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

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.Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

The association of multiple anti-hypertensive medication classes with Alzheimer’s disease incidence across sex, race, and ethnicity

<div><p>Background</p><p>Antihypertensive treatments have been shown to reduce the risk of Alzheimer’s disease (AD). The renin-angiotensin system (RAS) has been implicated in AD, and thus RAS-acting AHTs (angiotensin converting enzyme inhibitors (ACEIs), and angiotensin-II receptor blockers (ARBs)) may offer differential and additional protective benefits against AD compared with other AHTs, in addition to hypertension management.</p><p>Methods</p><p>In a retrospective cohort design, we examined the medical and pharmacy claims of a 20% sample of Medicare beneficiaries from 2007 to 2013, and compared rates of AD diagnosis for 1,343,334 users of six different AHT drug treatments, 65 years of age or older (4,215,338 person-years). We compared AD risk between RAS and non-RAS AHT drug users, and between ACEI users and ARB users, by sex and race/ethnicity. Models adjusted for age, socioeconomic status, underlying health, and comorbidities.</p><p>Findings</p><p>RAS-acting AHTs were slightly more protective against onset of AD than non-RAS-acting AHTs for males, (male OR = 0.931 (CI: 0.895–0.969)), but not so for females (female OR = 0.985 (CI: 0.963–1.007)). Relative to other AHTs, ARBs were superior to ACEIs for both men (male ARB OR = 0.834 (CI: 0.788–0.884); male ACEI OR = 0.978 (CI: 0.939–1.019)) and women (female ARB OR = 0.941 (CI: 0.913–0.969); female ACEI OR = 1.022 (CI: 0.997–1.048)), but only in white men and white and black women. No association was shown for Hispanic men and women.</p><p>Conclusion</p><p>Hypertension management treatments that include RAS-acting ARBs may, in addition to lowering blood pressure, reduce AD risk, particularly for white and black women and white men. Additional studies and clinical trials that include men and women from different racial and ethnic groups are needed to confirm these findings. Understanding the potentially beneficial effects of certain RAS-acting AHTs in high-risk populations is of great importance.</p></div

Genome Stability of Lyme Disease Spirochetes: Comparative Genomics of Borrelia burgdorferi Plasmids

Lyme disease is the most common tick-borne human illness in North America. In order to understand the molecular pathogenesis, natural diversity, population structure and epizootic spread of the North American Lyme agent, Borrelia burgdorferi sensu stricto, a much better understanding of the natural diversity of its genome will be required. Towards this end we present a comparative analysis of the nucleotide sequences of the numerous plasmids of B. burgdorferi isolates B31, N40, JD1 and 297. These strains were chosen because they include the three most commonly studied laboratory strains, and because they represent different major genetic lineages and so are informative regarding the genetic diversity and evolution of this organism. A unique feature of Borrelia genomes is that they carry a large number of linear and circular plasmids, and this work shows that strains N40, JD1, 297 and B31 carry related but non-identical sets of 16, 20, 19 and 21 plasmids, respectively, that comprise 33–40% of their genomes. We deduce that there are at least 28 plasmid compatibility types among the four strains. The B. burgdorferi ∼900 Kbp linear chromosomes are evolutionarily exceptionally stable, except for a short ≤20 Kbp plasmid-like section at the right end. A few of the plasmids, including the linear lp54 and circular cp26, are also very stable. We show here that the other plasmids, especially the linear ones, are considerably more variable. Nearly all of the linear plasmids have undergone one or more substantial inter-plasmid rearrangements since their last common ancestor. In spite of these rearrangements and differences in plasmid contents, the overall gene complement of the different isolates has remained relatively constant

Empirical studies in health economics: health, health insurance, and health policy

This dissertation is composed of three empirical studies that examine topics related to health, health insurance, and health policy. The first chapter evaluates the effects of prescription drug cost sharing on primary care utilization and preventable hospitalizations. This paper uses exogenous variation in drug cost sharing that was introduced by the Medicare Modernization Act to assess cross-price effects on the use of complement services, and associated offset effects on health. The second chapter further examines the Medicare Modernization Act, by investigating its effects on prescription drug usage, and testing if those changes had health effects on emergency department utilization. These two papers contribute to the body of evidence on the effects of drug insurance design details on health and health care utilization. Finally, the third chapter analyzes five European policies that expanded health insurance eligibility to farmers in the 1950s, 1960s, and 1970s, and assesses the effects of the policies on the educational attainment of the children of the affected cohort. This paper contributes to evidence on the role of health policies in interrupting the intergenerational transmission of socioeconomic status.Cette thèse est composée de trois études empiriques qui examinent des sujets reliés à la santé, l'assurance santé, et la politique de santé. Le premier chapitre évalue les effets du partage des coûts des médicaments prescrits sur l'utilisation des soins de santé primaires et sur les hospitalisations évitables. Cette étude utilise une variation exogène dans le partage des coûts des médicaments qui a été introduit par le « Medicare Modernization Act » pour évaluer les effets croisés des prix sur l'utilisation des services complémentaires, et les effets associés de compensation sur la santé. Le deuxième chapitre examine plus en détail le « Medicare Modernization Act », en investiguant ses effets sur l'utilisation de médicaments prescrits, et en testant si ces changements ont eu un impact sur utilisation des services de santé d'urgence. Ces deux papiers contribuent au corpus de données sur les effets des termes de l'assurance médicaments sur la santé et l'utilisation des services de santé. En dernier lieu, le troisième chapitre analyse cinq politiques européennes qui ont élargi l'éligibilité de l'assurance maladie aux fermiers dans les années 1950, 1960 et 1970, et évalue les effets de ces politiques sur le niveau de scolarité des enfants de la cohorte affectée. Cette étude contribue à l'évidence sur le rôle des politiques de santé dans l'interruption de la transmission intergénérationnelle du statut socioéconomique

Sex and Race Differences in the Association Between Statin Use and the Incidence of Alzheimer Disease

IMPORTANCE To our knowledge, no effective treatments exist for Alzheimer disease, and new molecules are years away. However, several drugs prescribed for other conditions have been associated with reducing its risk. OBJECTIVE To analyze the association between statin exposure and Alzheimer disease incidence among Medicare beneficiaries. DESIGN, SETTING, AND PARTICIPANTS We examined the medical and pharmacy claims of a 20% sample of Medicare beneficiaries from 2006 to 2013 and compared rates of Alzheimer disease diagnosis for 399979 statin users 65 years of age or older with high or low exposure to statins and with drug molecules for black, Hispanic, and non-Hispanic white people, and men and women of Asian, Native American, or unkown race/ethnicity who are referred to as "other." MAIN OUTCOMES AND MEASURES The main outcome was incident diagnosis of Alzheimer disease based on the International Classification of Diseases, Ninth Revision, Clinical Modification. We used Cox proportional hazard models to analyze the association between statin exposure and Alzheimer disease diagnosis for different sexes, races and ethnicities, and statin molecules. RESULTS The 399979 study participants included 7794 (1.95%) black men, 24484 (6.12%) black women, 11200 (2.80%) Hispanic men, 21458 (5.36%) Hispanic women, 115059 (28.77%) white men, and 195181 (48.80%) white women. High exposure to statins was associated with a lower risk of Alzheimer disease diagnosis for women (hazard ratio [HR], 0.85; 95% CI, 0.82-0.89; P<. 001) and men (HR, 0.88; 95% CI, 0.83-0.93; P<.001). Simvastatin was associated with lower Alzheimer disease risk for white women (HR, 0.86; 95% CI, 0.81-0.92; P<.001), white men (HR, 0.90; 95% CI, 0.82-0.99; P=.02), Hispanic women (HR, 0.82; 95% CI, 0.68-0.99; P=.04), Hispanic men (HR, 0.67; 95% CI,0.50-0.91; P=.01), and black women (HR, 0.78; 95% CI, 0.66-0.93; P=.005). Atorvastatin was associated with a reduced risk of incident Alzheimer disease diagnosis for white women (HR, 0.84, 95% CI, 0.78-0.89), black women (HR, 0.81, 95% CI, 0.67-0.98), and Hispanic men (HR, 0.61, 95% CI, 0.42-0.89) and women (HR, 0.76, 95% CI, 0.60-0.97).Pravastatin and rosuvastatin were associated with reduced Alzheimer disease risk for white women only (HR, 0.82, 95% CI, 0.70-0.95 and HR, 0.81, 95% CI, 0.67-0.98, respectively). High statin exposure was not associated with a statistically significant lower Alzheimer disease risk among black men. CONCLUSIONS AND RELEVANCE The reduction in Alzheimer disease risk varied across statin molecules, sex, and race/ethnicity. Clinical trials that include racial and ethnic groups need to confirm these findings. Because statins may affect Alzheimer disease risk, physicians should consider which statin is prescribed to each patient.National Institute on Aging of the National Institutes of Health [1RC4AG039036-01, P30AG043073-01]; University of Southern California Zumberge Research Fund [1R34AG049652]; Amgen12 month embargo; Published Online: December 12, 2016.This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Sex and Race Differences in the Association Between Statin Use and the Incidence of Alzheimer Disease

IMPORTANCE To our knowledge, no effective treatments exist for Alzheimer disease, and new molecules are years away. However, several drugs prescribed for other conditions have been associated with reducing its risk. OBJECTIVE To analyze the association between statin exposure and Alzheimer disease incidence among Medicare beneficiaries. DESIGN, SETTING, AND PARTICIPANTS We examined the medical and pharmacy claims of a 20% sample of Medicare beneficiaries from 2006 to 2013 and compared rates of Alzheimer disease diagnosis for 399979 statin users 65 years of age or older with high or low exposure to statins and with drug molecules for black, Hispanic, and non-Hispanic white people, and men and women of Asian, Native American, or unkown race/ethnicity who are referred to as "other." MAIN OUTCOMES AND MEASURES The main outcome was incident diagnosis of Alzheimer disease based on the International Classification of Diseases, Ninth Revision, Clinical Modification. We used Cox proportional hazard models to analyze the association between statin exposure and Alzheimer disease diagnosis for different sexes, races and ethnicities, and statin molecules. RESULTS The 399979 study participants included 7794 (1.95%) black men, 24484 (6.12%) black women, 11200 (2.80%) Hispanic men, 21458 (5.36%) Hispanic women, 115059 (28.77%) white men, and 195181 (48.80%) white women. High exposure to statins was associated with a lower risk of Alzheimer disease diagnosis for women (hazard ratio [HR], 0.85; 95% CI, 0.82-0.89; P<. 001) and men (HR, 0.88; 95% CI, 0.83-0.93; P<.001). Simvastatin was associated with lower Alzheimer disease risk for white women (HR, 0.86; 95% CI, 0.81-0.92; P<.001), white men (HR, 0.90; 95% CI, 0.82-0.99; P=.02), Hispanic women (HR, 0.82; 95% CI, 0.68-0.99; P=.04), Hispanic men (HR, 0.67; 95% CI,0.50-0.91; P=.01), and black women (HR, 0.78; 95% CI, 0.66-0.93; P=.005). Atorvastatin was associated with a reduced risk of incident Alzheimer disease diagnosis for white women (HR, 0.84, 95% CI, 0.78-0.89), black women (HR, 0.81, 95% CI, 0.67-0.98), and Hispanic men (HR, 0.61, 95% CI, 0.42-0.89) and women (HR, 0.76, 95% CI, 0.60-0.97).Pravastatin and rosuvastatin were associated with reduced Alzheimer disease risk for white women only (HR, 0.82, 95% CI, 0.70-0.95 and HR, 0.81, 95% CI, 0.67-0.98, respectively). High statin exposure was not associated with a statistically significant lower Alzheimer disease risk among black men. CONCLUSIONS AND RELEVANCE The reduction in Alzheimer disease risk varied across statin molecules, sex, and race/ethnicity. Clinical trials that include racial and ethnic groups need to confirm these findings. Because statins may affect Alzheimer disease risk, physicians should consider which statin is prescribed to each patient.National Institute on Aging of the National Institutes of Health [1RC4AG039036-01, P30AG043073-01]; University of Southern California Zumberge Research Fund [1R34AG049652]; Amgen12 month embargo; Published Online: December 12, 2016.This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Presence of Multiple Variants of Borrelia burgdorferi in the Natural Reservoir Peromyscus leucopus Throughout a Transmission Season

White-footed mice (Peromyscus leucopus) serve as the principal reservoir for Borrelia burgdorferi and have been shown to remain infected for life. Complex infections with multiple genetic variants of B. burgdorferi occur in mice through multiple exposures to infected ticks or through exposure to ticks infected with multiple variants of B. burgdorferi. Using a combination of cloning and single strand conformation polymorphism (SSCP), B. burgdorferi ospC variation was assessed in serial samples collected from individual P. leucopus during a single transmission season. In individuals with ospC variation, at least seven ospC variants were recognized at each time point. One to four of these variants predominated at each time point; however, the predominant variants seldom remained consistent in an individual mouse throughout the entire sampling period. These results confirmed that mice in southern Maryland were persistently infected with multiple variants of B. burgdorferi throughout the transmission season. However, the presence of multiple ospC variants and the fluctuations in the frequency of these variants indicates that either new ospC variants are regularly introduced to this mouse population and predominate while the existing infections are cleared, or that the variation detected in the genetic profile at different time points reflects a complex mixture of B. burgdorferi populations whose relative frequencies may continually change. Key Words: Borrelia—Ixodes—Lyme disease