Association of combination statin and antihypertensive therapy with reduced Alzheimer's disease and related dementia risk

被引:47
作者
Barthold, Douglas [1 ]
Joyce, Geoffrey [2 ]
Brinton, Roberta Diaz [3 ]
Wharton, Whitney [4 ,5 ]
Kehoe, Patrick Gavin [6 ]
Zissimopoulos, Julie [7 ]
机构
[1] Univ Washington, Dept Pharm, Comparat Hlth Outcomes Policy & Econ CHOICE Inst, Seattle, WA 98195 USA
[2] Univ Southern Calif, Schaeffer Ctr Hlth Policy & Econ, Sch Pharm, Los Angeles, CA 90007 USA
[3] Univ Arizona Hlth Sci, Ctr Innovat Brain Sci, Tucson, AZ USA
[4] Emory Univ, Sch Nursing, Atlanta, GA 30322 USA
[5] Emory Univ, Sch Med, Dept Neurol, Atlanta, GA 30322 USA
[6] Univ Bristol, Bristol Med Sch, Translat Hlth Sci, Bristol, Avon, England
[7] Univ Southern Calif, Price Sch Publ Policy, Schaeffer Ctr Hlth Policy & Econ, Los Angeles, CA 90007 USA
基金
英国医学研究理事会; 美国国家卫生研究院;
关键词
MILD COGNITIVE IMPAIRMENT; RENIN-ANGIOTENSIN SYSTEM; CHOLESTEROL; BRAIN; METABOLISM; DECLINE; IMPACT; TRIALS; ACE;
D O I
10.1371/journal.pone.0229541
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Background Hyperlipidemia and hypertension are modifiable risk factors for Alzheimer's disease and related dementias (ADRD). Approximately 25% of adults over age 65 use both antihypertensives (AHTs) and statins for these conditions. While a growing body of evidence found statins and AHTs are independently associated with lower ADRD risk, no evidence exists on simultaneous use for different drug class combinations and ADRD risk. Our primary objective was to compare ADRD risk associated with concurrent use of different combinations of statins and antihypertensives. Methods In a retrospective cohort study (2007-2014), we analyzed 694,672 Medicare beneficiaries in the United States (2,017,786 person-years) who concurrently used both statins and AHTs. Using logistic regression adjusting for age, socioeconomic status and comorbidities, we quantified incident ADRD diagnosis associated with concurrent use of different statin molecules (atorvastatin, pravastatin, rosuvastatin, and simvastatin) and AHT drug classes (two renin-angiotensin system (RAS)-acting AHTs, angiotensin converting enzyme inhibitors (ACEIs) or angiotensin-II receptor blockers (ARBs), vs non-RAS-acting AHTs). Findings Pravastatin or rosuvastatin combined with RAS-acting AHTs reduce risk of ADRD relative to any statin combined with non-RAS-acting AHTs: ACEI+pravastatin odds ratio (OR) = 0.942 (CI: 0.899-0.986, p = 0.011), ACEI+rosuvastatin OR = 0.841 (CI: 0.794-0.892, p< 0.001), ARB+pravastatin OR = 0.794 (CI: 0.748-0.843, p< 0.001), ARB+rosuvastatin OR = 0.818 (CI: 0.765-0.874, p< 0.001). ARBs combined with atorvastatin and simvastatin are associated with smaller reductions in risk, and ACEI with no risk reduction, compared to when combined with pravastatin or rosuvastatin. Among Hispanics, no combination of statins and RAS-acting AHTs reduces risk relative to combinations of statins and non-RAS-acting AHTs. Among blacks using ACEI+rosuvastatin, ADRD odds were 33% lower compared to blacks using other statins combined with non-RAS-acting AHTs (OR = 0.672 (CI: 0.5480.825, p<0.001)). Conclusion Among older Americans, use of pravastatin and rosuvastatin to treat hyperlipidemia is less common than use of simvastatin and atorvastatin, however, in combination with RAS-acting AHTs, particularly ARBs, they may be more effective at reducing risk of ADRD. The number of Americans with ADRD may be reduced with drug treatments for vascular health that also confer effects on ADRD.
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页数:15
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