Advertisement

Drugs

, Volume 32, Issue 3, pp 260–278 | Cite as

The Effects of Antihypertensive Drugs on Serum Lipids and Lipoproteins

I. Diuretics
  • Richard P. Ames
Review Article

Summary

Potassium-losing diuretic drugs, when used in the treatment of hypertension, cause unfavourable short term alterations in blood lipid and lipoprotein concentrations. The disturbance is characterised by increases in total cholesterol of 4 to 13%, in low density lipoprotein (LDL) cholesterol of 7 to 29%, in very-low density lipoprotein (VLDL) cholesterol of 7 to 56%, and in total triglyceride of 14 to 37%. The disturbance is variable among patients and over time in individual patients; it is absent in some. In long term treatment the data are fragmentary, but total cholesterol and triglycerides usually return to baseline values or below.

The variability of the lipid response to diuretics has several consequences: firstly, it necessitates a sizeable study population (minimum of 30 patients) in order to document convincingly its presence or absence; secondly, lipoprotein fractions must be examined to define the pattern of the disturbance; and thirdly, the subsidence of the diuretic-induced lipid effects in long term treatment may be more apparent than real because even larger decreases have been noted in untreated groups in the few studies that wisely included these important controls for comparison. While the cause of the lipid-lipoprotein aberration is unclear, existing data suggest that certain attributes of the study population influence the response, i.e. age, habitual diet, hormonal milieu (gender), baseline cholesterol concentrations, and induced glucose intolerance. The apparent absence of lipid alterations with indapamide needs to be substantiated and compared with low doses of a standard thiazidetype drug.

The lipid-lipoprotein effects of diuretics seem inconsequentially small, but they may contribute to the disappointing failure of diuretic-based regimens to lower the incidence of coronary heart disease in hypertensive patients. Nevertheless, diuretic-based treatment remains the only therapeutic regimen of proven benefit to congestive heart failure in patients with hypertension, and it is superior to β-blockade in preventing stroke. Hence, alternative antihypertensive drug regimens must be compared prospectively with diuretics in order to verify any theoretic superiority.

Keywords

Total Cholesterol High Density Lipoprotein Cholesterol HCTZ Diuretic Therapy Indapamide 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Amery A, Birkenhager N, Brixko P, Bulpitt C, Clement D, et al. Mortality and morbidity results from the European Working Party on High Blood Pressure in the Elderly Trial. Lancet 1: 1349–1354, 1985PubMedCrossRefGoogle Scholar
  2. Amery A, Birkenhager W, Bulpitt C, Clement D, Deruyttere M, et al. Influence of antihypertensive therapy on serum cholesterol in elderly hypertensive patients. Acta Cardiologica 37: 235–244, 1982PubMedGoogle Scholar
  3. Ames RP, Hill P. Elevation of serum lipid levels during diuretic therapy of hypertension. American Journal of Medicine 61: 748–757, 1976PubMedCrossRefGoogle Scholar
  4. Ames RP, Hill P. Raised serum lipid concentrations during diuretic treatment of hypertension: a study of predictive indexes. Clinical Science and Molecular Medicine 55 (Suppl.4): 311S–314S, 1978Google Scholar
  5. Ames RP, Hill P. Improvement of glucose tolerance and lowering of glycohemoglobin and serum lipid concentrations after discontinuation of antihypertensive drug therapy. Circulation 65: 899–904, 1982aPubMedCrossRefGoogle Scholar
  6. Ames RP, Hill P. Antihypertensive therapy and the risk of coronary heart disease. Journal of Cardiovascular Pharmacology 4 (Suppl. 2): S206–S212, 1982bPubMedGoogle Scholar
  7. Ames RP, Hill P. Disturbance in serum total cholesterol and lipoprotein cholesterol ratios during control of hypertension with beta-adrenoceptor blocking drugs. Abstract. Clinical Research 30: 630A, 1982Google Scholar
  8. Ames RP, Peacock P. Serum cholesterol during treatment of hypertension with diuretic drugs. Archives of Internal Medicine 144: 710–714, 1984PubMedCrossRefGoogle Scholar
  9. Basabe J, Grant A, Johnson B, Krees S, Lopez N, et al. Structural modification of therapeutic agents and their effect on insulin secretion. Proceedings of the Seventh Congress of the International Diabetes Federation, pp. 476–484, Excerpta Medica, Amsterdam, 1971Google Scholar
  10. Bauer JH, Brooks CS, Weinstein J, Wilcox HH, Heimberg M, et al. Effects of diuretic and propranolol on plasma lipoprotein lipids. Clinical Pharmacology and Therapeutics 30: 35–43, 1981PubMedCrossRefGoogle Scholar
  11. Beling S, Vukovich RA, Neiss ES, Zisblatt MS, Webb E, et al. Long-term experience with indapamide. American Heart Journal 106: 258–262, 1983PubMedCrossRefGoogle Scholar
  12. Berglund G, Andersson O. Beta-blockers or diuretics in hypertension? A six-year follow-up of blood pressure and metabolic side effects. Lancet 1: 744–747, 1981PubMedCrossRefGoogle Scholar
  13. Berglund G, Sannerstedt R, Andersson O, Wedel H, Wilhelmsen L, et al. Coronary heart disease after treatment of hypertension. Lancet 1: 1–5, 1978PubMedCrossRefGoogle Scholar
  14. Boehringer K, Meier A, Weidmann P, Schiffl H, Mordasini R, et al. Einfluss von Hydrochlorothiazid/Amiloride allein oder in Kombination mit a-Methyldopa auf die Serumlipoproteine. Schweizerische Medizinische Wochenschrift 111: 525–530, 1981PubMedGoogle Scholar
  15. Boehringer K, Weidmann P, Mordasini R, Schiffl H, Bachmann C, et al. Menopause-dependent plasma lipoprotein alterations in diuretic-treated women. Annals of Internal Medicine 97: 206–209, 1982PubMedGoogle Scholar
  16. Bottiger LE, Carlson LA. Risk factors for ischemic vascular death for men in the Stockholm prospective study. Atherosclerosis 36: 389–408, 1980CrossRefGoogle Scholar
  17. Breckenridge A, Dollery CT, Welborn TA, Fraser R. Glucose tolerance in hypertensive patients on long-term diuretic therapy. Lancet 1: 61–64, 1967PubMedCrossRefGoogle Scholar
  18. Chrysant SG, Neller GK, Dillard B, Frohlich ED. Effects of diuretics on lipid metabolism in patients with essential hypertension. Angiology 27: 707–711, 1976PubMedCrossRefGoogle Scholar
  19. Colodi G, Cevaro G, Lombardo F, Moratti P, Cicuttini L, et al. L’indapamide nei trattamento dell’ ipertensione arteriosa essenziale dell’ anziano: influenza sui metabolismo glico-lipidico. Bollettino della Societa Italiana di Cardiologia 26: 1527–1530, 1981PubMedGoogle Scholar
  20. Colton T. Statistics in medicine, Little, Brown and Company, Boston, 1974Google Scholar
  21. Crane MG, Harris JJ. Effect of spironolactone in hypertensive patients. American Journal of the Medical Sciences 260: 311–330, 1970PubMedCrossRefGoogle Scholar
  22. Crisp AJ, Kennedy PGE, Hoffbrand BI, Ebutt AF, Carruthers M. Lipids and lipoprotein fractions after cyclopenthiazide and oxprenolol: a double-blind crossover study. Current Medical Research and Opinion 7: 101–103, 1980PubMedCrossRefGoogle Scholar
  23. DeCarvalho JGR, Dunn FG, Chrysant SG, Frohlich ED. Ticrynafen, a novel uricosuric antihypertensive natriuretic agent. Archives of Internal Medicine 138: 53–57, 1978CrossRefGoogle Scholar
  24. Fajans SS, Floyd Jr JC, Knopf RF, Rull J, Guntsche EM, et al. Benzothiadiazine suppression of insulin release from normal and abnormal islet tissue in man. Journal of Clinical Investigation 45: 481–492, 1966PubMedCrossRefGoogle Scholar
  25. Freis ED. Should mild hypertension be treated? New England Journal of Medicine 307: 306–309, 1981CrossRefGoogle Scholar
  26. Ginsberg H, Olefsky J, Kimmerling G, Crapo P, Reaven G. Induction of hypertriglyceridemia by a low fat diet. Journal of Clinical Endocrinology and Metabolism 42: 729–735, 1976PubMedCrossRefGoogle Scholar
  27. Glück Z, Baumgartner G, Weidmann P, Peheim E, Bachmann C, et al. Increased ratio between serum beta- and alpha-lipoproteins during diuretic therapy: an adverse effect? Clinical Science and Molecular Medicine 55: 325S–328S, 1978Google Scholar
  28. Glück Z, Weidmann P, Mordasini R, Peheim E, Bachmann C, et al. Einfluss einer diureticktherapie auf die serumlipoproteine: ein unerwünschter effect? Schweizerische Medizinische Wochenschrift 109: 104–108, 1979PubMedGoogle Scholar
  29. Glück Z, Weidmann P, Mordasini R, Bachmann C, Riesen W, et al. Increased serum low-density lipoprotein cholesterol in men treated short-term with the diuretic chlorthalidone. Metabolism 29: 240–245, 1980PubMedCrossRefGoogle Scholar
  30. Goldman AI, Steele BW, Schnaper HW, Fitz AE, Frohlich ED, et al. Serum lipoprotein levels during chlorthalidone therapy. Journal of the American Medical Association 224: 1691–1695, 1980CrossRefGoogle Scholar
  31. Gordon T, Kannel WB. Premature mortality from coronary heart disease: the Framingham study. Journal of the American Medical Association 215: 1617–1625, 1971PubMedCrossRefGoogle Scholar
  32. Greenberg G, Brennan PJ, Miall WE. Effects of diuretic and beta-blocker therapy in the Medical Research Council Trial. American Journal of Medicine 76(2A): 45–51, 1984PubMedCrossRefGoogle Scholar
  33. Grimm Jr RH, Leon AS, Hunninghake DB, Lenz K, Hannan P, et al. Effects of thiazide diuretics on plasma lipids and lipoproteins in mildly hypertensive patients. Annals of Internal Medicine 94: 7–11, 1981PubMedGoogle Scholar
  34. GrimmJr RH, Leon AS, Hunninghake DB, Blackburn H. Diuretics and plasma lipids: effects of thiazides and spironolactone; in Noseda et al. (Eds) Lipoproteins and coronary atherosclerosis, pp. 371–376, Elsevier Biomedical Press, Amsterdam, 1982Google Scholar
  35. Grimm Jr RH, Neaton JD, McDonald M, Case J, McGill E, et al. Beneficial effects from systematic dosage reduction of the diuretic, chlorthalidone: a randomized study within a clinical trial. American Heart Journal 109: 858–865, 1985PubMedCrossRefGoogle Scholar
  36. Helderman JH, Elahi D, Andersen KD, Raises GS, Tobin JD, et al. Prevention of the glucose intolerance of thiazide diuretics by maintenance of body potassium. Diabetes 32: 106–111, 1983PubMedCrossRefGoogle Scholar
  37. Helgeland A. Treatment of mild hypertension: a five-year controlled drug trial. The Oslo study. American Journal of Medicine 69: 725–732, 1980CrossRefGoogle Scholar
  38. Helgeland A, Hjermann I, Holme I, Leren P. Serum triglycerides and serum uric acid in untreated and thiazide-treated patients with mild hypertension. American Journal of Medicine 64: 34–38, 1978aPubMedCrossRefGoogle Scholar
  39. Helgeland A, Hjermann I, Leren P, Enger S, Holme I. High density lipoprotein cholesterol and antihypertensive drugs: the Oslo study. British Medical Journal 2: 403, 1978bPubMedCrossRefGoogle Scholar
  40. Holland OB, Nixon JV, Kuhnert LV. Diuretic-induced ventricular ectopic activity. American Journal of Medicine 70: 762–768, 1981PubMedCrossRefGoogle Scholar
  41. Horgan JH, O’Donovan A, Teo KK. Echocardiographic evaluation of left ventricular function in patients showing an antihypertensive and biochemical response to indapamide. Postgraduate Medical Journal 57 (Suppl. 2): 64–67, 1981PubMedGoogle Scholar
  42. Hypertension Detection and Follow-up Program (HDFP) Cooperative Group. Five-year findings of the Hypertension Detection and Follow-up Program. I. Reduction in mortality of persons with high blood pressure, including mild hypertension. Journal of the American Medical Association 242: 2562–2571, 1979CrossRefGoogle Scholar
  43. Hypertension Detection and Follow-up Program (HDFP) Cooperative Group. Five-year findings of the Hypertension Detection and Follow-up Program. III. Reduction in stroke incidence among persons with high blood pressure. Journal of the American Medical Association 247: 633–638, 1982CrossRefGoogle Scholar
  44. Hypertension Detection and Follow-up Program Cooperative Group. Effect of stepped care treatment on the incidence of myocardial infarction and angina pectoris. Hypertension 6 (Suppl. I): I–198–I–206, 1984Google Scholar
  45. Johnson B, Bye C, Labrooy J, Munro-Faure D, Slack J. The relation of antihypertensive treatment to plasma lipids and other vascular risk factors in hypertension. Clinical Science and Molecular Medicine 47: 9–10, 1974Google Scholar
  46. Johnson BF. The emerging problem of plasma lipid changes during antihypertensive therapy. Journal of Cardiovascular Pharmacology 4 (Suppl. 2): S213–S221, 1982PubMedCrossRefGoogle Scholar
  47. Johnson BJ, Romero L, Johnson J, Marwaha R. Comparative effects of propranolol and prazosin upon serum lipids in thiazide-treated hypertensive patients. American Journal of Medicine 76(2A): 109–112, 1984PubMedCrossRefGoogle Scholar
  48. Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure. The 1984 report of the Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure. Archives of Internal Medicine 144: 1045–1057, 1984CrossRefGoogle Scholar
  49. Jones JU, Dunn FG, Fife R, Lorimer AR, Kellett RG. Benzothiadizine diuretics and death from myocardial infarction in hypertension. Clinical Science and Molecular Medicine 55: 315S–317S, 1978Google Scholar
  50. Joos C, Kewitz H, Reinhold-Kourniati D. Effects of diuretics on plasma lipoproteins in healthy men. European Journal of Clinical Pharmacology 17: 251–257, 1980PubMedCrossRefGoogle Scholar
  51. Kannel WB. Handbook of coronary risk probability, American Heart Association, New York, 1972Google Scholar
  52. Kannel WB, Castelli WP, Gordon T. Cholesterol in the prediction of atherosclerotic diseases. Annals of Internal Medicine 90: 85–91, 1979PubMedGoogle Scholar
  53. Kannel WB, Dawber JR. Hypertension as an ingredient of the cardiovascular risk profile. British Journal of Hospital Medicine 11: 500–523, 1974Google Scholar
  54. Kannel WB, Gordon T, McGee D. Diuretics and serum cholesterol. Correspondence. Lancet 1: 1362–1363, 1977CrossRefGoogle Scholar
  55. Lasser NL, Grandits G, Caggiulla AW, Cutler JA, Grimm Jr RH, et al. Effects of antihypertensive therapy on plasma lipids and lipoproteins in the Multiple Risk Factor Intervention Trial. American Journal of Medicine 76(2A): 52–66, 1984PubMedCrossRefGoogle Scholar
  56. Leren P, Eide I, Foss OP, Helgeland A, Hjermann I, et al. Antihypertensive drugs and blood lipids: the Oslo study. Journal of Cardiovascular Pharmacology 4: S222–S224, 1982PubMedCrossRefGoogle Scholar
  57. Leth A. Changes in plasma and extracellular fluid volumes in patients with essential hypertension during long-term treatment with hydrochlorothiazide. Circulation 42: 479–485, 1970PubMedCrossRefGoogle Scholar
  58. Logan RL, Thomson M, Riemersma RA, Oliver MF, Olsson AG, et al. Risk factors for ischemic heart disease in normal men aged 40. Lancet 1: 949–955, 1978PubMedCrossRefGoogle Scholar
  59. Medical Research Council Working Party. MRC trial of treatment of mild hypertension: principal results. British Medical Journal 291: 97–104, 1985CrossRefGoogle Scholar
  60. Meier A, Weidmann P, Mordasini R, Riesen W, Bachmann C. Reversal or prevention of diuretic-induced alterations in serum lipoproteins with beta blockers. Atherosclerosis 41: 415–419, 1982PubMedCrossRefGoogle Scholar
  61. Mironneau J, Gargouil YM. Actions de l’indapamide sur la musculature lisse. Revue Medicine 18: 1587–1590, 1977Google Scholar
  62. Morgan TO, Adams WR, Hodgson M, Gibbend RW. Failure of therapy to improve prognosis in elderly males with hypertension. Medical Journal of Australia 2: 27–31, 1980PubMedGoogle Scholar
  63. Morledge JH. Clinical efficacy and safety of indapamide in essential hypertension. American Heart Journal 106: 229–232, 1983PubMedCrossRefGoogle Scholar
  64. Multiple Risk Factor Intervention Trial (MRFIT) Research Group. Multiple risk factor intervention trial. Journal of the American Medical Association 248: 1465–1477, 1982CrossRefGoogle Scholar
  65. Perera GA. Diagnosis and natural history of hypertensive vascular disease. American Journal of Medicine 4: 416–422, 1948PubMedCrossRefGoogle Scholar
  66. Report by the Management Committee. The Australian therapeutic trial in mild hypertension. Lancet 1: 1261–1267, 1980Google Scholar
  67. Scalabrino A, Galeone F, Giuntoli F, Guidi G, Birindelli A, et al. Clinical investigation on long-term effects of indapamide in patients with essential hypertension. Current Therapeutic Research 35: 17–22, 1984Google Scholar
  68. Schiffl H, Weidmann P, Mordasini R, Riesen W, Bachmann C. Reversal of diuretic-induced increases in serum low-density lipoprotein cholesterol by the beta blocker pindolol. Metabolism 31: 411–415, 1982PubMedCrossRefGoogle Scholar
  69. Schoenfeld MR, Goldberger E. Hypercholesterolemia induced by thiazides: a pilot study. Current Therapeutic Research 6: 180–184, 1964PubMedGoogle Scholar
  70. Shah S, Khatri I, Freis ED. Mechanism of antihypertensive effect of thiazide diuretics. American Heart Journal 95: 611–618, 1978PubMedCrossRefGoogle Scholar
  71. Smith WM. Treatment of mild hypertension. Results of a ten-year intervention trial. Circulation Research40 (Suppl. 1): 98–105, 1977CrossRefGoogle Scholar
  72. Stamler J. Population studies. In evy et al. (Eds) Nutrition, lipids, and coronary heart disease, p. 72, Raven Press, New York, 1979Google Scholar
  73. Steinbrechen UP, Witztum JL. Glucosylation of low-density lipoproteins to an extent comparable to that seen in diabetes slows their catabolism. Diabetes 33: 130–134, 1984CrossRefGoogle Scholar
  74. Tarazi RC, Dustan HP, Frohlich ED. Long-term thiazide therapy in essential hypertension. Circulation 41: 709–717, 1970PubMedCrossRefGoogle Scholar
  75. Valimaki M, Harna K, Nikkila EA. Serum lipoproteins and indices of glucose tolerance during diuretic therapy: a comparison between hydrochlorothiazide and piretanide. Journal of Cardiovascular Pharmacology 4: 525–530, 1983CrossRefGoogle Scholar
  76. VanBrummelen P, Gevers Leuven VA, Van Gent CM. Influence of hydrochlorothiazide on the plasma levels of triglycerides, total cholesterol and HDL-cholesterol in patients with hypertension. Current Medical Research and Opinion 6:24–29, 1979PubMedCrossRefGoogle Scholar
  77. Veterans Administration Cooperative Study Group on Antihypertensive Agents: Effects of treatment on morbidity in hypertension. I. Results in patients with diastolic blood pressures averaging 115 through 129mm Hg. Journal of the American Medical Association 202: 1028–1034, 1967Google Scholar
  78. Veterans Administration Cooperative Study Group on Antihypertensive Agents. Effects of treatment on morbidity in hypertension. II. Results in patients with diastolic blood pressures averaging 90 through 114mm Hg. Journal of the American Medical Association 213: 1143–1152, 1970CrossRefGoogle Scholar
  79. Veterans Administration Cooperative Study Group on Antihypertensive Agents. Comparative effects of ticrynafen and hydrochlorothiazide in treatment of hypertension. New England Journal of Medicine 301: 293–297, 1979CrossRefGoogle Scholar
  80. Veterans Administration Cooperative Study Group on Antihypertensive Agents. Comparison of propranolol and hydrochlorothiazide for the initial treatment of hypertension. I. Results in short-term titration with emphasis on racial differences in response. Journal of the American Medical Association 248: 1996–2003, 1982aCrossRefGoogle Scholar
  81. Veterans Administration Cooperative Study Group on Antihypertensive Agents. Comparison of propranolol and hydrochlorothiazide for the initial treatment of hypertension. II. Results of long-term therapy. Journal of the American Medical Association 248: 2004–2011, 1982bCrossRefGoogle Scholar
  82. Veterans Administration Cooperative Study Group on Antihypertensive Agents. Efficacy of nadolol alone and combined with bendroflumethiazide and hydralazine for systemic hypertension. American Journal of Cardiology 52: 1230–1237, 1983CrossRefGoogle Scholar
  83. Weidmann P, Meier A, Mordasini R, Riesen W, Bachmann C, et al. Diuretic treatment and serum lipoproteins: effects of tienilic acid and indapamide. Klinische Wochenschrift 59: 343–346, 1981PubMedCrossRefGoogle Scholar
  84. Weidmann P, Schiffl H, Mordasini R, Meier A, Boehringer K, et al. Effects of diuretics alone or in combination with betablockers on serum lipoproteins. In Noseda et al. (Eds) Lipoproteins and coronary atherosclerosis, pp. 363–370, Elsevier Biomedical Press, Amsterdam, 1982Google Scholar
  85. Weidmann P, Gerber A. Effects of treatment with diuretics on serum lipoproteins. Journal of Cardiovascular Pharmacology 6: S260–S268, 1984PubMedCrossRefGoogle Scholar
  86. Wilcox RG. Randomized study of six beta-blockers and a thiazide diuretic in essential hypertension. British Medical Journal 2: 383–385, 1978PubMedCrossRefGoogle Scholar
  87. Williams HR, Borhani NO, Schnaper WH, Schneider KA, Slotkoff L. The relationship between diuretics and serum cholesterol in HDFP participants. Abstract. Journal of the American College of Cardiology 1: 623, 1983Google Scholar

Copyright information

© ADIS Press Limited 1986

Authors and Affiliations

  • Richard P. Ames
    • 1
  1. 1.St Luke’s-Roosevelt Hospital and College of Physicians and SurgeonsColumbia UniversityNew YorkNYUSA

Personalised recommendations