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.