The menopausal transition is a time of accelerating risk of cardiovascular disease (CVD), and promoting cardiovascular health during midlife is an important period of time to prevent CVD in women. The association of menopause with cardiovascular risk factors or subclinical atherosclerosis has not previously been evaluated in South Asian American women, a population with a disproportionately higher CVD burden compared with other race/ethnic groups. The objective of this study was to evaluate the association of menopause with CVD risk factors and subclinical cardiometabolic disease markers. We studied women aged 40 to 84 years from the Mediators of Atherosclerosis in South Asians Living in America study. The association of self-reported menopausal status with multiple demographic and clinical variables was assessed with linear and logistic regression adjusted for age and cardiovascular health behaviors. In a secondary ("age-restricted") analysis, postmenopausal participants outside the age range of premenopausal participants were excluded. In the age-restricted sample, menopause was associated with a higher adjusted odds of hypertension (odds ratio = 1.19, 95% confidence interval [CI] 1.02 to 1.41), and higher systolic blood pressure (β = 6.34, 95% CI 0.82 to 11.87), and significantly higher subcutaneous fat area (β = 42.8, 95% CI 5.8 to 91.4). No significant associations between menopause and ectopic fat deposition, coronary artery calcium, or carotid intima-media thickness were observed. In South Asian American women in the Mediators of Atherosclerosis in South Asians Living in America study, menopause was associated with cardiovascular risk factors and higher subcutaneous fat deposition. Menopausal status is an important factor to examine and address CVD risk factors.

Background

Coronavirus disease 2019 (COVID-19) data from race/ethnic subgroups remain limited, potentially masking subgroup-level heterogeneity. We evaluated differences in outcomes in Asian American/Pacific Islander (AAPI) and Hispanic/Latino subgroups compared with non-Hispanic White patients hospitalized with COVID-19.

Methods

In the American Heart Association COVID-19 registry including 105 US hospitals, mortality and major adverse cardiovascular events in adults age ≥18 years hospitalized with COVID-19 between March-November 2020 were evaluated. Race/ethnicity groups included AAPI overall and subgroups (Chinese, Asian Indian, Vietnamese, and Pacific Islander), Hispanic/Latino overall and subgroups (Mexican, Puerto Rican), compared with non-Hispanic White (NHW).

Results

Among 13,511 patients, 7% were identified as AAPI (of whom 17% were identified as Chinese, 9% Asian Indian, 8% Pacific Islander, and 7% Vietnamese); 35% as Hispanic (of whom 15% were identified as Mexican and 1% Puerto Rican); and 59% as NHW. Mean [SD] age at hospitalization was lower in Asian Indian (60.4 [17.4] years), Pacific Islander (49.4 [16.7] years), and Mexican patients (57.4 [16.9] years), compared with NHW patients (66.9 [17.3] years, p<0.01). Mean age at death was lower in Mexican (67.7 [15.5] years) compared with NHW patients (75.5 [13.5] years, p<0.01). No differences in odds of mortality or MACE in AAPI or Hispanic patients relative to NHW patients were observed after adjustment for age.

Conclusions

Pacific Islander, Asian Indian, and Mexican patients hospitalized with COVID-19 in the AHA registry were significantly younger than NHW patients. COVID-19 infection leading to hospitalization may disproportionately burden some younger AAPI and Hispanic subgroups in the US.

Background

Prior studies have demonstrated a cross-sectional association between elevated plasminogen activator inhibitor-1 (PAI-1) levels and nonalcoholic fatty liver disease (NAFLD). However, there are no prospective longitudinal assessments of the association between PAI-1 and NAFLD. We aimed to describe the association between PAI-1 levels in early adulthood with NAFLD in midlife.

Methods

Among the 5115 participants in the coronary artery risk development in young adults (CARDIA) study, participants were randomly selected from a subset that was free of obesity, diabetes and hypertension at the 1992-1993 exam and attended the 2005-2006 exam (n = 996). A subset of participants (n = 896) also had CT liver fat measured (2010-2011). Participants with secondary causes of steatosis were excluded (n = 87). NAFLD was defined as liver attenuation ≤51 Hounsfield units. Logistic regression models assessed the association between PAI-1 and NAFLD.

Results

Of 809 participants, 53% were female, 37% black with a mean age of 32 years. Median PAI-1 level at 1st assessment (1992-1993) was 23.4 ng/mL among participants with NAFLD vs 11.9 ng/mL among those without NAFLD (P < .0001). Median PAI-1 level at 2nd assessment (2005-2006) was 55.6 ng/mL among participants with NAFLD vs 19.5 ng/mL among those without NAFLD (P < .0001). Higher PAI-1 levels were independently associated with NAFLD (1st assessment adjusted OR [AOR] 2.16 per 1 standard deviation higher log(PAI-1) level (95% confidence interval [CI] 1.63-2.85); 2nd assessment AOR 2.71 (95% CI 2.03-3.61)).

Conclusions

Plasma PAI-1 levels in young adulthood were independently associated with NAFLD in midlife. Further studies may indicate whether PAI-1 plays a role in NAFLD pathophysiology.

Background

Cardiovascular health (CVH) has been defined by the American Heart Association (AHA) as the presence of the "Life's Simple 7" ideal lifestyle and clinical factors. CVH is known to predict longevity and freedom from cardiovascular disease, the leading cause of death for women in the United States. DNA methylation markers of aging have been aggregated into a composite epigenetic age score, which is associated with cardiovascular morbidity and mortality. However, it is unknown whether poor CVH is associated with acceleration of aging as measured by DNA methylation markers in epigenetic age.

Methods and results

We performed a cross-sectional analysis of racially/ethnically diverse post-menopausal women enrolled in the Women's Health Initiative cohort recruited between 1993 and 1998. Epigenetic age acceleration (EAA) was calculated using DNA methylation data on a subset of participants and the published Horvath and Hannum methods for intrinsic and extrinsic EAA. CVH was calculated using the AHA measures of CVH contributing to a 7-point score. We examined the association between CVH score and EAA using linear regression modeling adjusting for self-reported race/ethnicity and education. Among the 2,170 participants analyzed, 50% were white and mean age was 64 (7 SD) years. Higher or more favorable CVH scores were associated with lower extrinsic EAA (~ 6 months younger age per 1 point higher CVH score, p < 0.0001), and lower intrinsic EAA (3 months younger age per 1 point higher CVH score, p < 0.028).

Conclusions

These cross-sectional observations suggest a possible mechanism by which ideal CVH is associated with greater longevity.

Background

South Asian Americans experience disproportionately high burden of cardiovascular diseases. Estimating predicted heart failure (HF) risk distribution may facilitate targeted prevention. We estimated the distribution of 10-year predicted risk of incident HF in South Asian Americans and evaluated the associations with social determinants of health and clinical risk factors.

Methods and results

In the Mediators of Atherosclerosis in South Asians Living in America (MASALA) Study, we calculated 10-year predicted HF risk using the Pooled Cohort Equations to Prevent Heart Failure multivariable model. Distributions of low (<1%), intermediate (1%-5%), and high (≥5%) HF risk, identified overall and by demographic and clinical characteristics, were compared. We evaluated age- and sex-adjusted associations of demographic characteristics and coronary artery calcium with predicted HF risk category using ordinal logistic regression. In 1159 participants (48% women), with a mean age of 57 ± 9 years, 40% had a low, 37% had an intermediate, and 24% had a high HF risk. Significant differences in HF risk distribution existed across demographic (income, education, birthplace) and clinical (diabetes, hypertension, body mass index, coronary artery calcium) groups (P < .01). Significant associations with high predicted HF risk were observed for a family of income 75,000/year or more (adjusted odds ratio 0.5 [95% confidence interval (CI) 0.4-0.7]), college education (0.6 [95% CI 0.4-0.9]), birthplace in another South Asian country (1.9 [95% CI 1.2-3.2], vs. born in India), and prevalent coronary artery calcium (2.6 [95% CI 1.9-3.6]).

Conclusions

Almost two-thirds of South Asian Americans in the MASALA cohort are at intermediate or high predicted 10-year HF risk, with varying risk across demographic and clinical characteristics.

Background & aims

Non-alcoholic fatty liver disease is an epidemic. Identifying modifiable risk factors for non-alcoholic fatty liver disease development is essential to design effective prevention programmes. We tested whether 25-year patterns of body mass index change are associated with midlife non-alcoholic fatty liver disease.

Methods

In all, 4423 participants from Coronary Artery Risk Development in Young Adults, a prospective population-based biracial cohort (age 18-30), underwent body mass index measurement at baseline (1985-1986) and 3 or more times over 25 years. At Year 25, 3115 had liver fat assessed by non-contrast computed tomography. Non-alcoholic fatty liver disease was defined as liver attenuation ≤40 Hounsfield Units after exclusions. Latent mixture modelling identified 25-year trajectories in body mass index per cent change (%Δ) from baseline.

Results

We identified four distinct trajectories of BMI%Δ: stable (26.2% of cohort, 25-year BMI %Δ = 3.1%), moderate increase (46.0%, BMI%Δ = 21.7%), high increase (20.9%, BMI%Δ = 41.9%) and extreme increase (6.9%, BMI%Δ = 65.9%). Y25 non-alcoholic fatty liver disease prevalence was higher in groups with greater BMI %Δ: 4.1%, 9.3%, 13.0%, and 17.6%, respectively (P-trend <.0001). In multivariable analyses, participants with increasing BMI%Δ had increasingly greater odds of non-alcoholic fatty liver disease compared to the stable group: OR: 3.35 (95% CI: 2.07-5.42), 7.80 (4.60-13.23) and 12.68 (6.68-24.09) for moderate, high and extreme body mass index increase, respectively. Associations were only moderately attenuated when adjusted for baseline or Y25 body mass index.

Conclusions

Trajectories of weight gain during young adulthood are associated with greater non-alcoholic fatty liver disease prevalence in midlife independent of metabolic covariates and baseline or concurrent body mass index highlighting the importance of weight maintenance throughout adulthood as a target for primary non-alcoholic fatty liver disease prevention.

Despite the well-established benefits of mineralocorticoid receptor agonists (MRAs) in heart failure with reduced ejection fraction, safety concerns remain in patients with concomitant diabetes mellitus (DM) because of common renal and electrolyte abnormalities in this population. We analyzed all-cause mortality and composite cardiovascular mortality and HF hospitalization over a median 9.9 months among 1,998 patients in the placebo arm of the Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study With Tolvaptan (EVEREST) trial by DM status and discharge MRA use. Of the 750 patients with DM, 59.2% were receiving MRAs compared with 62.5% in the non-DM patients. DM patients not receiving MRAs were older, more likely to be men, with an ischemic heart failure etiology and slightly worse renal function compared with those receiving MRAs. After adjustment for baseline risk factors, among DM patients, MRA use was not associated with either mortality (hazard ratio [HR] 0.93; 95% confidence interval [CI] 0.75 to 1.15) or the composite end point (HR 0.94; 95% CI 0.80 to 1.10). Similar findings were seen in non-DM patients (mortality [HR 1.01; 95% CI 0.84 to 1.22] or the composite end point [HR 0.98; 95% CI 0.85 to 1.13] [p >0.43 for DM interaction]). In conclusion, in-hospital initiation of MRA therapy was low (15% to 20%), and overall discharge MRA use was only 60% (with regional variation), regardless of DM status. There does not appear to be clear, clinically significant in-hospital hemodynamic or even renal differences between those on and off MRA. Discharge MRA use was not associated with postdischarge end points in patients hospitalized for worsening heart failure with reduced ejection fraction and co-morbid DM. DM does not appear to influence the effectiveness of MRA therapy.

The proportion of aging populations affected by dementia is increasing. There is an urgent need to identify biological aging markers in mid-life before symptoms of age-related dementia present for early intervention to delay the cognitive decline and the onset of dementia. In this cohort study involving 1,676 healthy participants (mean age 40) with up to 15 years of follow up, we evaluated the associations between cognitive function and two classes of novel biological aging markers: blood-based epigenetic aging and neuroimaging-based brain aging. Both accelerated epigenetic aging and brain aging were prospectively associated with worse cognitive outcomes. Specifically, every year faster epigenetic or brain aging was on average associated with 0.19-0.28 higher (worse) Stroop score, 0.04-0.05 lower (worse) RAVLT score, and 0.23-0.45 lower (worse) DSST (all false-discovery-rate-adjusted p <0.05). While epigenetic aging is a more stable biomarker with strong long-term predictive performance for cognitive function, brain aging biomarker may change more dynamically in temporal association with cognitive decline. The combined model using epigenetic and brain aging markers achieved the highest accuracy (AUC: 0.68, p<0.001) in predicting global cognitive function status. Accelerated epigenetic age and brain age at midlife may aid timely identification of individuals at risk for accelerated cognitive decline and promote the development of interventions to preserve optimal functioning across the lifespan.

More than 40 years after the 1978 Bethesda Conference on the Declining Mortality from Coronary Heart Disease provided the scientific community with a blueprint for systematic analysis to understand declining rates of coronary heart disease, there are indications the decline has ended or even reversed despite advances in our knowledge about the condition and treatment. Recent data show a more complex situation, with mortality rates for overall cardiovascular disease, including coronary heart disease and stroke, decelerating, whereas those for heart failure are increasing. To mark the 40th anniversary of the Bethesda Conference, the National Heart, Lung, and Blood Institute and the American Heart Association cosponsored the "Bending the Curve in Cardiovascular Disease Mortality: Bethesda + 40" symposium. The objective was to examine the immediate and long-term outcomes of the 1978 conference and understand the current environment. Symposium themes included trends and future projections in cardiovascular disease (in the United States and internationally), the evolving obesity and diabetes epidemics, and harnessing emerging and innovative opportunities to preserve and promote cardiovascular health and prevent cardiovascular disease. In addition, participant-led discussion explored the challenges and barriers in promoting cardiovascular health across the lifespan and established a potential framework for observational research and interventions that would begin in early childhood (or ideally in utero). This report summarizes the relevant research, policy, and practice opportunities discussed at the symposium.