Over the last 2 decades, mounting evidence has highlighted differences between women and men in the manifestation of common cardiovascular diseases (CVDs). A prevailing perception is that women are affected by the same types of CVD that affect men, albeit with delayed onset and often atypical symptoms. However, with respect to ischemic heart disease (IHD) and heart failure (HF), it is now increasingly recognized that women are more likely than men to develop coronary microvascular dysfunction (CMD) and HF with preserved ejection fraction (HFpEF), especially in the setting of vascular risk factors such as hypertension.^1-3 In effect, the broadening clinical experience of managing CVD conditions that manifest differently between women and men, combined with the accumulating data on sex-specific CVD presentations, suggest that cardiovascular pathophysiology is likely to be fundamentally different between the sexes. If true, then intrinsic sexual dimorphism in cardiovascular pathophysiology must plausibly extend from sexual dimorphism in cardiovascular physiology. To better understand how sex differences in earlier-life cardiovascular physiology may precede sex differences in later-life cardiovascular pathophysiology, we used population-based multicohort data to conduct a comprehensive sex-specific analysis of blood pressure (BP) trajectories over the life course, given that measures of BP elevation in the community represent the single most accessible metric of vascular aging as well as the largest contributor to IHD and HF risk in both women and men.^4-7

It has been reported that the triglyceride-glucose (TyG) index may serve as a simple and credible surrogate marker of insulin resistance (IR). However, its association with macrovascular and microvascular damage is unclear. Accordingly, the objective of the present study is to investigate the association of macrovascular and microvascular damage with the TyG index. A total of 2830 elderly participants from the Northern Shanghai Study (NSS) were enrolled. The TyG index was calculated as ln[fasting triglycerides (mg/dL) × fasting glucose (mg/dL)/2]. Parameters of vascular damage, including carotid-femoral pulse wave velocity (cf-PWV), brachial-ankle pulse wave velocity (ba-PWV), ankle–brachial index (ABI), carotid intima–media thickness (CMT), carotid plaque, estimated glomerular filtration rate (eGFR) and the urine albumin-to-creatinine ratio (UACR), were measured and calculated. In univariate logistic regression, an increased TyG index was associated with a higher risk of cf-PWV > 10 m/s, ba-PWV > 1800 cm/s, ABI < 0.9, microalbuminuria (MAU) and chronic kidney disease (CKD). In multivariable logistic regression, there was a significant increase in the risk of cf-PWV > 10 m/s (OR = 1.86, 95% confidence interval [95% CI] 1.37–2.53, Pfor trend < 0.001), ba-PWV > 1800 cm/s (OR = 1.39, [95% CI] 1.05–1.84, Pfor trend= 0.02), MAU (OR = 1.61, [95% CI] 1.22–2.13, Pfor trend < 0.001) and CKD (OR = 1.67, [95% CI] 1.10–1.50, Pfor trend= 0.02) after adjustment for age, sex, BMI, waist circumference, smoking habit, hypertension, family history of premature CVD, diabetes, HDL-C, LDL-C, insulin therapy and statin therapy. However, no significant relationship was observed between the TyG index and lower extremity atherosclerosis, carotid hypertrophy or carotid plaque. An elevated TyG index was significantly associated with a higher risk of arterial stiffness and nephric microvascular damage. This conclusion lends support to the clinical significance of the TyG index for the assessment of vascular damage.

Although physical activity is widely recommended for reducing cardiovascular and all-cause mortality risks, female individuals consistently lag behind male individuals in exercise engagement. The goal of this study was to evaluate whether physical activity derived health benefits may differ by sex. In a prospective study of 412,413 U.S. adults (55% female, age 44 ± 17 years) who provided survey data on leisure-time physical activity, we examined sex-specific multivariable-adjusted associations of physical activity measures (frequency, duration, intensity, type) with all-cause and cardiovascular mortality from 1997 through 2019. During 4,911,178 person-years of follow-up, there were 39,935 all-cause deaths including 11,670 cardiovascular deaths. Regular leisure-time physical activity compared with inactivity was associated with 24% (HR: 0.76; 95% CI: 0.73-0.80) and 15% (HR: 0.85; 95% CI: 0.82-0.89) lower risk of all-cause mortality in women and men, respectively (Wald F = 12.0, sex interaction P < 0.001). Men reached their maximal survival benefit of HR 0.81 from 300 min/wk of moderate-to-vigorous physical activity, whereas women achieved similar benefit at 140 min/wk and then continued to reach a maximum survival benefit of HR 0.76 also at ∼300 min/wk. Sex-specific findings were similar for cardiovascular death (Wald F = 20.1, sex interaction P < 0.001) and consistent across all measures of aerobic activity as well as muscle strengthening activity (Wald F = 6.7, sex interaction P = 0.009). Women compared with men derived greater gains in all-cause and cardiovascular mortality risk reduction from equivalent doses of leisure-time physical activity. These findings could enhance efforts to close the "gender gap" by motivating especially women to engage in any regular leisure-time physical activity.

It is well known that cardiovascular disease manifests differently in women and men. The underlying causes of these differences during the aging lifespan are less well understood. Sex differences in cardiac and vascular phenotypes are seen in childhood and tend to track along distinct trajectories related to dimorphism in genetic factors as well as response to risk exposures and hormonal changes during the life course. These differences underlie sex-specific variation in cardiovascular events later in life, including myocardial infarction, heart failure, ischemic stroke, and peripheral vascular disease. With respect to cardiac phenotypes, females have intrinsically smaller body size–adjusted cardiac volumes and they tend to experience greater age-related wall thickening and myocardial stiffening with aging. With respect to vascular phenotypes, sexual dimorphism in both physiology and pathophysiology are also seen, including overt differences in blood pressure trajectories. The majority of sex differences in myocardial and vascular alterations that manifest with aging seem to follow relatively consistent trajectories from the very early to the very later stages of life. This review aims to synthesize recent cardiovascular aging-related research to highlight clinically relevant studies in diverse female and male populations that can inform approaches to improving the diagnosis, management, and prognosis of cardiovascular disease risks in the aging population at large.

BACKGROUND: The American Heart Association recently published guidelines on how to clinically identify and categorize individuals with cardiovascular-kidney-metabolic (CKM) syndrome. The extent to which CKM syndrome prevalence and prognosis differ by sex remains unknown. This study aimed to examine the impact of sex on trends in prevalence over 30 years and the long-term prognosis of CKM syndrome in the United States. METHODS: We analyzed nationally representative National Health and Nutrition Examination Survey 1988 to 2018 data collected from 33 868 US adults (aged ≥20 years) who were under surveillance for all-cause mortality through December 31, 2019. We examined the sex-specific prevalence of CKM syndrome and sex-specific CKM associations with all-cause mortality. RESULTS: Of the 33 868 adults studied, the mean±SD age was 48.4±18.3 years with 52% women and 56% non-White. Overall prevalence of CKM syndrome increased steadily from 1988 to 2018 in both sexes, with a larger temporal rise in prevalent stage 3 CKM seen for men (from 18.9% to 22.4%) compared with women (from 13.9% to 15.2%). Over a median follow-up of 13.3 years, there were 8745 deaths. In the multivariable Cox regression analysis, worsening CKM severity was associated with all-cause mortality ( P <0.001 for both sexes), with greater magnitudes of risk seen in women (hazards ratio, 1.24–3.33) compared with men (hazards ratio, 0.85–2.60) across all stages (likelihood ratio test χ ² , 19.0; P _interaction <0.001); results were similar for cardiovascular mortality (likelihood ratio test χ ² , 22.3; P _interaction <0.001). CONCLUSIONS: Women, compared with men, exhibited a lower prevalence of CKM stage 3 but experienced excess mortality risk across the spectrum of multisystem CKM dysfunction. These findings underscore the importance of identifying mechanisms underlying joint cardiovascular, kidney, and metabolic system pathophysiology to close a potentially widening sex disparities gap in multiorgan disease risk.