Impact of optimal cholesterol levels on subclinical atherosclerosis in the absence of risk factors in young adults.

BACKGROUND AND AIMS: We aimed to assess the association of blood lipids with the prevalence, incidence, and progression of subclinical atherosclerosis among young individuals without dyslipidemia and other traditional cardiovascular risk factors (CVRFs). METHODS: A total of 1270 participants from the Coronary Artery Risk Development in Young Adults (CARDIA) study aged 32-46 years free of cardiovascular disease, diabetes, hypertension, current smoking, and dyslipidemia (total cholesterol [TC] ≥ 240 mg/dL, triglycerides [TG] ≥ 150 mg/dL, low-density lipoprotein cholesterol [LDL-C] ≥ 160 mg/dL, high-density lipoprotein cholesterol [HDL-C] < 40 mg/dL, or taking lipid-lowering medications) were included. A subgroup with optimal lipids within the low-CVRF group was defined with TC < 200 mg/dL, LDL-C < 100 mg/dL, non-HDL-C < 130 mg/dL, and women with HDL-C ≥ 50 mg/dL. RESULTS: 1-SD higher TC (25.9 mg/dL), LDL-C (24.7 mg/dL), and non-HDL-C (26.6 mg/dL) were associated with a greater risk of presence (hazard ratios: 1.30-1.36), incidence (1.30-1.32), and progression (1.31-1.35) of coronary artery calcium (CAC) and a 42-44% greater odds of composite mean carotid intima-media thickness (CIMT) ≥ 75th percentile [780 µm] (p < 0.05). Repeating the analyses in a subset of participants with a CAC score of zero did not alter the association of TC, LDL-C, and non-HDL-C with CIMT. In the subgroup with optimal lipids, these lipid indices remained associated with an increased risk of presence and incidence of CAC and greater CIMT measures. CONCLUSIONS: Among adults aged 32-46 years, in the absence of traditional CVRFs, elevated cholesterol levels, even within what is considered optimal, are associated with atherosclerosis and arteriopathy.

Association of Cardiovascular Health in Young Adulthood with Long-Term Blood Pressure Trajectories.

BACKGROUND: Cardiovascular health (CVH) in young adulthood (YA) has been associated with cardiovascular outcomes in older age. However, little is known about the relationship between YA CVH and mid-life BP trajectories. METHODS: Baseline CVH (defined by 7 of AHA's Life's Essential 8 [LE8] metrics, excluding BP) was measured in YA with individual metrics scored and averaged as a composite LE8 score. Categorical CVH status was defined as high, moderate, and low. Latent class analysis was used to identify trajectories of mid-BP (mean of SBP and DBP) from average ages 35 to 55 years. Multinomial logistic regression was used to estimate the association of YA CVH status (continuously and categorically) with mid-life BP trajectory group membership. RESULTS: There were 3,688 participants from the Coronary Artery Risk Development in Young Adults (CARDIA) study in YA with follow-up data for mid-life BP trajectories. We observed 3 BP trajectory groups, labeled as Persistently-Low, Middle, and High-Increasing. On average, each 10-points higher baseline LE8 score (mean [SD] of 73.5 [13.1]) in YA was associated with adjusted odds ratios of 0.78 (95% CI, 0.72-0.84) for membership in the Middle and 0.65 (0.57-0.73) for membership in the High-Increasing trajectory groups. Compared with categorical low CVH status at baseline, those with high CVH were significantly less likely to be in the Middle and High-Increasing BP trajectory groups. CONCLUSIONS: Moderate or low CVH status in YA is associated with elevated mid-life BP trajectory. These data suggest that young adult CVH promotion may be important for primordial prevention of hypertension.

Higher literacy is associated with better white matter integrity and cognition in middle age.

Introduction: Literacy can be a better measure of quality of education. Its association with brain health in midlife has not been thoroughly investigated. Methods: We studied, cross-sectionally, 616 middle-aged adults (mean age of 55.1 ± 3.6 years, 53% female and 38% Black) from the Coronary Artery Risk Development in Young Adults (CARDIA) study. We correlated literacy with cognitive tests, gray matter volumes, and fractional anisotropy (FA) values (indirect measures of white matter integrity) using linear regression. Results: The higher-literacy group (n = 499) performed better than the low-literacy group (n = 117) on all cognitive tests. There was no association between literacy and gray matter volumes. The higher-literacy group had greater total-brain FA and higher temporal, parietal, and occipital FA values after multivariable adjustments. Discussion: Higher literacy is associated with higher white matter integrity as well as with better cognitive performance in middle-aged adults. These results highlight the importance of focusing on midlife interventions to improve literacy skills.

Triglyceride-Glucose Index and Homeostasis Model Assessment-Insulin Resistance in Young Adulthood and Risk of Incident Congestive Heart Failure in Midlife: The Coronary Artery Risk Development in Young Adults Study.

Objective: This study aimed to assess the association between triglyceride-glucose (TyG) index/homeostasis model assessment-insulin resistance (HOMA-IR) within young adults and congestive heart failure (CHF), and to explore whether TyG index can replace HOMA-IR as a surrogate marker for IR in predicting the risk of CHF. Methods: A total of 4,992 participants between the ages of 18 and 30 years were enrolled from the Coronary Artery Risk Development in Young Adults (CARDIA) investigation [from 1985 to 1986 (year 0)]. A Cox proportional hazard regression analysis was conducted for assessing correlations between baseline TyG index/HOMA-IR and CHF events, together with the receiver operating characteristic (ROC) curve employed for scrutinizing TyG index/HOMA-IR and the risk of CHF. Results: During the 31-year follow-up period, 64 (1.3%) of the 4,992 participants developed CHF. In multivariable Cox proportional hazards models, adjusted for confounding factors for CHF, an increased risk of CHF was associated with a per-unit increase in the TyG index [hazard ratio (HR) 2.8; 95% confidence interval (CI), 1.7-4.7] and HOMA-IR (HR 1.2; 95% CI, 1.1-1.3). A Kaplan-Meier curve analysis showed that participants in the TyG index and HOMA-IR index Q4 group had a higher risk of CHF than those in the Q1 group. The area under curve (AUC) for the TyG index and HOMA-IR consisted of 0.67 (95% CI, 0.6-0.742) and 0.675 (95% CI, 0.604-0.746), respectively. There were no significant differences between the TyG index and HOMA-IR for AUC (p = 0.986). Conclusion: The higher TyG index and HOMA-IR are independent risk factors for CHF. The TyG index can replace HOMA-IR in young adulthood as a surrogate marker for IR to predict the risk of CHF.

Cadmium Exposure in Young Adulthood Is Associated with Risk of Nonalcoholic Fatty Liver Disease in Midlife.

BACKGROUND: Studies have suggested that cadmium (Cd) may be involved in the etiology of nonalcoholic fatty liver disease (NAFLD), but available data in human is sparse. AIMS: We aimed to examine Cd exposure in young adulthood in relation to prevalent NAFLD in midlife among American adults. METHODS: This study included 2446 participants from the Coronary Artery Risk Development in Young Adults study with toenail Cd measurement at exam year 2 (baseline) and computed tomography quantification of liver fat at exam year 25. Toenail Cd concentrations were considered as a reliable marker of long-term exposure. NAFLD was defined if liver attenuation < 51 Hounsfield units after excluding other possible causes of liver fat. Multivariable-adjusted logistic regression models were used to estimate the odds ratio of NAFLD by Cd exposure. RESULTS: Median toenail Cd concentration was 8.2 ppb (inter-quartile range 4.3-18.6 ppb). After 23 years from baseline, 580 participants with prevalent NAFLD (24% prevalence) in midlife were identified. Compared with individuals in the lowest quartile, those in the highest quartile of toenail Cd had a significantly higher odds of NAFLD (OR: 1.43, 95% CI: 1.02, 1.99, P for trend: 0.04) after adjustment for demographics, socioeconomics, major lifestyle factors, and baseline levels of body mass index, lipids, and fasting insulin. The association was not significantly modified by race, sex, BMI, or smoking status at baseline. CONCLUSIONS: Toenail Cd concentration was associated with a higher odds of prevalent NAFLD23 years later in life in this cohort of US general population.

Association of Chronic Respiratory Symptoms With Incident Cardiovascular Disease and All-Cause Mortality: Findings From the Coronary Artery Risk Development in Young Adults Study.

BACKGROUND: Respiratory and cardiovascular diseases (CVDs) frequently coexist; however, there is limited evidence on the relationship between chronic respiratory symptoms in young adulthood and late-onset CVD. RESEARCH QUESTION: Are chronic respiratory symptoms in young adulthood associated with CVD and all-cause mortality in later life? STUDY DESIGN AND METHODS: A total of 4,621 participants from the Coronary Artery Risk Development in Young Adults Study (CARDIA) cohort study aged 18 to 30 years were included. Chronic respiratory symptoms were identified through respiratory symptom questionnaires in two consecutive examinations. Incident CVD and all-cause mortality were adjudicated over 30-year follow-up. Multivariable Cox proportional hazards models were used to explore the association of chronic respiratory symptoms with incident CVD and all-cause mortality. RESULTS: During a median follow-up of 30.9 years, 284 CVD events (6.15%) and 378 deaths (8.18%) occurred. Following multivariable adjustment for demographic characteristics, cardiovascular risk factors, smoking, and lung function, the hazard ratios (95% CIs) for CVD events were 1.51 (1.18-1.93) for any respiratory symptom, 1.57 (1.18-2.09) for cough or phlegm, 1.31 (1.01-1.68) for wheeze, 1.73 (1.25-2.41) for shortness of breath, and 1.32 (1.01-1.71) for chest illnesses. Similar findings were also observed in all-cause mortality. Comparing zero vs three to four respiratory symptoms, the hazard ratios (95% CIs) were 1.97 (1.34-2.91) for CVD and 1.75 (1.23-2.47) for all-cause mortality. Similar results were observed in various sensitivity analyses. INTERPRETATION: Chronic respiratory symptoms in young adulthood are associated with an increased risk of CVD and all-cause mortality in midlife independent of established cardiovascular risk factors, smoking, and lung function. Identifying chronic respiratory symptoms in young adulthood may help provide prognostic information regarding future cardiovascular health. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov; No.: NCT00005130; URL: https://www. CLINICALTRIALS: gov.

Decision Tree-Based Classification for Maintaining Normal Blood Pressure Throughout Early Adulthood and Middle Age: Findings From the Coronary Artery Risk Development in Young Adults (CARDIA) Study.

BACKGROUND: For most individuals, blood pressure (BP) is related to multiple risk factors. By utilizing the decision tree analysis technique, this study aimed to identify the best discriminative risk factors and interactions that are associated with maintaining normal BP over 30 years and to reveal segments of a population with a high probability of maintaining normal BP. METHODS: Participants from the Coronary Artery Risk Development in Young Adults study aged 18-30 years with normal BP level at baseline visit (Y0, 1985-1986) were included in this study. RESULTS: Of 3,156 participants, 1,132 (35.9%) maintained normal BP during the follow-up period and 2,024 (64.1%) developed higher BP. Systolic BP (SBP) within the normal range, race, and body mass index (BMI) were the most discriminative factors between participants who maintained normal BP throughout midlife and those who developed higher BP. Participants with a baseline SBP level ≤92 mm Hg and White women with baseline BMI < 23 kg/m2 were the two segments of the population with the highest probability for maintaining normal BP throughout midlife (69.2% and 59.9%, respectively). Among Black participants aged >26.5 years with BMI > 27 kg/m2, only 5.4% of participants maintained normal BP throughout midlife. CONCLUSIONS: This study emphasizes the importance of early life factors to later life SBP and support efforts to maintain ideal levels of risk factors for hypertension at young ages. Whether policies to maintain lower BMI and SBP well below the clinical thresholds throughout young adulthood and middle age can reduce later age hypertension should be examined in future studies.

Intake of Vegetables and Fruits Through Young Adulthood Is Associated with Better Cognitive Function in Midlife in the US General Population.

BACKGROUND: Vegetables and fruits (VF) may differentially affect cognitive functions, presumably due to their various nutrient contents, but evidence from epidemiologic studies is limited. OBJECTIVES: The aim of this study was to examine the long-term association between VF intakes, including VF subgroups, in young adulthood and cognitive function in midlife. METHODS: A biracial cohort of 3231 men and women aged 18-30 y at baseline in 1985-1986 were followed up for 25 y in the Coronary Artery Risk Development in Young Adults Study. Diet was measured at baseline, and in examination years 7 and 20. Cognitive function was assessed at examination year 25 through the use of 3 tests: the Rey Auditory Verbal Learning Test (RAVLT), the Digit Symbol Substitution Test (DSST), and the Stroop test. The mean differences (MDs) with 95% CIs in cognitive scores across intake categories were estimated through the use of the multivariable-adjusted general linear regression model. RESULTS: Excluding potatoes, intake of whole vegetables was significantly associated with a better cognitive performance after adjustment for potential confounders in all 3 cognitive tests (quintile 5 compared with quintile 1-RAVLT, MD: 0.33; 95% CI: 0.01, 0.64; P-trend = 0.08; DSST, MD: 2.84; 95% CI: 0.93, 4.75; P-trend < 0.01; Stroop test, MD: -2.87; 95% CI: -4.24, -1.50; P-trend < 0.01]. Similarly, intake of fruits, except fruit juices, was significantly related to a better cognitive performance (quintile 5 compared with quintile 1-DSST, MD: 2.41; 95% CI: 0.70, 4.12; P-trend = 0.03). CONCLUSIONS: This study supports the long-term benefits of VF consumption on cognitive performance, except those VF with relatively low fiber content such as potatoes and fruit juices, among the middle-aged US general population.

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.

Racial discrimination and skin color in the CARDIA study: implications for public health research. Coronary Artery Risk Development in Young Adults.

OBJECTIVES: This study assessed whether skin color and ways of handling anger can serve as markers for experiences of racial discrimination and responses to unfair treatment in public health research. METHODS: Survey data on 1844 Black women and Black men (24 to 42 years old), collected in the year 5 (1990-1991) and year 7 (1992-1993) examinations of the Coronary Artery Risk Development in Young Adults (CARDIA) study, were examined. RESULTS: Skin color was not associated with self-reported experiences of racial discrimination in 5 of 7 specified situations (getting a job, at work, getting housing, getting medical care, in a public setting). Only moderate associations existed between darker skin color and being working class, having low income or low education, and being male (risk ratios under 2). Comparably moderate associations existed between internalizing anger and typically responding to unfair treatment as a fact of life or keeping such treatment to oneself. CONCLUSIONS: Self-reported experiences of racial discrimination and responses to unfair treatment should be measured directly in public health research; data on skin color and ways of handling anger are not sufficient.