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PurposeSouth Asian (SA) persons have increased risks for diabetes mellitus (DM) and atherosclerotic cardiovascular disease (ASCVD). We examined whether the association of DM with subclinical atherosclerosis assessed by coronary artery calcium (CAC) differs in SA versus other ethnic groups.MethodsWe studied adults from the Multi-Ethnic Study of Atherosclerosis and the Mediators of Atherosclerosis in South Asians Living in America studies without ASCVD. CAC was examined among those normoglycemic, pre-DM and DM. Logistic regression examined pre-DM and DM with the odds of any CAC > 0 and CAC ≥ 100.ResultsAmong 7562 participants, CAC > 0 and CAC ≥ 100 in those with DM was highest in non-Hispanic White (NHW) (80% and 48%) and SA (72% and 41%) persons. Adjusted Ln (CAC + 1) was highest in NHW (3.68 ± 0.21) and SA (3.60 ± 0.23) (p < .01) DM patients. SA and NHW adults with DM (vs normoglycemic) had highest odds of CAC > 0 (2.13 and 2.27, respectively, p < .01). For CAC ≥ 100, SA and Chinese adults had the highest odds (2.28 and 2.27, respectively, p < .01). Fasting glucose and glycated hemoglobin were most strongly associated with CAC among SA.ConclusionsDiabetes mellitus most strongly relates to any CAC in SA and NHW adults and CAC ≥ 100 in SA and Chinese adults, helping to explain the relation of DM with ASCVD in these populations.

ObjectivesTo determine the association between moderate-to-vigorous intensity physical activity (MVPA) trajectories (course over age and time) through the adult life course and onset of metabolic disease (diabetes and dyslipidaemia).MethodsWe analysed prospective community-based cohort data of 5115 participants in the Coronary Artery Risk Development in Young Adults study, who were black and white men and women aged 18-30 years at baseline (1985-1986) at four urban sites, collected through 30 years of follow-up. Individualised MVPA trajectories were developed for each participant using linear mixed models.ResultsLower estimated MVPA score at age 18 was associated with a 12% (95% CI 6% to 18%) higher odds of incident diabetes, a 4% (95% CI 1% to 7%) higher odds of incident low high-density lipoprotein (HDL) and a 6% (95% CI 2% to 11%) higher odds of incident high triglycerides. Each additional annual 1-unit reduction in the MVPA score was associated with a 6% (95% CI 4% to 9%) higher annual odds of diabetes incidence and a 4% (95% CI 2% to 6%) higher annual odds of high triglyceride incidence. Analysing various MVPA trajectory groups, participants who were in the most active group at age 18 (over 300 min/week), but with sharp declines in midlife, had higher odds of high low-density lipoprotein and low HDL incidence, compared with those in the most active group at age 18 with subsequent gains.ConclusionGiven recent trends in declining MVPA across the life course and associated metabolic disease risk, young adulthood is an important time period for interventions to increase and begin the maintenance of MVPA.

PurposeThis study aimed to evaluate associations between outpatient low-density lipoprotein cholesterol (LDL-C) testing and subsequent statin adherence and intensification in patients after an atherosclerotic cardiovascular (ASCVD) event.MethodsThis was a longitudinal study of adult members of Kaiser Permanente Northern California hospitalized with an ASCVD event (myocardial infarction or stroke) during January 01, 2016, to December 31, 2017, with follow-up through December 31, 2019. Outcomes were statin adherence (estimated using continuous medication gap [CMG]) and intensification (defined by an increased dose or switch to a higher-intensity statin) based on pharmacy dispensing. The exposure of interest was first outpatient LDL-C test after an ASCVD event. Baseline for follow-up was LDL-C test date or a date assigned using incidence density sampling. Multivariate logistic regression models were specified to estimate the odds ratios for statin adherence or intensification among those with vs without an LDL-C test, with adjustment for age, sex, race/ethnicity, smoking, hypertension, diabetes, body mass index, and estimated glomerular filtration rate.ResultsThere were 19,604 adults hospitalized with ASCVD, including 7054 adults not on high-intensity statins. The mean age was 69.5 years and 33.0% were female. Prevalence of good adherence (continuous medication gap ≤20%) was significantly higher (80.2% vs 75.9%; odds ratio 1.38; 95% confidence interval, 1.28-1.49; P

BackgroundAlthough physical activity is generally protective of cardiovascular disease (CVD), less is known about how young adult physical activity relates to premature CVD events. The objective of this study was to determine the association between level and change in physical activity from young adulthood to middle age and incidence of premature CVD events before age 60.MethodsWe analyzed data collected across four urban sites from nine visits over 30 years of follow-up (1985-2016) from the Coronary Artery Risk Development in Young Adults (CARDIA) study, a prospective community-based cohort study of 5115 Black and White women and men aged 18-30 years at baseline (1985-1986). Linear mixed models were used to develop individualized moderate-to-vigorous intensity self-reported physical activity trajectories per participant. Fatal and nonfatal coronary heart disease (CHD), heart failure, and stroke outcomes were analyzed separately and as a combined CVD event outcome.ResultsOverall, physical activity declined in young adults as they progressed through middle age. Lower physical activity scores (per 100 exercise units) in 18 year-olds were associated with higher odds of premature CHD (AOR 1.14, 95% CI 1.02-1.28), heart failure (AOR 1.21, 95% CI 1.05-1.38), stroke (AOR 1.20, 95% CI 1.04-1.39), and any CVD (AOR 1.15, 95% CI 1.06-1.24) events. Each additional annual 1-unit reduction in the physical activity score was associated with a higher annual odds of incident heart failure (1.07, 95% CI 1.02-1.13), stroke (1.06, 95% CI 1.00-1.13), and CVD (1.04, 95% CI 1.01-1.07) events. Meeting the minimum (AOR 0.74, 95% CI 0.0.57-0.96) and twice the minimum (AOR 0.55, 95% CI 0.34-0.91) Department of Health and Human Services physical activity guidelines through follow up was protective of premature CVD events.ConclusionsGiven recent trends in declining physical activity with age and associated premature CVD events, the transition from young adult to midlife is an important time period to promote physical activity.

BackgroundNon-alcoholic fatty liver disease (NAFLD) is associated with cardiovascular disease (CVD) risk factors that have been linked to cognitive decline. Whether NAFLD is associated with cognitive performance in midlife remains uncertain.MethodsCoronary Artery Risk Development in Young Adults study participants with CT examination and cognitive assessment at Y25 (2010-2011; n = 2809) were included. Cognitive function was reassessed at Y30. NAFLD was defined according to liver attenuation and treated both continuously and categorically (using ≤ 40 and ≤ 51 Hounsfield units to define severity) after exclusion for other causes of liver fat. Cognitive tests including the Digit Symbol Substitution (processing speed), Rey Auditory Verbal Learning (verbal memory), and Stroop (executive function) were analyzed with standardized z-scores. Linear models were constructed to (a) examine the cross-sectional associations of NAFLD with cognitive scores and (b) evaluate its predictive role in 5-year change in cognitive performance.ResultsParticipants' mean age (Y25) was 50.1 (SD 3.6) years (57% female; 48% black), with 392 (14%) having mild NAFLD and 281 (10%) having severe NAFLD. NAFLD was positively associated with CVD risk factors and inversely associated with cognitive scores. However, after adjustment for CVD risk factors, no associations were shown between NAFLD and cognitive scores (all βs ≈ 0). Similarly, no associations were observed with 5-year cognitive decline. CVD history, hypertension, smoking, diabetes and hypertriglyceridemia showed stronger associations with baseline cognitive scores and were predictive of subsequent cognitive decline (all P ≤ .05).ConclusionAmong middle-aged adults, inverse associations between NAFLD and cognitive scores were attenuated after adjustment for CVD risk factors, with the latter predictive of poorer cognitive performance both at baseline and follow-up.

IntroductionThe optimum physical activity dose to achieve during young adulthood to prevent hypertension using the 2017 American College of Cardiology/American Heart Association guidelines remains undefined. This study aims to determine the association between level and change in physical activity through the adult life course and the onset of hypertension using these 2017 definitions.MethodsIn 2020, prospective community-based cohort data of 5,115 Coronary Artery Risk Development in Young Adults study participants were analyzed. The cohort included Black and White men and women aged 18-30 years at baseline (1985-1986) at 4 urban sites, collected through 30 years of follow-up (2015-2016). Individualized physical activity trajectories were developed for each participant using linear mixed models.ResultsBlack women reported the lowest physical activity levels from young adulthood through middle age. Lower physical activity score (per 100 units) at age 18 years was associated with 4% (95% CI=1%, 7%, p=0.002) higher odds of hypertension incidence. Each additional 1-unit reduction per year in physical activity score was associated with 2% (95% CI=1%, 3%, p=0.001) higher annual odds of hypertension incidence. Meeting approximately the current minimum physical activity guideline levels at age 18 years and through follow-up was not protective of hypertension incidence; however, meeting approximately twice the current minimum physical activity guideline level at age 18 years and through follow-up was protective of hypertension incidence.ConclusionsModerate physical activity levels may need to exceed current minimum guidelines to prevent hypertension onset using 2017 American College of Cardiology/American Heart Association definitions.

AimsTo evaluate the prevalence of electrocardiogram (ECG) abnormalities in marijuana users as an indirect measure of subclinical cardiovascular disease (CVD).DesignLongitudinal and cross-sectional secondary data analysis from the CARDIA (Coronary Artery Risk Development in Young Adults) study.SettingFour communities in the United States.ParticipantsA total of 2585 participants from the 5115 black and white men and women recruited at age 18-30 years in 1985 to 1986 in CARDIA.MeasurementsECG abnormalities coded as minor and major abnormalities with the Minnesota code of electrocardiographic findings at year 20. Self-reported current (past 30 days) and computed cumulative life-time marijuana use (one 'marijuana-year' corresponds to 365 days of use) through assessments every 2-5 years. We fitted logistic regression models adjusting for sex, race, center, education, age, tobacco smoking, physical activity, alcohol use and body mass index.FindingsAmong the 2585 participants with an ECG at year 20, mean age was 46, 57% were women, 45% were black; 83% had past exposure to marijuana and 11% were using marijuana currently. One hundred and seventy-three participants (7%) had major abnormalities and 944 (37%) had minor abnormalities. Comparing current with never use in multivariable-adjusted models, the odds ratio (OR) for major ECG abnormalities was 0.60 [95% confidence interval (CI) = 0.32-1.15] and for minor ECG abnormalities 1.21 (95% CI = 0.87-1.68). Results did not change after stratifying by sex and race. Cumulative marijuana use was not associated with ECG abnormalities.ConclusionIn a middle-aged US population, life-time cumulative and occasional current marijuana use were not associated with increases in electrocardiogram abnormalities. This adds to the growing body of evidence that occasional marijuana use and cardiovascular disease events and markers of subclinical atherosclerosis are not associated.

ObjectiveTo examine the associations between change in plant-centered diet quality and type 2 diabetes risk and change in body size.Research design and methodsA prospective study conducted in the U.S. enrolled adults ages 18-30 years in 1985-1986 (examination year [Y0]) and followed them through 2015-2016. We analyzed the associations between change in plant-centered diet quality over 20 years (Y0-Y20) and diabetes (Y20-30; n = 2,534) and change (Y0-Y20 and Y20-30) in BMI, waist circumference (WC), and weight (n > 2,434). Plant-centered diet quality was measured using the A Priori Diet Quality Score (APDQS); a higher score favors nutritionally rich plant foods. Cox regression models were used to assess diabetes risk, and linear regression models were used to examine change in body size.ResultsDuring a mean follow-up of 9.3 (± 1.7) years, 206 case subjects with incident diabetes were observed. In multivariable analysis, participants with the largest increase in APDQS over 20 years had a 48% (95% CI 0.31-0.85; P trend < 0.001) lower risk of diabetes over the subsequent 10 years compared with participants whose score remained stable. Each 1-SD increment in APDQS over 20 years was associated with lower gains in BMI (-0.39 kg/m2; SE 0.14; P = 0.004), WC (-0.90 cm; SE 0.27; P < 0.001) and weight (-1.14 kg; SE 0.33; P < 0.001) during the same period, but not with subsequent changes.ConclusionsYoung adults who increased plant-centered diet quality had a lower diabetes risk and gained less weight by middle adulthood.

BackgroundBlood pressure (BP) and cholesterol are major modifiable risk factors for cardiovascular disease (CVD), but effects of exposures during young adulthood on later life CVD risk have not been well quantified.ObjectiveThe authors sought to evaluate the independent associations between young adult exposures to risk factors and later life CVD risk, accounting for later life exposures.MethodsThe authors pooled data from 6 U.S. cohorts with observations spanning the life course from young adulthood to later life, and imputed risk factor trajectories for low-density lipoprotein (LDL) and high-density lipoprotein cholesterols, systolic and diastolic BP starting from age 18 years for every participant. Time-weighted average exposures to each risk factor during young (age 18 to 39 years) and later adulthood (age ≥40 years) were calculated and linked to subsequent risks of coronary heart disease (CHD), heart failure (HF), or stroke.ResultsA total of 36,030 participants were included. During a median follow-up of 17 years, there were 4,570 CHD, 5,119 HF, and 2,862 stroke events. When young and later adult risk factors were considered jointly in the model, young adult LDL ≥100 mg/dl (compared with

ObjectiveTo evaluate 25-year physical activity (PA) trajectories from young to middle age and assess associations with the prevalence of coronary artery calcification (CAC).Patients and methodsThis study includes 3175 participants in the Coronary Artery Risk Development in Young Adults (CARDIA) study who self-reported PA by questionnaire at 8 follow-up examinations over 25 years (from March 1985-June 1986 through June 2010-May 2011). The presence of CAC (CAC>0) at year 25 was measured using computed tomography. Group-based trajectory modeling was used to identify PA trajectories with increasing age.ResultsWe identified 3 distinct PA trajectories: trajectory 1, below PA guidelines (n=1813; 57.1%); trajectory 2, meeting PA guidelines (n=1094; 34.5%); and trajectory 3, 3 times PA guidelines (n=268; 8.4%). Trajectory 3 participants had higher adjusted odds of CAC>0 (adjusted odds ratio [OR], 1.27; 95% CI, 0.95-1.70) vs those in trajectory 1. Stratification by race showed that white participants who engaged in PA 3 times the guidelines had higher odds of developing CAC>0 (OR, 1.80; 95% CI, 1.21-2.67). Further stratification by sex showed higher odds for white males (OR, 1.86; 95% CI, 1.16-2.98), and similar but nonsignificant trends were noted for white females (OR, 1.71; 95% CI, 0.79-3.71). However, no such higher odds of CAC>0 for trajectory 3 were observed for black participants.ConclusionWhite individuals who participated in 3 times the recommended PA guidelines over 25 years had higher odds of developing coronary subclinical atherosclerosis by middle age. These findings warrant further exploration, especially by race, into possible biological mechanisms for CAC risk at very high levels of PA.

BackgroundFor more than a decade, the presence of diabetes has been considered a coronary heart disease (CHD) "risk equivalent".ObjectiveThe objective of this study was to revisit the concept of risk equivalence by comparing the risk of subsequent CHD events among individuals with or without history of diabetes or CHD in a large contemporary real-world cohort over a period of 10 years (2002 to 2011).DesignPopulation-based prospective cohort analysis.ParticipantsWe studied a cohort of 1,586,061 adult members (ages 30-90 years) of Kaiser Permanente Northern California, an integrated health care delivery system.Main measurementsWe calculated hazard ratios (HRs) from Cox proportional hazard models for CHD among four fixed cohorts, defined by prevalent (baseline) risk group: no history of diabetes or CHD (None), prior CHD alone (CHD), diabetes alone (DM), and diabetes and prior CHD (DM + CHD).Key resultsWe observed 80,012 new CHD events over the follow-up period (~10,980,800 person-years). After multivariable adjustment, the HRs (reference: None) for new CHD events were as follows: CHD alone, 2.8 (95% CI, 2.7-2.85); DM alone 1.7 (95% CI, 1.66-1.74); DM + CHD, 3.9 (95% CI, 3.8-4.0). Individuals with diabetes alone had significantly lower risk of CHD across all age and sex strata compared to those with CHD alone (12.2 versus 22.5 per 1000 person-years). The risk of future CHD for patients with a history of either DM or CHD was similar only among those with diabetes of long duration (≥10 years).ConclusionsNot all individuals with diabetes should be unconditionally assumed to be a risk equivalent of those with prior CHD.

Aims/hypothesisThe impact of marijuana use on metabolic health is largely unknown. This study sought to clarify the cross-sectional and longitudinal associations between self-reported marijuana use, and prediabetes (defined as fasting glucose 5.6-6.9 mmol/l, 2 h glucose post OGTT 7.8-11.0 mmol/l or HbA1c 5.7-6.4% [39-47 mmol/mol]) and diabetes.MethodsData from the community-based Coronary Artery Risk Development in Young Adults (CARDIA) study were used to determine marijuana use and the presence of prediabetes and diabetes among participants. The association between marijuana use and the prevalence of prediabetes and diabetes was examined in 3,034 participants at CARDIA examination year 25 (2010-2011), while the incidence of prediabetes and diabetes according to previous marijuana use was assessed in 3,151 individuals who were free from prediabetes/diabetes at year 7 (1992-1993) and who returned for at least one of the four subsequent follow-up examinations over 18 years.ResultsThe percentage of individuals who self-reported current use of marijuana declined over the course of the study's follow-up. After multivariable adjustment, higher odds of prediabetes were found for individuals who reported current use of marijuana (OR 1.65 [95% CI 1.15, 2.38]) and a lifetime use of 100 times or more (OR 1.49 [95% CI 1.06, 2.11]), compared with individuals who reported never using marijuana. There was no association between marijuana use and diabetes at CARDIA examination year 25. Over 18 years of follow-up, a greater risk of prediabetes (but not diabetes) was found for individuals who reported a lifetime use of marijuana of 100 times or more (HR 1.39 [95% CI 1.13, 1.71]), compared with individuals who had never used marijuana.Conclusions/interpretationMarijuana use in young adulthood is associated with an increased risk of prediabetes by middle adulthood, but not with the development of diabetes by this age.