Antihypertensive Therapy Is Associated with Reduced Rate of Conversion to Alzheimer's Disease in Midregional Proatrial Natriuretic Peptide Stratified Subjects with Mild Cognitive Impairment

Abstract

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. 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. 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). 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.