Age-Related Development of Cardiac Remodeling and Dysfunction in Young Black and White Adults: The Coronary Artery Risk Development in Young Adults Study

Abstract

Background: Little is known about the timing of preclinical heart failure (HF) development, particularly among blacks. The primary aims of this study were to delineate age-related left ventricular (LV) structure and function evolution in a biracial cohort and to test the hypothesis that young-adult LV parameters within normative ranges would be associated with incident stage B-defining LV abnormalities over 25 years, independent of cumulative risk factor burden.

Methods: Data from the Coronary Artery Risk Development in Young Adults study were analyzed. Participants (n = 2,833) had a mean baseline age of 30.1 years; 45% were black, and 56% were women. Generalized estimating equation logistic regression was used to estimate age-related probabilities of stage B LV abnormalities (remodeling, hypertrophy, or dysfunction) and logistic regression to examine risk factor-adjusted associations between baseline LV parameters and incident abnormalities. Cox regression was used to assess whether baseline LV parameters associated with incident stage B LV abnormalities were also associated with incident clinical (stage C/D) HF events over >25 years' follow-up.

Results: Probabilities of stage B LV abnormalities at ages 25 and 60 years were 10.5% (95% CI, 9.4%-11.8%) and 45.0% (95% CI, 42.0%-48.1%), with significant race-sex disparities (e.g., at age 60, black men 52.7% [95% CI, 44.9%-60.3%], black women 59.4% [95% CI, 53.6%-65.0%], white men 39.1% [95% CI, 33.4%-45.0%], and white women 39.1% [95% CI, 33.9%-44.6%]). Over 25 years, baseline LV end-systolic dimension indexed to height was associated with incident systolic dysfunction (adjusted odds ratio per 1 SD higher, 2.56; 95% CI, 1.87-3.52), eccentric hypertrophy (1.34; 95% CI, 1.02-1.75), concentric hypertrophy (0.69; 95% CI, 0.51-0.91), and concentric remodeling (0.68; 95% CI, 0.58-0.79); baseline LV mass indexed to height^2.7 was associated with incident eccentric hypertrophy (1.70; 95% CI, 1.25-2.32]), concentric hypertrophy (1.63; 95% CI, 1.19-2.24), and diastolic dysfunction (1.24; 95% CI, 1.01-1.52). Among the entire cohort with baseline echocardiographic data available (n = 4,097; 72 HF events), LV end-systolic dimension indexed to height and LV mass indexed to height^2.7 were significantly associated with incident clinical HF (adjusted hazard ratios per 1 SD higher, 1.56 [95% CI, 1.26-1.93] and 1.42 [95% CI, 1.14-1.75], respectively).

Conclusions: Stage B LV abnormalities and related racial disparities were present in young adulthood, increased with age, and were associated with baseline variation in indexed LV end-systolic dimension and mass. Baseline indexed LV end-systolic dimension and mass were also associated with incident clinical HF. Efforts to prevent the LV abnormalities underlying clinical HF should start from a young age.

Keywords: Disparities; Heart failure; Left ventricle.

Figure 1.. Unadjusted Mean Patterns of Change in Left Ventricular Structure and Function Parameters with Age, Overall and by Race and Sex

Mean patterns of left ventricular (LV) changes with age were estimated using M-mode measures to maximize sample size. For comparison purposes, y axes are standardized to span 1.5 standard deviations, centered around the mean. P-values are as follows: p_rs, comparison by race-sex group; p_l, linear trend with age; p_lxrs, age*race-sex interaction; p_q, quadratic trend with age. With increasing age, relative wall thickness (RWT), indexed mass, and indexed left atrial dimension (LAD) increased, whereas the ratio of mitral early to late diastolic velocities (E/A) decreased. LV dimensions were nearly flat, and ejection fraction (EF) changed non-monotonically. Statistically significant race-sex differences were observed for EF, posterior wall thickness, interventricular septal thickness, RWT, indexed mass, and E/A ratio. The minimum and maximum sample sizes underlying any data point are as follows: overall 200 (for multiple parameters at age 40–44 years) to 2147 (for indexed LAD and E/A ratio at age 50–54 years); among Black men 31 (for multiple parameters at age 60–64 years) to 390 (for E/A ratio at age 50–54 years); among Black women 59 (for multiple parameters at age 60–64 years) to 575 (for indexed LAD at age 50–54 years); among White men 30 (for multiple parameters at age 40–44 years) to 562 (for E/A ratio at age 50–54 years); and among White women 40 (for multiple parameters at age 40–44 years) to 626 (for E/A ratio at age 50–54 years).

Figure 2.. Unadjusted Prevalence of Adverse Left Ventricular Outcomes with Age, Overall and by Race and Sex

The prevalences of adverse left ventricular (LV) outcomes were estimated by age. Age groups 55–59 and 60–64 years were combined due to small sample sizes in some race-sex groups at age 60–64 years. Diastolic dysfunction and stage B abnormalities are shown after age 40–44 years due to unavailability of measures at younger ages (see Methods). P-values are as follows: p_rs, comparison by race-sex group; p_l, linear trend with age; p_lxrs, age*race-sex interaction; p_q, quadratic trend with age. Blacks had higher prevalences than whites of all adverse LV outcomes, and race-sex differences were statistically significant for adverse geometry overall, concentric remodeling, concentric hypertrophy, and diastolic dysfunction. The minimum and maximum sample sizes underlying any data point are as follows: overall 200 (for adverse LV geometry at age 40–44 years) to 2070 (for diastolic dysfunction at age 50–54 years); among Black men 35 (for LV geometry at age 35–39 years) to 351 (for diastolic dysfunction at age 50–54 years); among Black women 66 (for any stage B abnormality at age 40–44 years) to 563 (for diastolic dysfunction at age 50–54 years); among White men 29 (for any stage B abnormality at age 40–44 years) to 535 (for diastolic dysfunction at age 50–54 years); and among White women 40 (for any stage B abnormality at age 40–44 years) to 621 (for diastolic dysfunction at age 50–54 years).