Childhood Cardiovascular Risk Factors and Adult Cardiovascular Events

Abstract

Background: Childhood cardiovascular risk factors predict subclinical adult cardiovascular disease, but links to clinical events are unclear.

Methods: In a prospective cohort study involving participants in the International Childhood Cardiovascular Cohort (i3C) Consortium, we evaluated whether childhood risk factors (at the ages of 3 to 19 years) were associated with cardiovascular events in adulthood after a mean follow-up of 35 years. Body-mass index, systolic blood pressure, total cholesterol level, triglyceride level, and youth smoking were analyzed with the use of i3C-derived age- and sex-specific z scores and with a combined-risk z score that was calculated as the unweighted mean of the five risk z scores. An algebraically comparable adult combined-risk z score (before any cardiovascular event) was analyzed jointly with the childhood risk factors. Study outcomes were fatal cardiovascular events and fatal or nonfatal cardiovascular events, and analyses were performed after multiple imputation with the use of proportional-hazards regression.

Results: In the analysis of 319 fatal cardiovascular events that occurred among 38,589 participants (49.7% male and 15.0% Black; mean [±SD] age at childhood visits, 11.8±3.1 years), the hazard ratios for a fatal cardiovascular event in adulthood ranged from 1.30 (95% confidence interval [CI], 1.14 to 1.47) per unit increase in the z score for total cholesterol level to 1.61 (95% CI, 1.21 to 2.13) for youth smoking (yes vs. no). The hazard ratio for a fatal cardiovascular event with respect to the combined-risk z score was 2.71 (95% CI, 2.23 to 3.29) per unit increase. The hazard ratios and their 95% confidence intervals in the analyses of fatal cardiovascular events were similar to those in the analyses of 779 fatal or nonfatal cardiovascular events that occurred among 20,656 participants who could be evaluated for this outcome. In the analysis of 115 fatal cardiovascular events that occurred in a subgroup of 13,401 participants (31.0±5.6 years of age at the adult measurement) who had data on adult risk factors, the adjusted hazard ratio with respect to the childhood combined-risk z score was 3.54 (95% CI, 2.57 to 4.87) per unit increase, and the mutually adjusted hazard ratio with respect to the change in the combined-risk z score from childhood to adulthood was 2.88 (95% CI, 2.06 to 4.05) per unit increase. The results were similar in the analysis of 524 fatal or nonfatal cardiovascular events.

Conclusions: In this prospective cohort study, childhood risk factors and the change in the combined-risk z score between childhood and adulthood were associated with cardiovascular events in midlife. (Funded by the National Institutes of Health.).

Figure 1.. Hazard Ratios for Cardiovascular Events at Younger and Older Ages.

Panel A shows the hazard ratios for fatal cardiovascular events, and Panel B shows the hazard ratios for fatal or nonfatal cardiovascular events. The spline of the hazard ratio is presented on a logarithmic scale across the distribution of the childhood combined-risk z scores, with 95% confidence intervals (shorter dashed lines). Younger age (<47.7 years) includes all the participants, among whom there were 157 fatal events and a mean of 797 fatal or nonfatal events across imputations. The older age group includes only the participants who were followed and had no event or had events at or after 47.7 years of age (a total of 18,352 participants, among whom 162 had a fatal cardiovascular event and 1049 either had a fatal event due to other causes or were not followed past the age of 47.6 years; the 17,141 remaining participants had a mean of 766 fatal or nonfatal events across imputations). The black circles indicate knots placed at the 5th, 25th, 50th, 75th, and 95th percentiles of the combined-risk z score.

Figure 2. (facing page). Cumulative Risk of Cardiovascular Events According to Categories of the Combined-Risk z Score and Age.

The cumulative risk of cardiovascular events is shown as the estimated probability according to the combined-risk z score and age (Kaplan–Meier method). The horizontal dashed line in each panel indicates the overall risk of the event. Panel A shows the hazard ratios for fatal cardiovascular events, and Panel B the hazard ratios for fatal or nonfatal cardiovascular events. All participants were included in these analyses; there were 319 fatal events and a mean of 1563 fatal or nonfatal events across imputations. In each panel, the inset shows the same data on an enlarged y axis. The columns of tabular data below the graphs correspond to the following ages (in years): 25.0, 27.5, 32.5, 37.5, 42.5, 47.5, 52.5, 57.5, and 62.5.