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Inflammatory biomarkers, hormone replacement therapy, and incident coronary heart disease. Prospective analysis from the women’s health initiative observational study
Preventive Cardiology
Methods: A nested case-control study of post-menopausal women free of CVD participating in the Woman’s Health Initiative (WHI) Observational Study, which was designed to determine risk factors for various health outcomes. 304 women who developed CHD, defined as first MI or CVD death, were matched by age, smoking and ethnicity with a comparable group (controls) free of disease during 2.9 years of follow-up. The effect of baseline CRP and interleukin-6 (IL-6) was assessed and related to hormone replacement (HRT) status. Results: The controls were more often current or past estrogen users. Standard CV risk factors were more prevalent in cases including a higher BMI, hypertension, family history of CAD, less exercise, higher LDL-C, lower HDL-C, higher triglycerides and ratio of total-C/HDL-C. Median CRP was higher in cases than controls, p⬍0.001 [cases 0.33 mg/dL (25–75th 0.14 – 0.71) vs. 0.25 mg/dL (25–75th 0.10 – 0.47) in controls], and IL-6 was also higher in cases. The odds ratio (OR) for CHD for the highest to lowest quartile was 2.3 for CRP and 3.3 for IL-6 and remained above 2 after adjustment for lipid and non-lipid risk factors. Current HRT use was associated with increased mean CRP, but not IL-6. When comparing women with similar levels of CRP and IL-6, the use of HRT did not influence the CHD risk. When stratified by HRT use, there was a graded positive relationship between CRP and CHD for users and nonusers of HRT across the spectrum of CRP. Conclusions: CRP and IL-6 are independent risk predictors of CHD among healthy post- menopausal women, and HRT increases the CRP. However, use or nonuse of HRT is less important as a risk determinant than baseline CRP and IL-6. Perspective: There is more to come when a similar analysis is provided from the WHI placebo-controlled trial of estrogens/progestins that demonstrated an increased rate of MI and stroke in women on treatment. This study adds to large body of literature demonstrating the powerful relationship between CRP and CHD when depicted by quartiles using the median. But the predictive value of a CRP above the median in an individual is relatively weak and needs to be placed in the context of other risk factors. MR
Abstracts Effects of Long-Term Treatment with AngiotensinConverting Enzyme Inhibitors in the Presence or Absence of Aspirin: A Systematic Review Teo KK, Yusuf S, Pfeffer M, et al., for the ACE Inhibitors Collaborative Group. Lancet 2002;360:1037– 43. Study Question: Aspirin can inhibit the production of vasodilating prostaglandins, which are increased by ACE inhibitors. This review sought to determine whether aspirin reduces the benefit of ACEi, when used in patients with LV dysfunction and heart failure. Methods: A systematic review of data for 22,060 patients who were involved in six randomized trials of ACEi in CHF, LV dysfunction, post-MI or secondary prevention. Each placebo-controlled study had specified cardiovascular outcomes and did not proscribe use of ASA. The end point for this analysis was a composite of major clinical outcomes that included death, MI, stroke, hospital admission for CHF or revascularization. Results: There were differences in the baseline characteristics between ASA and non-ASA users in the six trials, such as more ASA in the MI participants in HOPE and more beta-blockers in MI studies, and major vascular event rates were lower in ASA users on placebo. A highly significant reduction was noted for ACEi in combined major vascular events including MI, death, hospitalization for CHF, stroke and revascularization. There was no significant difference in the presence or absence of ASA, even when including the SOLVD trials, which had previously suggested mortality and rate of MI was not benefited when ACEi was combined with ASA. Conclusions: There is definite evidence of clinically important benefits from ACEi therapy in patients with CV disease irrespective of concomitant use of aspirin. Perspective: While ASA might reduce some of potential value of ACEi on vascular function and renal blood flow, the use of low dose ASA ⫹ ACEi in patients at risk for and with atherosclerotic disease and diabetes is safe and has become a standard of care. MR
Statin-Associated Myopathy With Normal Creatine Kinase Levels Phillips PS, Haas RH, Bannykh S, et al. Ann Intern Med 2002; 137:581–5.
Inflammatory Biomarkers, Hormone Replacement Therapy, and Incident Coronary Heart Disease. Prospective Analysis From the Women’s Health Initiative Observational Study
Study Question: Can the statin class of lipid lowering drugs cause a myopathy in the absence of elevated serum muscle creatine kinase (CK). Methods: Preliminary analysis of four cases participating in a randomized, double-blind crossover trial to determine whether patients with muscle symptoms possibly due to statins and normal CK can distinguish blinded statin therapy from placebo. Patients underwent muscle strength testing.
Pradhan AD, Manson JE, Rossouw JE, et al. JAMA 2002;288: 980 –7. Study Question: Is the increased level of high sensitivity CRP attributable to hormone replacement therapy (HRT) a clinical hazard?
ACC CURRENT JOURNAL REVIEW Jan/Feb 2003
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Methods: A nested case-control study of post-menopausal women free of CVD participating in the Woman’s Health Initiative (WHI) Observational Study, which was designed to determine risk factors for various health outcomes. 304 women who developed CHD, defined as first MI or CVD death, were matched by age, smoking and ethnicity with a comparable group (controls) free of disease during 2.9 years of follow-up. The effect of baseline CRP and interleukin-6 (IL-6) was assessed and related to hormone replacement (HRT) status. Results: The controls were more often current or past estrogen users. Standard CV risk factors were more prevalent in cases including a higher BMI, hypertension, family history of CAD, less exercise, higher LDL-C, lower HDL-C, higher triglycerides and ratio of total-C/HDL-C. Median CRP was higher in cases than controls, p⬍0.001 [cases 0.33 mg/dL (25–75th 0.14 – 0.71) vs. 0.25 mg/dL (25–75th 0.10 – 0.47) in controls], and IL-6 was also higher in cases. The odds ratio (OR) for CHD for the highest to lowest quartile was 2.3 for CRP and 3.3 for IL-6 and remained above 2 after adjustment for lipid and non-lipid risk factors. Current HRT use was associated with increased mean CRP, but not IL-6. When comparing women with similar levels of CRP and IL-6, the use of HRT did not influence the CHD risk. When stratified by HRT use, there was a graded positive relationship between CRP and CHD for users and nonusers of HRT across the spectrum of CRP. Conclusions: CRP and IL-6 are independent risk predictors of CHD among healthy post- menopausal women, and HRT increases the CRP. However, use or nonuse of HRT is less important as a risk determinant than baseline CRP and IL-6. Perspective: There is more to come when a similar analysis is provided from the WHI placebo-controlled trial of estrogens/progestins that demonstrated an increased rate of MI and stroke in women on treatment. This study adds to large body of literature demonstrating the powerful relationship between CRP and CHD when depicted by quartiles using the median. But the predictive value of a CRP above the median in an individual is relatively weak and needs to be placed in the context of other risk factors. MR
Abstracts Effects of Long-Term Treatment with AngiotensinConverting Enzyme Inhibitors in the Presence or Absence of Aspirin: A Systematic Review Teo KK, Yusuf S, Pfeffer M, et al., for the ACE Inhibitors Collaborative Group. Lancet 2002;360:1037– 43. Study Question: Aspirin can inhibit the production of vasodilating prostaglandins, which are increased by ACE inhibitors. This review sought to determine whether aspirin reduces the benefit of ACEi, when used in patients with LV dysfunction and heart failure. Methods: A systematic review of data for 22,060 patients who were involved in six randomized trials of ACEi in CHF, LV dysfunction, post-MI or secondary prevention. Each placebo-controlled study had specified cardiovascular outcomes and did not proscribe use of ASA. The end point for this analysis was a composite of major clinical outcomes that included death, MI, stroke, hospital admission for CHF or revascularization. Results: There were differences in the baseline characteristics between ASA and non-ASA users in the six trials, such as more ASA in the MI participants in HOPE and more beta-blockers in MI studies, and major vascular event rates were lower in ASA users on placebo. A highly significant reduction was noted for ACEi in combined major vascular events including MI, death, hospitalization for CHF, stroke and revascularization. There was no significant difference in the presence or absence of ASA, even when including the SOLVD trials, which had previously suggested mortality and rate of MI was not benefited when ACEi was combined with ASA. Conclusions: There is definite evidence of clinically important benefits from ACEi therapy in patients with CV disease irrespective of concomitant use of aspirin. Perspective: While ASA might reduce some of potential value of ACEi on vascular function and renal blood flow, the use of low dose ASA ⫹ ACEi in patients at risk for and with atherosclerotic disease and diabetes is safe and has become a standard of care. MR
Statin-Associated Myopathy With Normal Creatine Kinase Levels Phillips PS, Haas RH, Bannykh S, et al. Ann Intern Med 2002; 137:581–5.
Inflammatory Biomarkers, Hormone Replacement Therapy, and Incident Coronary Heart Disease. Prospective Analysis From the Women’s Health Initiative Observational Study
Study Question: Can the statin class of lipid lowering drugs cause a myopathy in the absence of elevated serum muscle creatine kinase (CK). Methods: Preliminary analysis of four cases participating in a randomized, double-blind crossover trial to determine whether patients with muscle symptoms possibly due to statins and normal CK can distinguish blinded statin therapy from placebo. Patients underwent muscle strength testing.
Pradhan AD, Manson JE, Rossouw JE, et al. JAMA 2002;288: 980 –7. Study Question: Is the increased level of high sensitivity CRP attributable to hormone replacement therapy (HRT) a clinical hazard?
ACC CURRENT JOURNAL REVIEW Jan/Feb 2003
28