Johannes F.E. Mann, MD; Hertzel C. Gerstein, MD; Janice Pogue, MSc; Jackie Bosch, MA; Salim Yusuf, MD; for the HOPE Investigators
Grant Support: By the Medical Research Council of Canada, the Ontario Heart Foundation, Aventis, Astra-Zeneca, NEGMA, and the Natural Source Vitamin E Producers Association.
Requests for Single Reprints: Jackie Bosch, MA, HOPE Office, McMaster University, Hamilton General Hospital, 527 Barton Street East, Hamilton, Ontario L8L 2X2, Canada.
Current Author Addresses: Dr. Mann: Department of Nephrology and Hypertension, Schwabing General Hospital, LMU, Kolner Platz 1, D-80804 Munchen, Germany.
Drs. Gerstein, Pogue, and Yusuf and Ms. Bosch: HOPE Office, McMaster University, Hamilton General Hospital, 237 Barton Street East, Hamilton, Ontario L8L 2X2, Canada.
Author Contributions: Conception and design: J.F.E. Mann, H.C. Gerstein, S. Yusuf.
Analysis and interpretation of the data: J.F.E. Mann, H.C. Gerstein, J. Pogue.
Drafting of the article: J.F.E. Mann, H.C. Gerstein, S. Yusuf.
Critical revision of the article for important intellectual content: J.F.E. Mann, H.C. Gerstein, J. Pogue, J. Bosch, S. Yusuf.
Final approval of the article: J.F.E. Mann, H.C. Gerstein, J. Bosch, S. Yusuf.
Provision of study materials or patients: J.F.E. Mann, H.C. Gerstein, J. Bosch.
Statistical expertise: J. Pogue.
Obtaining of funding: H.C. Gerstein, S. Yusuf.
Collection and assembly of data: J.F.E. Mann, J. Bosch.
The cardiovascular risk associated with early renal insufficiency is unknown. Clinicians are often reluctant to use angiotensin-converting enzyme inhibitors in patients with renal insufficiency.
To determine whether mild renal insufficiency increases cardiovascular risk and whether ramipril decreases that risk.
Post hoc analysis.
The Heart Outcomes and Prevention Evaluation (HOPE) study, a randomized, double-blind, multinational trial involving 267 study centers.
980 patients with mild renal insufficiency (serum creatinine concentration ≥ 124 µmol/L [≥ 1.4 mg/dL]) and 8307 patients with normal renal function (serum creatinine concentration < 124 µmol/L [<1.4 mg/dL]) Patients with a baseline serum creatinine concentration greater than 200 µmol/L (2.3 mg/dL) were excluded.
The primary outcome measure was incidence of cardiovascular death, myocardial infarction, or stroke.
Cumulative incidence of the primary outcome was higher in patients with renal insufficiency than in those without (22.2% vs. 15.1%; P < 0.001) and increased with serum creatinine concentration. Patients with renal insufficiency had a substantially increased risk for cardiovascular death (11.4% vs. 6.6%) and total mortality (17.8% vs. 10.6%) (P < 0.001 for both comparisons). The effect of renal insufficiency on the primary outcome (adjusted hazard ratio, 1.40 [95% CI, 1.16 to 1.69]) was independent of known cardiovascular risks and treatment. Ramipril reduced the incidence of the primary outcome in patients with and those without renal insufficiency (hazard ratio, 0.80 vs. 0.79; P > 0.2 for the difference).
In patients who had preexisting vascular disease or diabetes combined with an additional cardiovascular risk factor, mild renal insufficiency significantly increased the risk for subsequent cardiovascular events. Ramipril reduced cardiovascular risk without increasing adverse effects.
Mann JF, Gerstein HC, Pogue J, Bosch J, Yusuf S, for the HOPE Investigators. Renal Insufficiency as a Predictor of Cardiovascular Outcomes and the Impact of Ramipril: The HOPE Randomized Trial. Ann Intern Med. 2001;134:629–636. doi: 10.7326/0003-4819-134-8-200104170-00007
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Published: Ann Intern Med. 2001;134(8):629-636.
Cardiology, Coronary Risk Factors, Hypertension, Nephrology.
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