Alexander Arynchyn

Racial Differences in Incident Heart Failure among Young Adults

BACKGROUND The antecedents and epidemiology of heart failure in young adults are poorly understood. METHODS We prospectively assessed the incidence of heart failure over a 20-year period among 5115 blacks and whites of both sexes who were 18 to 30 years of age at baseline. Using Cox models, we examined predictors of hospitalization or death from heart failure. RESULTS Over the course of 20 years, heart failure developed in 27 participants (mean [+/-SD] age at onset, 39+/-6 years), all but 1 of whom were black. The cumulative incidence of heart failure before the age of 50 years was 1.1% (95% confidence interval [CI], 0.6 to 1.7) in black women, 0.9% (95% CI, 0.5 to 1.4) in black men, 0.08% (95% CI, 0.0 to 0.5) in white women, and 0% (95% CI, 0 to 0.4) in white men (P=0.001 for the comparison of black participants and white participants). Among blacks, independent predictors at 18 to 30 years of age of heart failure occurring 15 years, on average, later included higher diastolic blood pressure (hazard ratio per 10.0 mm Hg, 2.1; 95% CI, 1.4 to 3.1), higher body-mass index (the weight in kilograms divided by the square of the height in meters) (hazard ratio per 5.7 units, 1.4; 95% CI, 1.0 to 1.9), lower high-density lipoprotein cholesterol (hazard ratio per 13.3 mg per deciliter [0.34 mmol per liter], 0.6; 95% CI, 0.4 to 1.0), and kidney disease (hazard ratio, 19.8; 95% CI, 4.5 to 87.2). Three quarters of those in whom heart failure subsequently developed had hypertension by the time they were 40 years of age. Depressed systolic function, as assessed on a study echocardiogram when the participants were 23 to 35 years of age, was independently associated with the development of heart failure 10 years, on average, later (hazard ratio for abnormal systolic function, 36.9; 95% CI, 6.9 to 198.3; hazard ratio for borderline systolic function, 3.5; 95% CI, 1.2 to 10.2). Myocardial infarction, drug use, and alcohol use were not associated with the risk of heart failure. CONCLUSIONS Incident heart failure before 50 years of age is substantially more common among blacks than among whites. Hypertension, obesity, and systolic dysfunction that are present before a person is 35 years of age are important antecedents that may be targets for the prevention of heart failure. (ClinicalTrials.gov number, NCT00005130.)

Lung Function in Young Adults Predicts Airflow Obstruction 20 Years Later

OBJECTIVE The burden of obstructive lung disease is increasing, yet there are limited data on its natural history in young adults. To determine in a prospective cohort of generally healthy young adults the influence of early adult lung function on the presence of airflow obstruction in middle age. METHODS A longitudinal study was performed of 2496 adults who were 18 to 30 years of age at entry, did not report having asthma, and returned at year 20. Airflow obstruction was defined as an forced expiratory volume in 1 second/forced vital capacity ratio less than the lower limit of normal. RESULTS Airflow obstruction was present in 6.9% and 7.8% of participants at years 0 and 20, respectively. Less than 10% of participants with airflow obstruction self-reported chronic obstructive pulmonary disease. In cross-sectional analyses, airflow obstruction was associated with less education, smoking, and self-reported chronic obstructive pulmonary disease. Low forced expiratory volume in 1 second, forced expiratory volume in 1 second/forced vital capacity ratio, and airflow obstruction in young adults were associated with low lung function and airflow obstruction 20 years later. Of those with airflow obstruction at year 0, 52% had airflow obstruction 20 years later. The forced expiratory volume in 1 second/forced vital capacity at year 0 was highly predictive of airflow obstruction 20 years later (c-statistic 0.91; 95% confidence interval, 0.89-0.93). The effect of cigarette smoking on lung function decline with age was most evident in young adults with preexisting airflow obstruction. CONCLUSION Airflow obstruction is mostly unrecognized in young and middle-aged adults. Low forced expiratory volume in 1 second, low forced expiratory volume in 1 second/forced vital capacity ratio, airflow obstruction in young adults, and smoking are highly predictive of low lung function and airflow obstruction in middle age.

Obesity-Asthma Association: Is It Explained by Systemic Oxidant Stress?

BACKGROUND The mechanism for the obesity-asthma association is unknown. This study evaluated the hypothesis that systemic oxidant stress explains this association. METHODS This cross-sectional study used year-20 follow-up evaluation data of 2,865 eligible participants in the Coronary Artery Risk Development in Young Adults (CARDIA) cohort. Current asthma was self-reported. Oxidant stress primarily was assessed by plasma F2-isoprostane concentrations. Obesity measures included categories of BMI and dual-energy x-ray absorptiometry-assessed fat mass index (FMI) and lean mass index (LMI). Logistic and linear regressions were used for analyses. RESULTS Asthma was associated with higher plasma F2-isoprostane concentrations (p = 0.049); however, this association was not significant when adjusted for either gender or BMI. The BMI-asthma association was seen only among women (p = 0.03; gender-specific interaction, p = 0.01), and this association was not explained by plasma F2-isoprostane levels. Similarly, both FMI and LMI were positively associated with asthma in women (p = 0.20 and 0.01, respectively). These associations also were not explained by plasma F2-isoprostane levels. Similar results were obtained when plasma levels of oxidized low-density lipoprotein were used instead of F2-isoprostane levels to study the BMI-asthma association at the year-15 evaluation. CONCLUSIONS Systemic oxidant stress, primarily assessed by plasma F2-isoprostane concentrations, was not independently associated with asthma and, therefore, may not explain the obesity-asthma association in women. The asthma-oxidant stress association is confounded by gender and obesity. This study is limited by the inability to measure airway oxidant stress. It is possible that another (as yet undetermined) measure of systemic oxidant stress may be more relevant in asthma.

Loss of lung health from young adulthood and cardiac phenotypes in middle age

RATIONALE Chronic lung diseases are associated with cardiovascular disease. How these associations evolve from young adulthood forward is unknown. Understanding the preclinical history of these associations could inform prevention strategies for common heart-lung conditions. OBJECTIVES To use the Coronary Artery Risk Development in Young Adults (CARDIA) study to explore the development of heart-lung interactions. METHODS We analyzed cardiac structural and functional measurements determined by echocardiography at Year 25 of CARDIA and measures of pulmonary function over 20 years in 3,000 participants. MEASUREMENTS AND MAIN RESULTS Decline in FVC from peak was associated with larger left ventricular mass (β = 6.05 g per SD of FVC decline; P < 0.0001) and greater cardiac output (β = 0.109 L/min per SD of FVC decline; P = 0.001). Decline in FEV1/FVC ratio was associated with smaller left atrial internal dimension (β = -0.038 cm per SD FEV1/FVC decline; P < 0.0001) and lower cardiac output (β = -0.070 L/min per SD of FEV1/FVC decline; P = 0.03). Decline in FVC was associated with diastolic dysfunction (odds ratio, 3.39; 95% confidence interval, 1.37-8.36; P = 0.006). CONCLUSIONS Patterns of loss of lung health are associated with specific cardiovascular phenotypes in middle age. Decline in FEV1/FVC ratio is associated with underfilling of the left heart and low cardiac output. Decline in FVC with preserved FEV1/FVC ratio is associated with left ventricular hypertrophy and diastolic dysfunction. Cardiopulmonary interactions apparent with common complex heart and lung diseases evolve concurrently from early adulthood forward.

Quality Control and Reproducibility in M-Mode, Two-Dimensional, and Speckle Tracking Echocardiography Acquisition and Analysis: The CARDIA Study, Year 25 Examination Experience

Few large studies describe quality control procedures and reproducibility findings in cardiovascular ultrasound, particularly in novel techniques such as speckle tracking echocardiography (STE). We evaluate the echocardiography assessment performance in the Coronary Artery Risk Development in Young Adults (CARDIA) study Year 25 (Y25) examination (2010–2011) and report findings from a quality control and reproducibility program conducted to assess Field Center image acquisition and reading center (RC) accuracy.

Spirometry guidelines influence lung function results in a longitudinal study of young adults.

RATIONALE End of test criteria can influence spirometry results. Epidemiology studies initiated before adoption of the 1987 American Thoracic Society (ATS) guidelines typically used a 1 or 2 s plateau on the volume-time curve, not a minimum test duration of 6 s, to terminate a test. OBJECTIVES To determine the effect of changing guidelines on FEV(1), FVC and FEV(1)/FVC during a longitudinal study of young adults. METHODS Spirometry was performed on participants in the Coronary Artery Risk Development in Young Adults (CARDIA) study. Values obtained at entry and 2, 5 and 10 years later using accepted procedures were re-evaluated using the 2005 ATS-ERS guidelines, which were in effect for the year 20 exam. Generalized estimating equations were used to adjust tests with short exhalations that were acceptable by then current end of test criteria. RESULTS The percentage of participants at years 0, 2, 5, and 10 with exhalations less than 6 s but with an acceptable plateau was 33%, 29%, 9%, and 2%, respectively. Exhalations less than 6 s occurred more frequently in younger and female participants, and were associated with lower FVC and higher FEV(1)/FVC. For short exhalations the adjusted FVC was 47 ml and 110 ml higher than the measured FVC when 6 and 8 s exhalation times were used. CONCLUSIONS In longitudinal studies of young adults, changing end of test criteria may affect lung function, especially among younger and female participants. Determining adjusted values for tests with short exhalations may better represent the lung health of participants.

Rapid decline in lung function is temporally associated with greater metabolically active adiposity in a longitudinal study of healthy adults

Rationale Adiposity is associated with low lung function, but the longitudinal relationship between lung function and adiposity is inadequately studied. Objective To examine the bidirectional longitudinal associations between rapid decline in lung function and adiposity phenotypes in healthy adults. Methods This secondary analysis used a 25-year longitudinal dataset from the Coronary Artery Risk Development in Young Adults (CARDIA) study that enrolled 5115 participants. Measurements In the first analysis, metabolic syndrome at or before CARDIA year (Y) 10 (Y10) was the predictor, and subsequent rapid decline in forced vital capacity (FVC) or forced expiratory volume in 1 s (FEV1) between Y10 and Y20 was the outcome. In the second analysis, rapid decline was the predictor, and incident metabolic syndrome at Y20 and/or Y25 was the outcome. In the third analysis, rapid decline was the predictor, and subsequent CT-assessed regional fat depots at Y25 were the outcome. Results Metabolic syndrome at or before Y10 is temporally associated with rapid decline in FVC between Y10 and Y20 (adjusted p=0.04), but this association was explained by body mass index (BMI) at Y10. Rapid decline in FVC or FEV1 is temporally associated with greater incident metabolic syndrome at Y20 and/or Y25 (adjusted OR 2.10 (1.69, 2.61); p<0.001, and 1.56 (1.26, 1.94); p<0.001, respectively) and greater CT-assessed intrathoracic visceral adiposity at Y25 (adjusted standardised β 0.09; p<0.001 for both analyses). These associations were not explained by BMI levels prior to the outcome measurement. Conclusions Healthy adults with rapid decline in lung function are at risk for developing metabolic syndrome and for disproportionate accumulation of intrathoracic visceral fat. Metabolic abnormalities may be an early extrapulmonary manifestation of lung impairment that may be preventable by improving lung health.

Rapid decline in lung function in healthy adults predicts incident excess urinary albumin excretion later in life

Introduction Chronic lung disease, often characterised by rapid decline in lung function, is associated with vascular endothelial dysfunction (characterised by moderate to severe excess urinary albumin excretion (eUAE) but their longitudinal relationship is inadequately studied. In a bidirectional longitudinal examination of healthy adults, we analysed the following two hypotheses: (1) rapid decline (ie, highest tertile of lung function decline) predicts eUAE and (2) eUAE predicts rapid decline. Methods We performed a secondary data analysis from 3052 eligible participants from the Coronary Artery Risk Development in Young Adults (CARDIA) study. For analysis 1, the predictor was rapid decline in lung function between the peak value (attained at or before CARDIA visit year 10 or Y10 at a mean age of 35 years) and Y20; and the outcome was incident eUAE at Y20 and/or Y25. For analysis 2, the predictor was eUAE at Y10 and the outcome was rapid decline between Y10 and Y20. Results After adjustment for covariates in analysis 1, rapid decline in FEV1 or FVC between peak and Y20 predicted incident eUAE at Y20 and/or Y25 (OR 1.51 and 1.44, respectively; p≤0.05 for both analyses). In analysis 2, eUAE at Y10 did not predict subsequent rapid decline. Conclusions Healthy adults with rapid decline in lung function are at risk for developing vascular endothelial dysfunction, as assessed by incident eUAE, later in life.