Cardiovascular outcomes in high-risk hypertensive patients stratified by baseline glomerular filtration rate

Ann Intern Med. 2006 Feb 7;144(3):172-80. doi: 10.7326/0003-4819-144-3-200602070-00005.


Background: Chronic kidney disease is common in older patients with hypertension.

Objective: To compare rates of coronary heart disease (CHD) and end-stage renal disease (ESRD) events; to determine whether glomerular filtration rate (GFR) independently predicts risk for CHD; and to report the efficacy of first-step treatment with a calcium-channel blocker (amlodipine) or an angiotensin-converting enzyme inhibitor (lisinopril), each compared with a diuretic (chlorthalidone), in modifying cardiovascular disease (CVD) outcomes in high-risk patients with hypertension stratified by GFR.

Design: Post hoc subgroup analysis.

Setting: Multicenter randomized, double-blind, controlled trial.

Participants: Persons with hypertension who were 55 years of age or older with 1 or more risk factors for CHD and who were stratified into 3 baseline GFR groups: normal or increased (> or = 90 mL/min per 1.73 m2; n = 8126 patients), mild reduction (60 to 89 mL/min per 1.73 m2; n = 18,109 patients), and moderate or severe reduction (< 60 mL/min per 1.73 m2; n = 5662 patients).

Interventions: Random assignment to chlorthalidone, amlodipine, or lisinopril.

Measurements: Rates of ESRD, CHD, stroke, and combined CVD (CHD, coronary revascularization, angina, stroke, heart failure, and peripheral arterial disease).

Results: In participants with a moderate to severe reduction in GFR, 6-year rates were higher for CHD than for ESRD (15.4% vs. 6.0%, respectively). A baseline GFR of less than 53 mL/min per 1.73 m2 (compared with >104 mL/min per 1.73 m2) was independently associated with a 32% higher risk for CHD. Amlodipine was similar to chlorthalidone in reducing CHD (16.0% vs. 15.2%, respectively; hazard ratio, 1.06 [95% CI, 0.89 to 1.27]), stroke, and combined CVD (CHD, coronary revascularization, angina, stroke, heart failure, and peripheral arterial disease), but less effective in preventing heart failure. Lisinopril was similar to chlorthalidone in preventing CHD (15.1% vs. 15.2%, respectively; hazard ratio, 1.00 [CI, 0.84 to 1.20]), but was less effective in reducing stroke, combined CVD events, and heart failure.

Limitations: Proteinuria data were not available, and combination therapies were not tested.

Conclusions: Older high-risk patients with hypertension and reduced GFR are more likely to develop CHD than to develop ESRD. A low GFR independently predicts increased risk for CHD. Neither amlodipine nor lisinopril is superior to chlorthalidone in preventing CHD, stroke, or combined CVD, and chlorthalidone is superior to both for preventing heart failure, independent of level of renal function.

Trial registration: NCT00000542.

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Amlodipine / therapeutic use
  • Antihypertensive Agents / therapeutic use*
  • Cardiovascular Diseases / epidemiology
  • Cardiovascular Diseases / prevention & control*
  • Chlorthalidone / therapeutic use
  • Chronic Disease
  • Double-Blind Method
  • Female
  • Glomerular Filtration Rate*
  • Humans
  • Hypertension / complications
  • Hypertension / drug therapy*
  • Hypertension / physiopathology*
  • Kidney Diseases / complications
  • Kidney Diseases / physiopathology*
  • Kidney Failure, Chronic / epidemiology
  • Kidney Failure, Chronic / prevention & control*
  • Lisinopril / therapeutic use
  • Male
  • Middle Aged
  • Risk Factors


  • Antihypertensive Agents
  • Amlodipine
  • Lisinopril
  • Chlorthalidone

Associated data