Clinical Features Associated With Nascent Left Ventricular Diastolic Dysfunction in a Population Aged 40 to 55 Years

Abstract

Diastolic dysfunction (DD), an abnormality in cardiac left ventricular (LV) chamber compliance, is associated with increased morbidity and mortality. Although DD has been extensively studied in older populations, co-morbidity patterns are less well characterized in middle-aged subjects. We screened 156,434 subjects with transthoracic echocardiogram reports available through Vanderbilt's electronic heath record and identified 6,612 subjects 40 to 55 years old with an LV ejection fraction ≥50% and diastolic function staging. We tested 452 incident and prevalent clinical diagnoses for associations with early-stage DD (n = 1,676) versus normal function. There were 44 co-morbid diagnoses associated with grade 1 DD including hypertension (odds ratio [OR] = 2.02, 95% confidence interval [CI] 1.78 to 2.28, p <5.3 × 10-29), type 2 diabetes (OR 1.96, 95% CI 1.68 to 2.29, p = 2.1 × 10-17), tachycardia (OR 1.38, 95% CI 0.53 to 2.19, p = 2.9 × 10-6), obesity (OR 1.76, 95% CI 1.51 to 2.06, p = 1.7 × 10-12), and clinical end points, including end-stage renal disease (OR 3.29, 95% CI 2.19 to 4.96, p = 1.2 × 10-8) and stroke (OR 1.5, 95% CI 1.12 to 2.02, p = 6.9 × 10-3). Among the 60 incident diagnoses associated with DD, heart failure with preserved ejection fraction (OR 4.63, 95% CI 3.39 to 6.32, p = 6.3 × 10-22) had the most significant association. Among subjects with normal diastolic function and blood pressure at baseline, a blood pressure measurement in the hypertensive range at the time of the second echocardiogram was associated with progression to stage 1 DD (p = 0.04). In conclusion, DD was common among subjects 40 to 55 years old and was associated with a heavy burden of co-morbid disease.

Figure 1. Clinical diagnoses present before the echocardiogram independently associated with stage 1 DD

An independent set of diagnoses was identified by taking each of the 44 diagnoses associated with stage 1 DD at FDR q<0.01 and applying a multivariable logistic selection model incorporating all 44 diagnoses and covariates. Shown are the 9 diagnoses retained in the final selection model.

Figure 2. Clinical diagnoses assigned after the echocardiogram associated with DD stage 1 versus normal diastolic function

Subjects assigned a diagnosis prior to the echocardiogram were excluded from the analysis of that diagnosis. Logistic regression models were used to test for associations with each diagnosis and stage 1 DD and adjusted for age, gender, self-reported race and setting. Shown are all diagnoses associated with DD at FDR q<0.01. EF=ejection fraction.

Figure 3. Kaplan-Meier curves, stratified by DD stage, showing time to an incident clinical diagnosis of HFpEF

Subjects with any clinical heart failure diagnosis prior to the echocardiogram were excluded. The table shows the cumulative counts of HFpEF diagnoses and of subjects remaining at each year. Data were censored at 5 years. The p-value is based on a log-rank test statistic.

Figure 4. Association between DD progression or regression and hypertension status

All subjects in these analyses were normotensive at their first echocardiogram. The first pair of columns (Progressed) show the percentages of subjects, who progressed from normal diastolic function to grade 1 DD at the second echocardiogram, stratified by hypertension status at the second echocardiogram. The second pair of columns (Regressed) lists the percentages of subjects who went from grade 1 DD to normal diastolic function at their second echo. The numbers represent the counts underlying the percentages. P-values are for differences in proportions by Fisher’s exact test.