Current issues of ACP Journal Club are published in Annals of Internal Medicine


Renal impairment increased mortality and cardiovascular complications after myocardial infarction


ACP J Club. 2005 Mar-Apr;142:51. doi:10.7326/ACPJC-2005-142-2-051

Related Content in this Issue
• Companion Abstract and Commentary: Reduced glomerular filtration rate was associated with increased death, cardiovascular events, and hospitalization

Clinical Impact Ratings

GIM/FP/GP: 5 stars

Cardiology: 6 stars

Nephrology: 6 stars

Source Citation

Anavekar NS, McMurray JJ, Velazquez EJ, et al. Relation between renal dysfunction and cardiovascular outcomes after myocardial infarction. N Engl J Med. 2004;351:1285-95. [PubMed ID: 15385655]



In patients who have had myocardial infarction (MI), what is the relation of the severity of renal impairment to the risk for all-cause and cardiovascular (CV) mortality?


Design: Analysis within a randomized (allocation concealed*), blinded (clinicians, patients, and outcome assessors),* controlled trial (Valsartan in Acute Myocardial Infarction Trial [VALIANT] trial).

Setting: {931 centers in 24 countries}†.

Patients: 14 527 patients ≥ 18 years of age (mean age 66 y, 69% men) who had had acute MI within the previous 12 days that was complicated by clinical or radiologic signs of heart failure, left ventricular systolic dysfunction, or both. Patients with serum creatnine levels ≥ 221 µmol/L (2.5 mg/dL) were excluded.

Risk factors: Baseline glomerular filtration rate (GFR) was estimated using the Modification of Diet and Renal Disease equation, which incorporates age, race, sex, and serum creatinine level, and divided into 4 categories (< 45, 45 to 59.9, 60 to 74.9, and ≥ 75 mL/min per 1.73 m2 of body surface).

Outcomes: All-cause mortality and a composite CV endpoint of CV mortality, congestive heart failure, recurrent MI, resuscitation after cardiac arrest, and stroke.

Main results: Risk for all-cause mortality and the composite CV endpoint increased with decreasing estimated GFRs (Table). For estimated baseline GFR levels < 81.0 mL/min per 1.73 m2, each 10-unit decrease was associated with a hazard ratio of 1.10 (95% CI 1.08 to 1.12) for death and CV complications.


In patients who have had a myocardial infarction, the presence of renal disease increased the risk for all-cause and cardiovascular (CV) mortality and complications. Progressive reductions in renal function were associated with increasing mortality and CV complications.

*See Glossary.

Pfeffer MA, McMurray JJ, Velazquez EJ, et al. N Engl J Med. 2003;349:1893-906. 14610160

Source of funding: Novartis Phamaceuticals.

For correspondence: Dr. M.A. Pfeffer, Brigham and Women's Hospital, Boston, MA, USA. E-mail

Table. Association of estimated glomerular filtration rate (GFR) with risk for death and composite cardiovascular (CV) outcomes‡

Outcomes Adjusted hazard ratio (95% CI)§
GFR < 45 mL/min per 1.73 m2 GFR 45 to 59.9 mL/min per 1.73 m2 GFR 60 to 74.9 mL/min per m2
All-cause mortality 1.70 (1.50 to 1.93) 1.38 (1.24 to 1.54) 1.14 (1.02 to 1.27)
Composite CV endpoint 1.49 (1.35 to 1.65) 1.26 (1.16 to 1.37) 1.10 (1.02 to 1.19)

‡Patients with GFR ≥ 75.0 mL/min per 1.73 m2 were the reference group. Composite CV endpoint included CV mortality, reinfarction, congestive heart failure, resuscitation after cardiac arrest, and stroke. CI defined in Glossary.
§Variables in adjustment included 70 baseline characteristics.


Patients with renal insufficiency are easily identifiable, using equations that estimate GFR based on serum creatinine. In recent years, numerous studies have suggested that patients with estimated lower GFR have a higher incidence of future CV events and mortality than those with normal GFR. The large, well-done studies by Go and Anavekar and their colleagues confirm this both in the general population and in patients presenting with acute MI. For example, in the study by Go and colleagues, the age-standardized rate of death per 100 person-years in the general population was 14.1 when the estimated GFR was < 15 mL/min per 1.73 m2 and was 11.4, 4.8, and 1.1 when the estimated GFR was 15 to 29, 30 to 44, and 45 to 59 mL/min per 1.73 m2, respectively. Similar trends were also present for CV and hospitalization outcomes. These findings in large numbers of patients, throughout an entire range of GFRs, highlight the clinical and public health importance of this condition.

How can practitioners prevent future morbidity and mortality in these patients? It is evident that patients with moderate reductions of GFR (GFR 30 to 59 mL/min per 1.73 m2) benefit from established CV protective interventions, such as statins and angiotensin-converting enzyme inhibitors (1, 2). Given their high incidence of future CV events, patients with low GFR may derive an even greater benefit in absolute terms than does the general population. Thus, the importance of using such medications in these patients cannot be overemphasized, and observed deficiencies in health care must be remedied (3). Unfortunately, a number of clinical trials testing CV protective interventions deliberately excluded patients with more marked reductions in GFR. In addition, a recent large trial showed that hemodialysis patients were unresponsive to the benefits of statins (4). Thus, whether patients with GFR < 30 have a similar response to CV agents proven beneficial in the general population remains to be clarified.

In patients with GFR < 30 mL/min per 1.73 m2, is there any role for the treatment of potential novel risk factors that become pronouced with GFR decline? The studies by Go and Anavekar both describe a “dose-dependent,” independent association between decrements in GFR and future CV events. The risk in patients with GFR < 30 mL/min per 1.73 m2 was more than 3-fold that of patients with preserved GFR. These associations persisted after adjustment for established cardiovascular risk factors and other relevant comorbid conditions. Proposed novel mechanisms potentially amenable to therapeutic intervention include elevated calcium-phosphate product, hyperhomocysteinemia, anemia, and inflammation. However, whether low GFR is causally related to CV disease remains controversial. For example, in the study by Anavekar and colleagues, a portion of the independent association between low GFR and future CV events is expected to be noncausal residual confounding from such factors as concomitant renal vascular disease, generalized atherosclerosis, and renal hypoperfusion. Thus, while promising, the potential to reduce the burden of CV disease by treating unique renal pathogenic mechanisms remains uncertain. The CV benefits of erythropoietin and phosphate binders in these patients are the subject of ongoing clinical trials, and their results will inform both patient care and the causality debate.

Amit X. Garg, MD, MA, FRCPC
London Health Sciences Centre
London, Ontario, Canada


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