Association of left ventricular diastolic function with coronary artery calcium score: A Project Baseline Health Study

Abstract

Background: Coronary artery calcium (CAC) and left ventricular diastolic dysfunction (LVDD) are strong predictors of cardiovascular events and share common risk factors. However, their independent association remains unclear.

Methods: In the Project Baseline Health Study (PBHS), 2082 participants underwent cardiac-gated, non-contrast chest computed tomography (CT) and echocardiography. The association between left ventricular (LV) diastolic function and CAC was assessed using multidimensional network and multivariable-adjusted regression analyses. Multivariable analysis was conducted on continuous LV diastolic parameters and categorical classification of LVDD and adjusted for traditional cardiometabolic risk factors. LVDD was defined using reference limits from a low-risk reference group without established cardiovascular disease, cardiovascular risk factors or evidence of CAC, (n ​= ​560). We also classified LVDD using the American Society of Echocardiography recommendations.

Results: The mean age of the participants was 51 ​± ​17 years with 56.6% female and 62.6% non-Hispanic White. Overall, 38.1% had hypertension; 13.7% had diabetes; and 39.9% had CAC >0. An intertwined network was observed between diastolic parameters, CAC score, age, LV mass index, and pulse pressure. In the multivariable-adjusted analysis, e', E/e', and LV mass index were independently associated with CAC after adjustment for traditional risk factors. For both e' and E/e', the effect size and statistical significance were higher across increasing CAC tertiles. Other independent correlates of e' and E/e' included age, female sex, Black race, height, weight, pulse pressure, hemoglobin A1C, and HDL cholesterol. The independent association with CAC was confirmed using categorical analysis of LVDD, which occurred in 554 participants (26.6%) using population-derived thresholds.

Conclusion: In the PBHS study, the subclinical coronary atherosclerotic disease burden detected using CAC scoring was independently associated with diastolic function.

Gov identifier: NCT03154346.

Keywords: Blood pressure; Cardiovascular disease; Coronary artery calcium; Coronary artery disease; Heart failure; Hypertension; Left ventricular diastolic dysfunction.

Fig. 1.

Project Baseline Health Substudy. (A) Patients with available CT coronary calcium score and echocardiography were included in the study. (B) The healthy reference group (n = 560) included participants without evidence of established disease, major cardiovascular risk factors, or metabolic syndrome, and with a CAC score of 0. In addition, pregnant women were excluded. BHS, Baseline Health Study; CAC, coronary artery calcium; CKD, chronic kidney disease; CT, computed tomography; DCM, dilated cardiomyopathy; FG, fasting glucose; FPG, fasting plasma glucose; HCM, hypertrophic cardiomyopathy; TC, total cholesterol; TG, triglycerides.

Fig. 2.

Multidimensional clinical network, including echocardiographic parameters and CAC score. Edges with a Maximal Information Coefficient (MIC) above 0.10 are shown. Thicker and darker lines imply higher MIC. CAC score and its neighboring nodes (MIC above 0.15) are marked in red. ASCVD, atherosclerotic cardiovascular disease; CAC, coronary artery calcium; COPD, chronic pulmonary obstructive disease; DM, diabetes mellitus; E, mitral inflow velocity; E/A ratio, early and late diastolic peak velocities of mitral inflow; E/e’, mitral inflow to annular velocity ratio; e’, early diastolic mitral annular velocity; eGFR, estimated glomerular filtration rate; HDL-C, high-density lipoprotein-C; LAVI, left atrial volume index; LDL-C, low-density lipoprotein-C; LVEF, left ventricular ejection fraction; LVMI, left ventricular mass index; RWT, relative wall thickness. (For interpretation of the references to colour in this figure legend, the reader is referred to the Web version of this article.)

Fig. 3.

Age-specific percentiles of left ventricular diastolic function indexes from 560 low-risk reference group participants. The shaded area represents 95% confidence intervals of the 2.5% or 97.5% thresholds (red line) as derived from their Bootstrap distributions. LAV, left atrial volume; SV, stroke volume. (For interpretation of the references to colour in this figure legend, the reader is referred to the Web version of this article.)

Fig. 4.

Clinical correlates of left ventricular diastolic dysfunction. Variables considered included age, age, sex, race, smoking status (never smoker, past smoker, and current smoker), body height and weight, pulse pressure, heart rate, diabetes, chronic kidney disease, COPD, eGFR, cardiovascular disease, type of antihypertensive medication (beta-blockers, diuretics, calcium channel blockers, ACE inhibitors, angiotensin receptor blocker, and alpha antagonists), lipid-lowering drugs, total cholesterol, HDL cholesterol, LDL cholesterol, HbA1c and triglycerides. ACE, angiotensin-converting-enzyme; COPD, chronic obstructive pulmonary disease; eGFR, estimated glomerular filtration rate; HDL, high-density lipoprotein; LDL, low-density lipoprotein; LVDDF, left ventricular diastolic dysfunction.

Fig. 5.

Prevalence of left ventricular diastolic dysfunction (LVDDF) by CAC and 10-year ASCVD risk score. P < 0.001 for frequencies by CAC and/or 10-year ASCVD risk in Grade II LVDDF (P < 0.05 for all frequency trends in grade I LVDDF). ASCVD, atherosclerotic cardiovascular disease; CAC, coronary artery calcium; CV, cardiovascular disease.