Date of Award


Document Type

Open Access Thesis

Degree Name

Medical Doctor (MD)

First Advisor

Lawrence Young


Background: Proteinuria is a known cardiovascular risk factor in hypertensive or diabetic patients as well as the general population. Worsening renal function (WRF) has been shown to influence outcomes in the heart failure population. The prognostic value of these markers for renal dysfunction in patients after myocardial infarction is unclear. Methods: The Survival and Ventricular Enlargement trial (SAVE) randomized 2231 patients with left ventricular dysfunction between 3-16 days (average 11 days) post-MI to receive captopril or placebo; those with a serum creatinine above 2.5mg/dl were excluded from SAVE. WRF was defined as an increase in creatinine greater-than 0.3mg/dl measured from baseline to two weeks after randomization. A subset of 583 SAVE patients who underwent baseline dipstick urinalysis was also studied. We examined the predictive values of WRF and proteinuria on cardiovascular outcomes during 42 months of follow-up. We then explored the potential interaction between these markers of renal dysfunction and the response to angiotensin-converting enzyme (ACE) inhibition. Results: Proteinuria was present in 20.9% of patients who were generally older, more often hypertensive, and who had lower ejection fractions and glomerular filtration rates. Proteinuria was associated with an increased risk of death (HR 1.84, 95%CI 1.20-2.82). In 1854 subjects with paired serum creatinine measurements, WRF occurred in 223 subjects (12.0%) and had no significant association with ACE inhibitor therapy (p=0.38). WRF was a stronger predictor of death (HR 1.55, 95%CI 1.15-2.11) than baseline serum creatinine (HR 1.47, 95%CI 1.05-2.05). The absolute benefit of captopril therapy was greatest for patients with proteinuria (p=0.02), but not for those with WRF (p=0.40). Conclusions: Proteinuria and WRF were not uncommon in patients after myocardial infarction, and were strongly associated with increased risk for death and cardiovascular outcomes irrespective of baseline renal function. Patients randomized to captopril did not demonstrate more WRF than patients receiving placebo, and subjects with proteinuria who took captopril had the highest reduction in cardiovascular outcomes.


This is an Open Access Thesis.

Open Access

This Article is Open Access