Antihypertensive therapy is associated with reduced rate of conversion to Alzheimer's disease in midregional proatrial natriuretic peptide stratified subjects with mild cognitive impairment

Biol Psychiatry. 2011 Jul 15;70(2):145-51. doi: 10.1016/j.biopsych.2011.01.036. Epub 2011 Mar 31.

Abstract

Background: Hypertension is a major risk factor of Alzheimer's disease (AD); however, controlled studies on the effect of antihypertensive treatment on the risk of dementia are inconclusive. Therefore, a biological marker that predicts individual response to antihypertensive treatment would be of high clinical relevance. Midregional proatrial natriuretic peptide (MR-proANP), an inactive surrogate molecule of the mature atrial natriuretic peptide, is related to circulatory function and hypertension.

Methods: A sample population of 134 subjects with mild cognitive impairment (MCI) was followed for up to 6 years. Multivariable Cox regression analysis was conducted to predict conversion to AD based on all relevant variables.

Results: Baseline MR-proANP was significantly increased in the AD converter group (p < .0001). The conversion rate of patients treated with antihypertensive drugs was significantly reduced only in patients with elevated MR-proANP at baseline (p = .046). Using an optimized MR-proANP cutoff of 74 pmol/L, representing a value in the upper normal range, treatment with antihypertensive drugs reduced the conversion rate to AD by 36% (p = .035) for patients with levels >74 pmol/L. Further subgrouping by age (>/≤ 72 years at baseline) increased the positive correlation of antihypertensive treatment and MCI outcome for patients below the age of 72 years (conversion rate reduced by 74%, p = .016).

Conclusions: These data seem to support the notion of a potential impact of circulatory function for the prognosis of AD at a prodromal stage. The MR-proANP levels may be useful to predict the effect of antihypertensive treatment on conversion rates to AD in subjects with MCI.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Alzheimer Disease / etiology*
  • Antihypertensive Agents / adverse effects*
  • Atrial Natriuretic Factor / metabolism*
  • Blood Pressure / drug effects
  • Cognition Disorders / metabolism*
  • Cognition Disorders / physiopathology*
  • Disease Progression
  • Female
  • Humans
  • Hypertension / drug therapy
  • Kaplan-Meier Estimate
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Regression Analysis
  • Retrospective Studies

Substances

  • Antihypertensive Agents
  • Atrial Natriuretic Factor