@article {1418, title = {Temporal patterns of antihypertensive medication use among older adults, 1989 through 1992. An effect of the major clinical trials on clinical practice?}, journal = {JAMA}, volume = {273}, year = {1995}, month = {1995 May 10}, pages = {1436-8}, abstract = {

OBJECTIVE: To describe the changing patterns of antihypertensive medication use in the years immediately before and after the publication of the results of three major clinical trials of the treatment of hypertension in older adults.

DESIGN: In this cohort study, adults 65 years or older were examined annually on four occasions between June 1989 and May 1992, and the use of antihypertensive medications was assessed by inventory at each visit. The four visits defined the boundaries of three study periods. For each study period, participants receiving antihypertensive therapy were either continuous users (n = 1667, 1643, and 1605, respectively) or starters (n = 157, 142, 120) of hypertensive therapy. The large clinical trials that convincingly proved the efficacy and safety of low-dose diuretic therapy in older adults were published during the latter parts of period 2 and the early parts of period 3.

RESULTS: Among starters, the proportion initiating therapy on diuretics increased from 35.9\% in period 2 to 47.5\% in period 3, significantly so among women (P = .04). The proportions initiating other drugs displayed no significant trends. Among continuous users, the use of diuretics, beta-blockers, and vasodilators generally decreased over the 3-year period, while the use of calcium channel blockers and angiotensin-converting enzyme inhibitors increased significantly in each of the three periods (P < .05). The decline of 2.7\% in the prevalence of diuretic use in period 1 abated during period 2 (1.8\% decline), and it slowed significantly (P = .03) to almost a complete halt during period 3 (0.2\% decline). The rate of increase in the use of calcium channel blockers slowed significantly (P = .01) between period 1 (+6.7\%) and period 3 (+2.8\%).

CONCLUSIONS: Although other factors such as cost may have been important, the temporal trends in antihypertensive drug therapy coincided in time with and may have reflected in part the influence of the major clinical trials on the patterns of clinical practice.

}, keywords = {Aged, Antihypertensive Agents, Clinical Trials as Topic, Data Interpretation, Statistical, Drug Utilization Review, Female, Humans, Hypertension, Male, Practice Patterns, Physicians{\textquoteright}, United States}, issn = {0098-7484}, author = {Psaty, B M and Koepsell, T D and Yanez, N D and Smith, N L and Manolio, T A and Heckbert, S R and Borhani, N O and Gardin, J M and Gottdiener, J S and Rutan, G H} } @article {1491, title = {The association of antihypertensive agents with MRI white matter findings and with Modified Mini-Mental State Examination in older adults.}, journal = {J Am Geriatr Soc}, volume = {45}, year = {1997}, month = {1997 Dec}, pages = {1423-33}, abstract = {

OBJECTIVES: To examine the association of antihypertensive regimen with magnetic resonance imaging (MRI) white matter hyperintensity and with cognitive impairment in older adults.

DESIGN: Cross-sectional study.

SETTING: The Cardiovascular Health study, an observational prospective cohort study of risk factors for coronary heart disease and stroke in men and women 65 years of age and older.

PARTICIPANTS: 1268 men and women with pharmacologically treated hypertension.

MEASUREMENTS: Information on medication use, medical history, and health habits was collected at clinic examinations. Participants completed the Modified Mini-Mental State Examination (3MS) and underwent MRI examination. Without clinical information, study neuroradiologists assigned an overall grade of white matter signal intensity on MRI on a scale from 0 (no findings) to 9 (extensive findings).

RESULTS: Adjusted mean white matter grade was higher for users of calcium channel blockers (2.59, P = .007) and users of loop diuretics (2.60, P = .015) than for users of beta blockers (2.12). The association was present for both dihydropyridine and non-dihydropyridine calcium channel blockers. Adjusted mean 3MS scores were lower for users of calcium channel blockers (89.6, P < .002), especially dihydropyridines, and users of loop diuretics (89.7, P < .006) than for users of beta blockers (92.3). No statistically significant association could be shown for users of other drug regimens, including thiazides and ACE inhibitors.

CONCLUSION: In this study, users of antihypertensive regimens which included calcium channel blockers or loop diuretics had more severe white matter hyperintensity on MRI and worse performance on 3MS than users of beta blockers.

}, keywords = {Adrenergic beta-Antagonists, Aged, Aged, 80 and over, Antihypertensive Agents, Brain, Calcium Channel Blockers, Cognition, Cohort Studies, Cross-Sectional Studies, Diuretics, Female, Geriatric Assessment, Humans, Magnetic Resonance Imaging, Male, Risk Factors}, issn = {0002-8614}, author = {Heckbert, S R and Longstreth, W T and Psaty, B M and Murros, K E and Smith, N L and Newman, A B and Williamson, J D and Bernick, C and Furberg, C D} } @article {1493, title = {The association of antihypertensive medication with serum creatinine changes in older adults.}, journal = {Am J Hypertens}, volume = {10}, year = {1997}, month = {1997 Dec}, pages = {1368-77}, abstract = {

Many of the potential effects of antihypertensive therapy, including renal function, have been inadequately investigated in clinical trials in older adults. In an observational study, we examined the association between treatment with various classes of antihypertensive agents and 3-year changes in serum creatinine in 1296 older adults with treated hypertension and without prior renal disease (mean age 72.2 years; 60\% female; 30\% diabetic; 42\% with cardiovascular disease (CVD)) from the Cardiovascular Health Study. Baseline antihypertensive medications included thiazides (HCT), beta-adrenergic blockers, angiotensin converting enzyme inhibitors (ACE-I), calcium channel blockers (CCB), vasodilators (VAS), HCT + BB, HCT + ACE-I, HCT + CCB, HCT + VAS, loop diuretics (LOOP), and other combinations. Unadjusted results indicated that minimal changes in mean serum creatinine occurred over time for all therapies and only a few changes were statistically significant (HCT: +0.02 mg/dL, ACE-I: +0.04, CCB: +0.04; all P < .05; LOOP: +0.06 mg/dL; P < .001). In multivariate analyses with HCT users as the reference group and adjusting for baseline serum creatinine, age, sex, smoking, diabetes mellitus, CVD, height, weight, common carotid intima-media thickness, and use of allopurinol, phenytoin, cimetidine, and nonsteroidal antiinflammatory drugs, all of the relative changes were small and statistically nonsignificant except for HCT + VAS users (+0.07 mg/dL; P < .05). When users of the same therapy at baseline and follow-up were restricted, only LOOP users had significant albeit small changes in serum creatinine (+0.05 mg/dL; P < .05). Although results from clinical trials are needed to confirm these findings, these observational data suggest no major differences between specific antihypertensive therapies in 3-year serum creatinine changes in older adults without prior renal disease.

}, keywords = {Aged, Antihypertensive Agents, Cohort Studies, Creatinine, Female, Humans, Male}, issn = {0895-7061}, author = {Smith, N L and Psaty, B M and Heckbert, S R and Lemaitre, R N and Kates, D M and Rutan, G H and Bleyer, A} } @article {1503, title = {Correlates and prevalence of benzodiazepine use in community-dwelling elderly.}, journal = {J Gen Intern Med}, volume = {13}, year = {1998}, month = {1998 Apr}, pages = {243-50}, abstract = {

OBJECTIVE: To describe the prevalence of benzodiazepine use, sociodemographic and physical health factors associated with use, dosages taken, and directions for use among individuals aged 65 years and older.

DESIGN: Cross-sectional analysis of baseline data from the community-based, prospective observational Cardiovascular Health Study.

PATIENTS/PARTICIPANTS: Medicare eligibility lists from four U.S. communities were used to recruit a representative sample of 5,201 community-dwelling elderly, of which 5,181 participants met all study criteria.

MEASUREMENTS AND MAIN RESULTS: Among participants, 511 (9.9\%) were taking at least one benzodiazepine, primarily anxiolytics (73\%). Benzodiazepines were often prescribed to be taken pro re nata (PRN "as needed"), and 36.5\% of prescriptions with instructions to be taken regularly were taken at a dose lower than prescribed. Reported over-the-counter (OTC) sleep aid medication use was 39.2\% in benzodiazepine users and 3.3\% in nonusers. In a multivariate logistic model, the significant independent correlates of benzodiazepine use were being white (odds ratio [OR] 1.9; 95\% confidence interval [CI] 1.0, 3.4), female (OR 1.7; CI 1.4, 2.2), and living in Forsyth County, North Carolina, or Washington County, Maryland, compared with living in Sacramento County, California, or Allegheny County, Pennsylvania (OR 2.3; CI 1.4, 2.2); having coronary heart disease (OR 1.6; CI 1.2, 2.1), health status reported as poor or fair (OR 1.8; CI 1.4, 2.3), self-reported diagnosis of nervous or emotional disorder (OR 6.7; CI 5.1, 8.7), and reporting use of an OTC sleep aid medication (OR 18.7; CI 14.1, 24.7).

CONCLUSIONS: One in 10 participants reported taking a benzodiazepine, most frequently an anxiolytic, often at a lower dose than prescribed and usually PRN. The high prevalence of OTC sleep aid medication and benzodiazepine use may place the patient at increased risk of psychomotor impairment. Physicians should assess OTC sleep aid medication use when prescribing benzodiazepines.

}, keywords = {Aged, Aged, 80 and over, Benzodiazepines, Cross-Sectional Studies, Drug Utilization, Female, Humans, Male, Practice Patterns, Physicians{\textquoteright}, Socioeconomic Factors}, issn = {0884-8734}, author = {Gleason, P P and Schulz, R and Smith, N L and Newsom, J T and Kroboth, P D and Kroboth, F J and Psaty, B M} } @article {1507, title = {Temporal patterns in the medical treatment of congestive heart failure with angiotensin-converting enzyme inhibitors in older adults, 1989 through 1995.}, journal = {Arch Intern Med}, volume = {158}, year = {1998}, month = {1998 May 25}, pages = {1074-80}, abstract = {

BACKGROUND: Evidence from clinical trials in the past decade has consistently shown that angiotensin-converting enzyme (ACE) inhibitors reduce morbidity and mortality in patients with congestive heart failure (CHF). The extent to which clinical practice has adopted ACE inhibitor therapy is unknown.

METHODS: The Cardiovascular Health Study is a prospective observational study of 5201 community-dwelling adults aged 65 years and older. Prevalent CHF cases were identified on study entry (from June 10, 1989, through May 31, 1990) and incident CHF cases were identified throughout 5 years of follow-up. Medication data were collected from annual medication inventories. The percentage of patients with CHF using ACE inhibitors was calculated at each annual examination. Temporal trends in CHF treatment with ACE inhibitors between June 10, 1989, through May 31, 1990, and June 1, 1994, through May 31, 1995, were analyzed.

RESULTS: Use of ACE inhibitors to treat CHF increased slightly over time among prevalent cases at each annual examination: 26\% of prevalent CHF cases were treated in 1989-1990 compared with 36\% of prevalent cases in 1994-1995. This 10\% increase was statistically significant (P<.01). Participants with low ejection fractions were 2 times more likely to be treated with ACE inhibitors than were those with normal ejection fraction and this tendency did not change over time. Among cases newly diagnosed in the year before the 1990-1991 examination, 42\% were using ACE inhibitors; among those newly diagnosed in the year before 1994-1995, 40\% were using ACE inhibitors. This 2\% decrease was not statistically significant (P=.68).

CONCLUSION: These findings suggest that, while the medical management of CHF with ACE inhibitors has increased modestly over time in prevalent cases, these drugs may still be underused, especially among incident cases.

}, keywords = {Aged, Angiotensin-Converting Enzyme Inhibitors, Drug Utilization, Female, Heart Failure, Humans, Logistic Models, Male, Stroke Volume, Treatment Outcome, United States}, issn = {0003-9926}, author = {Smith, N L and Psaty, B M and Pitt, B and Garg, R and Gottdiener, J S and Heckbert, S R} } @article {591, title = {Antidiabetic treatment trends in a cohort of elderly people with diabetes. The cardiovascular health study, 1989-1997.}, journal = {Diabetes Care}, volume = {22}, year = {1999}, month = {1999 May}, pages = {736-42}, abstract = {

OBJECTIVE: This study characterizes the pharmaceutical treatment of type 2 diabetes from 1989-1990 to 1996-1997 in an elderly cohort.

RESEARCH DESIGN AND METHODS: A total of 5,888 adults aged > or = 65 years were recruited and attended a baseline clinic visit in 1989-1990 (n = 5,201, original cohort) or 1992-1993 (n = 687. African-American [new] cohort) as participants of the Cardiovascular Health Study. Fasting serum glucose (FSG) was measured at baseline. Medication use was ascertained by drug inventory at all annual clinic visits. Diabetes was defined at baseline as insulin or oral hypoglycemic agent (OHA) use or as having an FSG > or = 7.0 mmol/l (126 mg/dl), the current consensus definition of diabetes.

RESULTS: A total of 387 (7\%) original (FSG = 9.8 mmol/l [177 mg/dl]) and 115 (17\%) new (FSG = 10.6 mmol/l [191 mg/dl]) cohort members had pharmacologically treated diabetes at baseline. Among those in the original and in the new cohorts who survived follow-up, respectively, OHA use decreased from 80 to 48\% (P < 0.001) and from 67 to 50\% (P < 0.003) and insulin use increased from 20 to 33\% (P = 0.001) and from 33 to 37\% (P = 0.603). There were 396 (8\%) original (FSG = 8.8 mmol/l [159 mg/dl]) and 45 (7\%) new (FSG = 10.0 mmol/l [181 mg/dl]) cohort members with diabetes untreated at baseline. Among them, respectively, OHA use reached 38 and 30\% and insulin use reached 6 and 16\% in 1996-1997.

CONCLUSIONS: Diabetes was common in this elderly cohort, and > 80\% of treated patients with diabetes at baseline were not achieving fasting glucose goals of < or = 6.7 mmol/l (120 mg/dl). Many untreated at baseline remained untreated after 7 years of follow-up.

}, keywords = {Aged, Blood Glucose, Cardiovascular Diseases, Cohort Studies, Diabetes Mellitus, Drug Therapy, Female, Follow-Up Studies, Humans, Hypoglycemic Agents, Insulin, Male, Prospective Studies, Risk Factors, Time Factors, United States}, issn = {0149-5992}, doi = {10.2337/diacare.22.5.736}, author = {Smith, N L and Heckbert, S R and Bittner, V A and Savage, P J and Barzilay, J I and Dobs, A S and Psaty, B M} } @article {599, title = {Temporal trends in the use of anticoagulants among older adults with atrial fibrillation.}, journal = {Arch Intern Med}, volume = {159}, year = {1999}, month = {1999 Jul 26}, pages = {1574-8}, abstract = {

BACKGROUND: Several recent randomized clinical trials have demonstrated that warfarin sodium treatment, and to a lesser extent aspirin, reduces risk of stroke and death compared with placebo in persons with atrial fibrillation. Insufficient documentation exists on the extent to which the use of these therapies following trial publications has continued to increase in the elderly with atrial fibrillation.

METHODS: We used data from the Cardiovascular Health Study, a study of 5888 community-dwelling adults aged 65 years or older, to determine the prevalence of warfarin and aspirin use in persons with electrocardiogram-identified atrial fibrillation. Electrocardiogram examinations were conducted at baseline from 1989 through 1990, and at 6 subsequent annual examinations through 1995-1996. Medication data were collected by inventory methods at each examination. Temporal change in use of anticoagulants was analyzed by comparing percentage use in 1990 to use in each year through 1996.

RESULTS: The use of warfarin increased 4-fold from 13\% in 1990 to 50\% in 1996 among participants with prevalent atrial fibrillation (P<.001). Daily use of aspirin did not increase over time. Participants younger than 80 years were 4 times more likely to use warfarin in 1996 (P<.001) than those 80 years and older. Use of aspirin did not vary significantly with age.

CONCLUSIONS: Warfarin use in community-dwelling elderly persons with electrocardiogram-documented atrial fibrillation increased steadily following the first publication of its treatment benefit, reaching 50\% by 1996. In contrast, use of aspirin was unchanged during this same period. Continued efforts to promote appropriate anticoagulation therapy to physicians and their patients may still be needed.

}, keywords = {Aged, Anticoagulants, Aspirin, Atrial Fibrillation, Cerebrovascular Disorders, Drug Therapy, Electrocardiography, Female, Humans, Incidence, Male, Prevalence, Treatment Outcome, Warfarin}, issn = {0003-9926}, doi = {10.1001/archinte.159.14.1574}, author = {Smith, N L and Psaty, B M and Furberg, C D and White, R and Lima, J A and Newman, A B and Manolio, T A} } @article {869, title = {Statins and cognitive function in the elderly: the Cardiovascular Health Study.}, journal = {Neurology}, volume = {65}, year = {2005}, month = {2005 Nov 08}, pages = {1388-94}, abstract = {

OBJECTIVE: To examine the association of statin drug use on cognitive and MRI change in older adults.

METHODS: Participants in the Cardiovascular Health Study, a longitudinal study of people age 65 or older, were classified into three groups determined by whether they were taking statin drugs on a continuous basis, intermittently, or not at all. The untreated group was further divided into categories based on National Cholesterol Education Program recommendations for lipid-lowering treatment. Participants with prevalent or incident clinical TIA or stroke or with baseline Modified Mini-Mental State Examination (3MS) scores at or below 80 were excluded. Outcomes examined included rate of change on the 3MS over an average observational period of 7 years, along with changes in MRI white matter grade and measures of atrophy.

RESULTS: Three thousand three hundred thirty-four participants had adequate data for analysis. At baseline, the untreated group in which lipid-lowering drug treatment was recommended were slightly older, less likely to be on estrogen replacement, and had higher serum cholesterol and lower 3MS scores than the statin-treated group. The rate of decline on the 3MS was 0.48 point/year less in those taking statins compared with the untreated group for which treatment was recommended (p = 0.069) and 0.49 point/year less in statin users compared with the group in which lipid-lowering treatment was not recommended (p = 0.009). This effect remained after controlling for serum cholesterol levels. One thousand seven hundred thirty participants with baseline 3MS scores of > 80 underwent cranial MRI scans on two occasions separated by 5 years. There was no significant difference in white matter grade change or atrophy measures between groups.

CONCLUSION: Statin drug use was associated with a slight reduction in cognitive decline in an elderly population. This relationship could not be completely explained by the effect of statins on lowering of serum cholesterol.

}, keywords = {Aged, Aged, 80 and over, Aging, Anticholesteremic Agents, Atrophy, Brain, Cholesterol, Cognition Disorders, Cohort Studies, Dementia, Female, Humans, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Longitudinal Studies, Male, Memory Disorders, Nootropic Agents, Treatment Outcome}, issn = {1526-632X}, doi = {10.1212/01.wnl.0000182897.18229.ec}, author = {Bernick, C and Katz, R and Smith, N L and Rapp, S and Bhadelia, R and Carlson, M and Kuller, L} } @article {1106, title = {Common hemostasis and inflammation gene variants and venous thrombosis in older adults from the Cardiovascular Health Study.}, journal = {J Thromb Haemost}, volume = {7}, year = {2009}, month = {2009 Sep}, pages = {1499-505}, abstract = {

BACKGROUND/OBJECTIVES: Age-related changes in blood coagulation and fibrinolysis are associated with increased risk of thrombotic events. Inherited deficiencies of coagulation proteins, such as factor V (FV) Leiden and prothrombin G20210A, explain a small fraction of venous thromboembolic disease (VTE). Additional genetic factors are likely to underlie the etiology of VTE, some of which may become manifest at older ages.

METHODS: We tested 290 common SNPs within 51 thrombosis and inflammation genes for association with VTE in the Cardiovascular Health Study, a large, prospective cohort of older adults followed for up to 12 years.

RESULTS: There were 184 VTE events that occurred at mean age of 78 years. TagSNPs within four genes encoding FXIII subunit A (F13A), FVII activating protease (HABP2), protease activated receptor-1 (F2R) and the urokinase receptor (PLAUR) showed the strongest evidence for association with VTE, with each gene having a global P-value < 0.05 and at least one tagSNP false discovery rate (FDR) q-value < 0.05. The rs3024409 variant allele of F13A1 was associated with 1.66-fold increased risk of VTE, while the minor alleles of HABP2 rs6585234 and rs3862019, F2R rs253061 and rs153311, and PLAUR rs344782 were each associated with lower risk of VTE (hazard ratios in the range of 0.49-0.66). Consistent with the observed protective association for VTE risk, the HABP2 rs3862019 variant allele was also associated with lower activity levels of coagulation factors FVIII, FIX, FX and plasminogen. We also confirm previously reported associations between common variants of the coagulation FII, FV, FVIII, FXI, alpha-fibrinogen and protein C genes and risk of VTE.

CONCLUSIONS: These findings suggest that several novel common coagulation gene variants may be related to risk of VTE in older adults. Further studies in older adults are needed to validate these findings and assess functional molecular mechanisms.

}, keywords = {Aged, Alleles, Factor V, Factor VIII, Female, Hemostasis, Humans, Inflammation, Male, Middle Aged, Models, Genetic, Plasminogen, Prothrombin, Risk, Serine Endopeptidases, Venous Thrombosis}, issn = {1538-7836}, doi = {10.1111/j.1538-7836.2009.03522.x}, author = {Reiner, A P and Lange, L A and Smith, N L and Zakai, N A and Cushman, M and Folsom, A R} } @article {1121, title = {Replication of findings on the association of genetic variation in 24 hemostasis genes and risk of incident venous thrombosis.}, journal = {J Thromb Haemost}, volume = {7}, year = {2009}, month = {2009 Oct}, pages = {1743-6}, keywords = {Adolescent, Adult, Aged, Aged, 80 and over, Case-Control Studies, Cohort Studies, Female, Genetic Association Studies, Genetic Predisposition to Disease, Genetic Variation, Haplotypes, Hemostasis, Humans, Incidence, Male, Menopause, Middle Aged, Polymorphism, Single Nucleotide, Reproducibility of Results, Risk, Thrombophilia, Venous Thrombosis, Young Adult}, issn = {1538-7836}, doi = {10.1111/j.1538-7836.2009.03567.x}, author = {Smith, N L and Wiggins, K L and Reiner, A P and Lange, L A and Cushman, M and Heckbert, S R and Lumley, T and Rice, K M and Folsom, A R and Psaty, B M} } @article {1364, title = {Genetic variation in F3 (tissue factor) and the risk of incident venous thrombosis: meta-analysis of eight studies.}, journal = {J Thromb Haemost}, volume = {10}, year = {2012}, month = {2012 Apr}, pages = {719-22}, keywords = {Female, Gene Frequency, Genetic Predisposition to Disease, Genetic Variation, Humans, Incidence, Male, Middle Aged, Phenotype, Regression Analysis, Risk Assessment, Risk Factors, Thromboplastin, Venous Thrombosis}, issn = {1538-7836}, doi = {10.1111/j.1538-7836.2012.04665.x}, author = {Smith, N L and Heit, J A and Tang, W and Teichert, M and Chasman, D I and Morange, P-E} }