Demographic, environmental, and genetic predictors of metabolic side effects of hydrochlorothiazide treatment in hypertensive subjects

Anke Hilse Maitland-Van Der Zee, Stephen T Turner, Gary Lee Schwartz, Arlene B. Chapman, Olaf H. Klungel, Eric Boerwinkle

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Background: Thiazide diuretics are recommended for first-line treatment of hypertension. Although considered safe and effective, their use is associated with dyslipidemia, hyperglycemia, and an increased risk of developing type 2 diabetes. The aim of this study was to characterize interindividual variation in glucose and lipid responses to hydrochlorothiazide and to identify demographic, environmental, and genetic predictors associated with this variation. Methods: A community-based sample of 585 adults with essential hypertension (291 African Americans [150 women and 141 men] and 294 non-Hispanic whites [126 women and 168 men]) underwent monotherapy with hydrochlorothiazide for 4 weeks. Linear regression was used to construct prediction models for the changes in plasma total cholesterol, triglyceride, and glucose concentrations. Results: The mean changes (± standard deviation) in response to hydrochlorothiazide were 6.13 ± 22.8 mg/dL for total cholesterol, 17.21 ± 70 mg/dL for triglycerides, and 3.5 ± 9.5 mg/dL for plasma glucose. Ethnicity and baseline levels of the analytes were the only predictors that were significant for more than one response. Therefore, the mechanism for these metabolic effects are not entirely shared. Conclusions: Taken together, demographic, environmental, and genetic factors accounted for only 13% of the total variation in total cholesterol response, 17% of the variation in triglyceride response, and 11% of the variation in glucose response to hydrochlorothiazide, and less than half of this predicted variation in response was explained by measured genotypes.

Original languageEnglish (US)
Pages (from-to)1077-1083
Number of pages7
JournalAmerican Journal of Hypertension
Volume18
Issue number8
DOIs
StatePublished - Aug 2005

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Hydrochlorothiazide
Demography
Glucose
Triglycerides
Cholesterol
Sodium Chloride Symporter Inhibitors
Therapeutics
Dyslipidemias
Hyperglycemia
African Americans
Type 2 Diabetes Mellitus
Linear Models
Genotype
Hypertension
Lipids

Keywords

  • Cholesterol
  • glucose
  • Hydrochlorothiazide
  • pharmacogenetics
  • Side effects
  • Triglyceride

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Demographic, environmental, and genetic predictors of metabolic side effects of hydrochlorothiazide treatment in hypertensive subjects. / Maitland-Van Der Zee, Anke Hilse; Turner, Stephen T; Schwartz, Gary Lee; Chapman, Arlene B.; Klungel, Olaf H.; Boerwinkle, Eric.

In: American Journal of Hypertension, Vol. 18, No. 8, 08.2005, p. 1077-1083.

Research output: Contribution to journalArticle

Maitland-Van Der Zee, Anke Hilse ; Turner, Stephen T ; Schwartz, Gary Lee ; Chapman, Arlene B. ; Klungel, Olaf H. ; Boerwinkle, Eric. / Demographic, environmental, and genetic predictors of metabolic side effects of hydrochlorothiazide treatment in hypertensive subjects. In: American Journal of Hypertension. 2005 ; Vol. 18, No. 8. pp. 1077-1083.
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N2 - Background: Thiazide diuretics are recommended for first-line treatment of hypertension. Although considered safe and effective, their use is associated with dyslipidemia, hyperglycemia, and an increased risk of developing type 2 diabetes. The aim of this study was to characterize interindividual variation in glucose and lipid responses to hydrochlorothiazide and to identify demographic, environmental, and genetic predictors associated with this variation. Methods: A community-based sample of 585 adults with essential hypertension (291 African Americans [150 women and 141 men] and 294 non-Hispanic whites [126 women and 168 men]) underwent monotherapy with hydrochlorothiazide for 4 weeks. Linear regression was used to construct prediction models for the changes in plasma total cholesterol, triglyceride, and glucose concentrations. Results: The mean changes (± standard deviation) in response to hydrochlorothiazide were 6.13 ± 22.8 mg/dL for total cholesterol, 17.21 ± 70 mg/dL for triglycerides, and 3.5 ± 9.5 mg/dL for plasma glucose. Ethnicity and baseline levels of the analytes were the only predictors that were significant for more than one response. Therefore, the mechanism for these metabolic effects are not entirely shared. Conclusions: Taken together, demographic, environmental, and genetic factors accounted for only 13% of the total variation in total cholesterol response, 17% of the variation in triglyceride response, and 11% of the variation in glucose response to hydrochlorothiazide, and less than half of this predicted variation in response was explained by measured genotypes.

AB - Background: Thiazide diuretics are recommended for first-line treatment of hypertension. Although considered safe and effective, their use is associated with dyslipidemia, hyperglycemia, and an increased risk of developing type 2 diabetes. The aim of this study was to characterize interindividual variation in glucose and lipid responses to hydrochlorothiazide and to identify demographic, environmental, and genetic predictors associated with this variation. Methods: A community-based sample of 585 adults with essential hypertension (291 African Americans [150 women and 141 men] and 294 non-Hispanic whites [126 women and 168 men]) underwent monotherapy with hydrochlorothiazide for 4 weeks. Linear regression was used to construct prediction models for the changes in plasma total cholesterol, triglyceride, and glucose concentrations. Results: The mean changes (± standard deviation) in response to hydrochlorothiazide were 6.13 ± 22.8 mg/dL for total cholesterol, 17.21 ± 70 mg/dL for triglycerides, and 3.5 ± 9.5 mg/dL for plasma glucose. Ethnicity and baseline levels of the analytes were the only predictors that were significant for more than one response. Therefore, the mechanism for these metabolic effects are not entirely shared. Conclusions: Taken together, demographic, environmental, and genetic factors accounted for only 13% of the total variation in total cholesterol response, 17% of the variation in triglyceride response, and 11% of the variation in glucose response to hydrochlorothiazide, and less than half of this predicted variation in response was explained by measured genotypes.

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