@article {647, title = {Association between blood pressure level and the risk of myocardial infarction, stroke, and total mortality: the cardiovascular health study.}, journal = {Arch Intern Med}, volume = {161}, year = {2001}, month = {2001 May 14}, pages = {1183-92}, abstract = {

BACKGROUND: Recent reports have drawn attention to the importance of pulse pressure as a predictor of cardiovascular events. Pulse pressure is used neither by clinicians nor by guidelines to define treatable levels of blood pressure.

METHODS: In the Cardiovascular Health Study, 5888 adults 65 years and older were recruited from 4 US centers. At baseline in 1989-1990, participants underwent an extensive examination, and all subsequent cardiovascular events were ascertained and classified.

RESULTS: At baseline, 1961 men and 2941 women were at risk for an incident myocardial infarction or stroke. During follow-up that averaged 6.7 years, 572 subjects had a coronary event, 385 had a stroke, and 896 died. After adjustment for potential confounders, systolic blood pressure (SBP), diastolic blood pressure (DBP), and pulse pressure were directly associated with the risk of incident myocardial infarction and stroke. Only SBP was associated with total mortality. Importantly, SBP was a better predictor of cardiovascular events than DBP or pulse pressure. In the adjusted model for myocardial infarction, a 1-SD change in SBP, DBP, and pulse pressure was associated with hazard ratios (95\% confidence intervals) of 1.24 (1.15-1.35), 1.13 (1.04-1.22), and 1.21 (1.12-1.31), respectively; and adding pulse pressure or DBP to the model did not improve the fit. For stroke, the hazard ratios (95\% confidence intervals) were 1.34 (1.21-1.47) with SBP, 1.29 (1.17-1.42) with DBP, and 1.21 (1.10-1.34) with pulse pressure. The association between blood pressure level and cardiovascular disease risk was generally linear; specifically, there was no evidence of a J-shaped relationship. In those with treated hypertension, the hazard ratios for the association of SBP with the risks for myocardial infarction and stroke were less pronounced than in those without treated hypertension.

CONCLUSION: In this population-based study of older adults, although all measures of blood pressure were strongly and directly related to the risk of coronary and cerebrovascular events, SBP was the best single predictor of cardiovascular events.

}, keywords = {Aged, Blood Pressure, Female, Humans, Male, Myocardial Infarction, Prognosis, Proportional Hazards Models, Prospective Studies, Risk Factors, Stroke, Survival Rate, United States}, issn = {0003-9926}, doi = {10.1001/archinte.161.9.1183}, author = {Psaty, B M and Furberg, C D and Kuller, L H and Cushman, M and Savage, P J and Levine, D and O{\textquoteright}Leary, D H and Bryan, R N and Anderson, M and Lumley, T} } @article {811, title = {Respiratory muscle strength and the risk of incident cardiovascular events.}, journal = {Thorax}, volume = {59}, year = {2004}, month = {2004 Dec}, pages = {1063-7}, abstract = {

BACKGROUND: Maximal inspiratory pressure (MIP) is a measure of inspiratory muscle strength. The prognostic importance of MIP for cardiovascular events among elderly community dwelling individuals is unknown. Diminished forced vital capacity (FVC) is a risk factor for cardiovascular events which remains largely unexplained.

METHODS: MIP was measured at the baseline examination of the Cardiovascular Health Study. Participants had to be free of prevalent congestive heart failure (CHF), myocardial infarction (MI), and stroke.

RESULTS: Subjects in the lowest quintile of MIP had a 1.5-fold increased risk of MI (HR 1.48, 95\% CI 1.07 to 2.06) and cardiovascular disease (CVD) death (HR 1.54, 95\% CI 1.09 to 2.15) after adjustment for non-pulmonary function covariates. There was a potential inverse relationship with stroke (HR 1.36, 95\% CI 0.97 to 1.90), but there was little evidence of an association between MIP and CHF (HR 1.22, 95\% CI 0.93 to 1.60). The addition of FVC to models attenuated the HR associated with MIP only modestly; similarly, addition of MIP attenuated the HR associated with FVC only modestly.

CONCLUSIONS: A reduced MIP is an independent risk factor for MI and CVD death, and a suggestion of an increased risk for stroke. This association with MIP appeared to be mediated through mechanisms other than inflammation.

}, keywords = {Cardiovascular Diseases, Female, Follow-Up Studies, Forced Expiratory Volume, Humans, Male, Maximal Voluntary Ventilation, Prospective Studies, Respiratory Muscles, Risk Factors, Vital Capacity}, issn = {0040-6376}, doi = {10.1136/thx.2004.021915}, author = {van der Palen, J and Rea, T D and Manolio, T A and Lumley, T and Newman, A B and Tracy, R P and Enright, P L and Psaty, B M} } @article {1068, title = {Platelet count and the risk for thrombosis and death in the elderly.}, journal = {J Thromb Haemost}, volume = {7}, year = {2009}, month = {2009 Mar}, pages = {399-405}, abstract = {

AIM: Our aim was to examine the association between platelet count and the incidence of myocardial infarction, ischemic stroke, hemorrhagic stroke, venous thrombosis, and mortality.

METHODS AND RESULTS: Platelet count was measured at baseline in 1989-1990 and at 3 years follow-up, or at baseline (for a newly recruited group) in 1992-1993 in 5766 community-dwelling individuals aged 65 years and older (mean age at baseline, 73 years). During 12-15 years of follow-up, there were 821 incident myocardial infarctions, 807 ischemic strokes, 161 hemorrhagic strokes, 159 venous thrombotic events, and 3413 participants died. Platelet count was not associated with the occurrence of myocardial infarction, ischemic or hemorrhagic stroke, venous thrombosis, or cardiovascular mortality. Non-cardiovascular mortality was higher among both participants with low and with high platelet count. Adjusted non-cardiovascular mortality rates for platelet counts below 100, 100-199, 300-399, and above 400 x 10(9) L(-1) relative to the reference mortality rate in participants with platelet count values between 200 and 299 x 10(9) L(-1) were 1.89 (1.21-2.96), 1.08 (0.98-1.20), 1.20 (1.06-1.37), and 1.47 (1.14-1.90), respectively.

CONCLUSION: Platelet counts were not associated with vascular outcomes but low and high platelet counts were associated with non-cardiovascular mortality, including cancer mortality.

}, keywords = {Aged, Aged, 80 and over, Cause of Death, Cerebral Hemorrhage, Female, Humans, Male, Myocardial Infarction, Platelet Count, Risk, Stroke, Survival Analysis, Thrombosis, Venous Thrombosis}, issn = {1538-7836}, doi = {10.1111/j.1538-7836.2008.03267.x}, author = {van der Bom, J G and Heckbert, S R and Lumley, T and Holmes, C E and Cushman, M and Folsom, A R and Rosendaal, F R and Psaty, B M} } @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 {1549, title = {A screening study of drug-drug interactions in cerivastatin users: an adverse effect of clopidogrel.}, journal = {Clin Pharmacol Ther}, volume = {91}, year = {2012}, month = {2012 May}, pages = {896-904}, abstract = {

An analysis of a case-control study of rhabdomyolysis was conducted to screen for previously unrecognized cytochrome P450 enzyme (CYP) 2C8 inhibitors that may cause other clinically important drug-drug interactions. Medication use in cases of rhabdomyolysis using cerivastatin (n = 72) was compared with that in controls using atorvastatin (n = 287) for the period 1998-2001. The use of clopidogrel was strongly associated with rhabdomyolysis (odds ratio (OR) 29.6; 95\% confidence interval (CI), 6.1-143). In a replication effort that used the US Food and Drug Administration (FDA) Adverse Event Reporting System (AERS), it was found that clopidogrel was used more commonly in patients with rhabdomyolysis receiving cerivastatin (17\%) than in those receiving atorvastatin (0\%, OR infinity; 95\% CI = 5.2-infinity). Several medications were tested in vitro for their potential to cause drug-drug interactions. Clopidogrel, rosiglitazone, and montelukast were the most potent inhibitors of cerivastatin metabolism. Clopidogrel and its metabolites also inhibited cerivastatin metabolism in human hepatocytes. These epidemiological and in vitro findings suggest that clopidogrel may cause clinically important, dose-dependent drug-drug interactions with other medications metabolized by CYP2C8.

}, keywords = {Adverse Drug Reaction Reporting Systems, Aged, Aged, 80 and over, Aryl Hydrocarbon Hydroxylases, Case-Control Studies, Cytochrome P-450 CYP2C8, Cytochrome P-450 CYP3A, Cytochrome P-450 CYP3A Inhibitors, Drug Interactions, Female, Humans, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Male, Platelet Aggregation Inhibitors, Pyridines, Rhabdomyolysis, Ticlopidine}, issn = {1532-6535}, doi = {10.1038/clpt.2011.295}, author = {Floyd, J S and Kaspera, R and Marciante, K D and Weiss, N S and Heckbert, S R and Lumley, T and Wiggins, K L and Tamraz, B and Kwok, P-Y and Totah, R A and Psaty, B M} } @article {6566, title = {Novel loci associated with usual sleep duration: the CHARGE Consortium Genome-Wide Association Study.}, journal = {Mol Psychiatry}, volume = {20}, year = {2015}, month = {2015 Oct}, pages = {1232-9}, abstract = {

Usual sleep duration is a heritable trait correlated with psychiatric morbidity, cardiometabolic disease and mortality, although little is known about the genetic variants influencing this trait. A genome-wide association study (GWAS) of usual sleep duration was conducted using 18 population-based cohorts totaling 47 180 individuals of European ancestry. Genome-wide significant association was identified at two loci. The strongest is located on chromosome 2, in an intergenic region 35- to 80-kb upstream from the thyroid-specific transcription factor PAX8 (lowest P=1.1 {\texttimes} 10(-9)). This finding was replicated in an African-American sample of 4771 individuals (lowest P=9.3 {\texttimes} 10(-4)). The strongest combined association was at rs1823125 (P=1.5 {\texttimes} 10(-10), minor allele frequency 0.26 in the discovery sample, 0.12 in the replication sample), with each copy of the minor allele associated with a sleep duration 3.1 min longer per night. The alleles associated with longer sleep duration were associated in previous GWAS with a more favorable metabolic profile and a lower risk of attention deficit hyperactivity disorder. Understanding the mechanisms underlying these associations may help elucidate biological mechanisms influencing sleep duration and its association with psychiatric, metabolic and cardiovascular disease.

}, keywords = {Adult, African Americans, Aged, Dyssomnias, European Continental Ancestry Group, Female, Genetic Association Studies, Genome-Wide Association Study, Humans, Male, Middle Aged, Polymorphism, Single Nucleotide, Self Report, Sleep}, issn = {1476-5578}, doi = {10.1038/mp.2014.133}, author = {Gottlieb, D J and Hek, K and Chen, T-H and Watson, N F and Eiriksdottir, G and Byrne, E M and Cornelis, M and Warby, S C and Bandinelli, S and Cherkas, L and Evans, D S and Grabe, H J and Lahti, J and Li, M and Lehtim{\"a}ki, T and Lumley, T and Marciante, K D and P{\'e}russe, L and Psaty, B M and Robbins, J and Tranah, G J and Vink, J M and Wilk, J B and Stafford, J M and Bellis, C and Biffar, R and Bouchard, C and Cade, B and Curhan, G C and Eriksson, J G and Ewert, R and Ferrucci, L and F{\"u}l{\"o}p, T and Gehrman, P R and Goodloe, R and Harris, T B and Heath, A C and Hernandez, D and Hofman, A and Hottenga, J-J and Hunter, D J and Jensen, M K and Johnson, A D and K{\"a}h{\"o}nen, M and Kao, L and Kraft, P and Larkin, E K and Lauderdale, D S and Luik, A I and Medici, M and Montgomery, G W and Palotie, A and Patel, S R and Pistis, G and Porcu, E and Quaye, L and Raitakari, O and Redline, S and Rimm, E B and Rotter, J I and Smith, A V and Spector, T D and Teumer, A and Uitterlinden, A G and Vohl, M-C and Widen, E and Willemsen, G and Young, T and Zhang, X and Liu, Y and Blangero, J and Boomsma, D I and Gudnason, V and Hu, F and Mangino, M and Martin, N G and O{\textquoteright}Connor, G T and Stone, K L and Tanaka, T and Viikari, J and Gharib, S A and Punjabi, N M and R{\"a}ikk{\"o}nen, K and V{\"o}lzke, H and Mignot, E and Tiemeier, H} }