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1. New Insights into the Role of Visit-to-Visit Glycemic Variability and Blood Pressure Variability in Cardiovascular Disease Risk

   https://doi.org/10.1007/s11886-021-01454-x  

   Zhou, Jin J. ; Nuyujukian, Daniel S. ; Reaven, Peter D. ( April 2021 , Current Cardiology Reports)
2. Interactions Between Enhanced Polygenic Risk Scores and Lifestyle for Cardiovascular Disease, Diabetes, and Lipid Levels

   https://doi.org/10.1161/CIRCGEN.120.003128  

   Ye, Yixuan ; Chen, Xi ; Han, James ; Jiang, Wei ; Natarajan, Pradeep ; Zhao, Hongyu ( February 2021 , Circulation: Genomic and Precision Medicine)

   null (Ed.)

   Background: Both lifestyle and genetic factors confer risk for cardiovascular diseases, type 2 diabetes, and dyslipidemia. However, the interactions between these 2 groups of risk factors were not comprehensively understood due to previous poor estimation of genetic risk. Here we set out to develop enhanced polygenic risk scores (PRS) and systematically investigate multiplicative and additive interactions between PRS and lifestyle for coronary artery disease, atrial fibrillation, type 2 diabetes, total cholesterol, triglyceride, and LDL-cholesterol. Methods: Our study included 276 096 unrelated White British participants from the UK Biobank. We investigated several PRS methods (P+T, LDpred, PRS continuous shrinkage, and AnnoPred) and showed that AnnoPred achieved consistently improved prediction accuracy for all 6 diseases/traits. With enhanced PRS and combined lifestyle status categorized by smoking, body mass index, physical activity, and diet, we investigated both multiplicative and additive interactions between PRS and lifestyle using regression models. Results: We observed that healthy lifestyle reduced disease incidence by similar multiplicative magnitude across different PRS groups. The absolute risk reduction from lifestyle adherence was, however, significantly greater in individuals with higher PRS. Specifically, for type 2 diabetes, the absolute risk reduction from lifestyle adherence was 12.4% (95% CI, 10.0%–14.9%) in the top 1% PRS versus 2.8% (95% CI, 2.3%–3.3%) in the bottom PRS decile, leading to a ratio of >4.4. We also observed a significant interaction effect between PRS and lifestyle on triglyceride level. Conclusions: By leveraging functional annotations, AnnoPred outperforms state-of-the-art methods on quantifying genetic risk through PRS. Our analyses based on enhanced PRS suggest that individuals with high genetic risk may derive similar relative but greater absolute benefit from lifestyle adherence. 

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3. DNA Methylation Mediates the Association Between Individual and Neighborhood Social Disadvantage and Cardiovascular Risk Factors

   https://doi.org/10.3389/fcvm.2022.848768  

   Wang, Yi Zhe ; Zhao, Wei ; Ammous, Farah ; Song, Yanyi ; Du, Jiacong ; Shang, Lulu ; Ratliff, Scott M. ; Moore, Kari ; Kelly, Kristen M. ; Needham, Belinda L. ; et al ( May 2022 , Frontiers in Cardiovascular Medicine)

   Low socioeconomic status (SES) and living in a disadvantaged neighborhood are associated with poor cardiovascular health. Multiple lines of evidence have linked DNA methylation to both cardiovascular risk factors and social disadvantage indicators. However, limited research has investigated the role of DNA methylation in mediating the associations of individual- and neighborhood-level disadvantage with multiple cardiovascular risk factors in large, multi-ethnic, population-based cohorts. We examined whether disadvantage at the individual level (childhood and adult SES) and neighborhood level (summary neighborhood SES as assessed by Census data and social environment as assessed by perceptions of aesthetic quality, safety, and social cohesion) were associated with 11 cardiovascular risk factors including measures of obesity, diabetes, lipids, and hypertension in 1,154 participants from the Multi-Ethnic Study of Atherosclerosis (MESA). For significant associations, we conducted epigenome-wide mediation analysis to identify methylation sites mediating the relationship between individual/neighborhood disadvantage and cardiovascular risk factors using the JT-Comp method that assesses sparse mediation effects under a composite null hypothesis. In models adjusting for age, sex, race/ethnicity, smoking, medication use, and genetic principal components of ancestry, epigenetic mediation was detected for the associations of adult SES with body mass index (BMI), insulin, and high-density lipoprotein cholesterol (HDL-C), as well as for the association between neighborhood socioeconomic disadvantage and HDL-C at FDRq< 0.05. The 410 CpG mediators identified for the SES-BMI association were enriched for CpGs associated with gene expression (expression quantitative trait methylation loci, or eQTMs), and corresponding genes were enriched in antigen processing and presentation pathways. For cardiovascular risk factors other than BMI, most of the epigenetic mediators lost significance after controlling for BMI. However, 43 methylation sites showed evidence of mediating the neighborhood socioeconomic disadvantage and HDL-C association after BMI adjustment. The identified mediators were enriched for eQTMs, and corresponding genes were enriched in inflammatory and apoptotic pathways. Our findings support the hypothesis that DNA methylation acts as a mediator between individual- and neighborhood-level disadvantage and cardiovascular risk factors, and shed light on the potential underlying epigenetic pathways. Future studies are needed to fully elucidate the biological mechanisms that link social disadvantage to poor cardiovascular health.

    

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4. Relationship of cardiovascular disease risk and hearing loss in a clinical population

   https://doi.org/10.1038/s41598-023-28599-9  

   Baiduc, Rachael R. ; Sun, Joshua W. ; Berry, Caitlin M. ; Anderson, Melinda ; Vance, Eric A. ( December 2023 , Scientific Reports)

   Abstract Hearing loss has been associated with individual cardiovascular disease (CVD) risk factors and, to a lesser extent, CVD risk metrics. However, these relationships are understudied in clinical populations. We conducted a retrospective study of electronic health records to evaluate the relationship between hearing loss and CVD risk burden. Hearing loss was defined as puretone average (PTA 0.5,1,2,4 ) > 20 dB hearing level (HL). Optimal CVD risk was defined as nondiabetic, nonsmoking, systolic blood pressure (SBP) < 120 and diastolic (D)BP < 80 mm Hg, and total cholesterol < 180 mg/dL. Major CVD risk factors were diabetes, smoking, hypertension, and total cholesterol ≥ 240 mg/dL or statin use. We identified 6332 patients (mean age = 62.96 years; 45.5% male); 64.0% had hearing loss. Sex-stratified logistic regression adjusted for age, noise exposure, hearing aid use, and body mass index examined associations between hearing loss and CVD risk. For males, diabetes, hypertension, smoking, and ≥ 2 major CVD risk factors were associated with hearing loss. For females, diabetes, smoking, and ≥ 2 major CVD risk factors were significant risk factors. Compared to those with no CVD risk factors, there is a higher likelihood of hearing loss in patients with ≥ 2 major CVD risk factors. Future research to better understand sex dependence in the hearing loss-hypertension relationship is indicated. 

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5. Testosterone moderates the effects of social support on cardiovascular disease risk factors among older US men

   https://doi.org/10.1002/ajhb.23248  

   Gettler, Lee T. ; Sarma, Mallika S. ; Gengo, Rieti G. ; Oka, Rahul C. ; McKenna, James J. ( May 2019 , American Journal of Human Biology)

   Social support positively affects health through pathways such as shaping intrapersonal emotional and psychological well‐being. Lower testosterone often interrelates with psychological and behavioral orientations that are beneficial to participation in emotionally supportive relationships. Yet, little research has considered the ways in which testosterone may contribute to health outcomes related to emotional support.

   We draw on testosterone, social support data, and cardiovascular disease (CVD)‐relevant indicators (inflammatory markers; blood pressure [BP]) from older men (n = 366) enrolled in the National Health and Nutrition Examination Survey, a US nationally representative study. We test whether men's testosterone moderates associations between emotional social support and markers related to CVD risk.

   For men with relatively lower testosterone, higher levels of social support predicted lower white blood cell (WBC) counts, consistent with reduced inflammation. In contrast, men with higher testosterone exhibited elevated WBC counts with greater support. In a diverging pattern, men with lower testosterone had higher systolic and diastolic BP with higher support, whereas the slopes for systolic and diastolic BP, respectively, were comparatively flatter for men with higher levels of testosterone.

   We suggest that our findings are theoretically consistent with the idea that testosterone helps shape intrapersonal and interpersonal experiences and perceptions of men's emotional support networks, thereby affecting the health implications of that support. The somewhat divergent results for WBC count vs BP highlight the need for inclusion of other neuroendocrine markers alongside testosterone as well as refined measures of perceived and received support.

    

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