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

Abstract

Background: Respiratory and cardiovascular diseases (CVDs) frequently coexist; however, there is limited evidence on the relationship between chronic respiratory symptoms in young adulthood and late-onset CVD.

Research question: Are chronic respiratory symptoms in young adulthood associated with CVD and all-cause mortality in later life?

Study design and methods: A total of 4,621 participants from the Coronary Artery Risk Development in Young Adults Study (CARDIA) cohort study aged 18 to 30 years were included. Chronic respiratory symptoms were identified through respiratory symptom questionnaires in two consecutive examinations. Incident CVD and all-cause mortality were adjudicated over 30-year follow-up. Multivariable Cox proportional hazards models were used to explore the association of chronic respiratory symptoms with incident CVD and all-cause mortality.

Results: During a median follow-up of 30.9 years, 284 CVD events (6.15%) and 378 deaths (8.18%) occurred. Following multivariable adjustment for demographic characteristics, cardiovascular risk factors, smoking, and lung function, the hazard ratios (95% CIs) for CVD events were 1.51 (1.18-1.93) for any respiratory symptom, 1.57 (1.18-2.09) for cough or phlegm, 1.31 (1.01-1.68) for wheeze, 1.73 (1.25-2.41) for shortness of breath, and 1.32 (1.01-1.71) for chest illnesses. Similar findings were also observed in all-cause mortality. Comparing zero vs three to four respiratory symptoms, the hazard ratios (95% CIs) were 1.97 (1.34-2.91) for CVD and 1.75 (1.23-2.47) for all-cause mortality. Similar results were observed in various sensitivity analyses.

Interpretation: Chronic respiratory symptoms in young adulthood are associated with an increased risk of CVD and all-cause mortality in midlife independent of established cardiovascular risk factors, smoking, and lung function. Identifying chronic respiratory symptoms in young adulthood may help provide prognostic information regarding future cardiovascular health.

Clinical trial registration: ClinicalTrials.gov; No.: NCT00005130; URL: https://www.

Clinicaltrials: gov.

Keywords: CARDIA study; cardiovascular disease; chronic respiratory symptoms; cohort study; young adulthood.

Graphical abstract

Figure 1

Kaplan-Meier curves for each respiratory symptom and CVD. Kaplan-Meier curves are used to illustrate the association of any symptom (A), cough or phlegm (B), wheeze (C), shortness of breath (D), and chest illnesses (E) with CVD over 30 years’ follow-up. P values were calculated by using the log-rank test. CVD = cardiovascular disease.

Figure 2

Association of the presence of chronic respiratory symptom with cardiovascular disease. Model 1: unadjusted. Model 2: adjusted for baseline age, sex, race, BMI, smoking status, alcohol consumption, physical activity, systolic BP, fasting glucose, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol. Model 3: adjusted for baseline age, sex, race, and cumulative BMI, smoking status, alcohol consumption, physical activity, systolic BP, fasting glucose, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol. Model 4: adjusted for variables in model 3 plus cumulative lung function (FEV₁, FVC, or FEV₁/FVC). HR = hazard ratio.

Figure 3

Subgroup analyses of association between the number of chronic respiratory symptoms and cardiovascular disease and all-cause mortality stratified according to smoking status. Nonsmoking was determined as never or former smokers; smoking was determined as current smoker at year 0. HRs were adjusted for age, sex, race, and cumulative BMI, smoking status, alcohol consumption, physical activity, systolic BP, fasting glucose, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and lung function. HR = hazard ratio.