Phillip J Tully1, Jean-François Dartigues1, Stephanie Debette1, Catherine Helmer1, Sylvaine Artero1, Christophe Tzourio2. 1. From Neuroepidemiology, UMR897 (P.J.T., S.D., C.T.), and Epidemiology and Biostatistics, Institut National de la Santé et de la Recherche Médicale U897 (J.-F.D., C.H.), University of Bordeaux, France; Freemasons Foundation Centre for Men's Health (P.J.T.), Discipline of Medicine, School of Medicine, The University of Adelaide, Australia; Department of Neurology (S.D.), Bordeaux University Hospital, France; Department of Neurology (S.D.), Framingham Heart Study, Boston University School of Medicine, MA; INSERM U1061 (S.A.), La Colombière Hospital, University of Montpellier UM1; and INSERM (P.J.T., C.T.), Neuroepidemiology, UMR897, Bordeaux, France. 2. From Neuroepidemiology, UMR897 (P.J.T., S.D., C.T.), and Epidemiology and Biostatistics, Institut National de la Santé et de la Recherche Médicale U897 (J.-F.D., C.H.), University of Bordeaux, France; Freemasons Foundation Centre for Men's Health (P.J.T.), Discipline of Medicine, School of Medicine, The University of Adelaide, Australia; Department of Neurology (S.D.), Bordeaux University Hospital, France; Department of Neurology (S.D.), Framingham Heart Study, Boston University School of Medicine, MA; INSERM U1061 (S.A.), La Colombière Hospital, University of Montpellier UM1; and INSERM (P.J.T., C.T.), Neuroepidemiology, UMR897, Bordeaux, France. christophe.tzourio@u-bordeaux.fr.
Abstract
OBJECTIVE: To determine the association between discrete antihypertensive drug classes and incident dementia controlling for blood pressure variability (BPV) in the preceding 4 years. METHODS: A total of 6,537 participants (mean age 79 years, 62% women) in a prospective population-based cohort were followed up for incident dementia. A 4-year time lag period was created to classify drug exposure and measure blood pressure. BPV (percent coefficient of variation [CV]) was regressed against 9 antihypertensive drug classes (BPVreg). Cox regression models were employed to determine hazard ratios (HRs) for incident dementia thereafter according to drug class, adjusted for mean blood pressure, covariates, and BPV or BPVreg. RESULTS: Over a median 8.4 years follow-up (interquartile range 6.7-9.0), lower dementia risk was associated with nondihydropyridine calcium channel blocker (HR 0.56; 95% confidence interval [CI] 0.31-1.00, p = 0.05) and loop diuretics (HR 0.45; 95% CI 0.22-0.93, p = 0.03) after adjusting for CV-BPV. Similar findings were obtained in analyses restricted to antihypertensive drug users for nondihydropyridine calcium channel blocker (HR 0.52; 95% CI 0.28-0.95, p = 0.03) and loop diuretics (HR 0.40; 95% CI 0.19-0.83, p = 0.01). All systolic BPV × antihypertensive drug interaction terms were not different from p < 0.05. CONCLUSIONS: Nondihydropyridine calcium channel blocker and loop diuretics were associated with a reduced dementia risk independent of CV-BPV in the preceding 4 years. Systolic BPV was not the primary mechanism through which antihypertensive drug classes lower dementia risk.
OBJECTIVE: To determine the association between discrete antihypertensive drug classes and incident dementia controlling for blood pressure variability (BPV) in the preceding 4 years. METHODS: A total of 6,537 participants (mean age 79 years, 62% women) in a prospective population-based cohort were followed up for incident dementia. A 4-year time lag period was created to classify drug exposure and measure blood pressure. BPV (percent coefficient of variation [CV]) was regressed against 9 antihypertensive drug classes (BPVreg). Cox regression models were employed to determine hazard ratios (HRs) for incident dementia thereafter according to drug class, adjusted for mean blood pressure, covariates, and BPV or BPVreg. RESULTS: Over a median 8.4 years follow-up (interquartile range 6.7-9.0), lower dementia risk was associated with nondihydropyridine calcium channel blocker (HR 0.56; 95% confidence interval [CI] 0.31-1.00, p = 0.05) and loop diuretics (HR 0.45; 95% CI 0.22-0.93, p = 0.03) after adjusting for CV-BPV. Similar findings were obtained in analyses restricted to antihypertensive drug users for nondihydropyridine calcium channel blocker (HR 0.52; 95% CI 0.28-0.95, p = 0.03) and loop diuretics (HR 0.40; 95% CI 0.19-0.83, p = 0.01). All systolic BPV × antihypertensive drug interaction terms were not different from p < 0.05. CONCLUSIONS: Nondihydropyridine calcium channel blocker and loop diuretics were associated with a reduced dementia risk independent of CV-BPV in the preceding 4 years. Systolic BPV was not the primary mechanism through which antihypertensive drug classes lower dementia risk.
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