Serum androgens and risk of atrial fibrillation in older men: The Cardiovascular Health Study.
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ABSTRACT: Background
Decline in serum androgens is common among older men and has been associated with cardiovascular disease, although its role in risk of atrial fibrillation (AF) has not been well defined.Hypothesis
Low serum androgens are associated with an increased risk of AF.Methods
We examined the prospective associations between testosterone, its more active metabolite dihydrotestosterone (DHT), and sex hormone-binding globulin (SHBG) with risk of AF among 1019 otherwise healthy men with average age 76.3 ±4.9 years in the Cardiovascular Health Study.Results
After median follow-up of 9.5 years, 304 (30%) men developed AF. We detected a nonlinear association with risk of incident AF in both free and total DHT, in which subjects with the lowest levels had a higher risk of incident AF. After adjustment for demographics, clinical risk factors, left atrial diameter, and serum NT-proBNP levels, men with free DHT <0.16 ng/dL were at increased risk compared with men with higher levels (hazard ratio: 1.48, 95% confidence interval: 1.01-2.17, P <0.05). Sensitivity analyses confirmed that the increased risk was not cutpoint-specific, with a significant association noted up to cutpoints <~0.2 ng/dL. We also detected a complex nonlinear association between SHBG and incident AF, in which subjects in the middle quintile (52.9-65.3 nmol/L) had increased risk.Conclusions
Among older men, low free DHT is associated with an increased risk of incident AF. Further studies are needed to explore mechanisms for this association.
SUBMITTER: Rosenberg MA
PROVIDER: S-EPMC6013387 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:AimsAtrial fibrillation (AF) is the most common sustained arrhythmia in the elderly, and shares several risk factors with diastolic dysfunction, including hypertension and advanced age. The purpose of this study is to examine diastolic dysfunction as a risk for incident AF.Methods and resultsWe examined the association of echocardiographic parameters of diastolic function with the incidence of AF in 4480 participants enrolled in the Cardiovascular Health Study, an ongoing cohort of community-dwelling older adults from four US communities. Participants underwent baseline echocardiography in 1989-1990 and were followed for incident AF on routine follow-up and hospitalizations. After 50 941 person-years of follow-up (median follow-up time 12.1 years), 1219 participants developed AF. In multivariable-adjusted age-stratified Cox models, diastolic echocardiographic parameters were significantly associated with the risk of incident AF. The most significant parameters were the Doppler peak E-wave velocity and left atrial diameter, which demonstrated a positive nonlinear association [HR 1.5 (CI 1.3-1.9) and HR 1.7 (CI 1.4-2.1) for highest vs. lowest quintile, respectively], and Doppler A-wave velocity time integral, which displayed a U-shaped relationship with the risk of AF [HR 0.7 (CI 0.6-0.9) for middle vs. lowest quintile]. Each diastolic parameter displayed a significant association with adjusted NT-proBNP levels, although the nature of the association did not entirely parallel the risk of AF. Further cluster analysis revealed unique patterns of diastolic function that may identify patients at risk for AF.ConclusionIn a community-based population of older adults, echocardiographic measures of diastolic function are significantly associated with an increased risk of AF.
| S-EPMC3345546 | biostudies-literature
Project description:In this prospective cohort of 4462 older adults, incident atrial fibrillation (AF) was not statistically significantly associated with subsequent risk of incident fracture.AF is associated with stroke, heart failure, dementia, and death, but its association with fracture is unknown. Therefore, we examined the association of incident AF with the risk of subsequent fracture in the Cardiovascular Health Study (CHS) cohort.Of the CHS participants aged ?65 years, 4462 were followed between 1991 and 2009, mean follow-up 8.8 years. Incident AF was identified by annual study electrocardiogram (ECG), hospital discharge diagnosis codes, or Medicare claims. Fractures of the hip, distal forearm, humerus, or pelvis were identified using hospital discharge diagnosis codes or Medicare claims. We used Cox proportional hazard models to estimate hazard ratios (HRs) and 95 % confidence intervals (CIs) for the association between incident AF (time-varying) and the risk of subsequent fracture. We also evaluated whether AF was associated with risk of sustaining a fall.Crude incident fracture rate was 22.9 per 1000 person-years in participants with AF and 17.7 per 1000 person-years in participants without AF. Individuals with incident AF were not at significantly higher risk of hip fracture (adjusted HR = 1.09, 95 % CI 0.83-1.42) or fracture at any selected site (adjusted HR = 0.97, 95 % CI 0.77-1.22) or risk of sustaining a fall (adjusted HR = 1.00, 95 % CI = 0.87-1.16) compared with those without AF.In this cohort of older, community-dwelling adults, incident AF was not shown to be associated with falls or hip or other fractures.
| S-EPMC5782802 | biostudies-literature
Project description:BACKGROUND:Cardiac fibrosis is thought to play a central role in the pathogenesis of atrial fibrillation (AF). Retrospective studies have suggested that circulating fibrosis biomarkers are associated with AF, but prospective studies are limited. METHODS:We measured circulating levels of 2 fibrosis biomarkers, procollagen type III, N-terminal propeptide (PIIINP) and transforming growth factor ?1 among participants of the CHS, a population-based study of older Americans. We used Cox proportional hazards and competing risks models to examine adjusted risk of incident AF over a median follow-up of 8.8 years. RESULTS:Levels of PIIINP were assessed in 2,935 participants, of whom 767 developed AF. Compared with the median PIIINP level (4.45 ?g/L), adjusted hazard ratios (95% CIs) were 0.85 (0.72-1.00) at the 10th percentile, 0.93 (0.88-0.99) at the 25th percentile, 1.04 (0.95-1.04) at the 75th percentile, and 1.07 (0.90-1.26) at the 90th. Transforming growth factor ?1 levels, assessed in 1,538 participants with 408 cases of incident AF, were not associated with AF risk. CONCLUSION:In older adults, PIIINP levels were associated with risk of incident AF in a complex manner, with an association that appeared to be positive up to median levels but with little relationship beyond that. Further studies are required to confirm and possibly delineate the mechanism for this relationship.
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Project description:AimsAtrial fibrillation (AF) is the most common sustained arrhythmia. Increased body size has been associated with AF, but the relationship is not well understood. In this study, we examined the effect of increased height on the risk of AF and explore potential mediators and implications for clinical practice.Methods and resultsWe examined data from 5860 individuals taking part in the Cardiovascular Health Study, a cohort study of older US adults followed for a median of 13.6 (women) and 10.3 years (men). Multivariate linear models and age-stratified Cox proportional hazards and risk models were used, with focus on the effect of height on both prevalent and incident AF. Among 684 (22.6%) and 568 (27.1%) incident cases in women and men, respectively, greater height was significantly associated with AF risk [hazard ratio (HR)(women) per 10 cm 1.32, confidence interval (CI) 1.16-1.50, P < 0.0001; HR(men) per 10 cm 1.26, CI 1.11-1.44, P < 0.0001]. The association was such that the incremental risk from sex was completely attenuated by the inclusion of height (for men, HR 1.48, CI 1.32-1.65, without height, and HR 0.94, CI 0.85-1.20, with height included). Inclusion of height in the Framingham model for incident AF improved discrimination. In sequential models, however, we found minimal attenuation of the risk estimates for AF with adjustment for left ventricular (LV) mass and left atrial (LA) dimension. The associations of LA and LV size measurements with AF risk were weakened when indexed to height.ConclusionIndependent from sex, increased height is significantly associated with the risk of AF.
| S-EPMC3681530 | biostudies-literature
Project description:Increased height is a known independent risk factor for atrial fibrillation (AF). However, whether genetic determinants of height influence risk is uncertain. In this candidate gene study, we examined the association of 209 height-associated single-nucleotide polymorphisms (SNPs) with incident AF in 3,309 persons of European descent from the Cardiovascular Health Study, a prospective cohort study of older adults (aged ≥ 65 years) enrolled in 1989-1990. After a median follow-up period of 13.2 years, 879 participants developed incident AF. The height-associated SNPs together explained approximately 10% of the variation in height (P = 6.0 × 10(-8)). Using an unweighted genetic height score, we found a nonsignificant association with risk of AF (per allele, hazard ratio = 1.01, 95% confidence interval: 1.00, 1.02; P = 0.06). In weighted analyses, we found that genetically predicted height was strongly associated with AF risk (per 10 cm, hazard ratio = 1.30, 95% confidence interval: 1.03, 1.64; P = 0.03). Importantly, for all models, the inclusion of actual height completely attenuated the genetic height effect. Finally, we identified 1 nonsynonymous SNP (rs1046934) that was independently associated with AF and may warrant future study. In conclusion, we found that genetic determinants of height appear to increase the risk of AF, primarily via height itself. This approach of examining SNPs associated with an intermediate phenotype should be considered as a method for identifying novel genetic targets.
| S-EPMC4082343 | biostudies-literature
Project description:Background Ceramides exhibit multiple biological activities that may influence the pathophysiological characteristics of atrial fibrillation (AF). Whether the length of the saturated fatty acid carried by the ceramide or their sphingomyelin precursors are associated with AF risk is not known. Methods and Results Among 4206 CHS (Cardiovascular Health Study) participants (mean age, 76 years; 40% men) who were free of prevalent AF at baseline, we identified 1198 incident AF cases over a median 8.7 years of follow-up. We examined 8 sphingolipid species: ceramide and sphingomyelin species with palmitic acid and species with very-long-chain saturated fatty acids: arachidic; behenic; and lignoceric. In adjusted Cox regression analyses, ceramides and sphingomyelins with very-long-chain saturated fatty acids were associated with reduced AF risk (ie, per 2-fold higher ceramide with behenic acid hazard ratio, 0.71; 95% CI, 0.59-0.86; sphingomyelin with behenic acid hazard ratio, 0.60; 95% CI, 0.46-0.77). In contrast, ceramides and sphingomyelins with palmitic acid were associated with increased AF risk (ceramide with palmitic acid hazard ratio, 1.31; 95% CI, 1.03-1.66; sphingomyelin with palmitic acid hazard ratio, 1.73; 95% CI, 1.18-2.55). Associations were attenuated with adjustment for NT-proBNP (N-terminal pro-B-type natriuretic peptide), but did not differ significantly by age, sex, race, body mass index, or history of coronary heart disease. Conclusions Our findings suggest that several ceramide and sphingomyelin species are associated with incident AF, and that these associations differ on the basis of the fatty acid. Ceramides and sphingomyelins with palmitic acid were associated with increased AF risk, whereas ceramides and sphingomyelins with very-long-chain saturated fatty acids were associated with reduced AF risk.
| S-EPMC7070192 | biostudies-literature
Project description:Experimental studies suggest that long-chain n-3 polyunsaturated fatty acids (n-3 PUFAs) may reduce the risk of atrial fibrillation (AF). Prior studies evaluating fish or n-3 PUFA consumption from dietary questionnaires and incident AF have been conflicting. Circulating levels of n-3 PUFAs provide an objective measurement of exposure.Among 3326 US men and women ?65 years of age and free of AF or heart failure at baseline, plasma phospholipid levels of eicosapentaenoic acid, docosapentaenoic acid, and docosahexaenoic acid were measured at baseline by use of standardized methods. Incident AF (789 cases) was identified prospectively from hospital discharge records and study visit ECGs during 31 169 person-years of follow-up (1992-2006). In multivariable Cox models adjusted for other risk factors, the relative risk in the top versus lowest quartile of total n-3 PUFAs (eicosapentaenoic acid+docosapentaenoic acid+docosahexaenoic acid) levels was 0.71 (95% confidence interval, 0.57-0.89; P for trend=0.004) and of DHA levels was 0.77 (95% confidence interval, 0.62-0.96; P for trend=0.01). Eicosapentaenoic acid and docosapentaenoic acid levels were not significantly associated with incident AF. Evaluated nonparametrically, both total n-3 PUFAs and docosahexaenoic acid showed graded and linear inverse associations with incidence of AF. Adjustment for intervening events such as heart failure or myocardial infarction during follow-up did not appreciably alter results.In older adults, higher circulating total long-chain n-3 PUFA and docosahexaenoic acid levels were associated with lower risk of incident AF. These results highlight the need to evaluate whether increased dietary intake of these fatty acids could be effective for the primary prevention of AF.
| S-EPMC3302663 | biostudies-other
Project description:BACKGROUND:It is unknown whether atrial fibrillation (AF) is associated with an increased risk of sudden cardiac death (SCD) in the general population. This association was examined in 2 population-based cohorts. METHODS:In the Atherosclerosis Risk in Communities (ARIC) Study, we analyzed data from 15 439 participants (baseline age, 45-64 years; 55.2% women; and 26.6% black) from baseline (1987-1989) through December 31, 2001. In the Cardiovascular Health Study (CHS), we analyzed data from 5479 participants (baseline age, ?65 years; 58.2% women; and 15.4% black) from baseline (first cohort, 1989-1990; second cohort, 1992-1993) through December 31, 2006. The main outcome was physician-adjudicated SCD, defined as death from a sudden, pulseless condition presumed to be due to a ventricular tachyarrhythmia. The secondary outcome was non-SCD (NSCD), defined as coronary heart disease death not meeting SCD criteria. We used Cox proportional hazards models to assess the association between AF and SCD/NSCD, adjusting for baseline demographic and cardiovascular risk factors. RESULTS:In the ARIC Study, 894 AF, 269 SCD, and 233 NSCD events occurred during follow-up (median, 13.1 years). The crude incidence rates of SCD were 2.89 per 1000 person-years (with AF) and 1.30 per 1000 person-years (without AF). The multivariable hazard ratios (HRs) (95% CIs) of AF for SCD and NSCD were 3.26 (2.17-4.91) and 2.43 (1.60-3.71), respectively. In the CHS, 1458 AF, 292 SCD, and 581 NSCD events occurred during follow-up (median, 13.1 years). The crude incidence rates of SCD were 12.00 per 1000 person-years (with AF) and 3.82 per 1000 person-years (without AF). The multivariable HRs (95% CIs) of AF for SCD and NSCD were 2.14 (1.60-2.87) and 3.10 (2.58-3.72), respectively. The meta-analyzed HRs (95% CIs) of AF for SCD and NSCD were 2.47 (1.95-3.13) and 2.98 (2.52-3.53), respectively. CONCLUSIONS:Incident AF is associated with an increased risk of SCD and NSCD in the general population. Additional research to identify predictors of SCD in patients with AF is warranted.
| S-EPMC3578214 | biostudies-literature
Project description:Background The Framingham Risk Score estimates the 10-year risk of cardiovascular events. However, it performs poorly in older adults. We evaluated the incremental benefit of adding high-sensitivity cardiac troponin I (hs-cTnI) to the Framingham Risk Score. Methods and Results The HIMS (Health in Men Study) is a cohort study of community-dwelling men aged 70 to 89 years in Western Australia. Participants were identified from the electoral roll, with a subset undergoing plasma analysis. Hs- cTnI (Abbott Architect i2000 SR ) was measured in 1151 men without prior cardiovascular disease. The Western Australia Data Linkage System was used to identify incident cardiovascular events. After 10 years of follow-up, 252 men (22%) had a cardiovascular event ( CVE +) and 899 did not (CVE-). The Framingham Risk Score placed 148 (59%) CVE + and 415 (46%) CVE- in the high-risk category. In CVE - men, adding hs- cTnI affected the risk categories of 244 (27.2%) men, with 64.8% appropriately reclassified to a lower and 35.2% to a higher category, which decreased the number of high-risk men in the CVE- to 39%. In CVE + men, adding hs- cTnI affected the risk categories of 61 (24.2%), with 50.8% appropriately reclassified to a higher and 49.2% to a lower category and 82.5% remaining above the 15% risk treatment threshold. The net reclassification index was 0.305 ( P<0.001). Adding hs- cTnI increased the C-statistic modestly from 0.588 (95% CI , 0.552-0.624) to 0.624 (95% CI , 0.589-0.659) and improved model fit (likelihood ratio test, P<0.001). Conclusions Adding hs- cTnI to the Framingham Risk Score provided incremental prognostic benefit in older men, especially aiding reclassification of individuals into a lower risk category.
| S-EPMC6474925 | biostudies-literature
Project description:BackgroundLittle is known about the relationships of dihydrotestosterone (DHT), a more potent androgen than testosterone (T), with bone mineral density (BMD) and fracture risk. Our objectives were to evaluate the relationships of T, DHT and sex hormone binding globulin (SHBG) with BMD, fracture risk, and lean body mass (LBM).MethodsWe evaluated 1128 older men free of cardiovascular disease in a prospective cohort study using data from the Cardiovascular Health Study. T and DHT were measured by liquid chromatography-tandem mass spectrometry and SHBG by fluoroimmunoassay. Our outcomes included incident hip fracture (n = 106) over a median of 10.2 years and BMD and LBM by dual-energy x-ray absorptiometry (n = 439).ResultsIn Cox regression models mutually adjusted for T, SHBG, and covariates, each standard deviation increment in DHT (0.23 ng/ml) was associated with a 26% lower risk of hip fracture (adjusted hazard ratio [aHR] 0.74, 95% confidence interval (CI) 0.55-1.00, p = 0.049). Similarly, SHBG was associated with fracture in mutually adjusted models (aHR HR 1.26, 95% CI, 1.01-1.58, p = 0.045). In contrast, T (aHR, 1.16, 95% CI, 0.86-1.56, p = 0.324) was not significantly associated with fracture in mutually adjusted models. T, DHT and SHBG were not associated with BMD. T and DHT were both positively associated with LBM in individual models.ConclusionsIn older men, DHT was inversely associated with hip fracture risk and SHBG was positively associated with hip fracture risk, while T was not. Future studies should elucidate the mechanisms by which DHT affects bone health.
| S-EPMC9060596 | biostudies-literature