Physical activity trajectories, autonomic balance and cognitive function: The Coronary Artery Risk Development in Young Adults (CARDIA) study.

Physical activity (PA) plays an important role in cognitive health. However, the underlying mechanisms are not fully understood. Cardiac autonomic balance is influenced by PA and implicated in dementia pathogenesis. We examined whether autonomic balance mediates the association between PA and cognitive function. The sample included 1939 participants from the Coronary Artery Risk Development in Young Adults study who completed cognitive testing after 30-year follow-up (baseline: mean age 25.2 ± 3.5y; 58% women; 43% Black). Moderate to vigorous intensity PA (MVPA) was obtained in 7 consecutive examinations over 20 years (Year 0-Year 20). Cardiac autonomic balance was assessed at Year 20 via resting heart rate (RHR), standard deviation normal to normal (SDNN) and root mean square of successive differences (RMSSD). We used group-based trajectory modeling to identify homogenous MVPA trajectory groups, and formal mediation analysis to test whether autonomic function indices mediate the association between MVPA trajectories and cognition. We identified three distinct PA trajectory patterns: (1) Below MVPA guidelines (n = 1122; 57.9%); (2) Meeting MVPA guidelines (n = 652; 33.6%); and (3) Exceeding MVPA guidelines (n = 165; 8.5%). Meeting and exceeding MVPA guidelines were related to better autonomic balance overall, and to improved semantic fluency performance. Statistically, the association between higher MVPA level and verbal ability was mediated by SDNN and RMSSD, but not by RHR. In our sample of young and middle-aged adults, higher MVPA levels over time were associated with better cardiac autonomic function, which explained some of the associations between PA trajectories and better cognition.

The presence of emphysema on chest imaging and mid-life cognition.

BACKGROUND: Airflow obstruction is associated with cognitive dysfunction but studies have not assessed how emphysema, a structural phenotype of lung disease, might be associated with cognitive function independent from pulmonary function measured by spirometry. We aimed to determine the relationship between the presence of visually detectable emphysema on chest computed tomography (CT) imaging and cognitive function. METHODS: We examined 2491 participants, mean age of 50 years, from the Coronary Artery Risk Development in Young Adults study who were assessed for the presence of emphysema on chest CT imaging and had cognitive function measured 5 years later with a battery of six cognitive tests. RESULTS: Of those assessed, 172 (7%) had emphysema. After adjusting for age, sex, height, study centre, race, body mass index, education and smoking, visual emphysema was significantly associated with worse performance on most cognitive tests. Compared to those without emphysema, participants with emphysema performed worse on cognitive testing: 0.39 sd units lower (95% CI -0.53- -0.25) on the Montreal Cognitive Assessment, 0.27 sd units lower (95% CI -0.42- -0.12) on the Rey Auditory Verbal Learning Test, 0.29 sd units lower (95% CI -0.43- -0.14) on the Digit Symbol Substitution Test and 0.25 sd units lower (95% CI -0.42- -0.09) on letter fluency. Further adjustment for forced expiratory volume in 1 s (FEV1), peak FEV1 and annualised FEV1 decline did not attenuate these associations. CONCLUSIONS: The presence of emphysema on chest CT is associated with worse cognitive function, independent of airflow obstruction. These data suggest that emphysema may be a novel risk factor for cognitive impairment.

Association of negative financial shocks during the Great Recession with depressive symptoms and substance use in the USA: the CARDIA study.

BACKGROUND: The Great Recession of 2008 was marked by large increases in unemployment and decreases in the household wealth of many Americans. In the 21st century, there have also been increases in depressive symptoms, alcohol use and drug use among some groups in the USA. The objective of this analysis is to evaluate the influence of negative financial shocks incurred during the Great Recession on depressive symptoms, alcohol and drug use. METHODS: We employed a quasi-experimental fixed-effects design, using data from adults enrolled in the Coronary Artery Risk Development in Young Adults (CARDIA) study. Our financial shock predictors were within-person change in employment status, income and debt to asset ratio between 2005 and 2010. Our outcomes were within-person change in depressive symptoms score, alcohol use and past 30-day drug use. RESULTS: In adjusted models, we found that becoming unemployed and experiencing a drop in income and were associated with an increase in depressive symptoms. Incurring more debts than assets was also associated with an increase in depressive symptoms and a slight decrease in daily alcohol consumption (mL). CONCLUSION: Our findings suggest that multiple types of financial shocks incurred during an economic recession negatively influence depressive symptoms among black and white adults in the USA, and highlight the need for future research on how economic recessions are associated with health.

Health Care Service Utilization and Cost Among Adults with Autism Spectrum Disorders in a U.S. Integrated Health Care System.

Objectives: To compare health care utilization patterns and cost among insured adults with autism spectrum disorder (ASD), adults with attention-deficit and hyperactivity disorder (ADHD), and adults with neither condition (general population [GP] controls). Method: We conducted a case-control study among adults (≥18 years) who were members of Kaiser Permanente Northern California (KPNC) for at least 9 months each year from 2008 to 2012. Cases (N = 1507) were adults with an ASD diagnosis (ICD-9-CM 299.0-299.8) recorded in the electronic medical record on at least two separate occasions by December 31, 2012. Two control groups, adults with ADHD (N = 9042) defined by ICD-9-CM code 314 and GP (N = 15,070), were randomly selected and frequency matched to cases on gender and age. Health care utilization and cost data were obtained from KPNC databases for the year 2012. Results: Compared with adults with ADHD, adults with ASD had significantly higher utilization of outpatient visits for primary care (74.2% vs. 66.6%), mental health (43.3% vs. 33.2%), and laboratory services (60.9% vs. 54.4%). Hospitalizations for ambulatory care sensitive diagnoses (5.4% vs. 2.3%) were less frequent overall but more common among adults with ASD than with ADHD. Group differences were larger comparing adults with ASD with GP controls. Gynecology visits and screening for cervical cancer were significantly less common among women with ASD than among women with ADHD (35% vs. 50%) or GP (35% vs. 49%). Total annual mean healthcare costs for adults with ASD were 20% higher than costs for adults with ADHD and double costs for GP. Conclusion: Adults with ASD had significantly higher rates of utilization across most health care service areas compared with adults with ADHD or GP; however, women with ASD were significantly less likely to have gynecology visits and have screening for cervical cancer. Lay Summary: We conducted a study among adults (≥18 years) who were members of Kaiser Permanente Northern California (KPNC) from 2008 to 2012. We compared how often people attended different types of health care and costs of health care among adults with autism spectrum disorder (ASD), adults with attention-deficit and hyperactivity disorder (ADHD), and adults with neither condition (general population [GP] controls). The study included 1507 adults with ASD, 9042 with ADHD but not ASD, and 15,070 GP controls with no ASD or ADHD. Health care and cost data were obtained from KPNC databases for the year 2012. The study found that adults with ASD used more outpatient visits for primary care, mental health, and laboratory services than adults with ADHD. Gynecology visits and screening for cervical cancer were less common among women with ASD than among women with ADHD or GP. Health care costs for adults with ASD were higher than costs for adults with ADHD and costs for GP. In conclusion, adults with ASD had higher rates of use of most health care service areas than adults with ADHD or GP; however, women with ASD were less likely to have gynecology visits and have screening for cervical cancer.

Clinical importance of non-participation in a maximal graded exercise test on risk of non-fatal and fatal cardiovascular events and all-cause mortality: CARDIA study.

While poor performance during a maximal graded exercise test (GXT) predicts cardiovascular events and premature mortality, the potential clinical importance of non-participation in a GXT, either for medical or non-medical reasons, is currently unknown. Data are from 4086 and 3547 Coronary Artery Risk Development in Young Adults (CARDIA) participants who attended the Year 7 (ages 25-37years) and/or 20 exams (ages 38-50years), respectively, which included a GXT. Cox proportional hazard models were used to examine the effect of GXT disposition (at Year 7 and 20, separately) on risk of non-fatal and fatal cardiovascular events and all-cause mortality obtained through 28years of follow-up. A GXT was not conducted or completed according to protocol in 12.9% and 19.1% of participants attending the Year 7 and 20 exams, respectively. After adjustment, participants who missed the Year 20 GXT for medical reasons had a higher risk of cardiovascular events [HR: 4.06 (95% CI: 1.43, 11.5)] and all-cause mortality [HR: 3.07 (95% CI: 1.11, 12.3)] compared to GXT completers; participants who missed at Year 20 for non-medical reasons also had higher risk of all-cause mortality [HR: 2.53 (95% CI: 1.61, 3.99)]. Findings suggest that non-participation in a GXT, regardless of medical or non-medical reason, to be an important predictor of excess risk of adverse health outcomes and premature mortality. Additional patient follow-up, including identification of potential targets for intervention (e.g., weight management and smoking cessation programs), should be conducted at the point of a missed GXT.

Impact of Increased Early Statin Administration on Ischemic Stroke Outcomes: A Multicenter Electronic Medical Record Intervention.

BACKGROUND: Statin administration early in ischemic stroke may influence outcomes. Our aim was to determine the clinical impact of increasing statin administration early in ischemic stroke hospitalization. METHODS AND RESULTS: This is a retrospective analysis of a multicenter electronic medical record (EMR) intervention to increase early statin administration in ischemic stroke across all 20 hospitals of an integrated healthcare delivery system. A stroke EMR order set was modified from an "opt-in" to "opt-out" mode of statin ordering. Outcomes were mortality by 90 days, discharge disposition, and increase in stroke severity. We examined the relationship between intervention and outcome using autoregressive integrated moving average (ARIMA) time-series modeling. The EMR intervention increased both overall in-hospital statin administration (from 87.2% to 90.7%, P<0.001) and early statin administration (from 16.9% to 26.3%, P<0.001). ARIMA models showed a small increase in the rate of survival (difference in probability [Pdiff]=0.02, P=0.016) and discharge to home or rehabilitation facility (Pdiff=0.04, P=0.034) associated with the intervention. The increase in statin administration <8 hours was associated with much larger increases in survival (Pdiff=0.17, P=0.033) and rate of discharge to home or rehabilitation (Pdiff=0.29, P=0.011), as well as a decreased rate of neurological deterioration in-hospital (Pdiff=-0.14, P=0.026). CONCLUSIONS: A simple EMR change increased early statin administration in ischemic stroke and was associated with improved clinical outcomes. This is, to our knowledge, the first EMR intervention study to show that a modification of an electronic order set resulted in improved clinical outcomes.

Long-term Microvascular Disease Outcomes in Patients With Type 2 Diabetes After Bariatric Surgery: Evidence for the Legacy Effect of Surgery.

OBJECTIVE: To identify and quantify any legacy effect of bariatric surgery on risk of incident microvascular disease in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: We conducted a retrospective observational cohort study (n = 4,683; 40% racial/ethnic minority) of patients with type 2 diabetes who underwent bariatric surgery from 2001 through 2011. The primary outcome measure was incident microvascular disease defined as a composite indicator of the first occurrence of retinopathy, neuropathy, and/or nephropathy. The Cox proportional hazards framework was used to investigate the associations between type 2 diabetes remission/relapse status and time to microvascular disease. RESULTS: Covariate-adjusted analyses showed that patients who experienced type 2 diabetes remission had 29% lower risk of incident microvascular disease compared with patients who never remitted (hazard ratio [HR] 0.71 [95% CI 0.60, 0.85]). Among patients who experienced a relapse after remission, the length of time spent in remission was inversely related to the risk of incident microvascular disease; for every additional year of time spent in remission prior to relapse, the risk of microvascular disease was reduced by 19% (HR 0.81 [95% CI 0.67, 0.99]) compared with patients who never remitted. CONCLUSIONS: Our results indicate that remission of type 2 diabetes after bariatric surgery confers benefits for risk of incident microvascular disease even if patients eventually experience a relapse of their type 2 diabetes. This provides support for a legacy effect of bariatric surgery, where even a transient period of surgically induced type 2 diabetes remission is associated with lower long-term microvascular disease risk.

Impact of bariatric surgery on life expectancy in severely obese patients with diabetes: a decision analysis.

OBJECTIVE: To create a decision analytic model to estimate the balance between treatment risks and benefits for severely obese patients with diabetes. BACKGROUND: Bariatric surgery leads to many desirable metabolic changes, but long-term impact of bariatric surgery on life expectancy in patients with diabetes has not yet been quantified. METHODS: We developed a Markov state transition model with multiple Cox proportional hazards models and logistic regression models as inputs to compare bariatric surgery versus no surgical treatment for severely obese diabetic patients. The model is informed by data from 3 large cohorts: (1) 159,000 severely obese diabetic patients (4185 had bariatric surgery) from 3 HMO Research Network sites; (2) 23,000 subjects from the Nationwide Inpatient Sample; and (3) 18,000 subjects from the National Health Interview Survey linked to the National Death Index. RESULTS: In our main analyses, we found that a 45-year-old woman with diabetes and a body mass index (BMI) of 45 kg/m gained an additional 6.7 years of life expectancy with bariatric surgery (38.4 years with surgery vs 31.7 years without surgery). Sensitivity analyses revealed that the gain in life expectancy decreased with increasing BMI, until a BMI of 62 kg/m is reached, at which point nonsurgical treatment was associated with greater life expectancy. Similar results were seen for both men and women in all age groups. CONCLUSIONS: For most severely obese patients with diabetes, bariatric surgery seems to improve life expectancy; however, surgery may reduce life expectancy for the super obese with BMIs over 62 kg/m.

Vascular factors and multiple measures of early brain health: CARDIA brain MRI study.

OBJECTIVE: To identify early changes in brain structure and function that are associated with cardiovascular risk factors (CVRF). DESIGN: Cross-sectional brain Magnetic Resonance I (MRI) study. SETTING: Community based cohort in three U.S. sites. PARTICIPANTS: A Caucasian and African-American sub-sample (n= 680; mean age 50.3 yrs) attending the 25 year follow-up exam of the Coronary Artery Risk Development in Young Adults Study. PRIMARY AND SECONDARY OUTCOMES: 3T brain MR images processed for quantitative estimates of: total brain (TBV) and abnormal white matter (AWM) volume; white matter fractional anisotropy (WM-FA); and gray matter cerebral blood flow (GM-CBF). Total intracranial volume is TBV plus cerebral spinal fluid (TICV). A Global Cognitive Function (GCF) score was derived from tests of speed, memory and executive function. RESULTS: Adjusting for TICV and demographic factors, current smoking was significantly associated with lower GM-CBF and TBV, and more AWM (all <0.05); SA with lower GM-CBF, WM-FA and TBV (p=0.01); increasing BMI with decreasing GM-CBF (p<0003); hypertension with lower GM-CBF, WM-FA, and TBV and higher AWM (all <0.05); and diabetes with lower TBV (p=0.007). The GCS was lower as TBV decreased, AWM increased, and WM-FA (all p<0.01). CONCLUSION: In middle age adults, CVRF are associated with brain health, reflected in MRI measures of structure and perfusion, and cognitive functioning. These findings suggest markers of mid-life cardiovascular and brain health should be considered as indication for early intervention and future risk of late-life cerebrovascular disease and dementia.

Fitness change effects on midlife metabolic outcomes.

PURPOSE: Fitness decline, high body mass index (BMI), and insulin resistance (IR) are associated with worsening cardiometabolic risk factors prospectively; modification of the fitness change effect by BMI and IR remains unknown. METHODS: Participants from the Coronary Artery Risk Development in Young Adults study without diabetes at year 0 (Y0) (n = 2048, 43.4% men; mean age, 25 yr) had fitness quantified by treadmill at Y0 and Y20. Y0 BMI was normal (nBMI <25 kg·m) or high (hBMI ≥25 kg·m). Y0 IR status was insulin sensitive (IS) (homeostatic model assessment IR <1.84 (75th percentile)) or insulin resistant (IR) (homeostatic model assessment IR ≥1.84). Four groups were established: nBMI/IS, hBMI/IS, nBMI/IR, and hBMI/IR. Y0 fitness was low (<33rd percentile for sex) or average high (≥33rd percentile for sex). Fitness change (treadmill time: Y20-Y0) was maintained (increase or decline ≤20th percentile for sex) or decreased (decline >20th percentile for sex). The outcomes were incident diabetes and percentage change over 25 yr in weight, waist girth, blood pressure, and lipid profile. Analysis was by multiple linear regression and proportional hazards regression with adjustment for individual characteristics. RESULTS: Maintained fitness after 20 yr was associated with greater increase in HDL cholesterol and less increase in weight, waist girth, blood pressure, and triglycerides than decreased fitness, similarly for the groups defined by BMI and IR. Maintained fitness reduced the rate of incident diabetes in IS but not IR participants. CONCLUSIONS: Maintained fitness after 20 yr was associated with more favorable middle-age cardiometabolic risk factors than decreased fitness; this benefit might be blunted by baseline IR.

Sedentary screen time and left ventricular structure and function: the CARDIA study.

INTRODUCTION: Sedentary screen time (watching TV or using a computer) predicts cardiovascular outcomes independently from moderate and vigorous physical activity and could affect left ventricular structure and function through the adverse consequences of sedentary behavior. PURPOSE: This study aimed to determine whether sedentary screen time is associated with measures of left ventricular structure and function. METHODS: The Coronary Artery Risk Development in Young Adults Study measured screen time by questionnaire and left ventricular structure and function by echocardiography in 2854 black and white participants, age 43-55 yr, in 2010-2011. Generalized linear models evaluated cross-sectional trends for echocardiography measures across higher categories of screen time and adjusting for demographics, smoking, alcohol, and physical activity. Further models adjusted for potential intermediate factors (blood pressure, antihypertensive medication use, diabetes, and body mass index). RESULTS: The relationship between screen time and left ventricular mass (LVM) differed in blacks versus whites. Among whites, higher screen time was associated with larger LVM (P < 0.001), after adjustment for height, demographics, and lifestyle variables. Associations between screen time and LVM persisted when adjusting for blood pressure, antihypertensive medication use, and diabetes (P = 0.008) but not with additional adjustment for body mass index (P = 0.503). Similar relationships were observed for screen time with LVM indexed to height, relative wall thickness, and mass-to-volume ratio. Screen time was not associated with left ventricular structure among blacks or left ventricular function in either race group. CONCLUSIONS: Sedentary screen time is associated with greater LVM in white adults, and this relationship was largely explained by higher overall adiposity. The lack of association in blacks supports a potential qualitative difference in the cardiovascular consequences of sedentary screen-based behavior.

White blood cell count in young adulthood and coronary artery calcification in early middle age: coronary artery risk development in young adults (CARDIA) study.

White blood cell (WBC) count is associated with incident coronary heart disease (CHD). Data are sparse regarding its association in young adults with future coronary artery calcification (CAC). Our study was conducted among coronary artery risk development in young adults (CARDIA) participants (n=3,094). We examined the association between baseline (Y0) WBC counts and CHD risk factors using linear regression models. We further assessed prospective associations between Y0 WBC and inflammatory biomarkers during the follow-up, and the presence of CAC 15 and 20 years later. In total, 272 and 566 subjects had CAC scores>0 at year (Y) 15 and Y20, respectively. Baseline total WBC counts were cross-sectionally associated with SBP, BMI, and smoking, or HDL-cholesterol (p≤0.01) at Y0, and prospectively associated with C-reactive protein at Y7, Y15, and Y20, and fibrinogen at Y5 and Y20 (p<0.01). After adjustment for potential confounding factors, baseline neutrophil count was borderline associated with CAC presence 15 years later (OR=1.18 per unit, 95% CI 1.00-1.44) and total WBC (OR=1.07, 95% CI 0.96-1.19) or eosinophil (OR=1.12, 95%CI 1.00-1.25) was borderline associated with CAC presence at Y20. Baseline total WBC counts in young adults was associated prospectively with CAC presence 20 years later after adjusting for age, sex, and race. Results are attenuated when other risk factors are accounted for. Our results suggest the possible early involvement of WBC, particularly eosinophils, in the early stages of atherosclerosis.

Indirect effect of financial strain on daily cortisol output through daily negative to positive affect index in the Coronary Artery Risk Development in Young Adults Study.

Daily affect is important to health and has been linked to cortisol. The combination of high negative affect and low positive affect may have a bigger impact on increasing HPA axis activity than either positive or negative affect alone. Financial strain may both dampen positive affect as well as increase negative affect, and thus provides an excellent context for understanding the associations between daily affect and cortisol. Using random effects mixed modeling with maximum likelihood estimation, we examined the relationship between self-reported financial strain and estimated mean daily cortisol level (latent cortisol variable), based on six salivary cortisol assessments throughout the day, and whether this relationship was mediated by greater daily negative to positive affect index measured concurrently in a sample of 776 Coronary Artery Risk Development in Young Adults (CARDIA) Study participants. The analysis revealed that while no total direct effect existed for financial strain on cortisol, there was a significant indirect effect of high negative affect to low positive affect, linking financial strain to elevated cortisol. In this sample, the effects of financial strain on cortisol through either positive affect or negative affect alone were not significant. A combined affect index may be a more sensitive and powerful measure than either negative or positive affect alone, tapping the burden of chronic financial strain, and its effects on biology.

Geographic variation in cardiovascular procedure use among Medicare fee-for-service vs Medicare Advantage beneficiaries.

IMPORTANCE: Little is known about how different financial incentives between Medicare Advantage and Medicare fee-for-service (FFS) reimbursement structures influence use of cardiovascular procedures. OBJECTIVE: To compare regional cardiovascular procedure rates between Medicare Advantage and Medicare FFS beneficiaries. DESIGN, SETTING, AND PARTICIPANTS: Cross-sectional study of Medicare beneficiaries older than 65 years between 2003-2007 comparing rates of coronary angiography, percutaneous coronary intervention (PCI), and coronary artery bypass graft (CABG) surgery across 32 hospital referral regions in 12 states. MAIN OUTCOMES AND MEASURES: Rates of coronary angiography, PCI, and CABG surgery. RESULTS: We evaluated a total of 878,339 Medicare Advantage patients and 5,013,650 Medicare FFS patients. Compared with Medicare FFS patients, Medicare Advantage patients had lower age-, sex-, race-, and income-adjusted procedure rates per 1000 person-years for angiography (16.5 [95% CI, 14.8-18.2] vs 25.9 [95% CI, 24.0-27.9]; P < .001) and PCI (6.8 [95% CI, 6.0-7.6] vs 9.8 [95% CI, 9.0-10.6]; P < .001) but similar rates for CABG surgery (3.1 [95% CI, 2.8-3.5] vs 3.4 [95% CI, 3.1-3.7]; P = .33). There were no significant differences between Medicare Advantage and Medicare FFS patients in the rates per 1000 person-years of urgent angiography (3.9 [95% CI, 3.6-4.2] vs 4.3 [95% CI, 4.0-4.6]; P = .24) or PCI (2.4 [95% CI, 2.2-2.7] vs 2.7 [95% CI, 2.5-2.9]; P = .16). Procedure rates varied widely across hospital referral regions among Medicare Advantage and Medicare FFS patients. For angiography, the rates per 1000 person-years ranged from 9.8 to 40.6 for Medicare Advantage beneficiaries and from 15.7 to 44.3 for Medicare FFS beneficiaries. For PCI, the rates ranged from 3.5 to 16.8 for Medicare Advantage and from 4.7 to 16.1 for Medicare FFS. The rates for CABG surgery ranged from 1.5 to 6.1 for Medicare Advantage and from 2.5 to 6.0 for Medicare FFS. Across regions, we found no statistically significant correlation between Medicare Advantage and Medicare FFS beneficiary utilization for angiography (Spearman r = 0.19, P = .29) and modest correlations for PCI (Spearman r = 0.33, P = .06) and CABG surgery (Spearman r = 0.35, P = .05). Among Medicare Advantage beneficiaries, adjustment for additional cardiac risk factors had little influence on procedure rates. CONCLUSIONS AND RELEVANCE: Although Medicare beneficiaries enrolled in capitated Medicare Advantage programs had lower angiography and PCI procedure rates than those enrolled in Medicare FFS, the degree of geographic variation in procedure rates was substantial among Medicare Advantage beneficiaries and was similar in magnitude to that observed among Medicare FFS beneficiaries.

Cardiovascular predictors of long-term outcomes after non-traumatic subarachnoid hemorrhage.

BACKGROUND AND PURPOSE: Cardiac injury is common after subarachnoid hemorrhage (SAH) and is associated with adverse early outcomes, but long-term effects are unknown. The first aim of this study was to compare the long-term rates of death, stroke, and cardiac events in SAH survivors versus a matched population without SAH. The second aim was to quantify the effects of cardiac injury on the outcome rates. METHODS: This was a retrospective cohort study of patients with and without non-traumatic SAH. For aim #1, the predictor variable was SAH and the outcome variables were all-cause and cerebrovascular mortality, stroke, cardiac mortality, acute coronary syndrome (ACS), and heart failure (HF) admission. A multivariable Cox proportional hazards analysis was performed. For aim #2, the predictor variables were cardiac injury (elevated serum cardiac enzymes or a diagnosis code for ACS) and dysfunction (pulmonary edema on X-Ray or a diagnosis code for HF). RESULTS: Compared with 4,695 members without SAH, the 910 SAH patients had higher rates of all-cause mortality (hazard ratio [HR 2.6], 95% confidence intervals [CI] 2.0-3.4), cerebrovascular mortality (HR 30.6, CI 13.5-69.4), and stroke (HR 10.2, CI 7.5-13.8). Compared with the non-SAH group, the SAH patients with cardiac injury had increased rates of all-cause mortality (HR 5.3, CI 3.0-9.3), cardiac mortality (HR 7.3, CI 1.7-31.6), and heart failure (HR 4.3, CI 1.53-11.88). CONCLUSIONS: SAH survivors have increased long-term mortality and stroke rates compared with a matched non-SAH population. SAH-induced cardiac injury is associated with an increased risk of death and heart failure hospitalization.

ADHD medications and risk of serious cardiovascular events in young and middle-aged adults.

CONTEXT: More than 1.5 million US adults use stimulants and other medications labeled for treatment of attention-deficit/hyperactivity disorder (ADHD). These agents can increase heart rate and blood pressure, raising concerns about their cardiovascular safety. OBJECTIVE: To examine whether current use of medications prescribed primarily to treat ADHD is associated with increased risk of serious cardiovascular events in young and middle-aged adults. DESIGN, SETTING, AND PARTICIPANTS: Retrospective, population-based cohort study using electronic health care records from 4 study sites (OptumInsight Epidemiology, Tennessee Medicaid, Kaiser Permanente California, and the HMO Research Network), starting in 1986 at 1 site and ending in 2005 at all sites, with additional covariate assessment using 2007 survey data. Participants were adults aged 25 through 64 years with dispensed prescriptions for methylphenidate, amphetamine, or atomoxetine at baseline. Each medication user (n = 150,359) was matched to 2 nonusers on study site, birth year, sex, and calendar year (443,198 total users and nonusers). MAIN OUTCOME MEASURES: Serious cardiovascular events, including myocardial infarction (MI), sudden cardiac death (SCD), or stroke, with comparison between current or new users and remote users to account for potential healthy-user bias. RESULTS: During 806,182 person-years of follow-up (median, 1.3 years per person), 1357 cases of MI, 296 cases of SCD, and 575 cases of stroke occurred. There were 107,322 person-years of current use (median, 0.33 years), with a crude incidence per 1000 person-years of 1.34 (95% CI, 1.14-1.57) for MI, 0.30 (95% CI, 0.20-0.42) for SCD, and 0.56 (95% CI, 0.43-0.72) for stroke. The multivariable-adjusted rate ratio (RR) of serious cardiovascular events for current use vs nonuse of ADHD medications was 0.83 (95% CI, 0.72-0.96). Among new users of ADHD medications, the adjusted RR was 0.77 (95% CI, 0.63-0.94). The adjusted RR for current use vs remote use was 1.03 (95% CI, 0.86-1.24); for new use vs remote use, the adjusted RR was 1.02 (95% CI, 0.82-1.28); the upper limit of 1.28 corresponds to an additional 0.19 events per 1000 person-years at ages 25-44 years and 0.77 events per 1000 person-years at ages 45-64 years. CONCLUSIONS: Among young and middle-aged adults, current or new use of ADHD medications, compared with nonuse or remote use, was not associated with an increased risk of serious cardiovascular events. Apparent protective associations likely represent healthy-user bias.

Nonoptimal lipids commonly present in young adults and coronary calcium later in life: the CARDIA (Coronary Artery Risk Development in Young Adults) study.

BACKGROUND: Dyslipidemia causes coronary heart disease in middle-aged and elderly adults, but the consequences of lipid exposure during young adulthood are unclear. OBJECTIVE: To assess whether nonoptimal lipid levels during young adulthood cause atherosclerotic changes that persist into middle age. DESIGN: Prospective cohort study. SETTING: 4 cities in the United States. PARTICIPANTS: 3258 participants from the 5115 black and white men and women recruited at age 18 to 30 years in 1985 to 1986 for the CARDIA (Coronary Artery Risk Development in Young Adults) study. MEASUREMENTS: Low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol, triglycerides, and coronary calcium. Time-averaged cumulative exposures to lipids between age 20 and 35 years were estimated by using repeated serum lipid measurements over 20 years in the CARDIA study; these measurements were then related to coronary calcium scores assessed later in life (45 years [SD, 4]). RESULTS: 2824 participants (87%) had nonoptimal levels of LDL cholesterol (>or=2.59 mmol/L [>or=100 mg/dL]), HDL cholesterol (<1.55 mmol/L [<60 mg/dL]), or triglycerides (>or=1.70 mmol/L [>or=150 mg/dL]) during young adulthood. Coronary calcium prevalence 2 decades later was 8% in participants who maintained optimal LDL levels (<1.81 mmol/L [<70 mg/dL]), and 44% in participants with LDL cholesterol levels of 4.14 mmol/L (160 mg/dL) or greater (P < 0.001). The association was similar across race and sex and strongly graded, with odds ratios for coronary calcium of 1.5 (95% CI, 0.7 to 3.3) for LDL cholesterol levels of 1.81 to 2.56 mmol/L (70 to 99 mg/dL), 2.4 (CI, 1.1 to 5.3) for levels of 2.59 to 3.34 mmol/L (100 to 129 mg/dL), 3.3 (CI, 1.3 to 7.8) for levels of 3.37 to 4.12 mmol/L (130 to 159 mg/dL), and 5.6 (CI, 2.0 to 16) for levels of 4.14 mmol/L (160 mg/dL) or greater, compared with levels less than 1.81 mmol/L (<70 mg/dL), after adjustment for lipid exposure after age 35 years and other coronary risk factors. Both LDL and HDL cholesterol levels were independently associated with coronary calcium after participants who were receiving lipid-lowering medications or had clinically abnormal lipid levels were excluded. LIMITATION: Coronary calcium, although a strong predictor of future coronary heart disease, is not a clinical outcome. CONCLUSION: Nonoptimal levels of LDL and HDL cholesterol during young adulthood are independently associated with coronary atherosclerosis 2 decades later. PRIMARY FUNDING SOURCE: National Heart, Lung, and Blood Institute.

Low cardiovascular risk is associated with favorable left ventricular mass, left ventricular relative wall thickness, and left atrial size: the CARDIA study.

BACKGROUND: Echocardiographic measures of left ventricular (LV) mass and relative wall thickness and left atrial (LA) size predict future cardiovascular morbidity and mortality. The aim of this study was to compare young adults with low cardiovascular risk (body mass index, 18.5-24.9 kg/m(2); blood pressure < 120/80 mmHg; no tobacco use, no diabetes, and physical fitness) with those without these characteristics with regard to LV mass and relative wall thickness and LA size, to determine the protective effect of a healthy lifestyle on the development of these characteristics. METHODS: Cross-sectional assessment of 4059 black and white men and women aged 23 to 35 years in the Coronary Artery Risk Development in Young Adults (CARDIA) study at the year 5-examination, when risk factors were measured, and echocardiography to assess LV mass and relative wall thickness were performed. Physical fitness was measured at baseline using a symptom-limited maximal treadmill test. All other covariates were measured concurrently with echocardiography. RESULTS: Gender, body mass index, and systolic blood pressure were associated with LV mass and relative wall thickness and LA size in multivariate models. Additional correlates of LV mass/height(2.7) ratio were tobacco use, resting heart rate (inverse), self-reported physical activity, gender (male higher), and age. Age was associated with LV relative wall thickness but not other measures of LV size. Additional correlates of LA diameter/height ratio were tobacco use, resting heart rate (inverse), serum glucose, and self-reported physical activity. Seven hundred ninety of 4059 subjects (19%) were classified as having low risk; black race was less likely in the low-risk group. Those with low risk had lower LV mass/height(2.7) ratios (32.0 vs 34.6 g/m(2.7), P < .0001), better LV relative wall thickness (0.33 vs 0.35, P < .0001), and lower LA diameter/height ratios (2.02 vs 2.08 cm/m, P < .01). CONCLUSIONS: A low cardiovascular risk profile in young adulthood is associated with more favorable LV mass, LV relative wall thickness, and LA size. This may be one mechanism of lifestyle protection against cardiovascular morbidity and mortality.

Modeling multisystem biological risk in young adults: The Coronary Artery Risk Development in Young Adults Study.

Although much prior research has focused on identifying the roles of major regulatory systems in health risks, the concept of allostatic load (AL) focuses on the importance of a more multisystems view of health risks. How best to operationalize allostatic load, however, remains the subject of some debate. We sought to test a hypothesized metafactor model of allostatic load composed of a number of biological system factors, and to investigate model invariance across sex and ethnicity. Biological data from 782 men and women, aged 32-47, from the Oakland, CA and Chicago, IL sites of the Coronary Artery Risk Development in Young Adults Study (CARDIA) were collected as part of the Year 15exam in 2000. These include measures of blood pressure, metabolic parameters (glucose, insulin, lipid profiles, and waist circumference), markers of inflammation (interleukin-6, C-reactive protein, and fibrinogen), heart rate variability, sympathetic nervous system activity (12-hr urinary norepinephrine and epinephrine) and hypothalamic-pituitary-adrenal axis activity (diurnal salivary free cortisol). A "metafactor" model of AL as an aggregate measure of six underlying latent biological subfactors was found to fit the data, with the metafactor structure capturing 84% of variance of all pairwise associations among biological subsystems. There was little evidence of model variance across sex and/or ethnicity. These analyses extend work operationalizing AL as a multisystems index of biological dysregulation, providing initial support for a model of AL as a metaconstruct of inter-relationships among multiple biological regulatory systems, that varies little across sex or ethnicity.

Active commuting and cardiovascular disease risk: the CARDIA study.

BACKGROUND: There is little research on the association of lifestyle exercise, such as active commuting (walking or biking to work), with obesity, fitness, and cardiovascular disease (CVD) risk factors. METHODS: This cross-sectional study included 2364 participants enrolled in the Coronary Artery Risk Development in Young Adults (CARDIA) study who worked outside the home during year 20 of the study (2005-2006). Associations between walking or biking to work (self-reported time, distance, and mode of commuting) with body weight (measured height and weight); obesity (body mass index [BMI], calculated as weight in kilograms divided by height in meters squared, >or= 30); fitness (symptom-limited exercise stress testing); objective moderate-vigorous physical activity (accelerometry); CVD risk factors (blood pressure [oscillometric systolic and diastolic]); and serum measures (fasting measures of lipid, glucose, and insulin levels) were separately assessed by sex-stratified multivariable linear (or logistic) regression modeling. RESULTS: A total of 16.7% of participants used any means of active commuting to work. Controlling for age, race, income, education, smoking, examination center, and physical activity index excluding walking, men with any active commuting (vs none) had reduced likelihood of obesity (odds ratio [OR], 0.50; 95% confidence interval [CI], 0.33-0.76), reduced CVD risk: ratio of geometric mean triglyceride levels (trig(active))/(trig(nonactive)) = 0.88 (95% CI, 0.80 to 0.98); ratio of geometric mean fasting insulin (FI(active))/(FI(nonactive)) = 0.86 (95% CI, 0.78 to 0.93); difference in mean diastolic blood pressure (millimeters of mercury) (DBP(active)) - (DBP(nonactive)) = -1.67 (95% CI, -3.20 to -0.15); and higher fitness: mean difference in treadmill test duration (in seconds) in men (TT(active)) - (TT(nonactive)) = 50.0 (95% CI, 31.45 to 68.59) and women (TT(active)) - (TT(nonactive)) = 28.77 (95% CI, 11.61 to 45.92). CONCLUSIONS: Active commuting was positively associated with fitness in men and women and inversely associated with BMI, obesity, triglyceride levels, blood pressure, and insulin level in men. Active commuting should be investigated as a modality for maintaining or improving health.