Renal dysfunction in older age groups and mortality after acute myocardial infarction

Multiple observational and randomized trials support the finding that renal insufficiency has a significant, independent, graded effect on the risk of cardiovascular events and cardiovascular mortality. Data from the 35,847 patients in the US Renal Data System show a cumulative post-transplant incidence of myocardial infarction (MI) of 5.6% at 1 year and 11.1% at 3 years.¹ Graft failure increased the hazard ratio for MI to 2.78 (confidence interval [CI], 2.41-3.19), suggesting a significant role for renal failure in increasing the risk of subsequent events. Usual risk factors, including age, diabetes, cardiovascular disease (angina, prior MI, and peripheral vascular disease), also increased the risk of MI.

In acute MI, there is a well-defined independent role for renal insufficiency in predicting short-and long-term mortality. Renal insufficiency has been shown to be a variable correlating with 1-year mortality after primary percutaneous coronary intervention for acute MI. Using a 7-variable score derived from the Controlled Abciximab and Device Investigation to Lower Late Angioplasty Complications (CADILLAC) trial and validated in the Stent Primary Angioplasty in Myocardial Infarction (PAMI) trial, renal insufficiency was given a point score of 3 (low risk, ≤ 2; intermediate risk, 3-5; high risk, ≥ 6), making it a potent predictor of mortality (other variables include age > 65 years [2 points]; Killip class 2/3 [3 points]; left ventricular ejection fraction < 40% [4 points]; anemia [2 points]; 3-vessel coronary artery disease [2 points]; and Thrombolysis in Myocardial Infarction flow grade [2 points]).²

The Valsartan in Acute Myocardial Infarction (VALIANT) trial examined the independent effect of varying degrees of renal insufficiency on acute MI outcome in 14,527 patients using a 70-variable model. For a glomerular filtration rate (GFR) < 81 mL/min/1.73 m² (estimated by the Modification Diet in Renal Disease equation), each 10-unit reduction in GFR was associated with a 1.10-fold increase in the hazard ratio, independent of other variables.³

Mortality is adversely affected not only by the initial GFR, but also by a deterioration in GFR during admission. A study of 1038 acute ST-elevation MI (STEMI) patients, 9.6% of whom developed worsening renal function (an increase of ≥ 0.5 mg/dL in serum creatinine level) during their hospitalization, showed that both an initially decreased GFR of < 60 mL/min/1.73 m² and worsening renal function were independent predictors of in-hospital and 1-year mortality. Decreased GFR was associated with an in-hospital mortality odds ratio of 2.8 (95% CI, 1.3-5.9) and a 1-year hazard ratio of 2.8 (95% CI, 1.6-4.9); worsening renal function was associated with an in-hospital mortality odds ratio of 11.4 (95% CI, 6.6-19.5) and a 1-year hazard ratio of 7.2 (95% CI, 4.9-10.4).⁴

The increased risk of mortality extends to patients with acute coronary syndromes. A study of 1400 consecutive patients undergoing culprit lesion stenting for unstable angina/non-STEMI showed a graded effect of renal insufficiency on in-hospital mortality, assessed by calculated admission GFR (0%, GFR > 130 mL/min/1.73 m²; 0.4%, GFR = 90-129 mL/min/1.73 m²; 2.6%, GFR = 60-89 mL/min/1.73 m²; 5.1%, GFR < 60 mL/min/1.73 m²). Patients with a GFR < 60 mL/min/1.73 m² had an in-hospital mortality hazard ratio of 4.0 (95% CI, 1.8-9.1) and long-term (3-year) mortality hazard ratio of 2.6 (95% CI, 1.5-4.5).⁵ Renal insufficiency was a potent independent predictor of in-hospital and long-term mortality.

Why does renal function predict outcome? Renal dysfunction shares “common soil” with cardiovascular disease. Age, hypertension with associated left ventricular hypertrophy, diastolic and systolic dysfunction, dyslipidemia, diabetes mellitus, and peripheral vascular disease are associated with the risk of developing both conditions.

Renal patients are often undertreated with standard therapies for acute coronary syndromes (including lytics, glycoprotein IIb/IIIa inhibitors, anticoagulants, and revascularization strategies) and secondary prevention (including statins, beta blockers, angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, and aspirin), clearly increasing the risk of acute mortality, morbidity, and recurrent events. Renal insufficiency is associated with neurohumoral activation of the renin-angiotensin-aldosterone system and sympathetic nervous system, similar to cardiovascular disease, but it makes treatment of cardiovascular patients with appropriate agents shown to decrease mortality and events less likely.

Renal dysfunction is associated with anemia, endothelial dysfunction, increased homocysteine levels, procoagulant coagulopathy, systemic inflammation, hyperparathyroidism with increased calcium-phosphate product and ectopic calcification, immunosuppression, and increased risk of contrast-induced nephropathy, all factors potentially increasing risk. The mechanism by which renal insufficiency increases cardiovascular mortality is currently unexplained, but it is clear that renal insufficiency has an independent, graded effect on events and mortality across the spectrum of cardiovascular patients and that aggressive, appropriate care is mandatory.