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Effects of Antihypertensive Therapy on Serum Lipids

Bertram L. Kasiske, MD; Jennie Z. Ma, MS; Roberto S. N. Kalil, MD; and Thomas A. Louis, PhD
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From the University of Minnesota College of Medicine and Hennepin County Medical Center, Minneapolis, Minnesota. Requests for Reprints: Bertram L. Kasiske, MD, Department of Medicine, Hennepin County Medical Center, 701 Park Avenue, Minneapolis, MN 55415. Acknowledgment: The authors thank Ms. Jan Lovick and Ms. Anita Goth for their help in preparing the manuscript. A list of the studies included in the meta-analysis is available on request.

Copyright ©2004 by the American College of Physicians

Ann Intern Med. 1995;122(2):133-141. doi:10.7326/0003-4819-122-2-199501150-00010
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Purpose: To compare and contrast the effects of antihypertensive agents on serum lipids and blood pressure in different patient populations.

Data Sources: A MEDLINE search and bibliographies from recent comprehensive reviews were used to identify trials that provided sufficient data to calculate the change in one or more serum lipid values measured before and after antihypertensive therapy.

Study Selection: 474 controlled and uncontrolled clinical trials investigated the effects of 85 antihypertensive agents on lipids and blood pressure in more than 65 000 patients.

Data Extraction: Data on triglyceride and total, low-density lipoprotein (LDL), and high-density lipoprotein (HDL) cholesterol levels; blood pressure; patient characteristics; and study design.

Data Synthesis: Differences in the effects of agents, adjusted for differences in patient populations and study design, were examined using multiple linear regression analysis that was weighted by study quality and inverse variance. Diuretics caused relative increases in cholesterol levels (regression coefficient = 0.13 mmol/L; 95% CI, 0.09 to 0.18 mmol/L) that were greater with higher doses (additional effect of high dose, 0.12 mmol/L; CI, 0.04 to 0.20 mmol/L) and were worse in blacks than in nonblacks (additional effect in blacks, 0.13 mmol/L; CI, 0.01 to 0.26 mmol/L). β-blockers caused increases in triglyceride levels (0.35 mmol/L; CI, 0.31 to 0.39 mmol/L) that were substantially smaller for agents with intrinsic sympathomimetic activity (amelioration of β-blocker increase, −0.21 mmol/L; CI, −0.27 to −0.16 mmol/L). When combined with cardioselectivity, β-blockers with intrinsic sympathomimetic activity favorably affected lipids and reduced both total (−0.14 mmol/L; CI, −0.24 to −0.04 mmol/L) and LDL cholesterol levels (−0.17 mmol/L; CI, −0.28 to −0.07 mmol/L). α-Blockers beneficially affected total cholesterol (−0.23 mmol/L; CI, −0.28 to −0.18 mmol/L), LDL cholesterol (−0.20 mmol/L; CI, −0.25 to −0.15 mmol/L), triglycerides (−0.07 mmol/L; CI, −0.11 to −0.03 mmol/L), and, in younger persons, HDL cholesterol (0.02 mmol/L; 0.01 to 0.04 mmol/L). Converting enzyme inhibitors reduced triglycerides (−0.07 mmol/L; CI, −0.12 to −0.02 mmol/L), and, in patients with diabetes, total cholesterol (−0.22 mmol/L; CI, −0.34 to −0.10 mmol/L). Vasodilators reduced total (−0.22 mmol/l; CI, −0.30 to −0.10 mmol/L) and LDL cholesterol (−0.22 mmol/L; CI, −0.29 to −0.11 mmol/L) and increased HDL cholesterol (0.06 mmol/L; CI, 0.02 to 0.09 mmol/L).

Conclusion: With the exception of calcium antagonists, nearly all antihypertensive agents affect serum lipids. These effects differ among patient populations.


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Figure 1.
Effect of patient characteristics on lipid changes caused by antihypertensive therapy.t

The effect of race on diuretic-associated changes in low density lipoprotein (LDL) cholesterol levels (mean ± SE) is shown in the left panel. Only groups for which race was reported in the study are included. Numbers in parentheses refer to the number of experimental groups with fewer than 50% blacks (15% ± 16%) or 50% or more blacks (86% ± 20%). The effect of sex on diuretic-associated changes in triglycerides is shown in the middle panel. Numbers in parentheses refer to the number of experimental groups with fewer than 50% men (27% ± 18%) or 50% or more men (82% ± 19%). The effect of diabetes on changes in cholesterol levels after treatment with an angiotensin-converting enzyme (ACE) inhibitor is shown in the right panel. Numbers in parentheses refer to the number of experimental groups with fewer than 50% patients with diabetes (1% ± 5%) or 50% or more patients with diabetes (100%). Significance was tested using an unweighted -test.

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