Abstract
IMPORTANCE
Most literature on the association between cardiovascular health (CVH) and incident cardiovascular disease (CVD) and mortality has relied on single midlife measurements. Understanding how cumulative CVH over time influences later-life CVD and mortality may aid early prevention.
OBJECTIVE
To determine whether cumulative CVH, as measured by the American Heart Association Life’s Essential 8 (LE8) from age 18 to 45 years, is associated with incident CVD and mortality in midlife.
DESIGN, SETTING, AND PARTICIPANTS
This cohort study, the Coronary Artery Risk Development in Young Adults (CARDIA) study, collected CVH data for participants from 4 US centers from 1985 to 2020. Multivariate Cox proportional hazard models assessed the associations of (1) cumulative LE8 score by quartile, (2) cumulative LE8 score and score at age 45 years, and (3) cumulative LE8 score and LE8 score slope from age 18 to 45 years with incident CVD and mortality after age 45 years.
MAIN OUTCOMES AND MEASURES
Incident CVD and all-cause mortality. Cumulative LE8 score was calculated as the area under the curve of the LE8 score (0–100, higher is better CVH) over time from age 18 to 45 years.
RESULTS
There were 4832 CARDIA participants (2690 [55.7%] female and 2142 [44.3%] male) with a mean (SD) cumulative LE8 score from age 18 to 45 years of 2018.8 (95.0) point × years. Compared with quartile 1 (Q1, ie, lowest CVH), Q2, Q3, and Q4 had significantly lower hazards for CVD (Q2 HR, 0.44; 95% CI, 0.32–0.61; Q3 HR, 0.26; 95% CI, 0.18–0.38; Q4 HR, 0.12; 95% CI, 0.07–0.21) and mortality (Q2 HR, 0.51; 95% CI, 0.36–0.71; Q3 HR, 0.38; 95% CI, 0.26–0.55; Q4 HR, 0.29; 95% CI, 0.18–0.45) after age 45 years. When cumulative LE8 score from age 18 to 45 years and LE8 score at age 45 years were in the model together, both were significantly associated with lower risk for CVD. Likewise, both cumulative LE8 score and positive slope of (improving) LE8 score from age 18 to 45 years were significantly associated with lower hazards for incident CVD after age 45 years.
CONCLUSIONS AND RELEVANCE
Greater cumulative CVH and improvement in CVH during young adulthood, as well as better CVH in middle age, were all independently associated with lower risk for incident CVD in midlife. These results emphasize the importance of maintaining and improving CVH throughout young adulthood.
Established by the American Heart Association (AHA) in 2010 as a novel guide to assessing current cardiovascular health (CVH), Life’s Simple 7 scores provided a quantitative metric that allowed health care professionals and consumers to measure and monitor CVH throughout the course of patients’ lives.1,2 In 2022, AHA created Life’s Essential 8 (LE8), adding sleep duration and an updated 100-point scoring system, providing greater granularity and detection of interindividual and intraindividual differences in CVH.3 Higher LE8 scores (ie, better CVH) have been associated with lower rates of cardiovascular disease (CVD), other illnesses, and mortality, serving as powerful tools for CVD research.4–13
Previous LE8 research using the National Health and Nutrition Examination Survey (NHANES) has shown that LE8 scores are usually suboptimal by young adulthood, decline over time, and are associated with CVD risk later in life.14–18 Conversely, young adults in optimal CVH (ie, higher LE8 scores) have significantly lower rates of premature CVD, underscoring the importance of having high LE8 scores as early as possible.19,20 Prior studies have focused on CVH measured at a single time point.19,21 However, there is limited understanding of how CVH integrated over time, or cumulative CVH, relates to the rates of developing CVD or mortality. This cumulative approach has been studied extensively in low-density lipoprotein cholesterol (LDL-C) levels and nicotine exposure (ie, pack-years).22–26 However, it has not been applied to CVH more broadly.
To address this gap, we sought to examine the associations between cumulative CVH through young adulthood and the subsequent risk of developing CVD and mortality in midlife and whether these associations are independent of single point-in-time measurements of CVH. Cumulative CVH was measured in “point × years” (ie, integrating the area under the curve [AUC] for LE8 score over time). We also sought to analyze how the slope of change in LE8 score during young adulthood in the context of cumulative score is associated with the risk of developing CVD events in midlife. Change in CVH over time was deemed points up (ie, change in LE8 score points per year).
Methods
Study Sample
The Coronary Artery Risk Development in Young Adults (CAR-DIA) study is a longitudinal, community-based cohort study begun in 1985–1986 with the enrollment of 5115 Black or White men and women aged 18 to 30 years at 4 centers across the US. Race was self-reported by participants at enrollment. Additional details of the CARDIA study are described in the eMethods in Supplement 1.
Exposures and Covariates
We quantified CVH according to the criteria established by the AHA’s LE8 score, including diet, physical activity, smoking, sleep, body mass index (BMI, calculated as weight in kilograms divided by height in meters squared), non–high-density lipoprotein cholesterol, blood glucose, and blood pressure as outlined in eTable 1 in Supplement 1.3 Each CVH metric was scored on a scale of 0 to 100 points, and overall LE8 score was calculated as the unweighted mean of all 8 metrics. Because sleep data were only collected after the year 15 examination, the sleep score was imputed using a methodology reviewed and approved by the CARDIA Design and Analysis committee.27 The sleep imputation methodology and sensitivity analysis are described in the Supplement 1.
Outcomes
Event ascertainment and adjudication in CARDIA has been described.28 The primary outcome for the present study was incident CVD through 2022, including fatal or nonfatal myocardial infarction, coronary revascularization (nonelective), heart failure, stroke, transient ischemic attack, hospitalized unstable angina, carotid or peripheral arterial disease requiring intervention, or other fatal heart or atherosclerotic disease. The secondary outcome was all-cause mortality.
Statistical Analysis
We sought to investigate the association of cumulative LE8 score through early adulthood with subsequent CVD events and mortality in midlife. We set age 45 years as the start of outcome follow-up time (Figure 1). Therefore, cumulative LE8 score for age 18 to 45 years is the primary exposure, and incident CVD and mortality after age 45 years are the outcomes of interest. We included 4832 participants with follow up data after age 45 years, excluding participants who withdrew consent (n = 1), underwent transgender treatment (n = 2), those who had fewer than 2 LE8 score measurements (n = 23), and those who experienced CVD events (n = 70) or died (n = 187) before age 45 years.
Figure 1. Study Design.
In 1985–86, CARDIA enrolled 5115 participants aged 18 to 30 years, of whom 4832 participants were included in this analysis (see the Methods in Supplement 1 for exclusion criteria). These participants completed 10 examinations in the following 35 years. The exposure window for measuring cumulative cardiovascular health (CVH) and the slope of CVH began at age 18 years and concluded at age 45 years. The outcome window, when participants were monitored for incident cardiovascular disease (CVD) events and mortality, occurred from age 45 years to examination year 35 (during which patients were 53–65 years old).
Cumulative LE8 score was calculated using a nonparametric cubic spline–based mixed-effects model to compute the participant-specific cumulative AUC of LE8 score from age 18 to 45 years. Then, the AUC of LE8 score from age 18 to 45 years was calculated as an overall cumulative score and expressed in point × years (Figure 1). The unit integrates the LE8 level across the exposure period into 1 cumulative value. This approach allows a flexible shape for an individual’s trajectory over the period. The time course of cumulative LE8 score was further characterized in 2 ways. First, the slope of LE8 trajectory from age 18 to 45 years was estimated, with a positive slope indicating an increasing LE8 score over time. Second, the LE8 score AUC from age 18 to 31 years and age 32 to 45 years was calculated separately; they represent the early and later exposure period, respectively, during early adulthood.
We stratified the study sample into 4 quartiles by cumulative LE8 score and compared characteristics across quartiles using analysis of variance for continuous variables or χ2 tests for categorical variables. Additionally, we stratified participants into 4 mutually exclusive groups based on cumulative LE8 score above or below the median and positive or negative LE8 score slope. Kaplan-Meier curves were used to display survival free of CVD and total mortality, and a log-rank test compared the survival time across subgroups.
We assessed the relationship of cumulative LE8 score before age 45 years with outcomes after age 45 years using multivariable Cox proportional hazards regression models, adjusting for age, gender, race, and highest educational attainment. Cumulative LE8 score was fitted in the model as a categorical variable (percentile by quartile: 0–25th [lowest], >25th-50th, >50th-75th, and >75th-100th) and as a continuous variable (per 20 points higher LE8 point × years). To assess whether cumulative LE8 score was associated with outcomes independent of a single LE8 score measure at age 45 years, we fitted a model with both covariates. We created additional Cox models to examine whether any of the individual LE8 metrics had an outsized impact on the risk of developing CVD.
Results
Participant Characteristics
There were 4832 CARDIA participants (2690 [55.7%] female and 2142 [44.3%] male) with a mean (SD) cumulative LE8 score from age 18 to 45 years of 2018.8 (95.0) point × years. Table 1 displays the clinical characteristics of the study participants stratified by cumulative LE8 score quartile from age 18 to 45 years. The difference between the mean Q1 and Q4 cumulative LE8 scores was 626 point × years (Table 1). Q4 had the lowest proportion of male and Black participants and the highest average years of education, while age varied very little across the quartiles. As expected, participants in Q4 of LE8 score had the most favorable levels of CVH health metrics (ie, BMI, blood pressure, blood lipid levels, serum glucose value, nicotine exposure, Healthy Eating Index diet score, and physical activity), followed sequentially by Q3, Q2, and Q1 (Table 1).
Table 1.
Clinical Characteristics of Study Cohorta
| Variable | No. (%)b | |||
|---|---|---|---|---|
| Quartile 1 (n = 1208) |
Quartile 2 (n = 1208) |
Quartile 3 (n = 1208) |
Quartile 4 (n = 1208) |
|
| Age, mean (SD), y | 24.5 (3.8) | 24.7 (3.7) | 24.9 (3.7) | 25.5 (3.4) |
| Sex | ||||
| Female | 684 (56.6) | 575 (47.6) | 634 (52.5) | 797 (66.0) |
| Male | 524 (43.4) | 633 (52.4) | 574 (47.5) | 411 (34.0) |
| Race | ||||
| Black | 815 (67.5) | 740 (61.3) | 603 (49.9) | 286 (23.7) |
| White | 393 (32.5) | 468 (38.7) | 605 (50.1) | 922 (76.3) |
| Education, mean (SD), y | 14.1 (2.3) | 14.8 (2.5) | 15.6 (2.5) | 16.9 (2.4) |
| Body mass index, mean (SD)c | 27.6 (6.4) | 24.8 (4.8) | 23.3 (3.7) | 22.1 (2.6) |
| Systolic BP, mean (SD), mm Hg | 113.6 (11.6) | 111.1 (10.6) | 109.2 (10.1) | 107.0 (9.8) |
| Diastolic BP, mean (SD), mm Hg | 70.4 (10.5) | 68.2 (9.8) | 68.2 (8.8) | 67.2 (8.2) |
| Total cholesterol, mean (SD), mg/dL | 186.3 (37.0) | 178.0 (33.2) | 174.6 (31.1) | 168.0 (27.7) |
| HDL cholesterol, mean (SD), mg/dL | 49.3 (12.7) | 52.6 (13.5) | 54.8 (12.9) | 56.4 (12.2) |
| Serum glucose, mean (SD), mg/dL | 83.7 (13.9) | 82.4 (12.2) | 80.9 (10.7) | 81.0 (7.8) |
| Diabetes treatment | 4 (0.3) | 0 | 2 (0.2) | 0 |
| Hypertension treatment | 57 (4.7) | 30 (2.5) | 10 (0.8) | 6 (0.5) |
| Current smoker | 684 (57.1) | 451 (37.7) | 226 (18.8) | 59 (4.9) |
| HEI diet score, mean (SD) | 57.1 (7.9) | 59.3 (8.2) | 61.9 (8.6) | 68.6 (8.7) |
| Physical activity, mean (SD), min/wk | 340.5 (356.9) | 409.7 (368.3) | 434.9 (368.8) | 453.6 (347.6) |
| LE8 score, mean (SD) | ||||
| Examination at year 0, point × years | 63.4 (9.8) | 72.0 (7.5) | 78.0 (7.3) | 85.6 (7.2) |
| At age 45 y, point × years | 53.8 (7.2) | 64.2 (5.1) | 71.9 (5.0) | 82.3 (6.3) |
| Cumulative (age 18–45 y), point × years | 1707 (140.3) | 1929 (52.8) | 2106 (52.9) | 2333 (104.2) |
| Slope (per point-year) | −0.46 (0.34) | −0.32 (0.32) | −0.19 (0.31) | −0.03 (0.31) |
Abbreviations: BP, blood pressure; HDL, high-density lipoprotein; HEI, Healthy Eating Index; LE8, Life’s Essential 8.
SI conversion factors: To convert total and HDL cholesterol to mmol/L, multiply by 0.0259; serum glucose to mmol/L, multiply by 0.0555.
Cumulative LE8 score does not include sleep scores because of limited sleep data. Sleep scores were imputed using demographic, socioeconomic, psychosocial, lifestyle, and clinical information collected from CARDIA study examinations.
Quartile 1, 0–25th percentile; quartile 2, >25th-50th percentile; quartile 3, >50th-75th percentile; quartile 4, >75th-100th percentile.
Calculated as weight in kilograms divided by height in meters squared.
Kaplan-Meier Analysis
During 14.2 years of follow up (68 591 person-years in total), there were 285 CVD events and 323 deaths from all causes. Figure 2A and B, respectively, display survival free of CVD and mortality, stratified by cumulative LE8 quartile. Participants in the highest quartile of cumulative LE8 score had minimal CVD events and mortality during follow-up. With each lower quartile (ie, poorer CVH), there was a corresponding higher risk of developing CVD or mortality (Figure 2A and B). For example, cumulative survival probability at 20 years was 80% for Q1 vs 95% for Q4.
Figure 2. Kaplan-Meier Curves for Cardiovascular Disease (CVD) Events and Mortality by Quartile (Q), Cumulative Life’s Essential 8 (LE8) Score, and Slope.
CVD event risk (A) and survival probability (B) are split by cumulative LE8 score quartile from age 18 to 45 years. CVD event risk (C) and survival probability (D) are split by (1) cumulative LE8 score above or below the median and (2) LE8 score slope greater than or equal to 0 or less than 0 from age 18 to 45 years. Quartile 1 indicates LE8 scores in the 0–25th percentile; quartile 2, greater than 25th to 50th percentile; quartile 3, greater than 50th to 75th percentile; and quartile 4, greater than 75th to 100th percentile.
We further examined the joint association of cumulative LE8 score and slope of change in LE8 score through young adulthood (age 18–45 years) with CVD event risk and mortality after age 45 years (Figure 2C and D). Participants with cumulative LE8 scores greater than the median, regardless of slope of CVH change, had the lowest CVD incidence and mortality. Among the participants with cumulative LE8 scores below the median, those with positive LE8 score slopes had lower CVD incidence and mortality vs those with negative slopes. In other words, participants with lower overall cumulative CVH who had LE8 scores that started lower and increased over time experienced less CVD and mortality than participants whose LE8 score started higher and declined over time (Figure 2C and 2D).
Multivariable-Adjusted Analysis
In the cumulative LE8 quartile analysis, participants in Q2, Q3, and Q4 (ie, the highest 3 quartiles of CVH) had substantially lower hazard ratios (HRs) for incident CVD (Table 2) and for mortality (eTable 2 in Supplement 1) compared with Q1 (ie, poorest CVH).
Table 2.
Incident CVD Risk Associated With Cumulative LE8 Scores in CARDIA Study Participants (1985–2023)a
| Quartile cumulative analysis | Continuous cumulative analysis | Slope and cumulative analysis | |||
|---|---|---|---|---|---|
| Covariate | HR (95% CI) | Covariate | HR (95% CI) | Covariate | HR (95% CI) |
| Cumulative LE8 score quartileb | |||||
| Q1 | Reference | Cumulative LE8 scorea | 0.97 (0.95–0.99) | Cumulative LE8 scorea | 0.95 (0.94–0.96) |
| Q2 | 0.44 (0.32–0.61) | LE8 score at age 45 ya | 0.96 (0.93–0.98) | Slopea | 0.65 (0.45–0.95) |
| Q3 | 0.26 (0.18–0.38) | NA | NA | NA | NA |
| Q4 | 0.12 (0.07–0.21) | NA | NA | NA | NA |
| Age at examination 1 | 1.04 (1.00–1.08) | Age at examination 1 | 1.04 (1.00–1.08) | Age at examination 1 | 1.04 (1.00–1.09) |
| Male sex | 1.78 (1.40–2.26) | Male sex | 1.84 (1.45–2.33) | Male sex | 1.82 (1.43–2.31) |
| Black race | 1.05 (0.81–1.35) | Black race | 1.01 (0.78–1.30) | Black race | 1.02 (0.79–1.32) |
| Maximal education (per year) | 0.96 (0.92–1.01) | Maximal education (per year) | 0.97 (0.93–1.02) | Maximal education (per year) | 0.97 (0.93–1.02) |
Abbreviations: CARDIA, Coronary Artery Risk Development in Young Adults; CVD, cardiovascular disease; LE8, Life’s Essential 8; HR, hazard ratio; NA, not applicable; Q, quartile.
Adjusting for age, sex, race, and maximal education, these Cox proportional hazard models calculate the HRs of developing CVD associated with cumulative LE8 score quartile (quartile cumulative analysis), cumulative LE8 score from age 18 to 45 years and LE8 score at age 45 years (continuous cumulative analysis), and cumulative LE8 score from age 18 to 45 years and slope of LE8 score from age 18 to 45 years (slope and cumulative analysis). Cumulative LE8 score was calculated in the unit of LE8 point × years. The unit for the cumulative LE8 score covariate (20-point higher LE8 score point × years) represents about a 1.0% difference in cumulative LE8 score (median cumulative LE8 score = 2084.9).
Q1, 0–25th percentile; Q2, >25th-50th percentile; Q3, >50th-75th percentile; Q4, >75th-100th percentile.
In the continuous cumulative analysis, higher cumulative LE8 score remained significantly and inversely associated with incident CVD (HR, 0.97; 95% CI, 0.95–0.99) (Table 2) and mortality (HR, 0.96; 95% CI, 0.93–0.98) (eTable 2 in Supplement 1) per 20-point × years, even after adjustment for LE8 score at age 45 years. In other words, living 1 year with a 20– point × year higher cumulative LE8 score (ie, approximately a 1.0% higher cumulative LE8 score) was associated with a 3% lower risk of incident CVD and 4% lower risk of mortality on average. In addition, a 1-point higher LE8 score at age 45 years was associated with 4% lower hazard of incident CVD. When examined individually, none of the 8 metrics appeared to dominate the association of overall cumulative LE8 score with incident CVD (eTable 3 in Supplement 1).
In the slope analysis, both higher cumulative LE8 score (HR, 0.95; 95% CI, 0.94–0.96) and positive slope of LE8 score from age 18 to 45 years (HR, 0.65; 95% CI, 0.45–0.95) were independently associated with lower hazards for incident CVD (Table 2). However, positive slope was not associated with lower risk of mortality (eTable 2 in Supplement 1).
Interestingly, with cumulative LE8 scores incorporated into the models, self-identified Black race (compared with White race) was not significantly associated with greater risk of developing CVD (quartile analysis HR, 1.05; 95% CI, 0.81–1.35; continuous analysis HR, 1.01; 95% CI, 0.78–1.30; slope analysis HR, 1.02; 95% CI, 0.79–1.32) (Table 2). A similar finding was observed in the models assessing mortality risk (eTable 2 in Supplement 1).
In point-in-time analysis of LE8 score at age 45 years, with no adjustment for cumulative LE8 score, a 1-point higher LE8 score at age 45 years was associated with a lower risk of incident CVD (HR, 0.94; 95% CI, 0.93–0.95) and mortality (HR, 0.95; 95% CI, 0.94–0.96), after adjusting for age, sex, race, and maximal education (Table 3).
Table 3.
Incident CVD and Mortality Risk by LE8 Score at Age 45 Years and Between Age 18 to 31 Years and Age 32 to 45 Yearsa
| Analysis | Hazard ratio (95% CI) | |
|---|---|---|
| CVD risk | Mortality risk | |
| Point-in-time analysis at age 45 y | ||
| LE8 score at age 45 y | 0.94 (0.93–0.95) | 0.95 (0.94–0.96) |
| Age at examination 1 | 1.04 (1.00–1.08) | 1.00 (0.96–1.04) |
| Male sex | 1.86 (1.46–2.36) | 1.31 (1.05–1.64) |
| Black race | 1.00 (0.78–1.29) | 1.12 (0.88–1.43) |
| Maximal education (per year) | 0.96 (0.92–1.01) | 0.91 (0.86–0.99) |
| Age-stratified cumulative analysis | ||
| Cumulative LE8 score (per 20-point higher LE8 score × years) | ||
| Age 18–31 y | 0.98 (0.95–1.02) | 0.96 (0.93–1.00) |
| Age 32–45 y | 0.91 (0.88–0.94) | 0.95 (0.92–0.98) |
| Age at examination 1 | 1.04 (1.00–1.08) | 1.00 (0.96–1.04) |
| Male sex | 1.82 (1.43–2.31) | 1.29 (1.04–1.62) |
| Black race | 1.02 (0.79–1.32) | 1.14 (0.89–1.45) |
| Maximal education (per year) | 0.97 (0.93–1.02) | 0.92 (0.87–0.97) |
Abbreviations: CVD, cardiovascular disease; LE8, Life’s Essential 8.
Adjusting for age, sex, race, and maximal education, the point-in-time analysis at age 45 years evaluated the hazard ratios associated with LE8 score at age 45 years. Adjusting for age, sex, race, and maximal education, the age-stratified cumulative analysis evaluated the hazard ratios associated with cumulative LE8 score at age 18 to 31 years and age 32 to 45 years.
Finally, our age-stratified analysis demonstrated that cumulative LE8 score has a differential association with risk of later incident CVD and mortality based on age. From age 32 to 45 years, a 20–point × year higher cumulative LE8 score was significantly associated with risk of developing CVD (HR, 0.91; 95% CI, 0.88–0.94) and mortality (HR, 0.95; 95% CI, 0.92–0.98). However, these associations were not significant from age 18 to 31 years (Table 3).
Discussion
Principal Findings
We observed that cumulative CVH, measured as LE8 score over time, during young adulthood is significantly and inversely associated with developing CVD and with mortality in midlife. This association remained significant even after adjusting for a point-in-time measurement of LE8 at age 45 years. The slope of change in CVH from age 18 to 45 years is significantly and inversely associated with developing CVD, even after accounting for the cumulative score. Specifically, a positive slope of LE8 score through young adulthood, indicating improving CVH, is associated with lower likelihood of developing CVD. Finally, adjustment for cumulative LE8 score through young adulthood eliminated the differences in incident midlife CVD and mortality between Black and White participants.
Current Findings in Context
Previous research has demonstrated that CVH is suboptimal in young adulthood and declines over time; conversely, young adults with high CVH have low rates of premature CVD.3,14,19,21,29,30 Most of the analyses that have examined the relationship between CVH and incident CVD and mortality have focused on single point-in-time measures of CVH.14,19,21 Using a similar paradigm to the pack-years research in nicotine and cumulative LDL-C exposure literature, we examined how cumulative LE8 score would be associated with developing CVD and mortality.22–26 The longitudinal nature of the CARDIA cohort study permitted this cumulative approach by integrating the LE8 score over time for participants.
We observed broad sociodemographic differences across strata of cumulative LE8 score through young adulthood. Those with the highest CVH were more likely to identify as White, identify as women, and have higher education attainment. Those with the highest LE8 score at age 18 years tended to maintain higher scores throughout, although LE8 scores generally declined across the sample. These population-level declines in CVH are consistent with prior analyses and demonstrate potential areas for improvement in CVH for US adults as they age.14,21,31,32
There was an inverse dose-response association of cumulative LE8 score through young adulthood with midlife CVD events and total mortality in Kaplan-Meier curves and multivariable-adjusted Cox models. In the quartile analysis, membership in Q2, Q3, and Q4 was associated with 56%, 74%, and 88% of the risk of developing CVD, respectively, compared with membership in Q1. Similar risk reductions were seen in the mortality analysis.
Clinical Implications
Point × years may be a useful method for finding high-risk young adults and targeting them for primary and primordial prevention. Participants in Q2 had about half the risk of developing CVD and mortality in midlife as those in Q1, despite only having a mean of approximately 200-point × years higher cumulative LE8 score. For context, an increase from 0 to 90 minutes of moderate physical activity per week (13 minutes per day) over 20 years would be a 200-point × years increase.
Expanding on the categorical quartile analysis, the continuous analysis demonstrated that approximately a 1% increase in cumulative LE8 score was associated with a 3% reduction in risk of developing CVD. Notably, this result was independently significant of an individual’s point-in-time LE8 score at age 45 years. The continuous framework of cumulative LE8 can give young adults an actionable scale for improving their CVH regardless of their starting point.
Importantly, the precision of the LE8 scoring system has its limitations. For example, an individual whose BMI decreases from 34 to 25 experiences the same LE8 score change as someone whose BMI goes from 30 to 29, even though there are substantial clinical differences in their weight loss. However, despite its limitations, the LE8 scoring system and the use of point × years allow for substantially more granularity than 1-time measurements and former methodologies of estimating CVH.1,21,33
Furthermore, point × years may be a helpful tool in explaining the long time course of developing CVD. Although point-in-time measurements of LE8 score at age 45 years were significantly associated with risk of developing CVD, explaining this to a patient in a way that fosters a growth mindset may be difficult.
The slope analysis suggests if 2 individuals had the same cumulative LE8 score from age 18 to 45 years, but one had a slope of 0 (ie, their LE8 score stayed the same for 27 years) and the other had a slope of 1 (ie, their LE8 score increased by 1 point each year for 27 years), even though they have the same AUC, the one with a slope of 1 would be associated with a 38% lower risk of developing CVD. Thus, improvement in CVH, or points up, during young adulthood was associated with significantly lower risk of developing CVD. Clinically, points up could be used to show patients the impact that improvements in CVH can have on the associated risk of developing CVD. In public health, this paradigm could be used to examine differing rates of CVH decline among various populations or to inform early-life interventions.
We observed that increased cumulative CVH from age 32 to 45 years, but not from age 18 to 31 years, was associated with lower incident CVD and mortality. This is consistent with the finding that positive slope in CVH for the same cumulative score was associated with lower CVD and mortality risk. This paradigm has been found in nicotine exposure, which is why “years since quitting” (in conjunction with pack-years) is clinically relevant.34–37
Point × years and points up could be useful ways to communicate and promote CVH to young adult patients. Given the recent promising research on harnessing gamification to encourage patients to change their health behaviors, further research could examine the potential for using point × years and points up in the LE8 paradigm to improve young adult CVH.38
Limitations
The unweighted approach of LE8 was chosen by the AHA to measure current CVH status. This allows the upstream health factors such as diet and physical activity to work through the downstream factors such as blood pressure and BMI. Therefore, our analysis does not have the same predictive utility as weighted approaches like AHA’s 10-year and 30-year CVD outcome risk calculators. Sleep data were not collected until the CARDIA years 15 examination, requiring imputation for earlier examinations. However, a sensitivity analysis without the imputed sleep data found no significant differences. Furthermore, this approach was validated internally in CARDIA with “drop out and predict” validation and externally in comparison with contemporaneous sleep data from representative young adults in the NHANES from the same age, sex, and race groups. CARDIA cohort’s composition of Black and White participants limits its generalizability beyond these racial groups. Our methodologies for measuring cumulative CVH and slope do not account for all the variability in an individual’s CVH. Finally, there is a potential for residual confounding, which was mitigated by robust statistical adjustments.
Conclusions
Greater cumulative time at higher CVH during young adulthood, assessed by higher LE8 scores, correlates with lower subsequent risk of developing CVD. Adjusting for cumulative CVH, improvement in CVH during young adulthood was associated with significantly lower risk for developing CVD in midlife. Thus, change matters. In 2 young adults with the same cumulative CVH score, the one with greater improvements in CVH may have a reduced risk of developing cardiovascular disease. Finally, point × years and points up may be useful constructs for monitoring, communicating, and promoting CVH in patients.
Supplementary Material
Key Points.
Question
What is the association between cumulative cardiovascular health (CVH) through young adulthood and incident cardiovascular disease (CVD) in midlife?
Findings
This cohort study found that higher cumulative Life’s Essential 8 (LE8) score from age 18 to 45 years, independent of LE8 score at age 45 years, and a positive slope of (improving) LE8 score from age 18 to 45 years were significantly associated with lower hazards for incident CVD after age 45 years.
Meaning
Cumulative CVH as measured by LE8 may be a useful method for identifying the highest-risk young adults and targeting them for primary and primordial prevention strategies.
Funding/Support:
The Coronary Artery Risk Development in Young Adults (CARDIA) study is supported by the National Heart, Lung, and Blood Institute (contracts 75N92023D00002, 75N92023D00003, 75N92023D00004, 75N92023D00005, and 75N92023D00006).
Role of the Funder/Sponsor:
The funder had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; or decision to submit the manuscript for publication.
Footnotes
Conflict of Interest Disclosures: None reported.
Contributor Information
James Walker, Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
Daniel Won, Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
James Guo, Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
Jamal S. Rana, Kaiser Permanente Oakland Medical Center, Oakland, California.
Norrina B. Allen, Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
Hongyan Ning, Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
Donald M. Lloyd-Jones, Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois; Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois; Department of Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
Data Sharing Statement:
See Supplement 2.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Data Availability Statement
See Supplement 2.