Incident Hospitalization with Major Cardiovascular Diseases and Subsequent Risk of ESKD: Implications for Cardiorenal Syndrome
Authors: Ishigami Junichi , Cowan Logan T. , Demmer Ryan T. , Grams Morgan E. , Lutsey Pamela L. , Carrero Juan-Jesus , Coresh Josef , Matsushita Kunihiro 
Published: January 2020

Significance Statement
Whether incident cardiovascular disease increases the long-term risk of ESKD is not well studied. The authors assessed the association of incident major cardiovascular diseases (heart failure, atrial fibrillation, coronary heart disease, and stroke) with risk of ESKD in 9047 participants of a prospective cohort study. They found that each of these major cardiovascular diseases was significantly and independently associated with the risk of ESKD, with a particularly strong association for heart failure. The association was stronger for heart failure with preserved ejection fraction compared with heart failure with reduced ejection fraction. These findings highlight the importance of managing kidney disease after cardiovascular disease. The potentially distinct contribution to ESKD of heart failure with preserved ejection fraction versus heart failure with reduced ejection fraction deserves future investigation.

Background
Cardiorenal syndrome is a well known concept, bolstered by extensive investigations of CKD as a risk factor of cardiovascular disease. However, data on whether cardiovascular disease increases long-term risk of ESKD are sparse.

Methods
We assessed the association of incident hospitalization with major cardiovascular diseases (heart failure, atrial fibrillation, coronary heart disease, and stroke) with subsequent risk of ESKD among individuals enrolled in the Atherosclerosis Risk in Communities study; the analysis included 9047 individuals without prevalent cardiovascular disease at their fourth study visit. Each relevant incident cardiovascular disease event was entered into multivariable Cox proportional hazard models as a time-varying exposure to estimate hazard ratios.

Results
During a median follow-up of 17.5 years, there were 2598 cases of hospitalization with cardiovascular disease (heart failure, n=1269; atrial fibrillation, n=1337; coronary heart disease, n=696; and stroke, n=559) and 210 cases of incident ESKD. The incidence of major cardiovascular disease was associated with increased risk of ESKD, with the highest risk for heart failure (hazard ratio, 11.40; 95% confidence interval, 8.38 to 15.50), followed by coronary heart disease, atrial fibrillation, and stroke. When we analyzed heart failure with preserved ejection fraction and heart failure with reduced ejection fraction separately, the risk was nominally higher for heart failure with preserved ejection fraction.

Conclusions
Major incident cardiovascular disease events were associated with ESKD, independent of kidney risk factors. In particular, heart failure showed a very strong association with ESKD. Our findings highlight the importance of monitoring and managing kidney disease in patients with cardiovascular disease. The potentially distinct contribution to ESKD of heart failure with preserved versus reduced ejection fraction deserves future investigation.