Social and Psychosocial Determinants of Racial and Ethnic Differences in Cardiovascular Health in the United States Population.

BACKGROUND: Social and psychosocial factors are associated with cardiovascular health (CVH). Our objective was to examine the contributions of individual-level social and psychosocial factors to racial and ethnic differences in population CVH in the NHANES (National Health and Nutrition Examination Surveys) 2011 to 2018, to inform strategies to mitigate CVH inequities. METHODS: In NHANES participants ages ≥20 years, Kitagawa-Blinder-Oaxaca decomposition estimated the statistical contribution of individual-level factors (education, income, food security, marital status, health insurance, place of birth, depression) to racial and ethnic differences in population mean CVH score (range, 0-14, accounting for diet, smoking, physical activity, body mass index, blood pressure, cholesterol, blood glucose) among Hispanic, non-Hispanic Asian, or non-Hispanic Black adults compared with non-Hispanic White adults. RESULTS: Among 16 172 participants (representing 255 million US adults), 24% were Hispanic, 12% non-Hispanic Asian, 23% non-Hispanic Black, and 41% non-Hispanic White. Among men, mean (SE) CVH score was 7.45 (2.3) in Hispanic, 8.71 (2.2) in non-Hispanic Asian, 7.48 (2.4) in non-Hispanic Black, and 7.58 (2.3) in non-Hispanic White adults. In Kitagawa-Blinder-Oaxaca decomposition, education explained the largest component of CVH differences among men (if distribution of education were similar to non-Hispanic White participants, CVH score would be 0.36 [0.04] points higher in Hispanic, 0.24 [0.04] points lower in non-Hispanic Asian, and 0.23 [0.03] points higher in non-Hispanic Black participants; P<0.05). Among women, mean (SE) CVH score was 8.03 (2.4) in Hispanic, 9.34 (2.1) in non-Hispanic Asian, 7.43 (2.3) in non-Hispanic Black, and 8.00 (2.5) in non-Hispanic White adults. Education explained the largest component of CVH difference in non-Hispanic Black women (if distribution of education were similar to non-Hispanic White participants, CVH score would be 0.17 [0.03] points higher in non-Hispanic Black participants; P<0.05). Place of birth (born in the United States versus born outside the United States) explained the largest component of CVH difference in Hispanic and non-Hispanic Asian women (if distribution of place of birth were similar to non-Hispanic White participants, CVH score would be 0.36 [0.07] points lower and 0.49 [0.16] points lower, respectively; P<0.05). CONCLUSIONS: Education and place of birth confer the largest statistical contributions to the racial and ethnic differences in mean CVH score among US adults.

Development and Validation of a Long-Term Incident Heart Failure Risk Model.

BACKGROUND: Average lifetime risk for heart failure (HF) is high but differs significantly across and within sex-race groups. No models for estimating long-term risk for HF exist, which would allow for earlier identification and interventions in high-risk subsets. The authors aim to derive 30-year HF risk equations. METHODS: Adults between the ages of 20 to 59 years and free of cardiovascular disease at baseline from 5 population-based cohorts were included. Among 24 838 participants (55% women, 25% Black based on self-report), follow-up consisted of 599 551 person-years. Sex- and race-specific 30-year HF risk equations were derived and validated accounting for competing risk of non-HF death. HF was based on a clinical diagnosis. Model discrimination and calibration were assessed using 10-fold cross-validation. Finally, the model was applied to varying risk factor patterns for systematic examination. RESULTS: The rate of incident HF was 4.0 per 1000 person-years. Harrell C statistics were 0.82 (0.80-0.83) and 0.84 (0.82-0.85) in White and Black men and 0.84 (0.82-0.85) and 0.85 (0.83-0.87) in White and Black women, respectively. Hosmer-Lemeshow calibration was acceptable, with χ2 <30 in all subgroups. Risk estimation varied across sex-race groups: for example, in an average 40-year-old nonsmoker with an untreated systolic blood pressure of 140 mm Hg and body mass index of 30 kg/m2, risk was estimated to be 22.8% in a Black man, 13.7% in a White man, 13.0% in a Black woman, and 12.1% in a White woman. CONCLUSIONS: Sex- and race-specific equations for prediction of long-term risk of HF demonstrated high discrimination and adequate calibration.

Status of Cardiovascular Health in US Adults and Children Using the American Heart Association's New "Life's Essential 8" Metrics: Prevalence Estimates From the National Health and Nutrition Examination Survey (NHANES), 2013 Through 2018.

BACKGROUND: The American Heart Association recently published an updated algorithm for quantifying cardiovascular health (CVH)-the Life's Essential 8 score. We quantified US levels of CVH using the new score. METHODS: We included individuals ages 2 through 79 years (not pregnant or institutionalized) who were free of cardiovascular disease from the National Health and Nutrition Examination Surveys in 2013 through 2018. For all participants, we calculated the overall CVH score (range, 0 [lowest] to 100 [highest]), as well as the score for each component of diet, physical activity, nicotine exposure, sleep duration, body mass index, blood lipids, blood glucose, and blood pressure, using published American Heart Association definitions. Sample weights and design were incorporated in calculating prevalence estimates and standard errors using standard survey procedures. CVH scores were assessed across strata of age, sex, race and ethnicity, family income, and depression. RESULTS: There were 23 409 participants, representing 201 728 000 adults and 74 435 000 children. The overall mean CVH score was 64.7 (95% CI, 63.9-65.6) among adults using all 8 metrics and 65.5 (95% CI, 64.4-66.6) for the 3 metrics available (diet, physical activity, and body mass index) among children and adolescents ages 2 through 19 years. For adults, there were significant differences in mean overall CVH scores by sex (women, 67.0; men, 62.5), age (range of mean values, 62.2-68.7), and racial and ethnic group (range, 59.7-68.5). Mean scores were lowest for diet, physical activity, and body mass index metrics. There were large differences in mean scores across demographic groups for diet (range, 23.8-47.7), nicotine exposure (range, 63.1-85.0), blood glucose (range, 65.7-88.1), and blood pressure (range, 49.5-84.0). In children, diet scores were low (mean 40.6) and were progressively lower in higher age groups (from 61.1 at ages 2 through 5 to 28.5 at ages 12 through 19); large differences were also noted in mean physical activity (range, 63.1-88.3) and body mass index (range, 74.4-89.4) scores by sociodemographic group. CONCLUSIONS: The new Life's Essential 8 score helps identify large group and individual differences in CVH. Overall CVH in the US population remains well below optimal levels and there are both broad and targeted opportunities to monitor, preserve, and improve CVH across the life course in individuals and the population.

Associations of Clinical and Social Risk Factors With Racial Differences in Premature Cardiovascular Disease.

BACKGROUND: Racial differences in cardiovascular disease (CVD) are likely related to differences in clinical and social factors. The relative contributions of these factors to Black-White differences in premature CVD have not been investigated. METHODS: In Black and White adults aged 18 to 30 years at baseline in the CARDIA study (Coronary Artery Risk Development in Young Adults), the associations of clinical, lifestyle, depression, socioeconomic, and neighborhood factors across young adulthood with racial differences in incident premature CVD were evaluated in sex-stratified, multivariable-adjusted Cox proportional hazards models using multiply imputed data assuming missing at random. Percent reduction in the ß estimate (log-hazard ratio [HR]) for race quantified the contribution of each factor group to racial differences in incident CVD. RESULTS: Among 2785 Black and 2327 White participants followed for a median 33.9 years (25th-75th percentile, 33.7-34.0), Black (versus White) adults had a higher risk of incident premature CVD (Black women: HR, 2.44 [95% CI, 1.71-3.49], Black men: HR, 1.59 [1.20-2.10] adjusted for age and center). Racial differences were not statistically significant after full adjustment (Black women: HR, 0.91 [0.55-1.52], Black men: HR 1.02 [0.70-1.49]). In women, the largest magnitude percent reduction in the ß estimate for race occurred with adjustment for clinical (87%), neighborhood (32%), and socioeconomic (23%) factors. In men, the largest magnitude percent reduction in the ß estimate for race occurred with an adjustment for clinical (64%), socioeconomic (50%), and lifestyle (34%) factors. CONCLUSIONS: In CARDIA, the significantly higher risk for premature CVD in Black versus White adults was statistically explained by adjustment for antecedent multilevel factors. The largest contributions to racial differences were from clinical and neighborhood factors in women, and clinical and socioeconomic factors in men.

Atherosclerotic Cardiovascular Disease or Heart Failure: First Cardiovascular Event in Adults With Prediabetes and Diabetes.

BACKGROUND: Individuals with prediabetes and diabetes are at increased risk of atherosclerotic cardiovascular disease (ASCVD) and heart failure (HF). Whether ASCVD or HF is more likely to occur first in these populations within different race-sex groups is unknown. OBJECTIVE: To determine the competing risk for the first cardiovascular event by subtype in Black and white men and women with prediabetes and diabetes. METHODS: Individual-level data from adults without ASCVD or HF were pooled from 6 population-based cohorts. We estimated the competing cumulative incidences of ASCVD, HF and noncardiovascular death as the first event in middle-aged (40-59 years) and older (60-79 years) adults, stratified by race and sex, with normal fasting plasma glucose (FPG < 100 mg/dL), prediabetes (FPG 100-125 mg/dL) and diabetes (FPG ≥ 126 mg/dL or on antihyperglycemic agents) at baseline. Within each race-sex group, we estimated risk the adjusted hazard ratio of ASCVD, HF and noncardiovascular death in adults with prediabetes and diabetes relative to adults with normoglycemia after adjusting for cardiovascular risk factors. RESULTS: In 40,117 participants with 638,910 person-years of follow-up, 5781 cases of incident ASCVD and 3179 cases of incident HF occurred. In middle-aged adults with diabetes, competing cumulative incidence of ASCVD as a first event was higher than HF in white men (35.4% vs 11.6%), Black men (31.6% vs 15.1%) and white women (24.3% vs 17.2%) but not in Black women (26.4% vs 28.4%). Within each group, the adjusted hazard ratio of ASCVD and HF was significantly higher in adults with diabetes than in adults with normal FPG levels. Findings were largely similar in middle-aged adults with prediabetes and older adults with prediabetes or diabetes. CONCLUSIONS: Black women with diabetes are more likely to develop HF as their first CVD event, whereas individuals with diabetes from other race-sex groups are more likely to present first with ASCVD. These results can inform the tailoring of primary prevention therapies for either HF- or ASCVD-specific pathways based on individual-level risk.

Epigenetic Age Acceleration Reflects Long-Term Cardiovascular Health.

[Figure: see text].

Comparison of State-of-the-Art Neural Network Survival Models with the Pooled Cohort Equations for Cardiovascular Disease Risk Prediction.

BACKGROUND: The Pooled Cohort Equations (PCEs) are race- and sex-specific Cox proportional hazards (PH)-based models used for 10-year atherosclerotic cardiovascular disease (ASCVD) risk prediction with acceptable discrimination. In recent years, neural network models have gained increasing popularity with their success in image recognition and text classification. Various survival neural network models have been proposed by combining survival analysis and neural network architecture to take advantage of the strengths from both. However, the performance of these survival neural network models compared to each other and to PCEs in ASCVD prediction is unknown. METHODS: In this study, we used 6 cohorts from the Lifetime Risk Pooling Project (with 5 cohorts as training/internal validation and one cohort as external validation) and compared the performance of the PCEs in 10-year ASCVD risk prediction with an all two-way interactions Cox PH model (Cox PH-TWI) and three state-of-the-art neural network survival models including Nnet-survival, Deepsurv, and Cox-nnet. For all the models, we used the same 7 covariates as used in the PCEs. We fitted each of the aforementioned models in white females, white males, black females, and black males, respectively. We evaluated models' internal and external discrimination power and calibration. RESULTS: The training/internal validation sample comprised 23216 individuals. The average age at baseline was 57.8 years old (SD = 9.6); 16% developed ASCVD during average follow-up of 10.50 (SD = 3.02) years. Based on 10 × 10 cross-validation, the method that had the highest C-statistics was Deepsurv (0.7371) for white males, Deepsurv and Cox PH-TWI (0.7972) for white females, PCE (0.6981) for black males, and Deepsurv (0.7886) for black females. In the external validation dataset, Deepsurv (0.7032), Cox-nnet (0.7282), PCE (0.6811), and Deepsurv (0.7316) had the highest C-statistics for white male, white female, black male, and black female population, respectively. Calibration plots showed that in 10 × 10 validation, all models had good calibration in all race and sex groups. In external validation, all models overestimated the risk for 10-year ASCVD. CONCLUSIONS: We demonstrated the use of the state-of-the-art neural network survival models in ASCVD risk prediction. Neural network survival models had similar if not superior discrimination and calibration compared to PCEs.

Analysis of apoB Concentrations Across Early Adulthood and Predictors for Rates of Change Using CARDIA Study Data.

The cumulative exposure to apolipoprotein B (apoB)-containing lipoproteins in the blood during early adult life is a central determinant of atherosclerotic cardiovascular disease risk. To date, the patterns and rates of change in apoB through early adult life have not been described. Here, we used NMR to measure apoB concentrations in up to 3055 Coronary Artery Risk Development in Young Adults (CARDIA) Study participants who attended the years 2 (Y2), 7 (Y7), 15 (Y15), 20 (Y20), and 30 (Y30) exams. We examined individual-level spaghetti plots of apoB change, and we calculated average annualized rate of apoB concentration change during follow-up. We used multivariable linear regression models to assess the associations between CARDIA participant characteristics and annualized rates of apoB change. Male sex, higher measures of adiposity, lower HDL-C, lower Healthy Eating Index, and higher blood pressures were observed more commonly in individuals with higher apoB level at Y2 and Y20. Inter- and intra-individual variation in apoB concentration over time was substantial-while the mean (SD) rate of change was 0.52 (1.0) mg/dl/year, the range of annualized rates of change was -6.26 to +9.21 mg/dl/year. At baseline, lower first apoB measurement, female sex, White race, lower BMI, and current tobacco use were associated with apoB increase. We conclude that the significant variance in apoB level over time and the modest association between baseline measures and rates of apoB change suggest that the ability to predict an individual's future apoB serum concentrations, and thus their cumulative apoB exposure, after a one-time assessment in young adulthood is low.

Ten-Year Risk-Prediction Equations for Incident Heart Failure Hospitalizations in Chronic Kidney Disease: Findings from the Chronic Renal Insufficiency Cohort Study and the Multi-Ethnic Study of Atherosclerosis.

BACKGROUND: Heart failure (HF) is a leading contributor to cardiovascular morbidity and mortality in the population with chronic kidney disease (CKD). HF risk prediction tools that use readily available clinical parameters to risk-stratify individuals with CKD are needed. METHODS: We included Black and White participants aged 30-79 years with CKD stages 2-4 who were enrolled in the Chronic Renal Insufficiency Cohort (CRIC) study and were without self-reported cardiovascular disease. We assessed model performance of the Pooled Cohort Equations to Prevent Heart Failure (PCP-HF) to predict incident hospitalizations due to HF and refit the PCP-HF in the population with CKD by using CRIC data-derived coefficients and survival from CRIC study participants in the CKD population (PCP-HFCKD). We investigated the improvement in HF prediction with inclusion of estimated glomerular filtration rate (eGFR) and urine albumin-to-creatinine ratio (UACR) into the PCP-HFCKD equations by change in C-statistic, net reclassification improvement (NRI), and integrated discrimination improvement index (IDI). We validated the PCP-HFCKD with and without eGFR and UACR in Multi-Ethnic Study of Atherosclerosis (MESA) participants with CKD. RESULTS: Among 2328 CRIC Study participants, 340 incident HF hospitalizations occurred over a mean follow-up of 9.5 years. The PCP-HF equations did not perform well in most participants with CKD and had inadequate discrimination and insufficient calibration (C-statistic 0.64-0.71, Greenwood-Nam-D'Agostino (GND) chi-square statistic P value < 0.05), with modest improvement and good calibration after being refit (PCP-HFCKD: C-statistic 0.61-0.78), GND chi-square statistic P value > 0.05). Addition of UACR, but not eGFR, to the refit PCP-HFCKD improved model performance in all race-sex groups (C-statistic [0.73-0.81], GND chi-square statistic P value > 0.05, delta C-statistic ranging from 0.03-0.11 and NRI and IDI P values < 0.01). External validation of the PCP-HFCKD in MESA demonstrated good discrimination and calibration. CONCLUSIONS: Routinely available clinical data that include UACR in patients with CKD can reliably identify individuals at risk of HF hospitalizations.

Development and Validation of a Large Synthetic Cohort for the Study of Cardiovascular Health Across the Life Span.

We developed and validated a synthetic cohort approach to examine numbers of cardiovascular risk factors (CRFs) and adverse clinical events, including incident cardiovascular disease and all-cause mortality, across the life span from ages 20 years to 90 years. The current analysis included 40,875 participants from 7 large, population-based longitudinal epidemiologic studies (1948-2016). On the basis of a joint multilevel imputation model, we multiply imputed each participant's life-span numbers of CRFs and events using available records. To validate the imputed values, we partially removed the observed data and then compared the imputed and observed values. The complete life-span synthetic data set reflected the original observed data trends well. In our validation sample, the distributions of imputed CRFs and events were close to the observed distributions but with less variability. Bland-Altman plots indicated that there was a slightly negative trend in general, and the agreement bias was relatively small for the continuous CRFs. The hypothetical linear regression model suggested that the relationships between the CRFs and events were preserved in the imputed data set. This approach generated valid estimates of CRFs and events across the life span for African-American and White participants. The synthetic cohort may be sufficiently accurate to be useful in assessing the origins and timing of accumulating cardiovascular risk that can inform efforts to avoid cardiovascular disease development.

Distribution and Correlates of Incident Heart Failure Risk in South Asian Americans: The MASALA Study.

BACKGROUND: South Asian Americans experience disproportionately high burden of cardiovascular diseases. Estimating predicted heart failure (HF) risk distribution may facilitate targeted prevention. We estimated the distribution of 10-year predicted risk of incident HF in South Asian Americans and evaluated the associations with social determinants of health and clinical risk factors. METHODS AND RESULTS: In the Mediators of Atherosclerosis in South Asians Living in America (MASALA) Study, we calculated 10-year predicted HF risk using the Pooled Cohort Equations to Prevent Heart Failure multivariable model. Distributions of low (<1%), intermediate (1%-5%), and high (≥5%) HF risk, identified overall and by demographic and clinical characteristics, were compared. We evaluated age- and sex-adjusted associations of demographic characteristics and coronary artery calcium with predicted HF risk category using ordinal logistic regression. In 1159 participants (48% women), with a mean age of 57 ± 9 years, 40% had a low, 37% had an intermediate, and 24% had a high HF risk. Significant differences in HF risk distribution existed across demographic (income, education, birthplace) and clinical (diabetes, hypertension, body mass index, coronary artery calcium) groups (P < .01). Significant associations with high predicted HF risk were observed for a family of income 75,000/year or more (adjusted odds ratio 0.5 [95% confidence interval (CI) 0.4-0.7]), college education (0.6 [95% CI 0.4-0.9]), birthplace in another South Asian country (1.9 [95% CI 1.2-3.2], vs. born in India), and prevalent coronary artery calcium (2.6 [95% CI 1.9-3.6]). CONCLUSIONS: Almost two-thirds of South Asian Americans in the MASALA cohort are at intermediate or high predicted 10-year HF risk, with varying risk across demographic and clinical characteristics.

Association of fasting glucose with lifetime risk of incident heart failure: the Lifetime Risk Pooling Project.

BACKGROUND: Given the rising prevalence of dysglycemia and disparities in heart failure (HF) burden, we determined race- and sex-specific lifetime risk of HF across the spectrum of fasting plasma glucose (FPG). METHODS: Individual-level data from adults without baseline HF was pooled from 6 population-based cohorts. Modified Kaplan-Meier analysis, Cox models adjusted for the competing risk of death, and Irwin's restricted mean were used to estimate the lifetime risk, adjusted hazard ratio (aHR), and years lived free from HF in middle-aged (40-59 years) and older (60-79 years) adults with FPG < 100 mg/dL, prediabetes (FPG 100-125 mg/dL) and diabetes (FPG ≥ 126 mg/dL or on antihyperglycemic agents) across race-sex groups. RESULTS: In 40,117 participants with 638,910 person-years of follow-up, 4846 cases of incident HF occurred. The lifetime risk of HF was significantly higher among middle-aged White adults and Black women with prediabetes (range: 6.1% [95% CI 4.8%, 7.4%] to 10.8% [95% CI 8.3%, 13.4%]) compared with normoglycemic adults (range: 3.5% [95% CI 3.0%, 4.1%] to 6.5% [95% CI 4.9%, 8.1%]). Middle-aged Black women with diabetes had the highest lifetime risk (32.4% [95% CI 26.0%, 38.7%]) and aHR (4.0 [95% CI 3.0, 5.4]) for HF across race-sex groups. Middle-aged adults with prediabetes and diabetes lived on average 0.9-1.6 and 4.1-6.0 fewer years free from HF, respectively. Findings were similar in older adults except older Black women with prediabetes did not have a higher lifetime risk of HF. CONCLUSIONS: Prediabetes was associated with higher lifetime risk of HF in middle-aged White adults and Black women, with the association attenuating in older Black women. Black women with diabetes had the highest lifetime risk of HF compared with other race-sex groups.

Association between incarceration and incident cardiovascular disease events: results from the CARDIA cohort study.

BACKGROUND: Incarceration has been associated with higher cardiovascular risk, yet data evaluating its association with cardiovascular disease events are limited. The study objective was to evaluate the association between incarceration and incident fatal and non-fatal cardiovascular disease (CVD) events. METHODS: Black and white adults from the community-based Coronary Artery Risk Development in Young Adult (CARDIA) study (baseline 1985-86, n = 5105) were followed through August 2017. Self-reported incarceration was measured at baseline (1985-1986) and Year 2 (1987-1988), and fatal and non-fatal cardiovascular disease events, including coronary heart disease, stroke, and heart failure, and all-cause mortality, were captured through 2017. Analyses were completed in September 2019. Cumulative CVD incidence rates and Cox proportional hazards were compared overall by incarceration status. An interaction between incarceration and race was identified, so results were also analyzed by sex-race groups. RESULTS: 351 (6.9%) CARDIA participants reported a history of incarceration. Over 29.0 years mean follow-up, CVD incidence rate was 3.52 per 1000 person-years in participants with a history of incarceration versus 2.12 per 1000 person-years in participants without a history of incarceration (adjusted HR = 1.33 [95% CI, 0.90-1.95]). Among white men, incarceration was associated with higher risk of incident cardiovascular disease (adjusted HR = 3.35 [95% CI, 1.54-7.29) and all-cause mortality (adjusted HR = 2.52 [95% CI, 1.32-4.83]), but these associations were not statistically significant among other sex-race groups after adjustment. CONCLUSIONS: Incarceration was associated with incident cardiovascular disease rates, but associations were only significant in one sex-race group after multivariable adjustment.

Low Awareness of Nonalcoholic Fatty Liver Disease in a Population-Based Cohort Sample: the CARDIA Study.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the United States, yet little is known about NAFLD awareness in individuals with incidental fatty liver on imaging. OBJECTIVE: To assess the level of awareness of imaging-defined NAFLD among individuals with and without metabolic risk factors. DESIGN: Cross-sectional analysis within a prospective longitudinal population-based cohort study conducted in four U.S. cities. PARTICIPANTS: Adults age 43 to 55 years enrolled in the Coronary Artery Risk Development in Young Adults (CARDIA) Study who underwent computed tomography and a personal health questionnaire at the year 25 exam (2010-2011, n = 2788). MAIN MEASURES: NAFLD was defined as liver attenuation ≤ 51 Hounsfield units after exclusion of other causes of liver fat. Participants were considered "NAFLD aware" if they reported being told previously by a doctor or nurse that they had "fatty liver." KEY RESULTS: NAFLD prevalence was 23.9%. Only 16 of 667 (2.4%) participants with CT-defined NAFLD were aware of a NAFLD diagnosis. NAFLD aware participants were more likely to be white (81.3% vs. 53.5%, p = 0.03) and have the metabolic syndrome (87.5% vs. 59.3%, p = 0.02) and/or hypertension (75.0% vs. 50.2%, p = 0.05). In multivariable analyses adjusted for demographics, metabolic syndrome and hypertension remained predictive of NAFLD awareness. CONCLUSION: There is low awareness of NAFLD among individuals with hepatic steatosis on imaging, even among those with metabolic risk factors. These findings highlight an opportunity to raise public and practitioner awareness of NAFLD with the goal of increasing diagnosis and implementing early treatment strategies.

Association of cardiovascular health through early adulthood and health-related quality of life in middle age: The Coronary Artery Risk Development in Young Adults (CARDIA) Study.

Previous studies have linked cardiovascular health (CVH) and health-related quality of life (HRQoL), but only in cross-sectional analyses where temporality cannot be established. The aim of this study was to determine trajectories of CVH from early adulthood to middle age, and examine their association with HRQoL in middle age. This analysis, conducted in 2018, included 3275 participants of the Coronary Artery Risk Development in Young Adults (CARDIA) study who completed a year 30 follow-up exam in 2015/2016. Group-based trajectory modeling was used to create CVH trajectories, according to American Heart Association definitions, from baseline through follow-up year 20. HRQoL was assessed by the Medical Outcomes Study 12-Item Short Form Health Survey at year 30, which included the physical component summary score (PCS), the mental component summary score (MCS), and overall self-rated health (SRH). The mean (SD) age of the sample was 55.1 (3.6) years, 1868 (57%) were women, and 1541 (47%) were black. Five CVH trajectories were identified, 31% of CARDIA participants maintained ideal CVH during follow-up. Maintaining ideal CVH was associated with higher PCS and MCS, and lower odds of fair/poor SRH as compared to the other trajectory groups. Compared to the consistently low CVH group, those who maintained ideal CVH had on average a 5.9 point higher PCS (95% CI, 4.2-7.7), a 2.5-point higher MCS (95% CI, 0.5-4.4), and 84% lower odds of fair/poor SRH (95% CI, 0.09, 0.31). Our findings suggest that maintaining ideal CVH from early adulthood results in higher health-related quality of life in middle age.

Trends in Levels of Lipids and Apolipoprotein B in US Youths Aged 6 to 19 Years, 1999-2016.

Importance: Favorable trends occurred in the lipid levels of US youths through 2010, but these trends may be altered by ongoing changes in the food supply, obesity prevalence, and other factors. Objective: To analyze trends in levels of lipids and apolipoprotein B in US youths during 18 years from 1999 through 2016. Design, Setting, and Participants: Serial cross-sectional analysis of US population-weighted data for youths aged 6 to 19 years from the National Health and Nutrition Examination Surveys for 1999 through 2016. Linear temporal trends were analyzed using multivariable regression models with regression coefficients (ß) reported as change per 1 year. Exposures: Survey year; examined periods spanned 10 to 18 years based on data availability. Main Outcomes and Measures: Age- and race/ethnicity-adjusted mean levels of high-density lipoprotein (HDL), non-HDL, and total cholesterol. Among fasting adolescents (aged 12-19 years), mean levels of low-density lipoprotein cholesterol, geometric mean levels of triglycerides, and mean levels of apolipoprotein B. Prevalence of ideal and adverse (vs borderline) levels of lipids and apolipoprotein B per pediatric lipid guidelines. Results: In total, 26 047 youths were included (weighted mean age, 12.4 years; female, 51%). Among all youths, the adjusted mean total cholesterol level declined from 164 mg/dL (95% CI, 161 to 167 mg/dL) in 1999-2000 to 155 mg/dL (95% CI, 154 to 157 mg/dL) in 2015-2016 (ß for linear trend, -0.6 mg/dL [95% CI, -0.7 to -0.4 mg/dL] per year). Adjusted mean HDL cholesterol level increased from 52.5 mg/dL (95% CI, 51.7 to 53.3 mg/dL) in 2007-2008 to 55.0 mg/dL (95% CI, 53.8 to 56.3 mg/dL) in 2015-2016 (ß, 0.2 mg/dL [95% CI, 0.1 to 0.4 mg/dL] per year) and non-HDL cholesterol decreased from 108 mg/dL (95% CI, 106 to 110 mg/dL) to 100 mg/dL (95% CI, 99 to 102 mg/dL) during the same years (ß, -0.9 mg/dL [95% CI, -1.2 to -0.6 mg/dL] per year). Among fasting adolescents, geometric mean levels of triglycerides declined from 78 mg/dL (95% CI, 74 to 82 mg/dL) in 1999-2000 to 63 mg/dL (95% CI, 58 to 68 mg/dL) in 2013-2014 (log-transformed ß, -0.015 [95% CI, -0.020 to -0.010] per year), mean levels of low-density lipoprotein cholesterol declined from 92 mg/dL (95% CI, 89 to 95 mg/dL) to 86 mg/dL (95% CI, 83 to 90 mg/dL) during the same years (ß, -0.4 mg/dL [95% CI, -0.7 to -0.2 mg/dL] per year), and mean levels of apolipoprotein B declined from 70 mg/dL (95% CI, 68 to 72 mg/dL) in 2005-2006 to 67 mg/dL (95% CI, 65 to 70 mg/dL) in 2013-2014 (ß, -0.4 mg/dL [95% CI, -0.7 to -0.04 mg/dL] per year). Favorable trends were generally also observed in the prevalence of ideal and adverse levels. By the end of the study period, 51.4% (95% CI, 48.5% to 54.2%) of all youths had ideal levels for HDL, non-HDL, and total cholesterol; among adolescents, 46.8% (95% CI, 40.9% to 52.6%) had ideal levels for all lipids and apolipoprotein B, whereas 15.2% (95% CI, 13.1% to 17.3%) of children aged 6 to 11 years and 25.2% (95% CI, 22.2% to 28.2%) of adolescents aged 12 to 19 years had at least 1 adverse level. Conclusions and Relevance: Between 1999 and 2016, favorable trends were observed in levels of lipids and apolipoprotein B in US youths aged 6 to 19 years.

Associations of Dietary Cholesterol or Egg Consumption With Incident Cardiovascular Disease and Mortality.

Importance: Cholesterol is a common nutrient in the human diet and eggs are a major source of dietary cholesterol. Whether dietary cholesterol or egg consumption is associated with cardiovascular disease (CVD) and mortality remains controversial. Objective: To determine the associations of dietary cholesterol or egg consumption with incident CVD and all-cause mortality. Design, Setting, and Participants: Individual participant data were pooled from 6 prospective US cohorts using data collected between March 25, 1985, and August 31, 2016. Self-reported diet data were harmonized using a standardized protocol. Exposures: Dietary cholesterol (mg/day) or egg consumption (number/day). Main Outcomes and Measures: Hazard ratio (HR) and absolute risk difference (ARD) over the entire follow-up for incident CVD (composite of fatal and nonfatal coronary heart disease, stroke, heart failure, and other CVD deaths) and all-cause mortality, adjusting for demographic, socioeconomic, and behavioral factors. Results: This analysis included 29 615 participants (mean [SD] age, 51.6 [13.5] years at baseline) of whom 13 299 (44.9%) were men and 9204 (31.1%) were black. During a median follow-up of 17.5 years (interquartile range, 13.0-21.7; maximum, 31.3), there were 5400 incident CVD events and 6132 all-cause deaths. The associations of dietary cholesterol or egg consumption with incident CVD and all-cause mortality were monotonic (all P values for nonlinear terms, .19-.83). Each additional 300 mg of dietary cholesterol consumed per day was significantly associated with higher risk of incident CVD (adjusted HR, 1.17 [95% CI, 1.09-1.26]; adjusted ARD, 3.24% [95% CI, 1.39%-5.08%]) and all-cause mortality (adjusted HR, 1.18 [95% CI, 1.10-1.26]; adjusted ARD, 4.43% [95% CI, 2.51%-6.36%]). Each additional half an egg consumed per day was significantly associated with higher risk of incident CVD (adjusted HR, 1.06 [95% CI, 1.03-1.10]; adjusted ARD, 1.11% [95% CI, 0.32%-1.89%]) and all-cause mortality (adjusted HR, 1.08 [95% CI, 1.04-1.11]; adjusted ARD, 1.93% [95% CI, 1.10%-2.76%]). The associations between egg consumption and incident CVD (adjusted HR, 0.99 [95% CI, 0.93-1.05]; adjusted ARD, -0.47% [95% CI, -1.83% to 0.88%]) and all-cause mortality (adjusted HR, 1.03 [95% CI, 0.97-1.09]; adjusted ARD, 0.71% [95% CI, -0.85% to 2.28%]) were no longer significant after adjusting for dietary cholesterol consumption. Conclusions and Relevance: Among US adults, higher consumption of dietary cholesterol or eggs was significantly associated with higher risk of incident CVD and all-cause mortality in a dose-response manner. These results should be considered in the development of dietary guidelines and updates.

Alcohol Use and Cardiovascular Disease Risk in Patients With Nonalcoholic Fatty Liver Disease.

BACKGROUND & AIMS: Cardiovascular disease (CVD) is the leading cause of death among patients with nonalcoholic fatty liver disease (NAFLD). Moderate drinking (vs abstinence) is associated with lower risk of CVD in the general population. We assessed whether alcohol use is associated with CVD risk in patients with NAFLD. METHODS: We analyzed data from participants in the Coronary Artery Risk Development in Young Adults longitudinal cohort study of 5115 black and white young adults, 18-30 years old, recruited from 4 cities in the United States from 1985 through 1986. Participants self-reported alcohol use at study entry and then again after 15, 20, and 25 years. At year 25 (2010-2011), participants underwent computed tomography examination of the thorax and abdomen and tissue Doppler echocardiography with myocardial strain measured by speckle tracking. Coronary artery calcification was defined as an Agatston score above 0. NAFLD was defined as liver attenuation <51 Hounsfield Units after exclusions. Drinkers reported 1-21 (men) or 1-14 (women) standard drinks/week at years 15, 20, or 25. Nondrinkers reported no alcohol use at years 15, 20, and 25. RESULTS: Of the 570 participants with NAFLD (mean age, 50 years; 54% black; 46% female), 332 (58%) were drinkers; significantly higher proportions of drinkers were white, male, and with higher levels of education compared with nondrinkers (P < .05 for all). Higher proportions of drinkers had obesity, diabetes, and metabolic syndrome compared with nondrinkers (P < .01). There was no difference in liver attenuation between groups (P = .12). After multivariable adjustment, there was no association between alcohol use and CVD risk factors (diabetes, hypertension, hyperlipidemia) or subclinical CVD measures (coronary artery calcification, early transmitral velocity/late (atrial) transmitral velocity (E/A) ratio, global longitudinal strain). CONCLUSIONS: In a population-based sample of individuals with NAFLD in midlife, prospectively assessed alcohol use is not associated with significant differences in risk factors for CVD or markers of subclinical CVD. In contrast to general population findings, alcohol use may not reduce the risk of CVD in patients with NAFLD.

A point-based prediction model for cardiovascular risk in orthotopic liver transplantation: The CAR-OLT score.

Cardiovascular disease (CVD) complications are important causes of morbidity and mortality after orthotopic liver transplantation (OLT). There is currently no preoperative risk-assessment tool that allows physicians to estimate the risk for CVD events following OLT. We sought to develop a point-based prediction model (risk score) for CVD complications after OLT, the Cardiovascular Risk in Orthotopic Liver Transplantation risk score, among a cohort of 1,024 consecutive patients aged 18-75 years who underwent first OLT in a tertiary-care teaching hospital (2002-2011). The main outcome measures were major 1-year CVD complications, defined as death from a CVD cause or hospitalization for a major CVD event (myocardial infarction, revascularization, heart failure, atrial fibrillation, cardiac arrest, pulmonary embolism, and/or stroke). The bootstrap method yielded bias-corrected 95% confidence intervals for the regression coefficients of the final model. Among 1,024 first OLT recipients, major CVD complications occurred in 329 (32.1%). Variables selected for inclusion in the model (using model optimization strategies) included preoperative recipient age, sex, race, employment status, education status, history of hepatocellular carcinoma, diabetes, heart failure, atrial fibrillation, pulmonary or systemic hypertension, and respiratory failure. The discriminative performance of the point-based score (C statistic = 0.78, bias-corrected C statistic = 0.77) was superior to other published risk models for postoperative CVD morbidity and mortality, and it had appropriate calibration (Hosmer-Lemeshow P = 0.33). CONCLUSION: The point-based risk score can identify patients at risk for CVD complications after OLT surgery (available at www.carolt.us); this score may be useful for identification of candidates for further risk stratification or other management strategies to improve CVD outcomes after OLT. (Hepatology 2017;66:1968-1979).

Body mass index trajectories in young adulthood predict non-alcoholic fatty liver disease in middle age: The CARDIA cohort study.

BACKGROUND & AIMS: Non-alcoholic fatty liver disease is an epidemic. Identifying modifiable risk factors for non-alcoholic fatty liver disease development is essential to design effective prevention programmes. We tested whether 25-year patterns of body mass index change are associated with midlife non-alcoholic fatty liver disease. METHODS: In all, 4423 participants from Coronary Artery Risk Development in Young Adults, a prospective population-based biracial cohort (age 18-30), underwent body mass index measurement at baseline (1985-1986) and 3 or more times over 25 years. At Year 25, 3115 had liver fat assessed by non-contrast computed tomography. Non-alcoholic fatty liver disease was defined as liver attenuation ≤40 Hounsfield Units after exclusions. Latent mixture modelling identified 25-year trajectories in body mass index per cent change (%Δ) from baseline. RESULTS: We identified four distinct trajectories of BMI%Δ: stable (26.2% of cohort, 25-year BMI %Δ = 3.1%), moderate increase (46.0%, BMI%Δ = 21.7%), high increase (20.9%, BMI%Δ = 41.9%) and extreme increase (6.9%, BMI%Δ = 65.9%). Y25 non-alcoholic fatty liver disease prevalence was higher in groups with greater BMI %Δ: 4.1%, 9.3%, 13.0%, and 17.6%, respectively (P-trend <.0001). In multivariable analyses, participants with increasing BMI%Δ had increasingly greater odds of non-alcoholic fatty liver disease compared to the stable group: OR: 3.35 (95% CI: 2.07-5.42), 7.80 (4.60-13.23) and 12.68 (6.68-24.09) for moderate, high and extreme body mass index increase, respectively. Associations were only moderately attenuated when adjusted for baseline or Y25 body mass index. CONCLUSIONS: Trajectories of weight gain during young adulthood are associated with greater non-alcoholic fatty liver disease prevalence in midlife independent of metabolic covariates and baseline or concurrent body mass index highlighting the importance of weight maintenance throughout adulthood as a target for primary non-alcoholic fatty liver disease prevention.