Metabolic outcome during 1 year in newly detected hypertensives: results of the Antihypertensive Treatment and Lipid Profile in a North of Sweden Efficacy Evaluation (ALPINE study)

J Hypertens. 2003 Aug;21(8):1563-74. doi: 10.1097/01.hjh.0000084723.53355.76.


Objective: The aim of the Antihypertensive Treatment and Lipid Profile in a North of Sweden Efficacy Evaluation study was to compare the long-term effect of the commonly used inexpensive medication with a low-dose diuretic (hydrochlorothiazide), alone or in combination with a beta-adrenoceptor (atenolol), with that of more modern but also more expensive antihypertensive treatment with an angiotensin-II-receptor blocker (candesartan), alone or in combination with a calcium antagonist (felodipine), and to do so in newly diagnosed patients with primary hypertension. The objectives included comparisons of the effects on the glucose metabolism, lipoprotein metabolism, electrolytes, blood pressure, and subjective symptoms.

Design: A 1-year, prospective randomized, double-blind, controlled trial.

Subjects: In an investigator-initiated study, we included 392 patients (mean age 55 years, 48% men); 370 patients (94%) had never been treated with antihypertensive drugs before the study. No patient was lost to follow-up.

Results: Both treatment regimens lowered blood pressure well (23/13 mmHg in the hydrochlorothiazide group and 21/13 mmHg in the candesartan group), with a majority of patients needing two drugs. Fasting levels of both serum insulin and plasma glucose increased in the hydrochlorothiazide group in contrast to unaffected levels in the candesartan group. Diabetes mellitus was diagnosed in nine patients during follow-up, in eight patients in the hydrochlorothiazide group (4.1%) and in one patient (0.5%) in the candesartan group (P = 0.030). Triglycerides increased and high-density lipoprotein-cholesterol decreased more in the hydrochlorothiazide group than in the candesartan group. Both the low-density lipoprotein/high-density lipoprotein and the apolipoprotein B/apolipoprotein A-I ratios increased in the hydrochlorothiazide group. At 12 months, 18 patients in the hydrochlorothiazide group versus five in the candesartan group had a 'metabolic syndrome', as defined by the World Health Organization (P = 0.007) despite 1 year of active blood pressure-lowering therapy. There were less (P = 0.020) adverse events in the candesartan group, but no major differences in the subjective symptoms assessment profile. One subject in each group had a myocardial infarction.

Conclusion: Antihypertensive treatment with a diuretic, if needed combined with a beta-adrenoceptor blocker, was associated with an aggravated metabolic profile; this was not so for patients treated with an angiotensin-II-receptor blocker, if needed combined with a calcium antagonist. An antihypertensive treatment strategy that costs more in the short run but has no metabolic adverse effects may have a health economic impact in the long term.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antihypertensive Agents / administration & dosage*
  • Antihypertensive Agents / adverse effects
  • Apolipoproteins / blood
  • Atenolol / administration & dosage*
  • Atenolol / adverse effects
  • Blood Glucose / metabolism
  • Blood Pressure / drug effects
  • Drug Therapy, Combination
  • Electrolytes / metabolism
  • Female
  • Glucose Tolerance Test
  • Humans
  • Hydrochlorothiazide / administration & dosage*
  • Hydrochlorothiazide / adverse effects
  • Hypertension / drug therapy*
  • Hypertension / metabolism*
  • Insulin / blood
  • Lipids / blood
  • Male
  • Metabolic Syndrome / metabolism
  • Middle Aged
  • Prospective Studies


  • Antihypertensive Agents
  • Apolipoproteins
  • Blood Glucose
  • Electrolytes
  • Insulin
  • Lipids
  • Hydrochlorothiazide
  • Atenolol