Comparison of C-reactive protein and low-density lipoprotein cholesterol levels in the prediction of first cardiovascular events

goals. Exclusion criteria included diastolic pressure ⬍95 mm Hg, diabetes, urine protein/creatinine ⬎2.5, non-BP renal disease and CHF. The end-point was rate of change in glomerular filtration rate (GFR), a GFR reduction of 50% or ⬎25 mL/m/1.73m2, end-stage renal disease or death with a 4-year follow-up. Results: The average age was 54 years, about 40% were female and average BP was 150/96 with a mean of 115 mm Hg. Mean serum creatinine was 2.2 mg/dL in men and 1.8 mg/dL in women, and GFR mean was 45 mL/min per 1.73 m2. The amlodipine arm was halted early. The final BP averaged 128/78 in the lower BP group and 141/85 in the usual BP group. The mean GFR slope from baseline did not differ between the groups defined by mean BP, and a lower BP did not reduce the rate of composite clinical outcome. None of the drug group comparisons showed significant differences in GFR slope. However, compared to metoprolol and amlodipine, the ramipril group had a risk reduction in composite outcome of 22% and 38%, respectively (p⫽0.04 for each). There was no difference in all-cause or cardiovascular mortality between BP groups and drug interventions. Conclusions: A lower BP goal provides no added benefit of slowing of progression of hypertensive nephrosclerosis in African Americans. ACE inhibitors appear to be more effective than beta-blockers and dihydropyridine calcium channel blockers in slowing GFR decline. Perspective: The benefits attributed to ACE inhibitors go beyond blood pressure control in persons with CAD, diabetes, hypertensive renal disease and others at high-risk. In large clinical trials of various subgroups ACEi have been shown to reduce rates of MI, fatal and non-fatal, need for revascularization, CHF, proteinuria and progression of renal disease. The benefits are independent of age and gender and similar in various ethnic groups. MR

Results: Mean age was 54.7 years, 25% had hypertension, 12% were smokers, 2.5% had diabetes, mean BMI was 25.9 kg/m2, and 44% were users of HRT. The approximate median CRP was 1.5 mg/L and LDL-C 125 mg/dL. In non-users of HRT, the first quintile of CRP was ⬍0.05 mg/L, the third quintile ⬎1.0 and ⬍2.0 mg/dL and fifth quintile ⬎4 mg/dL. The first quintile of LDL-C was about ⬍100 mg/dL, the third quintile 115–130 mg/dL and fifth quintile ⬎150 mg/dL. The age-adjusted relative risk for first CV event increased linearly from 1.5 in the second quintile to 3.6 in the fifth quintile, and major risk-factor–adjusted relative risk ranged from 1.4 in the second to 2.3 in the fifth. The risk-factor–adjusted relative risk ranged for LDL-C was not significant until the fourth quintile and reached 1.5 in the fifth quintile. The area under the ROC curve for predicting CV events (sensitivity vs. 1-specificity) for the risk-factor– adjusted RR was 0.81 for each biomarker. The distribution of CRP and LDL-C levels were only minimally correlated (r⫽0.08), suggesting each was detecting a different high-risk group. Using the median values as cutoffs, compared to low CRP ⫹ low LDL-C patients with a low LDL-C ⫹ high CRP or a high LDL-C ⫹ low CRP had a 50% greater risk of events. The risk attributable to a high CRP ⫹ high LDL-C was higher in non-users of HRT. Increasing levels of CRP from ⬍1 mg/L to ⬎3 mg/L increased the relative risk for CV events using the Framingham estimate of 10-year risk of events and cut points of LDL-C used in the ATP III guidelines. Conclusions: The C-reactive protein level is a stronger predictor of cardiovascular events than the LDL-C level and adds to the prognostic information derived from the Framingham risk score. Perspective: The data on CRP as a risk predictor are compelling, particularly in women. Clinicians should consider using the CRP for assessing CV risk in middle-aged and older men and women whose Global Risk Score is less 2% per year. As suggested by the authors, a statin trial in men and women with an LDL-C ⬍130 mg/dL and CRP above the median will be needed to help guide therapies. MR

Comparison of C-Reactive Protein and Low-Density Lipoprotein Cholesterol Levels in the Prediction of First Cardiovascular Events

Combined Use of Computed Tomography Coronary Calcium Scores and C-Reactive Protein Levels in Predicting Cardiovascular Events in Nondiabetic Individuals

Ridker PM, Rifai N, Rose L, et al. N Engl J Med 2002;347:1557– 65. Study Question: To compare the relative value of highsensitivity CRP and LDL cholesterol (LDL-C) for predicting cardiovascular events in apparently healthy women and determine whether the CRP provides added prognostic information after adjustment for all the components of the Framingham risk score. Methods: Assays of LDL-C and CRP were obtained on 27,929 women participating in the Women’s Health Study (WHS), a primary prevention trial designed to evaluate the utility of ASA and vitamin E in which women over 45 years of age were enrolled between 1992 and 1995. Participants were divided into quintiles of CRP and LDL-C. The discriminative value of predictive models was calculated on the basis of a minimal follow-up of 6 years.

Park R, Detrano R, Xiang M, et al. Circulation 2002;106:2073–7. Study Question: What is the value of the coronary artery calcium (CAC) score obtained by computed tomography (EBT), ultrasensitive C-reactive protein (CRP) and the combination for predicting coronary events in asymptomatic adults with a ⱖ10% 8-year risk of coronary events based on the Framingham risk equation? Methods: A prospective cohort study of 1461 subjects responded to public advertising and underwent a coronary risk assessment in the South Bay Heart Watch between 1990 and 1992. 1307 3-year survivors underwent a second

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