Hypertension with metabolic syndrome: Think thiazides are old hat? ALLHAT says think again

,; Stevermer, James

PURLs

Hypertension with metabolic syndrome: Think thiazides are old hat? ALLHAT says think again

J Fam Pract. 2008 May;57(5):306-310

By

Michael D. Mendoza, MD, MPH

James J. Stevermer, MD, MSPH

Outcomes support chlorthalidone despite its metabolic profile.

References

1. Wright JT, Jr, Harris-Haywood S, Pressel S, et al. Clinical outcomes by race in hypertensive patients with and without the metabolic syndrome: Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). Arch Intern Med. 2008;168:207-217.

2. Law MR, Wald NJ, Morris JK, Jordan RE. Value of low dose combination treatment with blood pressure lowering drugs: analysis of 354 randomised trials. BMJ. 2003;326:1427.-

3. Eberly LE, Cohen JD, Prineas R, Yang L. Intervention Trial Research group. Impact of incident diabetes and incident nonfatal cardiovascular disease on 18-year mortality: the Multiple Risk Factor Intervention Trial experience. Diabetes Care. 2003;26:848-854.

4. Pollare T, Lithell H, Berne C. A comparison of the effects of hydrochlorothiazide and captopril on glucose and lipid metabolism in patients with hyper-tension. N Engl J Med. 1989;321:868-873.

5. Mancia G, Grassi G, Zanchetti A. New-onset diabetes and antihypertensive drugs. J Hypertens. 2006;24:3-10.

6. Skarfors ET, Lithell HO, Selinus I, Aberg H. Do antihypertensive drugs precipitate diabetes? BMJ. 1989;298:1147-1152

7. Scholze J, Grimm E, Herrmann D, Unger T, Kintscher U. Optimal treatment of obesity-related hypertension: the Hypertension-Obesity-Sibutra-mine (HOS) study. Circulation. 2007;115:1991-1998.

8. Bakris G, Molitch M, Hewkin A, et al. STAR Investigators. Differences in glucose tolerance between fixed-dose antihypertensive drug combinations in people with metabolic syndrome. Diabetes Care. 2006;29:2592-2597.

9. Lewis EJ, Hunsicker LG, Bain RP, Rohde RD. The effect of angiotensin-converting-enzyme inhibition on diabetic nephropathy. The Collaborative Study Group. N Engl J Med. 1993;329:1456-1462.

10. Gianni M, Bosch J, Pogue J, et al. Effect of long-term ACE-inhibitor therapy in elderly vascular disease patients. Eur Heart J. 2007;28:1382-1388.

11. Abuissa H, Jones PG, Marso SP, O’Keefe JH Jr. Angiotensin-converting enzyme inhibitors or angiotensin receptor blockers for prevention of type 2 diabetes: a meta-analysis of randomized clinical trials. J Am Coll Cardiol. 2005;46:821-826.

12. Mykkänen L, Kuusisto J, Pyörälä K, Laakso M, Haffner SM. Increased risk of non-insulin-dependent diabetes mellitus in elderly hypertensive subjects. J Hypertens. 1994;12:1425-1432.

13. Giles TD, Sander GE. Pathophysiologic, diagnostic, and therapeutic aspects of the metabolic syndrome. J Clin Hypertens (Greenwich). 2005;7:669-678.

14. Mancia G. The association of hypertension and diabetes: prevalence, cardiovascular risk and protection by blood pressure reduction. Acta Diabetol. 2005;42(suppl 1):S17-S25.

15. Wagh A, Stone NJ. Treatment of metabolic syndrome. Expert Rev Cardiovasc Ther. 2004;2:213-228.

16. Hall WD, Clark LT, Wenger NK, et al. African-American Lipid and Cardiovascular Council. The metabolic syndrome in African Americans: a review. Ethn Dis. 2003;13:414-428.

17. ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group, Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial. Major outcomes in high-risk hypertensive patients randomized to angiotensin-converting enzyme inhibitor or calcium channel blocker vs diuretic: the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). JAMA. 2002;288:2981-2997.

18. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7). Bethesda, MD: US Department of Health and Human Services, National Heart, Lung, and Blood Institute; December 2003. Available at: http://www.nhlbi.nih.gov/guidelines/hypertension. Accessed March 31, 2008.

19. Black HR, Davis B, Barzilay J, et al. Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial. Metabolic and clinical outcomes in nondiabetic individuals with the metabolic syndrome assigned to chlorthalidone, amlodipine, or lisinopril as initial treatment for hypertension: a report from the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). Diabetes Care. 2008;31:353-360.

ILLUSTRATIVE CASE

Your new patient is a 57-year-old African American man. His blood pressure is 150/95 mm Hg, fasting glucose 115 mg/dL, body mass index 32, and triglycerides 155 mg/dL; he is on no prior medications. During the course of his care you diagnose hypertension with metabolic syndrome and decide to recommend an antihypertensive. Thiazide-type diuretics are your standard initial therapy, but this patient has metabolic syndrome, and you know that certain antihypertensive agents have a more favorable metabolic profile than thiazide diuretics. Furthermore, metabolic differences among races have been touted as reason to use other agents in black patients. Should you recommend a thiazide diuretic, or another agent?

Until now, we’ve had no simple approach to treating hypertension in patients with metabolic syndrome—and half or more of our hypertensive patients over the age of 55 have this disorder.

Now, however, we can base decisions on clinical outcomes data from a subgroup analysis of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT).¹ This new subgroup analysis supports use of thiazide-type diuretics in these patients—particularly in black patients—despite the more favorable metabolic profile of calcium channel blockers, alpha-blockers, and angiotensin-converting enzyme (ACE) inhibitors.

Cost is no longer as big a factor as it once was, now that ACE inhibitors and alpha-blockers, as well as thiazide diuretics, are available generically.

Does a better metabolic profile improve outcomes?

We have had reason to be concerned about the metabolic adverse effects of thiazide-type diuretics in the past. Studies published before this ALLHAT subgroup analysis showed that hydrochlorothiazide for essential hypertension had adverse effects on potassium, glucose, and lipid metabolism. Some speculated that these changes aggravate the metabolic changes in early diabetes^2-4 and may contribute to increased coronary heart disease risk.^5,6

FIGURE
Outcomes favor thiazides

We know many physicians who have adopted thiazide-type diuretics as the first-line treatment for hypertension in metabolic syndrome, but until now, data have been inadequate to support this decision.

A subgroup analysis from the ALLHAT¹ concludes: “The ALLHAT findings fail to support the preference for calcium channel blockers, alpha-blockers, or angiotensin-converting enzyme inhibitors compared with thiazide-type diuretics in patients with the metabolic syndrome, despite their more favorable metabolic profiles. This was particularly true for black participants.”

Hypertension Blood pressure target for patients enrolled in the ALLHAT was <140/90 mm Hg	Metabolic syndrome, in the subgroup analysis, was defined as hypertension plus 2 of the following risk factors for coronary heart disease:
	1. Obesity Body mass index at least 30	2. Lipid disorder Fasting triglyceride level >150 mg/dL and high-density lipoprotein cholesterol level <40 mg/dL in men, or <50 mg/dL in women	3. Glycemic disorder Fasting glucose level >100 mg/dL, or nonfasting glucose level >200 mg/dL, or history of diabetes