Differences in Epidemiology and Risk Factors for Atrial Fibrillation Between Women and Men

Atrial fibrillation (AF), the most common sustained cardiac arrhythmia, is one of the most frequent cardiovascular diseases among both women and men. Although age-adjusted AF incidence and prevalence is larger among men, women are older at the time of AF diagnosis and have larger risk for AF-associated adverse outcomes such as morality and stroke. Based on evidence from epidemiological studies, elevated body mass index seems to confer a higher risk of AF among men. However, evidence regarding sex differences in the association between diabetes mellitus, elevated blood pressure, and dysglycemia with AF remains conflicting. While men with AF have larger burden of coronary artery disease, women with AF tend to have a larger prevalence of heart failure and valvular heart disease. Recently, several women-specific risk factors including pregnancy and its complications and number of children have been associated with AF. Earlier age at menopause, despite being a strong marker of adverse cardiometabolic risk, does not seem to be associated with increased risk of AF. To reduce the AF burden in both genders, better understanding of the differences between women and men with regard to AF is central. Large-scale studies are needed to separately investigate and report on women and men. Besides observations from epidemiological and clinical studies, to improve our understanding of sexual dimorphism in AF, sufficiently large genome-wide association studies as well as well-powered Mendelian randomization studies are essential to shed light on the sex-specific nature of the associations of risk factors with AF

Subclinical Measures of Atherosclerosis: Genetics and Cardiovascular Risk Prediction

__Abstract__ Atherosclerosis is a chronic, progressive, systematic condition with a long asymptomatic phase. Atherosclerosis develops gradually as a subclinical condition over the life course and eventually becomes clinically apparent as ischemic heart disease, cerebrovascular disease, or peripheral arterial disease. Subclinical atherosclerosis, or preclinical atherosclerosis, refers to the early stage of the atherosclerosis process when within the vascular walls “something has started to change”, yet the cardiovascular disease is not clinically evident. Detecting the forthcoming disease at this stage, before the clinical manifestations, has gained interest over the past decade. Coronary artery calcifi cation, carotid intima-media thickness, and ankle- brachial index are three measures of subclinical atherosclerosis burden that can be detected and quantifi ed non-invasively

Genetic Research and Women’s Heart Disease: a Primer

PURPOSE OF REVIEW: This review provides a brief synopsis of sexual dimorphism in atherosclerosis with an emphasis on genetic studies aimed to better understand the atherosclerotic process and clinical outcomes in women. Such studies are warranted because development of atherosclerosis, impact of several traditional risk factors, and burden of coronary heart disease (CHD) differ between women and men. RECENT FINDINGS: While most candidate gene studies pool women and men and adjust for sex, some sex-specific studies provide evidence of association between candidate genes and prevalent and incident CHD in women. So far, most genome-wide association studies (GWAS) also failed to consider sex-specific associations. The few GWAS focused on women tended to have small sample sizes and insufficient power to reject the null hypothesis of no association even if associations exist. SUMMARY: Few studies consider that sex can modify the effect of gene variants on CHD. Sufficiently large-scale genetic studies in women of different race/ethnic groups, taking into account possible gene-gene and gene-environment interactions as well as hormone-mediated epigenetic mechanisms, are needed. Using the same disease definition for women and men might not be appropriate. Accurate phenotyping and inclusion of relevant outcomes in women, together with targeting the entire spectrum of atherosclerosis, could help address the contribution of genes to sexual dimorphism in atherosclerosis. Discovered genetic loci should be taken forward for replication and functional studies to elucidate the plausible underlying biological mechanisms. A better understanding of the etiology of atherosclerosis in women would facilitate future prevention efforts and interventions

Sex-specific normal values and determinants of infrarenal abdominal aortic diameter among non-aneurysmal elderly population

To establish age- and sex-specific distribution of the infrarenal abdominal aortic diameters (IAD) among non-aneurysmal elderly population and to investigate the associations between traditional cardiovascular risk factors and IAD in men and women. We included 4032 participants (mean age 67.2 years; 60.4% women) from the population-based Rotterdam Study, free of cardiovascular disease, who underwent IAD ultrasound assessment between 2009–2014. Linear regression analysis was used to identify determinants of IAD. The medians (inter-quartile range) of absolute IAD and body surface area (BSA)-adjusted IAD were 17.0 (15.0–18.0) mm and 9.3 (8.5–10.2) mm for women and 19.0 (18.0–21.0) mm and 9.4 (8.6–10.3) mm for men, respectively. There was a non-linear relationship between age and IAD. IAD increased steeply with advancing age and up to 70 years. After around 75 years of age, the diameter values reached a plateau. Waist circumference and diastolic blood pressure were associated with larger diameters in both sexes. Body mass index [Effect estimate (95% CI): 0.04 (0.00 to 0.08)], systolic blood pressure [− 0.01(− 0.02 to 0.00)], current smoking [0.35 (0.06 to 0.65)], total cholesterol levels [− 0.21 (− 0.31 to − 0.11)], and lipid-lowering medication [− 0.43 (− 0.67 to − 0.19)] were significantly associated with IAD in women. Sex differences in IAD values diminished after taking BSA into account. The increase in diameters was attenuated after 70 years. Differences were observed in the associations of several cardiovascular risk factors with IAD among men and women.</p

Sex-specific normal values and determinants of infrarenal abdominal aortic diameter among non-aneurysmal elderly population

To establish age- and sex-specific distribution of the infrarenal abdominal aortic diameters (IAD) among non-aneurysmal elderly population and to investigate the associations between traditional cardiovascular risk factors and IAD in men and women. We included 4032 participants (mean age 67.2 years; 60.4% women) from the population-based Rotterdam Study, free of cardiovascular disease, who underwent IAD ultrasound assessment between 2009–2014. Linear regression analysis was used to identify determinants of IAD. The medians (inter-quartile range) of absolute IAD and body surface area (BSA)-adjusted IAD were 17.0 (15.0–18.0) mm and 9.3 (8.5–10.2) mm for women and 19.0 (18.0–21.0) mm and 9.4 (8.6–10.3) mm for men, respectively. There was a non-linear relationship between age and IAD. IAD increased steeply with advancing age and up to 70 years. After around 75 years of age, the diameter values reached a plateau. Waist circumference and diastolic blood pressure were associated with larger diameters in both sexes. Body mass index [Effect estimate (95% CI): 0.04 (0.00 to 0.08)], systolic blood pressure [− 0.01(− 0.02 to 0.00)], current smoking [0.35 (0.06 to 0.65)], total cholesterol levels [− 0.21 (− 0.31 to − 0.11)], and lipid-lowering medication [− 0.43 (− 0.67 to − 0.19)] were significantly associated with IAD in women. Sex differences in IAD values diminished after taking BSA into account. The increase in diameters was attenuated after 70 years. Differences were observed in the associations of several cardiovascular risk factors with IAD among men and women.</p

Progression of arterial calcifications:what, where, and in whom?

Objectives: There is a lack of information on the development of arteriosclerosis over time. This study aims to assess long-term sex-specific changes in arterial calcifications in five arteries, and the influence of cardiovascular risk factors hereon. Methods: From a population-based cohort, 807 participants (mean baseline age, 65.8; SD, 4.2) underwent a non-contrast computed tomography (CT) examination between 2003 and 2006, and after a median follow-up of 14 years. We assessed incidences and changes in volumes of coronary artery calcification (CAC), aortic arch calcification (AAC), extracranial (ECAC) and intracranial carotid artery calcification (ICAC), and vertebrobasilar artery calcification (VBAC). We investigated the simultaneous presence of severe progression (upper quartile of percentual change volumes). Associations of cardiovascular risk factors with changes in calcification volumes were assessed using multivariate linear regression models. Results: The difference in AAC was most substantial; the median volume (mm3) increased from of 129 to 916 in men and from 93 to 839 in women. For VBAC, no change in volumes was observed though more than a quarter of participants without baseline VBAC developed VBAC during follow-up. Severe progression was most often observed in only one artery at the same time. Hypertension was most consistently associated with increase in calcifications. Associations of diabetes, hypercholesterolemia, and smoking with changes in calcifications varied across arteries and sex. Conclusions: We found a considerable incidence and increase in volumes of calcifications in different arteries, over a 14-year time interval. Cardiovascular risk factors were associated with increase of calcifications with sex-specific differential effects across arteries. Clinical relevance statement: There is a considerable incidence and increase in volumes of calcifications in different arteries, over a 14-year time interval. Cardiovascular risk factors are associated with increase of calcifications with sex-specific differential effects across arteries; thus, assessing changes in only one artery may thus not provide a good reflection of the systemic development of arteriosclerosis. Key Points: • Assessing change in arterial calcification in only one artery does not reflect the systemic development of arterial calcification. • Cardiovascular risk factors are associated with progression of arterial calcifications. • Progression of arterial calcification is sex and artery-specific. Graphical Abstract: [Figure not available: see fulltext.].</p

Progression of arterial calcifications:what, where, and in whom?

Objectives: There is a lack of information on the development of arteriosclerosis over time. This study aims to assess long-term sex-specific changes in arterial calcifications in five arteries, and the influence of cardiovascular risk factors hereon. Methods: From a population-based cohort, 807 participants (mean baseline age, 65.8; SD, 4.2) underwent a non-contrast computed tomography (CT) examination between 2003 and 2006, and after a median follow-up of 14 years. We assessed incidences and changes in volumes of coronary artery calcification (CAC), aortic arch calcification (AAC), extracranial (ECAC) and intracranial carotid artery calcification (ICAC), and vertebrobasilar artery calcification (VBAC). We investigated the simultaneous presence of severe progression (upper quartile of percentual change volumes). Associations of cardiovascular risk factors with changes in calcification volumes were assessed using multivariate linear regression models. Results: The difference in AAC was most substantial; the median volume (mm3) increased from of 129 to 916 in men and from 93 to 839 in women. For VBAC, no change in volumes was observed though more than a quarter of participants without baseline VBAC developed VBAC during follow-up. Severe progression was most often observed in only one artery at the same time. Hypertension was most consistently associated with increase in calcifications. Associations of diabetes, hypercholesterolemia, and smoking with changes in calcifications varied across arteries and sex. Conclusions: We found a considerable incidence and increase in volumes of calcifications in different arteries, over a 14-year time interval. Cardiovascular risk factors were associated with increase of calcifications with sex-specific differential effects across arteries. Clinical relevance statement: There is a considerable incidence and increase in volumes of calcifications in different arteries, over a 14-year time interval. Cardiovascular risk factors are associated with increase of calcifications with sex-specific differential effects across arteries; thus, assessing changes in only one artery may thus not provide a good reflection of the systemic development of arteriosclerosis. Key Points: • Assessing change in arterial calcification in only one artery does not reflect the systemic development of arterial calcification. • Cardiovascular risk factors are associated with progression of arterial calcifications. • Progression of arterial calcification is sex and artery-specific. Graphical Abstract: [Figure not available: see fulltext.].</p

The healthy beverage index is not associated with insulin resistance, prediabetes and type 2 diabetes risk in the Rotterdam Study

Purpose:Whether beverage quality affects changes in glycaemic traits and type 2 diabetes (T2D) risk is unknown. We examined associations of a previously developed Healthy Beverage Index (HBI) with insulin resistance, and risk of prediabetes and T2D. Methods: We included 6769 participants (59% female, 62.0 ± 7.8 years) from the Rotterdam Study cohort free of diabetes at baseline. Diet was assessed using food-frequency questionnaires at baseline. The HBI included 10 components (energy from beverages, meeting fluid requirements, water, coffee and tea, low-fat milk, diet drinks, juices, alcohol, full-fat milk, and sugar-sweetened beverages), with a total score ranging from 0 to 100. A higher score represents a healthier beverage pattern. Data on study outcomes were available from 1993 to 2015. Multivariable linear mixed models and Cox proportional-hazards regression models were used to examine associations of the HBI (per 10 points increment) with two measurements of HOMA-IR (a proxy for insulin resistance), and risk of prediabetes and T2D. Results: During follow-up, we documented 1139 prediabetes and 784 T2D cases. Mean ± SD of the HBI was 66.8 ± 14.4. Higher HBI score was not associated with HOMA-IR (β: 0.003; 95% CI − 0.007, 0.014), or with risk of prediabetes (HR: 1.01; 95% CI 0.97, 1.06), or T2D (HR: 1.01; 95% CI 0.96, 1.07). Conclusion: Our findings suggest no major role for overall beverage intake quality assessed with the HBI in insulin resistance, prediabetes and T2D incidence. The HBI may not be an adequate tool to assess beverage intake quality in our population.</p