LV diastolic dysfunction is associated with increased risk of cardiovascular disease in older adults, but data on diastolic function in young adults are limited. In CARDIA participants who were 23–35 years of age, we found that the prevalence of abnormal relaxation was 9.3% and the prevalence of SDD was 1.1%. After adjustment for clinical and demographic factors and over 20 years of follow up, the presence of SDD was associated with a hazard ratio for our composite outcome of 4.29 (95% CI: 1.97, 9.33), and presence of abnormal relaxation was associated with a hazard ratio of 1.64 (95% CI: 1.06, 2.52). To the best of our knowledge, our study is the first to examine the prognosis associated with diastolic dysfunction in an asymptomatic and ethnically diverse population of younger adults.
We also examined potential antecedents of diastolic dysfunction and found that systolic blood pressure was associated with both SDD and abnormal relaxation. Other traditional cardiovascular risk factors, including lipid profile, smoking status, or fasting blood glucose levels, were not significantly associated with SDD. Although it is possible that some degree of diastolic dysfunction was present at the baseline examination, we did observe that lipid profile and fasting glucose levels were prospectively associated with the presence of abnormal relaxation 5 years later. Increased exercise duration was inversely associated with SDD and abnormal relaxation. We also observed an association between pulmonary function parameters and diastolic dysfunction in asymptomatic young individuals.
In previous studies, investigators have examined the prognostic significance of diastolic dysfunction in community-dwelling adults (1
); however, these studies have overwhelmingly included older adults and very few black participants. Redfield et al. studied community-dwelling adults 45 years of age or older in Olmsted County, Minnesota, and found that the prevalence of diastolic abnormalities was 28% (1
). More than half of those individuals had no signs or symptoms of heart failure; however, even mild diastolic dysfunction predicted an increase in all-cause mortality. The World Health Organization Multinational Monitoring of Trends and Determinants in Cardiovascular Disease Project (MONICA) Augsburg study included a small number (<300) of younger individuals 25–35 years of age and found that the prevalence of diastolic dysfunction was 2.8% (7
). Although the definitions of diastolic dysfunction differed across studies, the prevalence of any diastolic abnormalities in our study was 10.4%, and both abnormal relaxation and SDD were associated with significantly increased risk for cardiovascular events and all-cause mortality.
In the present study, echocardiography was performed in 1990–1991, and we do not have data on more recently developed measures of diastolic function, including tissue Doppler imaging and speckle tracking. However, our classification scheme utilized easily measured markers of blood flow and LA and ventricular morphology. This classification has been validated in patients with coronary artery disease (21
) and hypertension (22
). Most importantly, the presence of diastolic dysfunction as defined by our classification scheme in the present study was associated with markedly increased incidence of cardiovascular disease and all-cause mortality.
Our findings suggest that SDD and abnormal relaxation may represent biologically distinct phenotypes in young adults. We found that traditional cardiovascular risk factors, including blood pressure, lipid profile, and glucose intolerance, were significantly associated with abnormal relaxation but not with SDD. Given that individuals with SDD had significantly increased LV internal diameter and increased LV mass, our findings regarding this entity should be interpreted with caution; we cannot exclude the possibility that diastolic dysfunction in individuals with SDD was due to an asymptomatic cardiomyopathy. Furthermore, individuals with SDD had abnormalities on electrocardiogram 5 years before echocardiography, suggesting long-standing structural heart disease. Nonetheless, although SDD may be due to a cardiomyopathy in this sample, its presence was not otherwise detected, and it was highly predictive of future morbidity and mortality in these individuals. Given that traditional cardiovascular risk factors were significantly associated with abnormal relaxation but not with SDD, individuals with abnormal relaxation may benefit the most from intensive primary and primordial prevention efforts, although further study is needed.
A limitation of our study was the lack of availability of tissue Doppler imaging and speckle tracking to define diastolic function, as we have discussed above. Another limitation is that 28% of the total study population had indeterminate diastolic function because of incomplete or missing data. After multiple imputations, members of this group were reclassified into normal diastolic function (≈75%), abnormal relaxation (23%), and severe diastolic dysfunction (2%), confirming that this is a heterogeneous group. The secondary analysis confirmed the results that were obtained before imputation and with exclusion of the indeterminate individuals. As expected in this young population, there was a relatively small proportion of individuals with severe diastolic dysfunction. After multiple imputations, we reclassified an additional 24 participants into this group, and the imputed results were concordant with those from the primary analysis. Another limitation is that CARDIA participants who did not return for echocardiography at year 5 were more likely to be men, black, and smokers.
Because echocardiography was not performed at the year 0 examination, we were unable to estimate the incidence of diastolic dysfunction. Thus, we cannot exclude the possibility that diastolic abnormalities were present at the baseline examination. In fact, given the association of electrocardiographic LV mass index with SDD, it is likely that structural abnormalities predate the echocardiographic examination.
We conducted an analysis to determine the prevalence, prospective risk markers, and prognosis associated with diastolic dysfunction in healthy young adults. We found that the prevalence of any diastolic abnormalities in adults 23–35 years of age was 10.4%, and these findings were associated with markedly increased risk for all-cause mortality and cardiovascular events. We also found that elevated systolic blood pressure, abnormal pulmonary function, and electrocardiographic evidence for cardiac structural abnormalities were associated with the presence of severe diastolic dysfunction 5 years later. Traditional cardiovascular risk factors, including blood pressure, lipid profile, and elevated fasting glucose levels, were associated with abnormal relaxation. Increased exercise duration and percentage of predicted FEV1 were inversely associated with the presence of diastolic dysfunction. Further study is needed to determine whether more intensive prevention efforts can reduce complications of diastolic dysfunction in young adults.