Coronary Artery Calcium for Personalized Allocation of Aspirin in Primary Prevention of Cardiovascular Disease in 2019: The MESA Study (Multi-Ethnic Study of Atherosclerosis).

BACKGROUND: Recent American College of Cardiology/American Heart Association Primary Prevention Guidelines recommended considering low-dose aspirin therapy only among adults 40 to 70 years of age who are at higher atherosclerotic cardiovascular disease (ASCVD) risk but not at high risk of bleeding. However, it remains unclear how these patients are best identified. The present study aimed to assess the value of coronary artery calcium (CAC) for guiding aspirin allocation for primary prevention by using 2019 aspirin meta-analysis data on cardiovascular disease relative risk reduction and bleeding risk. METHODS: The study included 6470 participants from the MESA Study (Multi-Ethnic Study of Atherosclerosis). ASCVD risk was estimated using the pooled cohort equations, and 3 strata were defined: <5%, 5% to 20%, and >20%. All participants underwent CAC scoring at baseline, and CAC scores were stratified as =0, 1 to 99, ≥100, and ≥400. A 12% relative risk reduction in cardiovascular disease events was used for the 5-year number needed to treat (NNT5) calculations, and a 42% relative risk increase in major bleeding events was used for the 5-year number needed to harm (NNH5) estimations. RESULTS: Only 5% of MESA participants would qualify for aspirin consideration for primary prevention according to the American College of Cardiology/American Heart Association guidelines and using >20% estimated ASCVD risk to define higher risk. Benefit/harm calculations were restricted to aspirin-naive participants <70 years of age not at high risk of bleeding (n=3540). The overall NNT5 with aspirin to prevent 1 cardiovascular disease event was 476 and the NNH5 was 355. The NNT5 was also greater than or similar to the NNH5 among estimated ASCVD risk strata. Conversely, CAC≥100 and CAC≥400 identified subgroups in which NNT5 was lower than NNH5. This was true both overall (for CAC≥100, NNT5=140 versus NNH5=518) and within ASCVD risk strata. Also, CAC=0 identified subgroups in which the NNT5 was much higher than the NNH5 (overall, NNT5=1190 versus NNH5=567). CONCLUSIONS: CAC may be superior to the pooled cohort equations to inform the allocation of aspirin in primary prevention. Implementation of current 2019 American College of Cardiology/American Heart Association guideline recommendations together with the use of CAC for further risk assessment may result in a more personalized, safer allocation of aspirin in primary prevention. Confirmation of these findings in experimental settings is needed.

Plasma ω-3 and ω-6 PUFA Concentrations and Risk of Atrial Fibrillation: The Multi-Ethnic Study of Atherosclerosis.

BACKGROUND: Current literature examining the prospective relation of circulating omega-3 (n-3) and omega-6 (n-6) PUFAs and atrial fibrillation (AF) is limited to predominantly white populations. OBJECTIVES: We investigated the association of circulating n-3 and n-6 PUFAs with incident AF in participants from the Multi-Ethnic Study of Atherosclerosis. METHODS: A total of 6229 participants (mean age = 62 y; 53% female; 39% white, 27% black, 22% Hispanic, and 12% Chinese) who were free of baseline AF and with plasma phospholipid PUFAs measured at baseline using GC were prospectively followed for the development of AF. Incident AF was ascertained using International Classification of Diseases-9 codes from hospital discharge records and Medicare claims data with follow-up through 2014. Multivariable Cox proportional hazards regression analysis was performed to determine the risk of incident AF. RESULTS: During a median follow-up of 12.9 y, 813 (13%) participants developed AF. Each higher SD increment in arachidonic acid (AA; 20:4n-6) concentrations was associated with an 11% decreased risk of incident AF (HR: 0.89; 95% CI: 0.82, 0.96). Similarly, higher overall n-6 PUFA concentrations were also associated with a reduced AF risk (HR per SD increment: 0.93; 95% CI: 0.87, 1.00). Although no significant overall associations were observed for any individual n-3 PUFAs, higher circulating concentrations of DHA (22:6n-3) and EPA (20:5n-3) were associated with a decreased AF risk in blacks and Hispanics (DHA only) but not whites or Chinese Americans. CONCLUSIONS: In a multiethnic cohort of individuals free of baseline cardiovascular disease, higher plasma concentrations of n-6 PUFAs, particularly AA, were associated with a reduced risk of incident AF. Important differences in AF risk were also noted across race/ethnicity for the n-3 PUFAs DHA and EPA.

A Plant-Centered Diet and Markers of Early Chronic Kidney Disease during Young to Middle Adulthood: Findings from the Coronary Artery Risk Development in Young Adults (CARDIA) Cohort.

BACKGROUND: Few studies have evaluated whether plant-centered diets prevent progression of early stage chronic kidney disease (CKD). OBJECTIVES: We examined the association between plant-centered diet quality and early CKD markers. METHODS: We prospectively examined 2869 black and white men and women in the Coronary Artery Risk Development in Young Adults Study free of diagnosed kidney failure in 2005-2006 [examination year 20 (Y20); mean age: 45.3 ± 3.6  y]. CKD marker changes from Y20 to 2015-2016 (Y30) were considered, including estimated glomerular filtration rate (eGFR; serum creatinine), urinary albumin-to-creatinine ratio (ACR), and both. Diet was assessed through interviewer-administered diet histories at Y0, Y7, and Y20, and plant-centered diet quality was quantified with the A Priori Diet Quality Score (APDQS). Linear regression models were used to examine the association of APDQS and subsequent 10-y changes in CKD markers. RESULTS: After adjustment for sociodemographic, behavioral, and diet factors, we found that higher APDQS was related to less adverse changes in CKD markers in the subsequent 10-y period. Compared with the lowest APDQS quintile, the highest quintile was associated with an attenuated increase in lnACR (-0.25 mg/g; 95% CI: -0.37, -0.13 mg/g; P-trend < 0.001), whereas the highest quintile was associated with an attenuated decrease in eGFR (4.45 mL·min-1·1.73 m-2; 95% CI: 2.46, 6.43 mL·min-1·1.73 m-2). There was a 0.50 lower increase in combined CKD markers [ln(ACR) z score - eGFR z score] when comparing the extreme quintiles. Associations remained similar after further adjustment for hypertension, diabetes, and obesity as potential mediating factors. The attenuated worsening CKD marker changes associated with higher APDQS strengthened across increasing initial CKD category; those with the best diet and microalbuminuria in Y10-Y20 returned to high normal albuminuria (all P-interaction < 0.001). CONCLUSIONS: Individuals who consumed plant-centered, high-quality diets were less likely to experience deterioration of kidney function through midlife, especially among participants with initial stage characterized as mild CKD.

Walnut consumption and cardiac phenotypes: The Coronary Artery Risk Development in Young Adults (CARDIA) study.

BACKGROUND AND AIMS: Observational studies and clinical trials have shown cardiovascular benefits of nut consumption, including walnuts. However, the relations of walnut consumption with systolic and diastolic function, risk factors for heart failure, are unknown. We examined the associations of walnut consumption with cardiac structure and function parameters in black and white adults enrolled in the Coronary Artery Risk Development in Young Adults (CARDIA) study. METHODS AND RESULTS: After exclusions, the study population included 3341 participants. Dietary intake was assessed using the CARDIA Diet History questionnaire at baseline, year 7 and year 20 exams. Cardiac structure and function were measured by echocardiography at year 25. Multivariable linear regression evaluated the associations of walnut consumption with blood pressure (BP), heart rate, and cardiac phenotypes, adjusting for age, sex, race, lifestyle habits, and clinical characteristics. We found the majority of walnut consumers compared to non-consumers were females, whites, and more highly educated, and had lower waist circumference, diastolic BP, and heart rate, and higher diet quality score. Even though cardiac structure and function measures were generally within normal ranges among participants, walnut consumers had significantly better values for diastolic function parameters A wave, E/A ratio, septal and lateral e' than non-consumers. Further adjustment for body mass index and diabetes status did not materially change the significance between walnut consumer groups. Systolic function parameters did not differ by walnut group. CONCLUSION: Compared to non-consumers, walnut consumption is associated with better diastolic dysfunction in young to middle-aged adults.

PTC1 and PTC2: New Indices of Blood Pressure Waveforms and Cardiovascular Disease.

Systolic and diastolic blood pressures provide information about cardiovascular disease (CVD) but are only extremes of the pressure waveform during the cardiac cycle. We developed summaries of the pressure decay, called PTC1 and PTC2, that are related to arterial compliance and to an existing proprietary summary that has been shown to predict CVD. We derived the summaries from a Windkessel model (consisting of a decaying exponential plus a dampened cosine, with an intercept so they are independent of calibration with blood pressure, unlike the proprietary measures), and we estimated them using nonlinear least squares with standard, free software. Among 6,228 adults from the Multi-Ethnic Study of Atherosclerosis, initially free of CVD in 2000-2002, mean PTC2 was 94 (standard deviation, 46) milliseconds. During median 15-year follow-up, there were 911 CVD events (including 609 incidents of coronary heart disease and 270 strokes). One-standard-deviation higher PTC2 was associated with 17% (95% confidence interval: 10, 24) lower CVD risk, after adjustment for traditional risk factors. Results were similar for PTC1. PTC1 and PTC2 are relatively straightforward to compute and add information beyond traditional risk factors for prediction of CVD. Our work enables others to replicate and extend our results with waveforms from any suitable device.

A prospective controlled study of metabolic and physiologic effects of kidney donation suggests that donors retain stable kidney function over the first nine years.

While there have been numerous studies of living kidney donors, most have been retrospective without suitable controls and have yielded conflicting results. To clarify this we studied 205 living donor candidates and 203 controls having no medical conditions precluding donation. Before and at six months, one, two, three, six, and nine years after donation we measured iohexol glomerular filtration rate, clinic blood pressure, urine protein excretion and metabolic parameters reported to be affected by kidney function. We measured 24 hour ambulatory blood pressure at three, six, and nine years and at six and nine years blood pressure after treadmill exercise, carotid-femoral pulse wave velocity and arterial elasticity. Between six months and nine years, the mean (95% confidence interval) change in glomerular filtration rate was significantly different among 133 donors 0·02 (-0·16-0·20) mL/min/1·73m2/year versus -1·26 (-1·52--1·00) mL/min/1·73m2/year in 113 healthy controls. Blood pressure, urine protein, urine albumin, glucose, hemoglobin A1c, insulin, and lipoproteins were not different in controls versus donors; but parathyroid hormone, homocysteine and uric acid remained higher at nine years. At six and nine years carotid-femoral pulse wave velocity was not different, but the mean small artery elasticity was significantly lower in 141 donors 6·1 mL/mmHg x100, versus 113 controls 7·1 mL/mmHg x100, and 6·1 mL/mmHg x100 in 137 donors versus 7·6 mL/mmHg x100 in 112 controls at six and nine years, respectively [significant adjusted difference of 1·1 mL/mmHg x100]. Thus, donors remain healthy with stable kidney function for the first nine years, but differences in metabolic and vascular parameters could be harbingers of adverse outcomes requiring future interventions.

Race-Based Differences in Lipoprotein(a)-Associated Risk of Carotid Atherosclerosis.

Objective- Lp(a) [lipoprotein(a)] is a well-described risk factor for atherosclerosis, but Lp(a)-associated risk may vary by race/ethnicity. We aimed to determine whether race/ethnicity modifies Lp(a)-related risk of carotid atherosclerotic plaque outcomes among black, white, Chinese, and Hispanic individuals. Approach and Results- Carotid plaque presence and score were assessed by ultrasonography at baseline (n=5155) and following a median 9.4 year period (n=3380) in MESA (Multi-Ethnic Study of Atherosclerosis) participants. Lp(a) concentrations were measured by immunoassay and examined as a continuous and categorical variable using clinically-based cutoffs, 30 and 50 mg/dL. Lp(a) was related to greater risk of prevalent carotid plaque at baseline in whites alone (all P<0.001): per log unit (relative risk, 1.05); Lp(a)≥30 mg/dL (relative risk, 1.16); and Lp(a)≥50 mg/dL (relative risk, 1.20). Lp(a) levels over 50 mg/dL were associated with a higher plaque score at baseline in whites (all P<0.001) and Hispanics ( P=0.04). In prospective analyses, whites with Lp(a) ≥50 mg/dL were found to have greater risk of plaque progression (relative risk, 1.12; P=0.03) and higher plaque scores (all P<0.001) over the 9.4-year follow-up. Race-based differences between whites and black participants were significant for cross-sectional associations and for carotid plaque score following the 9.4 year study period. Conclusions- Race was found to be a modifying variable in Lp(a)-related risk of carotid plaque, and Lp(a) levels may have greater influence on plaque burden in whites than in black individuals. Borderline results in Hispanics suggest that elevated Lp(a) may increase the risk of carotid plaque, but follow-up studies are needed.

Association of obesity with arterial stiffness: The Multi-Ethnic Study of Atherosclerosis (MESA).

Arterial stiffness (AS) and obesity are recognized as important risk factors of cardiovascular disease (CVD). The purpose of this study was to investigate the relationship between AS and obesity. AS was defined as high augmentation index (AIx) and low elasticity (C1, large artery elasticity; C2, small artery elasticity) in participants enrolled in the Multi-Ethnic Study of Atherosclerosis at baseline. We compared AIx, C1, and C2 by body mass index (BMI) (< 25, 25-29.9, 30-39.9, ⩾ 40 kg/m2) and waist-hip ratio (WHR) (< 0.85, 0.85-0.99, ⩾ 1). The obesity-AS association was tested across 10-year age intervals. Among 6177 participants (62 ± 10 years old, 52% female), a significant inverse relationship was observed between obesity and AS. After adjustments for CVD risk factors, participants with a BMI > 40 kg/m2 had 5.4% lower AIx (mean difference [Δ] = -0.82%; 95% CI: -1.10, -0.53), 15.4% higher C1 (Δ = 1.66 mL/mmHg ×10; 95% CI: 1.00, 2.33), and 40.2% higher C2 (Δ = 1.49 mL/mmHg ×100; 95% CI: 1.15, 1.83) compared to those with a BMI < 25 kg/m2 (all p for trend < 0.001). Participants with a WHR ⩾ 1 had 5.6% higher C1 (∆ = 0.92 mL/mmHg ×10; 95% CI: 0.47, 1.37) compared to those with a WHR < 0.85. The WHR had a significant interaction with age on AIx and C2, but not with BMI; the inverse relationships of the WHR with AIx and C2 were observed only in participants < 55 years between the normal (WHR < 0.85) and the overweight (0.85 ⩽ WHR < 0.99) groups. Different associations of WHR and BMI with arterial stiffness among older adults should be further investigated.

Association of C2, a derivative of the radial artery pressure waveform, with new onset of type 2 diabetes mellitus: the MESA study.

BACKGROUND: Although microvascular dysfunction is known to result from diabetes, it might also lead to diabetes. Lower values of C2, a derivative of the radial artery pressure waveform, indicate microvascular dysfunction and predict hypertension and cardiovascular disease (CVD). We studied the association of C2 with incident diabetes in subjects free of overt CVD. METHODS: Among multi-ethnic participants (n = 5214), aged 45-84 years with no diabetes, C2 was derived from the radial artery pressure waveform. Incident diabetes (N = 651) was diagnosed as new fasting glucose ≥ 126 mg/dL or antidiabetic medicine over ~ 10 years. The relative incidence density (RID) for incident diabetes per standard deviation (SD) of C2 was studied during ~ 10 years follow-up using four levels of adjustment. RESULTS: Mean C2 at baseline was 4.58 ± 2.85 mL/mmHg × 100. The RID for incident diabetes per SD of C2 was 0.90 (95% CI 0.82-0.99, P = 0.03). After adjustment for demographics plus body size, the corresponding RID was 0.81 (95% CI 0.73-0.89, P < 0.0001); body mass index (BMI) was the dominant covariate here. After adjustment for demographics plus cardiovascular risk factors, the RID was 0.98 (95% CI 0.89, 1.07, P = 0.63). After adjustment for all the parameters in the previous models, the RID was 0.87 (95% CI 0.78, 0.96, P = 0.006). CONCLUSIONS: In a multi-ethnic sample free of overt CVD and diabetes at baseline, C2 predicted incident diabetes after adjustment for demographics, BMI and CVD risk factors. Differences in arterial blood pressure wave morphology may indicate a long-term risk trajectory for diabetes, independently of body size and the classical risk factors.

Lp(a) [Lipoprotein(a)]-Related Risk of Heart Failure Is Evident in Whites but Not in Other Racial/Ethnic Groups.

Objective- Lp(a) [lipoprotein(a)] levels vary by race/ethnicity and were recently found to be associated with risk of heart failure (HF). We aimed to determine whether Lp(a)-related risk of HF is similar across different races and whether Lp(a) may further be related to HF with reduced ejection fraction or HF with preserved ejection fraction (HFpEF). Approach and Results- In 6809 participants of the MESA (Multi-Ethnic Study of Atherosclerosis), aged 45 to 84 years and free of cardiovascular disease, 308 incident HF events occurred during a median 13-year follow-up. Baseline Lp(a) concentrations were determined by immunoassay. Incident HF was adjudicated, distinguishing HF with reduced ejection fraction (ejection fraction, <45%) from HFpEF (ejection fraction, ≥45%). Cox regression assessed relations between Lp(a) and HF risk among 4 races/ethnicities. Lp(a) was examined as a continuous variable (per log unit) and using clinical cutoff values, 30 and 50 mg/dL. Lp(a) was related to greater risk of HF in whites alone: per log unit Lp(a) (hazard ratio [HR], 1.20; P=0.02); Lp(a) ≥30 mg/dL (HR, 1.69; P=0.01), Lp(a) ≥50 mg/dL (HR, 1.87; P=0.006). No significant relations were found in black, Hispanic, or Chinese participants, and significant race interactions were observed. Lp(a) was additionally related to greater risk of HFpEF in white participants: per log unit Lp(a) (HR, 1.48; P=0.001), Lp(a) ≥30 mg/dL (HR, 2.15; P=0.01), Lp(a) ≥50 mg/dL (HR, 2.60; P=0.004). Lp(a)-related risk of HF and HFpEF in whites was independent of aortic valve disease. Conclusions- In a multiethnic sample, Lp(a)-related risks of HF and HFpEF were only evident in white participants. If confirmed, these findings have implications in further Lp(a) research and clinical practice.

Obstructive Sleep Apnea and Structural/Functional Properties of the Thoracic Ascending Aorta: The Multi-Ethnic Study of Atherosclerosis (MESA).

BACKGROUND: Structural and functional properties of the proximal thoracic aorta have important implications in clinical and subclinical cardiovascular disease (CVD). We examined whether obstructive sleep apnea (OSA) is associated with proximal aortic size and aortic stiffness in a multi-ethnic community-based cohort. METHODS: The sample included the Multi-Ethnic Study of Atherosclerosis (MESA) Sleep Ancillary study participants without known CVD who underwent cardiac magnetic resonance imaging. The main exposure variable was OSA severity based on the polysomnography-derived apnea hypopnea index (AHI; normal, AHI <5/h; mild, 5≤ AHI <15/h; moderate to severe, AHI ≥15/h). The study outcomes were ascending aortic diameter (AoD, cm), aortic pulse wave velocity (AoPWV, m/s), and ascending aortic distensibility (AAD, %/mm Hg). Analyses were performed in the overall sample and in sex-specific strata, adjusted for multiple potential confounders. RESULTS: The 708 participants were 55.9% female and on average 68 years old (54-93 years). There was a significant trend (p < 0.0001) of greater mean (SD) AoD across the three OSA groups: normal (n = 87), 3.13 cm (0.35); mild (n = 215), 3.25 (0.34); moderate to severe (n = 406), 3.37 (0.36). In adjusted analysis, participants with moderate to severe OSA had a greater mean AoD compared with the normal group: adjusted mean difference (95% CI), 0.12 cm (0.05, 0.20), p = 0.002. This AoD gradient was observed in women but not in men (p for interaction = 0.02). No differences were found in AoPWV or AAD among the OSA groups. CONCLUSION: In a diverse community-based cohort, moderate to severe OSA (vs. no OSA) was associated with a larger ascending AoD in women.

Problematic eating behaviors and attitudes predict long-term incident metabolic syndrome and diabetes: The Coronary Artery Risk Development in Young Adults Study.

BACKGROUND: Problematic relationship to eating and food (PREF) captures a broad range of unhealthy eating behaviors. We previously reported that higher BMI is associated with PREF and graded by the number of PREF endorsed. In this study, we prospectively examined the association between PREF and metabolic syndrome and diabetes. METHOD: Eight PREF behaviors were assessed and summed to form the PREF score in 3800 black and white adults (age 27-41 years) in the Coronary Artery Risk Development in Young Adults Study. Diagnoses of incident metabolic syndrome and diabetes were made through 15 years of follow-up. Logistic regression estimated the association with metabolic syndrome. Proportional hazards regression estimated the association with diabetes. RESULTS: The odds ratio of metabolic syndrome was 1.25 per PREF point through 5 years of follow-up (95% CI: 1.17-1.34) and 1.17 per point from 5 to 10 years of follow-up (95% CI: 1.08-1.27). Hazard of diabetes was 1.20 per PREF point through 15 years of follow-up (95% CI: 1.12-1.28). Both associations attenuated after adjustment for BMI. DISCUSSION: Among participants with PREF, higher scores associate with metabolic syndrome and diabetes, with partial attenuation after adjustment for BMI. Early identification of PREF in middle-aged adults may reduce the burden of metabolic health outcomes.

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.

Questionnaire-based problematic relationship to eating and food is associated with 25 year body mass index trajectories during midlife: The Coronary Artery Risk Development In Young Adults (CARDIA) Study.

OBJECTIVE: Problematic eating behaviors and attitudes are of public health concern. Questionnaire-based assessment of these behaviors is important for large-scale research on eating behaviors. The questionnaire on eating and weight patterns-revised (QEWP-R) measures potential problematic behaviors and attitudes toward food (including anxieties, compensatory actions, overeating and loss of control, dieting, and shape concerns) that in aggregate may indicate diagnosable eating disorders. An important question regards the prevalence of these issues and their longitudinal associations with body mass index (BMI) in generally healthy middle aged adults. METHOD: Based on eight constructs measured on QEWP-R, we created a new problematic relationship to eating and food (PREF) scale by assigning a point for each construct endorsed. Analyses were conducted in 3,892 black and white men and women participating in the community-based Coronary Artery Risk Development in Young Adults (CARDIA) Study. The QEWP-R was administered in CARDIA year 10, when participants were aged 27-41 years. We used linear regression to model the relationship of individual constructs and the PREF scale to BMI over CARDIA follow-up. RESULTS: Fifty-five percent of participants had 1-5 points and 4% had 6-8 points on the PREF scale. Each separate construct was positively associated with BMI, except concern about weight and shape. Adjusting for age, race, sex, education, and study center, mean BMI at CARDIA year 10, the time of PREF assessment, was approximately 1.0-2.5 kg/m2 higher per PREF category. CONCLUSION: In middle age, problematic behaviors and attitudes toward food were common and associated with higher BMI.

Sleep-disordered breathing and electrocardiographic QRS-T angle: The MESA study.

INTRODUCTION: Sleep-disordered breathing (SDB) has been linked to sudden cardiac death (SCD) but the mechanism is unclear. Abnormal QRS-T angle, a novel electrocardiographic (ECG) marker of ventricular repolarization, has been linked to adverse cardiovascular outcomes including SCD. We hypothesized that individuals with SDB have more pronounced abnormality in QRS-T angle. METHODS: We performed a cross-sectional analysis from the Multi-Ethnic Study of Atherosclerosis (MESA) Exam Sleep ancillary study. We calculated the odds ratio (OR) of abnormal frontal and spatial QRS-T angle (defined as >sex-specific 95th percentile thresholds) related to the apnea-hypopnea index (AHI) using logistic regression, adjusting for demographics, body habitus, cardiovascular risks, and prevalent cardiovascular disease. Linear associations between AHI and frontal and spatial QRS-T angle, separately, were also examined using multiple regression models. RESULTS: A total of 1,804 participants (mean age 67.9 (±9.0) years, 55.3% women and 64.1% non-whites) were included in the study. Sleep-disordered breathing was common among participants (median AHI 8.6 events/hr IQR [3.2-19.5/hr]). Higher AHI was associated with the odds of abnormal frontal (≥81° in men and ≥79° in women) and spatial QRS-T angle (≥129.7° in men and ≥115.9° in women; OR [95%CI]: 1.25 [1.02-1.51], p = 0.03; 1.23 [1.01-1.50], p = 0.04 respectively per 1 SD [16.8 events/hr] increase in AHI). Similarly, linear associations were observed (frontal QRS-T angle: beta coefficient: 2.30° [0.92, 3.66], p = 0.001; spatial QRS-T angle: beta coefficient: 2.16° [0.67, 3.64], p = 0.005). CONCLUSION: In a racially/ethnically diverse community cohort, severity of SDB is associated with abnormal ventricular repolarization as measured by QRS-T angle.

Vascular function in breast cancer survivors on aromatase inhibitors: a pilot study.

PURPOSE: Aromatase inhibitors (AI) have been shown to reduce breast cancer-related mortality in women with estrogen positive (ER+) breast cancer. The use of AIs, however, has been associated with higher rates of hypertension, hyperlipidemia, and cardiovascular (CV) events. METHODS: A cross-sectional study of 25 healthy postmenopausal women and 36 women with curative intent breast cancer on an AI was performed to assess endothelial dysfunction, an indicator of risk for CV events. Consented subjects underwent vascular testing using the HDI/Pulse Wave CR-2000 Cardiovascular Profiling System and the EndoPAT2000 system. RESULTS: Mean age was 61.7 and 59.6 years (cases, controls). Most subjects were Caucasian and overweight. Controls had a lower mean systolic blood pressure (128.6 mmHg vs. 116.2 mmHg, p = 0.004). Median estradiol levels were reduced in cases (2 vs. 15 pg/ml, p < 0.0001). EndoPAT ratio (0.8 vs. 2.7, p < 0.0001) was significantly reduced in cases as compared to controls. Median large artery elasticity (12.9 vs. 14.6 ml/mmHg × 10, p = 0.12) and small artery elasticity (5.2 vs. 7.0 ml/mmHg × 100, p = 0.07) were also reduced though not statistically significant. There was no correlation between use of chemotherapy, radiation therapy, type of AI, or duration of AI use and endothelial function. When adjusting for differences in blood pressure, results remained significant. CONCLUSION: Breast cancer cases on AIs have reductions in endothelial function, a predictor of adverse CV disease. IMPACT: Vascular function changes in breast cancer cases on AIs compared to postmenopausal women. Further work is needed to evaluate vascular changes over time.

Towards new recommendations to reduce the burden of alcohol-induced hypertension in the European Union.

BACKGROUND: Hazardous and harmful alcohol use and high blood pressure are central risk factors related to premature non-communicable disease (NCD) mortality worldwide. A reduction in the prevalence of both risk factors has been suggested as a route to reach the global NCD targets. This study aims to highlight that screening and interventions for hypertension and hazardous and harmful alcohol use in primary healthcare can contribute substantially to achieving the NCD targets. METHODS: A consensus conference based on systematic reviews, meta-analyses, clinical guidelines, experimental studies, and statistical modelling which had been presented and discussed in five preparatory meetings, was undertaken. Specifically, we modelled changes in blood pressure distributions and potential lives saved for the five largest European countries if screening and appropriate intervention rates in primary healthcare settings were increased. Recommendations to handle alcohol-induced hypertension in primary healthcare settings were derived at the conference, and their degree of evidence was graded. RESULTS: Screening and appropriate interventions for hazardous alcohol use and use disorders could lower blood pressure levels, but there is a lack in implementing these measures in European primary healthcare. Recommendations included (1) an increase in screening for hypertension (evidence grade: high), (2) an increase in screening and brief advice on hazardous and harmful drinking for people with newly detected hypertension by physicians, nurses, and other healthcare professionals (evidence grade: high), (3) the conduct of clinical management of less severe alcohol use disorders for incident people with hypertension in primary healthcare (evidence grade: moderate), and (4) screening for alcohol use in hypertension that is not well controlled (evidence grade: moderate). The first three measures were estimated to result in a decreased hypertension prevalence and hundreds of saved lives annually in the examined countries. CONCLUSIONS: The implementation of the outlined recommendations could contribute to reducing the burden associated with hypertension and hazardous and harmful alcohol use and thus to achievement of the NCD targets. Implementation should be conducted in controlled settings with evaluation, including, but not limited to, economic evaluation.

Electrocardiographic abnormalities and mortality in aging survivors of childhood cancer: A report from the St Jude Lifetime Cohort Study.

BACKGROUND: Electrocardiography (ECG), predictive of adverse outcomes in the general population, has not been studied in cancer survivors. We evaluated the prevalence of ECG abnormalities and associations with mortality among childhood cancer survivors. METHODS: Major and minor abnormalities were coded per the Minnesota Classification system for participants in the St Jude Lifetime Cohort Study (n = 2,715) and community controls (n = 268). Odds ratios (ORs) and 95% CIs were calculated using multivariable logistic regression; and hazard ratios, using Cox proportional hazards regression. RESULTS: Survivors were a median age of 31.3 (range 18.4-63.8) years at evaluation and 7.4 (range 0-24.8) years at diagnosis. Prior therapies included cardiac-directed radiation (29.5%), anthracycline (57.9%), and alkylating (60%) chemotherapies. The prevalence of minor ECG abnormalities was similar among survivors and controls (65.2% vs 67.5%, P = .6). Major ECG abnormalities were identified in 10.7% of survivors and 4.9% of controls (P < .001). Among survivors, the most common major abnormalities were isolated ST/T wave abnormalities (7.2%), evidence of myocardial infarction (3.7%), and left ventricular hypertrophy with strain pattern (2.8%). Anthracyclines ≥300 mg/m2 (OR 1.7 95% CI 1.1-2.5) and cardiac radiation (OR 2.1 95% CI 1.5-2.9 [1-1,999 cGy], 2.6 95% CI 1.6-3.9 [2,000-2,999 cGy], 10.5 95% CI 6.5-16.9 [≥3,000 cGy]) were associated with major abnormalities. Thirteen participants had a cardiac-related death. Major abnormalities were predictive of all-cause mortality (hazard ratio 4.0 95% CI 2.1-7.8). CONCLUSIONS: Major ECG abnormalities are common among childhood cancer survivors, associated with increasing doses of anthracyclines and cardiac radiation, and predictive of both cardiac and all-cause mortality.

Collagen Turnover Markers in Relation to Future Cardiovascular and Noncardiovascular Disease: The Multi-Ethnic Study of Atherosclerosis.

BACKGROUND: Sustained remodeling of extracellular matrix can compromise organs and tissues. Procollagen type III N-terminal propeptide (PIIINP) and collagen type I carboxy-terminal telopeptide (ICTP) reflect collagen synthesis and degradation. We studied their predictive value for future death and disease. METHODS: A total of 3068 men and women in the Multi-Ethnic Study of Atherosclerosis who were free of cardiovascular disease (CVD) and in generally good health had a baseline blood sample taken for ICTP and PIIINP. Median follow-up was 13.0 years. Among 4 primary outcomes, CVD events (n = 697) were adjudicated, death (n = 571) was by death certificate, and chronic inflammatory-related severe hospitalization and death (ChrIRD, n = 726) and total cancer (n = 327) were classified using International Classification of Diseases codes. We used Poisson regression to study baseline ICTP and PIIINP relative to these outcomes. RESULTS: Mean (SD) PIIINP was 5.47 (1.95) µg/L and ICTP was 3.37 (1.70) µg/L. PIIINP and ICTP were highly correlated with each other and with estimated glomerular filtration rate (eGFR). Adjustment for age and eGFR attenuated relative risks, remaining 20%-30% per SD of both PIIINP and ICTP in prediction for total death and ChrIRD, and of PIIINP for cancer, with little additional attenuation by adjusting for risk factors and inflammatory biomarkers. CVD outcome was generally unrelated to PIIINP but became marginally inversely related to ICTP in the most adjusted model. CONCLUSIONS: The collagen biomarkers PIIINP and ICTP, in part through pathophysiologically parallel associations with renal function, predicted ChrIRD and total death. Moreover, PIIINP predicted future cancer. These collagen markers may help differentiate healthy from unhealthy aging.