Protection Agency.

6.
Circ Arrhythm Electrophysiol ; 12(10): e007390, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31607148

RESUMO

BACKGROUND: The prevalence of subclinical atrial fibrillation (AF) in the elderly general population is unclear. We sought to define the prevalence of subclinical AF in a community-based elderly population and to characterize subclinical AF and the incremental diagnostic yield of 4 versus 2 weeks of continuous ECG monitoring. METHODS: We conducted a cross-sectional analysis within the community-based multicenter observational ARIC study (Atherosclerosis Risk in Communities) using visit 6 (2016-2017) data. The 2616 ARIC study participants who wore a leadless, ambulatory ECG monitor (Zio XT Patch) for up to 2 weeks were aged 79±5 years, 42% men, and 26% black. In a subset, 386 participants without clinically recognized AF wore the monitor twice, each time for up to 2 weeks. We characterized the prevalence of subclinical AF (ie, AF detected on the Zio XT Patch without clinically recognized AF) over 2 weeks of monitoring and the diagnostic yield of 4 versus 2 weeks of monitoring. RESULTS: The prevalence of subclinical AF was 2.5%; the prevalence of subclinical AF was 3.3% among white men, 2.5% among white women, 2.1% among black men, and 1.6% among black women. Subclinical AF was mostly intermittent (75%). Among those with intermittent subclinical AF, 91% had AF burden ≤10% during the monitoring period. In a subset of 386 participants without clinical AF, 78% more subclinical AF was detected by 4 weeks versus 2 weeks of ECG monitoring. CONCLUSIONS: In our study, the prevalence of subclinical AF was lower than previously reported and monitoring beyond 2 weeks provided substantial incremental diagnostic yield. Future studies should focus on individuals with higher risk to increase diagnostic yield and consider continuous monitoring duration longer than 2 weeks.

7.
Thromb Res ; 182: 89-94, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31473403

RESUMO

INTRODUCTION: High molecular weight kininogen (HK) and prekallikrein (PK) are proteins in the kallikrein/kinin system of the coagulation cascade. They play an important role in the contact activation system of the intrinsic coagulation pathway, renin-angiotensin activation, and inflammation. Hence these proteins have been posited to affect the occurrence of cardiovascular events and thus to be potential therapeutic targets. Previous case-control studies have provided inconsistent evidence for an association of HK and PK with cardiovascular disease. METHODS: In the prospective population-based Atherosclerosis Risk in Communities(ARIC) Study, we used Cox proportional hazards regression models to investigate the association in 4195 middle-aged adults of plasma HK and PK concentrations in 1993-95 (linearly and in quartiles) with incident coronary heart disease, ischemic stroke, and heart failure through 2016. RESULTS: Over a mean of 18 years follow-up, we identified incident cardiovascular events (coronary heart disease and ischemic stroke) in 618 participants and heart failure in 667. We observed no significant relation between HK or PK and cardiovascular disease or heart failure, before and after adjusting for several potential confounding variables. CONCLUSIONS: We found no compelling evidence to support an association of plasma HK or PK concentrations with incident CHD, ischemic stroke, or heart failure.

8.
J Phys Act Health ; : 1-8, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31369998

RESUMO

BACKGROUND: This study assessed the independent associations between participation in self-reported sport and exercise activities and incident cardiovascular disease (CVD). METHODS: Data were from 13,204 participants in the Atherosclerosis Risk in Communities Study cohort (1987-2015). Baseline sport and exercise activities were assessed via the modified Baecke questionnaire. Incident CVD included coronary heart disease, heart failure, or stroke. Multivariable-adjusted Cox proportional hazard models assessed the association of participation in specific sport and exercise activities at enrollment with risk of CVD. RESULTS: During a median follow-up time of 25.2 years, 30% of the analytic sample (n = 3966) was diagnosed with incident CVD. In fully adjusted models, participation in racquet sports (hazard ratio [HR] 0.75; 95% confidence interval [CI], 0.61-0.93), aerobics (HR 0.75; 95% CI, 0.63-0.88), running (HR 0.68; 95% CI, 0.54-0.85), and walking (HR 0.89; 95% CI, 0.83-0.95) was significantly associated with a lower risk of CVD. There were no significant associations for bicycling, softball/baseball, gymnastics, swimming, basketball, calisthenics exercises, golfing with cart, golfing with walking, bowling, or weight training. CONCLUSIONS: Participation in specific sport and exercises may substantially reduce the risk for CVD.

9.
Cancer Causes Control ; 30(8): 791-797, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31165420

RESUMO

PURPOSE: Previous studies have reported that taller people have an increased risk of colorectal cancer (CRC). We examined the association of two height components-leg length and sitting height-with CRC risk in 14,532 individuals aged 45-64 years in the Atherosclerosis Risk in Communities study. METHODS: Anthropometrics were measured at baseline (1987-1989). Incident CRC cases (n = 382) were ascertained from 1987 to 2012. Cox proportional hazards regression was used to estimate multivariable-adjusted hazard ratios for CRC and colon cancer across quintiles of sex-specific leg length and sitting height. RESULTS: The highest (versus the lowest) quintile of leg length was associated with a 36% greater CRC risk (p-trend = 0.04), and 51% greater colon cancer risk (p-trend = 0.01). For the top four quintiles combined, risk was increased by 34% for CRC and by 45% for colon cancer versus the lowest quintile. Total height and sitting height were not significantly associated with CRC or colon cancer risk. A small number of cases (n = 57) limited our ability to conduct subgroup analyses for rectal cancer. CONCLUSIONS: A positive association of leg length with CRC and colon cancer risk suggests that biological mechanisms leading to greater leg length during puberty may explain the association between taller height and CRC.


Assuntos
Neoplasias Colorretais/epidemiologia , Perna (Membro)/anatomia & histologia , Aterosclerose/epidemiologia , Estatura , Estudos de Coortes , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Fatores de Risco
10.
J Geriatr Psychiatry Neurol ; : 891988719856692, 2019 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-31203748

RESUMO

Infections of herpes simplex virus type 1 (HSV-1), cytomegalovirus (CMV), Helicobacter pylori, and Chlamydia pneumoniae may play a role in cognitive decline via systemic inflammation. We hypothesized that Atherosclerosis Risk in Communities study participants who were seropositive in midlife for antibodies to HSV-1, CMV, H pylori, or C pneumoniae would have an accelerated rate of cognitive decline over 20 years. Atherosclerosis Risk in Communities performed a case-cohort study involving a stratified random sample of participants tested for serum immunoglobulin G antibodies to the pathogens of interest. We conducted a longitudinal study using this cohort. Cognitive change was measured using Z scores from the Delayed Word Recall (DWR), Digit Symbol Substitution (DSS), and Word Fluency (WF) Tests administered at visits 2 (1990-1992), 4 (1996-1998), and 5 (2011-2013). Linear regression models with generalized estimating equations and inverse probability of attrition weights were used to evaluate associations between infection and cognitive performance. Four hundred twenty-six participants were analyzed, of which 3% were seronegative for all 4 infections, 14% seropositive for one, 33% and 34% seropositive for 2 and 3, respectively, and 16% seropositive for all infections. At baseline, test scores were significantly lower for participants seropositive for H pylori and C pneumoniae. After baseline covariate adjustment, the rate of decline in DWR, DSS, WF, and global Z scores did not differ significantly by infection status for any of the 4 infections. There was also no significant association between the number of infections for which participants were seropositive and cognitive decline. Our study provides no evidence supporting a longitudinal relationship between seropositivity and cognitive decline.

11.
Cancer Epidemiol Biomarkers Prev ; 28(8): 1292-1299, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31167754

RESUMO

BACKGROUND: Laboratory and epidemiologic research suggests a protective role of magnesium in colorectal cancer development. We estimated the associations of serum and dietary magnesium with colorectal cancer incidence in the Atherosclerosis Risk in Communities (ARIC) study. METHODS: Serum magnesium concentration was measured in blood collected twice (1987-1989 and 1990-1992) and averaged. Dietary magnesium was assessed by food-frequency questionnaire administered twice (1987-1989 and 1993-1995) and averaged. For both dietary and serum magnesium, the averaged measures were categorized into quintiles for analysis. Analyses included 315 colorectal cancer cases among 13,009 participants for serum magnesium (followed for a median of 20.4 years), and 256 cases among 10,971 participants for dietary magnesium (followed for a median of 17.5 years). Cox proportional hazards regression was used to calculate multivariable-adjusted HRs and 95% confidence intervals (CI). RESULTS: Multivariable-adjusted HRs (95% CI) of colorectal cancer for the highest four quintiles compared with the first quintile of serum magnesium were as follows: Q2: 0.70 (0.49-0.99); Q3: 0.68 (0.47-1.00); Q4: 0.87 (0.62-1.21); and Q5: 0.79 (0.57-1.11; P trend = 0.04). An inverse association was present in females (HR for Q5 vs. Q1: 0.59, 95% CI: 0.36-0.98, P trend = 0.01), but not males (HR for Q5 vs. Q1: 1.10, 95% CI: 0.67-1.79, P trend = 0.92; P interaction = 0.34). Dietary magnesium was not statistically significantly associated with colorectal cancer risk. CONCLUSIONS: Our study found a higher risk of colorectal cancer with lower serum magnesium among females, but not males. IMPACT: If our findings are confirmed, maintaining adequate serum magnesium levels may be important for colorectal cancer prevention.

12.
J Clin Endocrinol Metab ; 104(10): 4600-4606, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31157875

RESUMO

PURPOSE: Based on the 2018 American College of Cardiology/American Heart Association cholesterol guidelines, the number of individuals eligible for statin therapy to reduce atherosclerotic cardiovascular disease risk has greatly expanded. Statins inhibit cholesterol biosynthesis, which can impair gonadal steroidogenesis. We evaluated the effect of statins on endogenous sex hormones in a large epidemiological study. METHODS: A total of 6814 Multi-Ethnic Study of Atherosclerosis (MESA) participants underwent the baseline examination. Of these, 6171 had measurements of serum sex hormones available: dehydroepiandrosterone (DHEA), SHBG, estradiol, and total and bioavailable testosterone. Multivariable linear regression models were used to assess the relationship of statin use with each sex hormone. RESULTS: A total of 345 women (17.4%) and 464 men (14.7%) were statin users (mean age, 67 years; 41% white, 29% black, 11% Chinese, and 19% Hispanic). Among the users vs nonusers of statins, the mean SHBG was 3.54 nmol/L (P < 0.01) lower in women and 3.37 nmol/L (P < 0.001) lower in men; the mean DHEA was 1.06 nmol/L (P < 0.05) lower in women and 0.70 nmol/L (P < 0.01) lower in men, after adjustment for potential confounders. With further propensity score adjustment, the mean DHEA and SHBG levels were 0.67 nmol/L (P < 0.05) and 3.49 nmol/L (P < 0.001) lower, respectively, for statin users vs nonusers. No statistically significant association was noted between estradiol, total testosterone, and bioavailable testosterone and statin use. CONCLUSION: Statin users have lower levels of SHBG and DHEA. This is especially relevant owing to the increasing use of statin therapy.

13.
Maturitas ; 125: 5-10, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31133217

RESUMO

OBJECTIVE: Whether endogenous testosterone concentrations are associated with atrial fibrillation (AF) development is not well established. We assessed the association between plasma total testosterone concentrations and incident AF in a population-based longitudinal study. STUDY DESIGN: Using data from the prospective Atherosclerosis Risk in Communities (ARIC) study, we identified incident AF among 9282 participants who had plasma total testosterone measured by liquid chromatography tandem mass spectrometry at Visit 4 (1996-1998). MAIN OUTCOME MEASURES: AF cases were identified by electrocardiograms performed during study visits, hospital records/discharge codes, and death certificates through 2013. We estimated hazard ratios (HRs) and 95% confidence intervals (95% CIs) for incident AF across quartiles of plasma total testosterone, stratified by sex, with multivariable Cox models. RESULTS: The mean age of the participant sample at ARIC Visit 4 was 63 years (range 52-75); 54.5% were women. Mean (SD) plasma total testosterone levels were 537 ng/dL (213) for men and 27.6 ng/dL (34.7) for women. Over a mean of 13.7 years of follow-up, 1664 incident cases of AF were identified. Comparing those in the highest quartile of plasma total testosterone concentration to those in the lowest quartile and after adjustment for potential confounding variables, there was a positive association between plasma total testosterone and incident AF in men (HR 1.33, 95% CI 1.07, 1.66), but no such association in women (HR 0.99, 95% CI 0.80, 1.22). Conclusion A higher plasma total testosterone concentration was associated with a modestly greater incidence rate of AF in men.


Assuntos
Aterosclerose/sangue , Fibrilação Atrial/sangue , Testosterona/sangue , Idoso , Eletrocardiografia , Feminino , Taxa de Filtração Glomerular , Humanos , Incidência , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Prospectivos , Fatores de Risco , Fatores Sexuais
14.
Am J Epidemiol ; 2019 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-31063194

RESUMO

Whether persons without prevalent cardiovascular disease (CVD) but elevated levels of high-sensitivity cardiac troponin T (hs-cTnT) or N-terminal pro-B-type natriuretic peptide (NTproBNP) are at high risk of infection is unknown. In the Atherosclerosis Risk in Communities Study, we estimated the hazard ratios (HRs) of incident hospitalization with infection in relation to plasma hs-cTnT and NTproBNP among participants without prevalent CVD, and contrasted with those with prevalent CVD (coronary heart disease, heart failure, stroke) from 1996 through 2013. In multivariable Cox model, prevalent CVD was significantly associated with risk of infection (HR, 1.31 [95%CI,1.19,1.45]). Among participants without prevalent CVD, hs-cTnT and NTproBNP were independently associated with infection risk in a graded fashion (e.g., HR 1.44 [1.24,1.69] for hs-cTnT ≥14ng/L and 1.28 [1.14,1.44] for 9-13ng/L vs. <3ng/L; and 1.57 [1.35,1.81] for NTproBNP ≥248.1pg/mL and 1.19 [1.06,1.34] for 137.2-248.0pg/mL vs. <48.1pg/mL). The 15-year cumulative incidence of hospitalization with infection was similar between participants with prevalent CVD and those without prevalent CVD but had hs-cTnT ≥14ng/L or NTproBNP ≥248.1pg/mL. Thus, hs-cTnT and NTproBNP were independently associated with infection risk. Persons without CVD but with elevated levels of hs-cTnT or NTproBNP should be recognized to have a similar infection risk as those with prevalent CVD.

15.
Am J Hypertens ; 32(8): 769-776, 2019 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-31090885

RESUMO

BACKGROUND: Greater arterial stiffness is associated independently with increased cardiovascular disease risk. The American Heart Association (AHA) has recommended following "Life's Simple 7 (LS7)" to optimize cardiovascular health; we tested whether better LS7 in middle age is associated with less arterial stiffness in later life. METHODS: We studied 4,232 black and white participants aged 45-64 years at the baseline (1987-89) visit of the Atherosclerosis Risk in Communities Study cohort who also had arterial stiffness measured in 2011-13 (mean ± SD interval: 23.6 ± 1.0 years). We calculated a 14-point summary score for baseline LS7 and classified participants as having "poor" (0-4), "average" (5-9), or "ideal" (10-14) cardiovascular health. We used logistic regression to calculate odds ratios (ORs) and 95% confidence intervals (95% CI) for arterial stiffening: a high carotid-femoral pulse wave velocity (cfPWV, ≥13.23 m/s) or a high central pulse pressure (central PP, ≥ 82.35 mm Hg). RESULTS: The age, race, sex, and heart rate-adjusted ORs (95% CI) for high cfPWV in the "ideal," "average," and "poor" LS7 summary categories were 1 (Reference), 1.30 (1.11, 1.53), and 1.68 (1.10,2.56), respectively (P-trend = 0.0003). Similarly, the adjusted ORs (95% CI) for high central PP across LS7 summary categories were 1 (Reference), 1.48 (1.27, 1.74), and 1.63 (1.04, 2.56), respectively (P-trend <0.0001). CONCLUSION: Greater LS7 score in middle age is associated with less arterial stiffness 2-3 decades later. These findings further support the AHA recommendation to follow LS7 for cardiovascular disease prevention.

16.
Arterioscler Thromb Vasc Biol ; 39(7): 1475-1482, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31092011

RESUMO

Objective- Alterations in the serum metabolome may be detectable in at-risk individuals before the onset of coronary heart disease (CHD). Identifying metabolomic signatures associated with CHD may provide insight into disease pathophysiology and prevention. Approach and Results- Metabolomic profiling (chromatography-mass spectrometry) was performed in 2232 African Americans and 1366 European Americans from the ARIC study (Atherosclerosis Risk in Communities). We applied Cox regression with least absolute shrinkage and selection operator to select metabolites associated with incident CHD. A metabolite risk score was constructed to evaluate whether the metabolite risk score predicted CHD risk beyond traditional risk factors. After 30 years of follow-up, we observed 633 incident CHD cases. Thirty-two metabolites were selected by least absolute shrinkage and selection operator to be associated with CHD, and 19 of the 32 showed significant individual associations with CHD, including a sugar substitute, erythritol. Theophylline (hazard ratio [95% CI] =1.16 [1.09-1.25]) and gamma-linolenic acid (hazard ratio [95% CI] =0.89 [0.81-0.97]) showed the greatest positive and negative associations with CHD, respectively. A 1 SD greater standardized metabolite risk score was associated with a 1.37-fold higher risk of CHD (hazard ratio [95% CI] =1.37 [1.27-1.47]). Adding the metabolite risk score to the traditional risk factors significantly improved model predictive performance (30-year risk prediction: Δ C statistics [95% CI] =0.016 [0.008-0.024], continuous net reclassification index [95% CI] =0.522 [0.480-0.556], integrated discrimination index [95% CI] =0.038 [0.019-0.065]). Conclusions- We identified 19 metabolites from known and novel metabolic pathways that collectively improved CHD risk prediction. Visual Overview- An online visual overview is available for this article.

17.
Circulation ; 139(23): 2642-2653, 2019 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-31030544

RESUMO

BACKGROUND: We assessed whether plasma troponin I measured by a high-sensitivity assay (hs-TnI) is associated with incident cardiovascular disease (CVD) and mortality in a community-based sample without prior CVD. METHODS: ARIC study (Atherosclerosis Risk in Communities) participants aged 54 to 74 years without baseline CVD were included in this study (n=8121). Cox proportional hazards models were constructed to determine associations between hs-TnI and incident coronary heart disease (CHD; myocardial infarction and fatal CHD), ischemic stroke, atherosclerotic CVD (CHD and stroke), heart failure hospitalization, global CVD (atherosclerotic CVD and heart failure), and all-cause mortality. The comparative association of hs-TnI and high-sensitivity troponin T with incident CVD events was also evaluated. Risk prediction models were constructed to assess prediction improvement when hs-TnI was added to traditional risk factors used in the Pooled Cohort Equation. RESULTS: The median follow-up period was ≈15 years. Detectable hs-TnI levels were observed in 85% of the study population. In adjusted models, in comparison to low hs-TnI (lowest quintile, hs-TnI ≤1.3 ng/L), elevated hs-TnI (highest quintile, hs-TnI ≥3.8 ng/L) was associated with greater incident CHD (hazard ratio [HR], 2.20; 95% CI, 1.64-2.95), ischemic stroke (HR, 2.99; 95% CI, 2.01-4.46), atherosclerotic CVD (HR, 2.36; 95% CI, 1.86-3.00), heart failure hospitalization (HR, 4.20; 95% CI, 3.28-5.37), global CVD (HR, 3.01; 95% CI, 2.50-3.63), and all-cause mortality (HR, 1.83; 95% CI, 1.56-2.14). hs-TnI was observed to have a stronger association with incident global CVD events in white than in black individuals and a stronger association with incident CHD in women than in men. hs-TnI and high-sensitivity troponin T were only modestly correlated ( r=0.47) and were complementary in prediction of incident CVD events, with elevation of both troponins conferring the highest risk in comparison with elevation in either one alone. The addition of hs-TnI to the Pooled Cohort Equation model improved risk prediction for atherosclerotic CVD, heart failure, and global CVD. CONCLUSIONS: Elevated hs-TnI is strongly associated with increased global CVD incidence in the general population independent of traditional risk factors. hs-TnI and high-sensitivity troponin T provide complementary rather than redundant information.

18.
Am J Med ; 132(8): 970-976, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30953632

RESUMO

INTRODUCTION: Venous thromboembolism incidence rates are 30%-100% higher in US blacks than whites. We examined the degree to which differences in the frequencies of socioeconomic, lifestyle, medical risk factors, and genetic variants explain the excess venous thromboembolism risk in blacks and whether some risk factors are more strongly associated with venous thromboembolism in blacks compared with whites. METHODS: We measured venous thromboembolism risk factors in black and white participants of the Atherosclerosis Risk in Communities study in 1987-1989 and followed them prospectively through 2015 for venous thromboembolism incidence. RESULTS: Over a mean of 22 years, we identified 332 venous thromboembolisms in blacks and 578 in whites, yielding 65% higher crude incidence rates per 1000 person-years in blacks. The age and sex-adjusted hazard ratio (95% confidence interval) of venous thromboembolism for blacks compared with whites was 2.04 (1.76, 2.37) for follow-up >10 years and was attenuated to 1.14 (0.89, 1.46) when adjusted for baseline confounders or mediators of the race association, which tended to be more common in blacks. For example, adjustment for just baseline weight, family income, and concentration of plasma factor VIII reduced the regression coefficient for race by 75%. There were no significant (P <0.05) 2-way multiplicative interactions of race with any risk factor, except with a 5-single nucleotide polymorphism (5-SNP) genetic risk score (a weaker venous thromboembolism risk factor in blacks) and with hospitalization for heart failure (a stronger venous thromboembolism risk factor in blacks). CONCLUSION: The higher incidence rate of venous thromboembolism in blacks than whites was mostly explained by blacks having higher frequencies of venous thromboembolism risk factors.

19.
Vasc Med ; 24(3): 224-229, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30898044

RESUMO

To optimize cardiovascular health, the American Heart Association (AHA) has recommended 'Life's Simple 7 (LS7)'. We tested the hypothesis that greater adherence to the LS7 cardiovascular risk metric is associated with reduced risk of developing abdominal aortic aneurysm (AAA). A total of 14,375 black and white participants aged 45-64 years at the baseline visit of the Atherosclerosis Risk in Communities (ARIC) study cohort were included in this analysis. A 14-point summary score for LS7 was calculated, and participants were classified as having poor (0-4), average (5-9), or ideal (10-14) cardiovascular health. We also counted the number of ideal components. Poisson regression was used to calculate incidence rates for AAA, and Cox regression to calculate hazard ratios adjusted for age, race, sex, and socioeconomic status. Over 25 years of follow-up, we identified 545 clinically manifest AAA events. Incident rates per 1000 person-years declined markedly across LS7 categories: 3.4 for the 'poor' category, 2.2 for 'average', and 0.9 for 'ideal'. Compared to individuals in the 'poor' LS7 category, individuals in the 'average' category had a 52% lower AAA risk (95% CI: 37% to 63%) and those in the 'ideal' category had an 80% lower risk (95% CI: 72% to 86%). For every additional ideal component, there was a 28% lower risk of AAA (95% CI: 23% to 33%). Greater adherence to the AHA's LS7 cardiovascular risk metric is associated with a reduced risk of clinically manifest AAA. These findings support the recommendation to follow LS7 for primary prevention of AAA.


Assuntos
Aneurisma da Aorta Abdominal/prevenção & controle , Estilo de Vida Saudável , Prevenção Primária/métodos , Comportamento de Redução do Risco , Afro-Americanos , Aneurisma da Aorta Abdominal/diagnóstico por imagem , Aneurisma da Aorta Abdominal/etnologia , Grupo com Ancestrais do Continente Europeu , Feminino , Nível de Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Proteção , Fatores de Risco , Estados Unidos/epidemiologia
20.
J Thromb Haemost ; 17(5): 818-826, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30803124

RESUMO

Essentials Ceruloplasmin (CP) is an acute-phase reactant and a potential biomarker of atherothrombotic risk. We assessed associations between CP and venous thromboembolism (VTE) risk in 9933 individuals. Higher circulating CP but not CP-related genes were associated with greater incident VTE rates. Circulating CP could be considered a non-causal biomarker of VTE risk in the community. SUMMARY: Background Ceruloplasmin (CP) is an acute-phase reactant and a potential biomarker of atherothrombotic risk. We assessed the associations between CP, CP-associated genetic variants and incident venous thomboembolism (VTE) in the Atherosclerosis Risk in Communities study. Methods and results In an observational study, 9933 men and women aged 53-75 years without prevalent VTE were included in 1996-1998 and followed through 2011. Circulating CP was measured in stored blood samples obtained in 1996-1998. Polymorphisms rs11708215 and rs13072552, which have been previously associated with CP concentrations, were measured in 8439 participants. VTEs were identified from hospital discharge codes and validated by physician review of medical records and imaging reports. Over a mean of 10.5 years of follow-up, 376 cases of VTE were identified. The association between circulating CP, CP-associated polymorphisms and the incidence of VTE was estimated. After adjustment for traditional risk factors and biomarkers, higher concentrations of circulating CP were associated with greater incident VTE rates (hazard ratio 1.82, 95% confidence interval 1.12-2.95, comparing the 87.5-100th percentile with the bottom quartile). Both rs11708215 and rs13072552 were associated with CP concentrations but not with VTE risk. Conclusions Even though high CP concentrations were associated with an increased VTE risk, CP-associated genetic variants were not associated with a higher risk of VTE. Our results suggest that circulating CP concentrations may not be causally related to the risk of incident VTE.

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