Secondhand smoke exposure is associated with abnormal P-wave axis.

OBJECTIVES: Secondhand smoke exposure (SHSE) is associated with increased risk of cerebrovascular accident (CVA). Abnormal P-wave axis (aPWA) is a marker for atriopathy that is also associated with CVA risk. We hypothesized that SHSE is associated with aPWA. METHODS: This analysis included 5986 non-smokers (age 61.7 ± 13.8 years, 45.8% men, 77.4% Whites) from the Third National Health and Nutrition Examination Survey. SHSE was defined as serum cotinine ≥1 ng/ml aPWA was defined as any P-wave axis outside of 0-75°. Multivariable logistic regression was used to examine the association between SHSE and aPWA, overall and among subgroups stratified by demographics and comorbidities. RESULTS: About 18.5% (n = 1109) of the participants had SHSE. aPWA was more prevalent among those with SHSE than those without (23.9% versus 19.8%, respectively, P-value = 0.003). In a model adjusted for sociodemographic and potential confounders, presence (versus absence) of SHSE was associated with increased odds of aPWA (odds ratio [95% confidence interval]: 1.28 [1.09, 1.50]; P-value = 0.003). This association was stronger among Whites vs non-Whites (interaction P-value = 0.04) and non-obese versus obese (interaction P-value = 0.04). Higher levels of serum cotinine were associated with increased odds of aPWA. Compared with serum cotinine level <1 ng/ml, serum cotinine ≥3 ng/ml and ≥6 ng/ml were associated with 35% (P-value = 0.002) and 38% (P-value = 0.002) increased odds of aPWA, respectively. CONCLUSIONS: SHSE is associated with abnormal atrial conduction, measured as aPWA, with possible effect modification by ethnicity and obesity. These findings underscore the harmful effects of SHSE on cardiovascular health which merits a personalized risk assessment when counseling patients on SHSE.

Testosterone use and shorter electrocardiographic QT interval duration in men living with and without HIV.

OBJECTIVES: Testosterone usage (T-use) may alter risk factors for sudden cardiac death in men living with HIV (MLWH). Electrocardiographic QT interval prolongation, which could potentiate ventricular arrhythmias, has previously been associated with HIV infection and, separately, with low testosterone levels. We investigated whether T-use shortens the QT interval duration in MLWH and HIV-uninfected men. METHODS: We utilized data from the Multicenter AIDS Cohort Study, a prospective, longitudinal study of HIV infection among men who have sex with men. Multivariable linear regression analyses were used to evaluate associations between T-use and corrected QT interval (QTc) duration. RESULTS: Testosterone usage was more common in MLWH compared with HIV-uninfected men (19% vs. 9%). In a multivariable regression analysis, T-use was associated with a 5.7 ms shorter QT interval [95% confidence interval (CI): -9.5 to -1.9; P = 0.003). Furthermore, stronger associations were observed for prolonged duration of T-use and recent timing of T-use. CONCLUSIONS: This study is the first known analysis of T-use and QTc interval in MLWH. Overall, our data demonstrate that recent T-use is associated with a shorter QTc interval. Increased T-use duration above a threshold of ≥ 50% of visits in the preceding 5 years was associated with a shorter QTc interval while lesser T-use duration was not.

Secondhand Smoke Exposure is Associated with Prevalent Heart Failure: Longitudinal Examination of the National Health and Nutrition Examination Survey.

INTRODUCTION: Serum cotinine is a sensitive and specific biomarker for tobacco exposure including second-hand smoke exposure (SHS). We sought to examine whether SHS is associated with heart failure (HF) among non-hospitalized adults. METHODS: This analysis included 11 219 non-smokers (age 48.4 ± 20.5 years, 55.9% women, 70.5% whites) from the United States Third National Health and Nutrition Examination (NHANES) years 1988-1994. SHS was defined as serum cotinine ≥1 ng/mL. To assess dose-response, cut-points of serum cotinine ≥3 ng/mL and ≥6 ng/mL were used. Multivariable logistic regression was used to examine the association between SHS and HF. The consistency of this association was tested among subgroups stratified by race, gender, and comorbidities. NHANES years 2003-2006 were examined for longitudinal comparison. RESULTS: 18.9% (n = 2125) of participants had SHS exposure while 3.7% (n = 416) had HF. After adjusting for covariates, SHS was associated with a 35% increased odds of HF with a dose-response relationship between levels of serum cotinine and HF. This association was stronger in males than females (interaction p-value = 0.03) and those with a history of CVD versus those without (interaction p-value < 0.001). This association persisted in the NHANES 2003-2006 analysis. CONCLUSION: There is a dose-response relationship between SHS and HF with possible effect modification by gender and prior CVD. This is a novel finding that underscores the harmful effects of passive smoking on the cardiovascular system and highlights the needs for further prohibition of smoking in public areas and a personalized risk assessment among high-risk groups, especially in regions with less-stringent public health policies. IMPLICATIONS: This study showed a novel association between secondhand smoke exposure and prevalent heart failure among non-smokers, adding to the list of harmful cardiovascular manifestations of secondhand smoke exposure. This was more apparent in men and those with a prior history of cardiovascular disease. Heart failure is a debilitating disease process, so this finding has important policy implications in low-income countries and poor communities with less-stringent health policies because they are known to have the highest levels of exposure. Smoke-free policies targeting these regions would thus yield substantial public health benefits.

Large-scale pharmacogenomic study of sulfonylureas and the QT, JT and QRS intervals: CHARGE Pharmacogenomics Working Group.

Sulfonylureas, a commonly used class of medication used to treat type 2 diabetes, have been associated with an increased risk of cardiovascular disease. Their effects on QT interval duration and related electrocardiographic phenotypes are potential mechanisms for this adverse effect. In 11 ethnically diverse cohorts that included 71 857 European, African-American and Hispanic/Latino ancestry individuals with repeated measures of medication use and electrocardiogram (ECG) measurements, we conducted a pharmacogenomic genome-wide association study of sulfonylurea use and three ECG phenotypes: QT, JT and QRS intervals. In ancestry-specific meta-analyses, eight novel pharmacogenomic loci met the threshold for genome-wide significance (P<5 × 10-8), and a pharmacokinetic variant in CYP2C9 (rs1057910) that has been associated with sulfonylurea-related treatment effects and other adverse drug reactions in previous studies was replicated. Additional research is needed to replicate the novel findings and to understand their biological basis.

Pharmacogenomics study of thiazide diuretics and QT interval in multi-ethnic populations: the cohorts for heart and aging research in genomic epidemiology.

Thiazide diuretics, commonly used antihypertensives, may cause QT interval (QT) prolongation, a risk factor for highly fatal and difficult to predict ventricular arrhythmias. We examined whether common single-nucleotide polymorphisms (SNPs) modified the association between thiazide use and QT or its component parts (QRS interval, JT interval) by performing ancestry-specific, trans-ethnic and cross-phenotype genome-wide analyses of European (66%), African American (15%) and Hispanic (19%) populations (N=78 199), leveraging longitudinal data, incorporating corrected standard errors to account for underestimation of interaction estimate variances and evaluating evidence for pathway enrichment. Although no loci achieved genome-wide significance (P<5 × 10-8), we found suggestive evidence (P<5 × 10-6) for SNPs modifying the thiazide-QT association at 22 loci, including ion transport loci (for example, NELL1, KCNQ3). The biologic plausibility of our suggestive results and simulations demonstrating modest power to detect interaction effects at genome-wide significant levels indicate that larger studies and innovative statistical methods are warranted in future efforts evaluating thiazide-SNP interactions.

Baseline cardiovascular risk in the INSIGHT Strategic Timing of AntiRetroviral Treatment (START) trial.

OBJECTIVES: The Strategic Timing of AntiRetroviral Treatment (START) trial has recruited antiretroviral-naïve individuals with high CD4 cell counts from all regions of the world. We describe the distribution of cardiovascular disease (CVD) risk factors, overall and by geographical region, at study baseline. METHODS: The distribution of CVD risk factors was assessed and compared by geographical region among START participants who had a baseline electrocardiogram (n = 4019; North America, 11%; Europe/Australia/Israel, 36%; South America, 26%; Asia, 4%; Africa, 23%; median age 36 years; 26% female). RESULTS: About 58.3% (n = 2344) of the participants had at least one CVD risk factor and 18.9% (n = 761) had two or more. The most common CVD risk factors were current smoking (32%), hypertension (19.3%) and obesity (16.5%). There were significant differences in the prevalence of CVD risk factors among geographical regions. The prevalence of at least one risk factor across regions was as follows: North America, 70.0%; Europe/Australia/Israel, 65.1%; South America, 49.4%; Asia, 37.0%; Africa, 55.8% (P-value < 0.001). Significant regional differences were also observed when risk factors were used as part of the Framingham and Data Collection on Adverse events of Anti-HIV Drugs (D:A:D) risk scores or used to define a favourable risk profile. CONCLUSIONS: CVD risk factors are common among START participants, and their distribution varies by geographical region. Better understanding of how and why CVD risk factors develop in people with HIV infection and their geographical distributions could shed light on appropriate strategies for CVD prevention and may inform the interpretation of the results of START, as CVD is expected to be a major fraction of the primary endpoints observed.

Resting heart rate and incident atrial fibrillation: A stratified Mendelian randomization in the AFGen consortium.

BACKGROUND: Both elevated and low resting heart rates are associated with atrial fibrillation (AF), suggesting a U-shaped relationship. However, evidence for a U-shaped causal association between genetically-determined resting heart rate and incident AF is limited. We investigated potential directional changes of the causal association between genetically-determined resting heart rate and incident AF. METHOD AND RESULTS: Seven cohorts of the AFGen consortium contributed data to this meta-analysis. All participants were of European ancestry with known AF status, genotype information, and a heart rate measurement from a baseline electrocardiogram (ECG). Three strata of instrumental variable-free resting heart rate were used to assess possible non-linear associations between genetically-determined resting heart rate and the logarithm of the incident AF hazard rate: <65; 65-75; and >75 beats per minute (bpm). Mendelian randomization analyses using a weighted resting heart rate polygenic risk score were performed for each stratum. We studied 38,981 individuals (mean age 59±10 years, 54% women) with a mean resting heart rate of 67±11 bpm. During a mean follow-up of 13±5 years, 4,779 (12%) individuals developed AF. A U-shaped association between the resting heart rate and the incident AF-hazard ratio was observed. Genetically-determined resting heart rate was inversely associated with incident AF for instrumental variable-free resting heart rates below 65 bpm (hazard ratio for genetically-determined resting heart rate, 0.96; 95% confidence interval, 0.94-0.99; p = 0.01). Genetically-determined resting heart rate was not associated with incident AF in the other two strata. CONCLUSIONS: For resting heart rates below 65 bpm, our results support an inverse causal association between genetically-determined resting heart rate and incident AF.