@article {635, title = {Risk factors for hospitalized gastrointestinal bleeding among older persons. Cardiovascular Health Study Investigators.}, journal = {J Am Geriatr Soc}, volume = {49}, year = {2001}, month = {2001 Feb}, pages = {126-33}, abstract = {

OBJECTIVES: We sought to estimate the incidence of hospitalization for upper and lower gastrointestinal bleeding among older persons and to identify independent risk factors.

DESIGN: Prospective cohort study.

SETTING: The Cardiovascular Health Study (CHS).

PARTICIPANTS: 5,888 noninstitutionalized men and women age 65 years or older in four U.S. communities enrolled in the CHS.

MEASUREMENTS: Gastrointestinal bleeding events during the period 1989 through 1998 were identified using hospital discharge diagnosis codes and confirmed by medical records review. Risk-factor information was collected in a standardized fashion at study baseline and annually during follow-up.

RESULTS: Among CHS participants (mean baseline age 73.3 years, 42\% male), the incidence of hospitalized gastrointestinal bleeding was 6.8/1,000 person-years. In multivariate analyses, advanced age, male sex, unmarried status, cardiovascular disease, difficulty with daily activities, use of multiple medications, and use of oral anticoagulants were independent risk factors. Compared with nonsmokers, subjects who smoked more than half a pack per day had a multivariate-adjusted hazard ratio (HR) of 2.14 (95\% confidence interval [CI] = 1.22-3.75) for upper gastrointestinal bleeding and a multivariate-adjusted HR of 0.21 (95\% CI = 0.03-1.54) for lower gastrointestinal bleeding. Aspirin users did not have an elevated risk of upper gastrointestinal bleeding (HR = 0.76, 95\% CI = 0.52-1.11), and users of other nonsteroidal anti-inflammatory drugs had a HR of 1.54 (95 \% CI = 0.99-2.36). Low ankle-arm systolic blood pressure index was associated with higher risk of gastrointestinal bleeding among subjects with clinical cardiovascular disease but not among those without clinical cardiovascular disease.

CONCLUSION: This study identifies risk factors for gastrointestinal bleeding, such as disability, that may be amenable to modification. The findings will help clinicians to identify older persons who are at high risk for gastrointestinal bleeding.

}, keywords = {Activities of Daily Living, Age Distribution, Aged, Aged, 80 and over, Anti-Inflammatory Agents, Non-Steroidal, Anticoagulants, Aspirin, Cardiovascular Diseases, Female, Gastrointestinal Hemorrhage, Hospitalization, Humans, Incidence, Male, Multivariate Analysis, Predictive Value of Tests, Proportional Hazards Models, Prospective Studies, Risk Factors, Smoking, United States}, issn = {0002-8614}, doi = {10.1046/j.1532-5415.2001.49032.x}, author = {Kaplan, R C and Heckbert, S R and Koepsell, T D and Furberg, C D and Polak, J F and Schoen, R E and Psaty, B M} } @article {860, title = {Vascular events, mortality, and preventive therapy following ischemic stroke in the elderly.}, journal = {Neurology}, volume = {65}, year = {2005}, month = {2005 Sep 27}, pages = {835-42}, abstract = {

BACKGROUND: The authors studied mortality, vascular events, and preventive therapies following ischemic stroke among adults aged > or =65 years.

METHODS: The authors identified 546 subjects with first ischemic stroke during 1989 to 2001 among Cardiovascular Health Study participants. Deaths, recurrent strokes, and coronary heart disease (CHD) events were identified over 3.2 years (median) follow-up.

RESULTS: During the first year of follow-up, rates were 105.4/1,000 for recurrent stroke and 59.3/1,000 for CHD. After the first year, the stroke rate was 52.0/1,000 and the CHD rate was 46.5/1,000. Cardioembolic strokes had the highest mortality (185.4/1,000) and recurrence rates (86.6/1,000). Lacunar strokes had the lowest mortality (119.3/1,000) and recurrence rates (43.0/1,000). Age and male sex predicted death and CHD, but not recurrence. Outcomes did not differ by race. Following stroke, 47.8\% used aspirin and 13.5\% used other antiplatelet agents; 52.6\% of patients with atrial fibrillation used warfarin; 31.3\% of hyperlipidemic subjects, 57.0\% of diabetic patients, and 81.5\% of hypertensive patients were drug-treated; and 40.0\% of hypertensive patients had blood pressure (BP) <140/90 mm Hg. Older subjects were less likely to use lipid-lowering therapy, women were less likely to have BP <140/90 mm Hg, and low-income subjects were less likely to use diabetes medications.

CONCLUSIONS: Recurrent strokes were nearly twice as frequent as coronary heart disease (CHD) events during the first year after initial stroke, but stroke and CHD rates were similar after the first year. Preventive drug therapies were underused, which may reflect clinical uncertainty due to the lack of clinical trials among the elderly. Utilization was lower among the oldest patients, women, and low-income individuals.

}, keywords = {Age Factors, Aged, Aged, 80 and over, Aging, Anticoagulants, Antihypertensive Agents, Brain Ischemia, Cohort Studies, Comorbidity, Coronary Artery Disease, Drug Utilization, Female, Humans, Hyperlipidemias, Hypertension, Hypolipidemic Agents, Male, Mortality, Prospective Studies, Recurrence, Sex Factors, Stroke, Treatment Outcome}, issn = {1526-632X}, doi = {10.1212/01.wnl.0000176058.09848.bb}, author = {Kaplan, R C and Tirschwell, D L and Longstreth, W T and Manolio, T A and Heckbert, S R and Lefkowitz, D and El-Saed, A and Psaty, B M} } @article {6061, title = {Association of heat shock proteins with all-cause mortality.}, journal = {Age (Dordr)}, volume = {35}, year = {2013}, month = {2013 Aug}, pages = {1367-76}, abstract = {

Experimental mild heat shock is widely known as an intervention that results in extended longevity in various models along the evolutionary lineage. Heat shock proteins (HSPs) are highly upregulated immediately after a heat shock. The elevation in HSP levels was shown to inhibit stress-mediated cell death, and recent experiments indicate a highly versatile role for these proteins as inhibitors of programmed cell death. In this study, we examined common genetic variations in 31 genes encoding all members of the HSP70, small HSP, and heat shock factor (HSF) families for their association with all-cause mortality. Our discovery cohort was the Rotterdam study (RS1) containing 5,974 participants aged 55 years and older (3,174 deaths). We assessed 4,430 single nucleotide polymorphisms (SNPs) using the HumanHap550K Genotyping BeadChip from Illumina. After adjusting for multiple testing by permutation analysis, three SNPs showed evidence for association with all-cause mortality in RS1. These findings were followed in eight independent population-based cohorts, leading to a total of 25,007 participants (8,444 deaths). In the replication phase, only HSF2 (rs1416733) remained significantly associated with all-cause mortality. Rs1416733 is a known cis-eQTL for HSF2. Our findings suggest a role of HSF2 in all-cause mortality.

}, keywords = {Aged, 80 and over, Aging, Cause of Death, Forecasting, Genotype, Heat-Shock Proteins, Humans, Longevity, Promoter Regions, Genetic, Retrospective Studies, Transcription, Genetic, United States}, issn = {1574-4647}, doi = {10.1007/s11357-012-9417-7}, author = {Broer, L and Demerath, E W and Garcia, M E and Homuth, G and Kaplan, R C and Lunetta, K L and Tanaka, T and Tranah, G J and Walter, S and Arnold, A M and Atzmon, G and Harris, T B and Hoffmann, W and Karasik, D and Kiel, D P and Kocher, T and Launer, L J and Lohman, K K and Rotter, J I and Tiemeier, H and Uitterlinden, A G and Wallaschofski, H and Bandinelli, S and D{\"o}rr, M and Ferrucci, L and Franceschini, N and Gudnason, V and Hofman, A and Liu, Y and Murabito, J M and Newman, A B and Oostra, B A and Psaty, B M and Smith, A V and van Duijn, C M} } @article {7253, title = {Large-scale pharmacogenomic study of sulfonylureas and the QT, JT and QRS intervals: CHARGE Pharmacogenomics Working Group.}, journal = {Pharmacogenomics J}, year = {2016}, month = {2016 Dec 13}, abstract = {

Sulfonylureas, a commonly used class of medication used to treat type 2 diabetes, have been associated with an increased risk of cardiovascular disease. Their effects on QT interval duration and related electrocardiographic phenotypes are potential mechanisms for this adverse effect. In 11 ethnically diverse cohorts that included 71 857 European, African-American and Hispanic/Latino ancestry individuals with repeated measures of medication use and electrocardiogram (ECG) measurements, we conducted a pharmacogenomic genome-wide association study of sulfonylurea use and three ECG phenotypes: QT, JT and QRS intervals. In ancestry-specific meta-analyses, eight novel pharmacogenomic loci met the threshold for genome-wide significance (P<5 {\texttimes} 10(-8)), and a pharmacokinetic variant in CYP2C9 (rs1057910) that has been associated with sulfonylurea-related treatment effects and other adverse drug reactions in previous studies was replicated. Additional research is needed to replicate the novel findings and to understand their biological basis.The Pharmacogenomics Journal advance online publication, 13 December 2016; doi:10.1038/tpj.2016.90.

}, issn = {1473-1150}, doi = {10.1038/tpj.2016.90}, author = {Floyd, J S and Sitlani, C M and Avery, C L and Noordam, R and Li, X and Smith, A V and Gogarten, S M and Li, J and Broer, L and Evans, D S and Trompet, S and Brody, J A and Stewart, J D and Eicher, J D and Seyerle, A A and Roach, J and Lange, L A and Lin, H J and Kors, J A and Harris, T B and Li-Gao, R and Sattar, N and Cummings, S R and Wiggins, K L and Napier, M D and St{\"u}rmer, T and Bis, J C and Kerr, K F and Uitterlinden, A G and Taylor, K D and Stott, D J and de Mutsert, R and Launer, L J and Busch, E L and M{\'e}ndez-Gir{\'a}ldez, R and Sotoodehnia, N and Soliman, E Z and Li, Y and Duan, Q and Rosendaal, F R and Slagboom, P E and Wilhelmsen, K C and Reiner, A P and Chen, Y-DI and Heckbert, S R and Kaplan, R C and Rice, K M and Jukema, J W and Johnson, A D and Liu, Y and Mook-Kanamori, D O and Gudnason, V and Wilson, J G and Rotter, J I and Laurie, C C and Psaty, B M and Whitsel, E A and Cupples, L A and Stricker, B H} } @article {7491, title = {Pharmacogenomics study of thiazide diuretics and QT interval in multi-ethnic populations: the cohorts for heart and aging research in genomic epidemiology.}, journal = {Pharmacogenomics J}, year = {2017}, month = {2017 Jul 18}, abstract = {

Thiazide diuretics, commonly used antihypertensives, may cause QT interval (QT) prolongation, a risk factor for highly fatal and difficult to predict ventricular arrhythmias. We examined whether common single-nucleotide polymorphisms (SNPs) modified the association between thiazide use and QT or its component parts (QRS interval, JT interval) by performing ancestry-specific, trans-ethnic and cross-phenotype genome-wide analyses of European (66\%), African American (15\%) and Hispanic (19\%) populations (N=78 199), leveraging longitudinal data, incorporating corrected standard errors to account for underestimation of interaction estimate variances and evaluating evidence for pathway enrichment. Although no loci achieved genome-wide significance (P<5 {\texttimes} 10(-8)), we found suggestive evidence (P<5 {\texttimes} 10(-6)) for SNPs modifying the thiazide-QT association at 22 loci, including ion transport loci (for example, NELL1, KCNQ3). The biologic plausibility of our suggestive results and simulations demonstrating modest power to detect interaction effects at genome-wide significant levels indicate that larger studies and innovative statistical methods are warranted in future efforts evaluating thiazide-SNP interactions.The Pharmacogenomics Journal advance online publication, 18 July 2017; doi:10.1038/tpj.2017.10.

}, issn = {1473-1150}, doi = {10.1038/tpj.2017.10}, author = {Seyerle, A A and Sitlani, C M and Noordam, R and Gogarten, S M and Li, J and Li, X and Evans, D S and Sun, F and Laaksonen, M A and Isaacs, A and Kristiansson, K and Highland, H M and Stewart, J D and Harris, T B and Trompet, S and Bis, J C and Peloso, G M and Brody, J A and Broer, L and Busch, E L and Duan, Q and Stilp, A M and O{\textquoteright}Donnell, C J and Macfarlane, P W and Floyd, J S and Kors, J A and Lin, H J and Li-Gao, R and Sofer, T and M{\'e}ndez-Gir{\'a}ldez, R and Cummings, S R and Heckbert, S R and Hofman, A and Ford, I and Li, Y and Launer, L J and Porthan, K and Newton-Cheh, C and Napier, M D and Kerr, K F and Reiner, A P and Rice, K M and Roach, J and Buckley, B M and Soliman, E Z and de Mutsert, R and Sotoodehnia, N and Uitterlinden, A G and North, K E and Lee, C R and Gudnason, V and St{\"u}rmer, T and Rosendaal, F R and Taylor, K D and Wiggins, K L and Wilson, J G and Chen, Y-DI and Kaplan, R C and Wilhelmsen, K and Cupples, L A and Salomaa, V and van Duijn, C and Jukema, J W and Liu, Y and Mook-Kanamori, D O and Lange, L A and Vasan, R S and Smith, A V and Stricker, B H and Laurie, C C and Rotter, J I and Whitsel, E A and Psaty, B M and Avery, C L} }