@article {691, title = {Cardiovascular risk factors and venous thromboembolism incidence: the longitudinal investigation of thromboembolism etiology.}, journal = {Arch Intern Med}, volume = {162}, year = {2002}, month = {2002 May 27}, pages = {1182-9}, abstract = {

BACKGROUND: The association between traditional cardiovascular risk factors and risk of venous thromboembolism (VTE) has not been extensively examined in prospective studies.

METHODS: To determine whether atherosclerotic risk factors are also associated with increased incidence of VTE, we conducted a prospective study of 19 293 men and women without previous VTE in 6 US communities between 1987 and 1998.

RESULTS: There were 215 validated VTE events (1.45 per 1000 person-years) during a median of 8 years of follow-up. The age-adjusted hazard ratio was 1.4 (95\% confidence interval [CI], 1.1-1.9) for men vs women, 1.6 (95\% CI, 1.2-2.2) for blacks vs whites, and 1.7 (95\% CI, 1.5-2.0) per decade of age. Cigarette smoking, hypertension, dyslipidemia, physical inactivity, and alcohol consumption were not associated with risk of VTE. Age-, race-, and sex-adjusted hazard ratios for body mass index categories (calculated as the weight in kilograms divided by the height in meters squared) of less than 25, 25 to less than 30, 30 to less than 35, 35 to less than 40, and 40 or more were 1.0, 1.5, 2.2, 1.5, and 2.7, respectively (P<.001 for the trend). Diabetes was also associated with an increased risk of VTE (adjusted hazard ratio, 1.5 [95\% CI, 1.0-2.1]).

CONCLUSIONS: Our data showing no relationship of some arterial risk factors with VTE corroborate the view that the etiology of VTE differs from atherosclerotic cardiovascular disease. In addition, the findings suggest a hypothesis that avoidance of obesity and diabetes or vigilance in prophylaxis in patients with those conditions may prevent some venous thromboses.

}, keywords = {Aged, Arteriosclerosis, Female, Humans, Incidence, Male, Middle Aged, Multivariate Analysis, Proportional Hazards Models, Prospective Studies, Pulmonary Embolism, Risk Factors, United States, Venous Thrombosis}, issn = {0003-9926}, doi = {10.1001/archinte.162.10.1182}, author = {Tsai, Albert W and Cushman, Mary and Rosamond, Wayne D and Heckbert, Susan R and Polak, Joseph F and Folsom, Aaron R} } @article {684, title = {A prospective study of venous thromboembolism in relation to factor V Leiden and related factors.}, journal = {Blood}, volume = {99}, year = {2002}, month = {2002 Apr 15}, pages = {2720-5}, abstract = {

The aim of this study was to examine the occurrence of venous thromboembolism (VTE) in relation to factor V-related risk factors. Using a nested case-control design combining 2 population-based prospective studies, we measured factor V Leiden, HR2 haplotype, activated protein C (APC) resistance, and plasma factor V antigen in 335 participants who developed VTE during 8 years of follow-up and 688 controls. The overall odds ratio (OR) of VTE was 3.67 (95\% CI, 2.20-6.12) in participants carrying factor V Leiden compared with noncarriers. APC resistance measured after predilution with factor V-deficient plasma conferred an OR of 2.58 (95\% CI, 1.62-4.10). All 3 participants homozygous for the HR2 haplotype had a VTE, and the OR of VTE for homozygosity was estimated to be 5.5 (95\% CI, 2.45-12.5). Carriers of the HR2 haplotype otherwise were not at increased risk of VTE overall (OR = 1.05; 95\% CI, 0.64-1.72), but double heterozygotes for HR2 and factor V Leiden carried an OR of idiopathic VTE of 16.3 (95\% CI, 1.7-159) compared with noncarriers. Factor V antigen also was not associated with VTE overall, but for participants with the combination of high factor V antigen plus factor V Leiden the OR of idiopathic VTE was 11.5 (95\% CI, 4.2-31.4). In the general population, APC resistance and factor V Leiden were important VTE risk factors; homozygosity for the HR2 haplotype may be a risk factor but was rare; otherwise, HR2 haplotype and factor V antigen were not risk factors except in carriers of factor V Leiden.

}, keywords = {Activated Protein C Resistance, Aged, Cohort Studies, Continental Population Groups, Factor V, Genotype, Haplotypes, Humans, Incidence, Longitudinal Studies, Middle Aged, Odds Ratio, Prospective Studies, Risk Factors, Thromboembolism, Venous Thrombosis}, issn = {0006-4971}, doi = {10.1182/blood.v99.8.2720}, author = {Folsom, Aaron R and Cushman, Mary and Tsai, Michael Y and Aleksic, Nena and Heckbert, Susan R and Boland, Lori L and Tsai, Albert W and Yanez, N David and Rosamond, Wayne D} } @article {793, title = {Deep vein thrombosis and pulmonary embolism in two cohorts: the longitudinal investigation of thromboembolism etiology.}, journal = {Am J Med}, volume = {117}, year = {2004}, month = {2004 Jul 01}, pages = {19-25}, abstract = {

PURPOSE: To determine the incidence of deep vein thrombosis and pulmonary embolism in two cohorts representing regions of the United States.

METHODS: The sample comprised 21,680 participants of the Atherosclerosis Risk in Communities study and the Cardiovascular Health Study. Subjects were aged >/=45 years, resided in six communities, and were followed for 7.6 years. All hospitalizations were identified and thromboses were validated by chart review.

RESULTS: The age-standardized incidence of first-time venous thromboembolism was 1.92 per 1000 person-years. Rates were higher in men than women, and increased with age in both sexes. There was no antecedent trauma, surgery, immobilization, or diagnosis of cancer for 48\% (175/366) of events. The 28-day case-fatality rate was 11\% (29/265) after a first venous thromboembolism and 25\% (17/67) for cancer-associated thrombosis. The recurrence rate 2 years after a first venous thromboembolism was 7.7\% per year (95\% confidence interval [CI]: 4.5\% to 10.9\% per year). Cancer was the only factor independently associated with 28-day fatality (relative risk [RR] = 5.2; 95\% CI: 1.4 to 19.9) or recurrent thrombosis (RR = 9.2; 95\% CI: 2.0 to 41.7).

CONCLUSION: The incidence of venous thromboembolism in this cohort of middle- and older-aged subjects was similar to that observed in more geographically homogeneous samples. Half of cases were idiopathic. Short-term mortality and 2-year recurrence rates were appreciable, especially among subjects with cancer. Based on this study we estimate that 187,000 cases of first-time venous thromboembolism are diagnosed yearly in the United States among those aged 45 years or older.

}, keywords = {Aged, Case-Control Studies, Cohort Studies, Female, Follow-Up Studies, Humans, Incidence, Male, Middle Aged, Neoplasms, Population Surveillance, Pulmonary Embolism, Recurrence, Risk Factors, Survival Rate, Venous Thrombosis}, issn = {0002-9343}, doi = {10.1016/j.amjmed.2004.01.018}, author = {Cushman, Mary and Tsai, Albert W and White, Richard H and Heckbert, Susan R and Rosamond, Wayne D and Enright, Paul and Folsom, Aaron R} } @article {918, title = {Metabolic syndrome and cardiovascular disease in older people: The cardiovascular health study.}, journal = {J Am Geriatr Soc}, volume = {54}, year = {2006}, month = {2006 Sep}, pages = {1317-24}, abstract = {

OBJECTIVES: To assess the prospective association between metabolic syndrome (MetS) and cardiovascular disease (CVD) in older people and to evaluate the effect of lowering the threshold for impaired fasting glucose (IFG) on the prevalence of IFG and MetS and the risk of CVD.

DESIGN: Prospective cohort study.

SETTING: Four field centers in U.S. communities.

PARTICIPANTS: Three thousand five hundred eighty-five subjects in the Cardiovascular Health Study free of diabetes mellitus and CVD at baseline (mean age 72, 62\% female, 14\% black).

MEASUREMENTS: Baseline measures of MetS components and adjudicated incident CVD events. MetS (2001) was defined first using the original criteria from the Third Adult Treatment Panel Report of the National Cholesterol Education Program (> or =3 of the following: large waist circumference (women >88 cm, men >102 cm), elevated triglycerides (> or =1.70 mmol/L), low high-density lipoprotein cholesterol (men <1.04 mmol/L, women <1.30 mmol/L), elevated fasting glucose (6.1-6.9 mmol/L), and high blood pressure (> or =130/85 mmHg or self-reported use of medications for hypertension). Subjects were also classified according to the revised definition of the MetS (2005) that applies the lower threshold for fasting glucose (5.6-6.9 mmol/L).

RESULTS: During follow-up (median 11 years), 818 coronary heart disease (CHD), 401 stroke, and 554 congestive heart failure (CHF) events occurred. Age- and race-adjusted hazard ratios (HRs) for CHD, stroke, and CHF were 1.30 (95\% confidence interval (CI) = 1.07-1.57), 0.94 (95\% CI = 0.73-1.21), and 1.40 (95\% CI = 1.12-1.76) for women and 1.35 (95\% CI = 1.10-1.66), 1.51 (95\% CI = 1.08-2.12), and 1.47 (95\% CI = 1.14-1.90) for men, respectively. Overall, women and men with MetS (2005) were 20\% to 30\% more likely to experience any CVD event than subjects without MetS (2005). Using the lower cut-point for IFG resulted in a near tripling in IFG prevalence (16\% to 46\%) and an additional 9\% classified with MetS (2005) but HRs similar to those estimated from the original MetS (2001) criteria. High blood pressure was the component most strongly associated with incident CHD.

CONCLUSION: Results from this study of an elderly, population-based cohort provide support for earlier investigations in primarily middle-aged populations that link the presence of MetS with the development of CVD and further underscore the importance of recognizing and treating its individual components, particularly high blood pressure.

}, keywords = {African Americans, Age Factors, Aged, Aged, 80 and over, Blood Glucose, Cardiovascular Diseases, Cohort Studies, European Continental Ancestry Group, Fasting, Female, Humans, Incidence, Male, Metabolic Syndrome, Risk Factors, Sex Factors}, issn = {0002-8614}, doi = {10.1111/j.1532-5415.2006.00862.x}, author = {McNeill, Ann Marie and Katz, Ronit and Girman, Cynthia J and Rosamond, Wayne D and Wagenknecht, Lynne E and Barzilay, Joshua I and Tracy, Russell P and Savage, Peter J and Jackson, Sharon A} } @article {977, title = {Risk factors for intracerebral hemorrhage in a pooled prospective study.}, journal = {Stroke}, volume = {38}, year = {2007}, month = {2007 Oct}, pages = {2718-25}, abstract = {

BACKGROUND AND PURPOSE: Few prospective studies have reported risk factors for intracerebral hemorrhage (ICH), and results are inconsistent. We studied risk factors for ICH in a pooled cohort of the Atherosclerosis Risk in Communities Study (ARIC) and the Cardiovascular Health Study (CHS).

METHODS: The ARIC cohort was recruited in 1987 to 1989 and involves 15 792 men and women, aged 45 to 64 years at baseline, sampled from 4 US communities. The CHS cohort was recruited in 1989 to 1993 and involves 5888 men and women, aged 65 or over at baseline, sampled from 4 US communities. Baseline measurements included many potential vascular risk factors. The cohorts were followed for incident stroke events.

RESULTS: Over 263 489 person-years of follow-up, 135 incident ICH events occurred. In a multivariable model, age, African-American ethnicity (versus Whites), and hypertension were positively associated with incident ICH, whereas low-density lipoprotein cholesterol and triglycerides were inversely related to incident ICH. Participants with systolic blood pressure >or=160 mm Hg or diastolic blood pressure >/=110 mm Hg had 5.55 (95\% CI 3.07 to 10.0) times the rate of ICH as nonhypertensives. Sex, smoking, alcohol intake, body mass index, waist-to-hip ratio, waist circumference, and diabetes were not related to ICH.

CONCLUSIONS: In this pooled cohort the risk factors for ICH were older age, African-American ethnicity, hypertension, lower LDL-C, and lower triglycerides.

}, keywords = {African Americans, Age Distribution, Cerebral Hemorrhage, Cholesterol, LDL, Female, Follow-Up Studies, Humans, Hypertension, Incidence, Male, Middle Aged, Multivariate Analysis, Predictive Value of Tests, Prevalence, Prospective Studies, Risk Factors, Stroke, Triglycerides}, issn = {1524-4628}, doi = {10.1161/STROKEAHA.107.487090}, author = {Sturgeon, Jared D and Folsom, Aaron R and Longstreth, W T and Shahar, Eyal and Rosamond, Wayne D and Cushman, Mary} } @article {1040, title = {High-density lipoprotein cholesterol and venous thromboembolism in the Longitudinal Investigation of Thromboembolism Etiology (LITE).}, journal = {Blood}, volume = {112}, year = {2008}, month = {2008 Oct 01}, pages = {2675-80}, abstract = {

We determined prospectively the risk of venous thromboembolism (VTE) in relation to baseline high-density lipoprotein cholesterol (HDL-c) in 19 049 participants of the Longitudinal Investigation of Thromboembolism Etiology (LITE), which was composed of 14 490 participants of the Atherosclerosis Risk in Communities (ARIC) study and 4559 participants of the Cardiovascular Health Study (CHS). In addition, we determined the risk of VTE in relation to baseline subfractions of HDL (HDL(2) and HDL(3)) and apolipoprotein A-I (apoA-I) in 14 488 participants of the ARIC study. Age-adjusted incidence rates of VTE by HDL-c quartile ranged from 1.64 to 1.91 per 1000 person-years in men and 1.40 to 1.94 per 1000 person-years in women; however, there was no apparent trend of VTE incidence across HDL-c quartiles for either sex. The multivariate adjusted hazard ratios of VTE by HDL-c quartiles (with quartile 4 as the reference) were nonsignificant for both sexes and ranged between 0.91 and 0.99 for men and 0.78 and 1.22 for women. Results did not differ in separate evaluations of idiopathic and secondary VTE. In the ARIC study, there was no trend of VTE hazard ratios across quartiles of HDL(2), HDL(3), or apoA-I. Low HDL-c does not appear to be an important VTE risk factor.

}, keywords = {Aged, Apolipoprotein A-I, Cholesterol, HDL, Female, Humans, Incidence, Longitudinal Studies, Male, Middle Aged, Proportional Hazards Models, United States, Venous Thromboembolism}, issn = {1528-0020}, doi = {10.1182/blood-2008-05-157412}, author = {Chamberlain, Alanna M and Folsom, Aaron R and Heckbert, Susan R and Rosamond, Wayne D and Cushman, Mary} } @article {1197, title = {Association of genome-wide variation with the risk of incident heart failure in adults of European and African ancestry: a prospective meta-analysis from the cohorts for heart and aging research in genomic epidemiology (CHARGE) consortium.}, journal = {Circ Cardiovasc Genet}, volume = {3}, year = {2010}, month = {2010 Jun}, pages = {256-66}, abstract = {

BACKGROUND: Although genetic factors contribute to the onset of heart failure (HF), no large-scale genome-wide investigation of HF risk has been published to date. We have investigated the association of 2,478,304 single-nucleotide polymorphisms with incident HF by meta-analyzing data from 4 community-based prospective cohorts: the Atherosclerosis Risk in Communities Study, the Cardiovascular Health Study, the Framingham Heart Study, and the Rotterdam Study.

METHODS AND RESULTS: Eligible participants for these analyses were of European or African ancestry and free of clinical HF at baseline. Each study independently conducted genome-wide scans and imputed data to the approximately 2.5 million single-nucleotide polymorphisms in HapMap. Within each study, Cox proportional hazards regression models provided age- and sex-adjusted estimates of the association between each variant and time to incident HF. Fixed-effect meta-analyses combined results for each single-nucleotide polymorphism from the 4 cohorts to produce an overall association estimate and P value. A genome-wide significance P value threshold was set a priori at 5.0x10(-7). During a mean follow-up of 11.5 years, 2526 incident HF events (12\%) occurred in 20 926 European-ancestry participants. The meta-analysis identified a genome-wide significant locus at chromosomal position 15q22 (1.4x10(-8)), which was 58.8 kb from USP3. Among 2895 African-ancestry participants, 466 incident HF events (16\%) occurred during a mean follow-up of 13.7 years. One genome-wide significant locus was identified at 12q14 (6.7x10(-8)), which was 6.3 kb from LRIG3.

CONCLUSIONS: We identified 2 loci that were associated with incident HF and exceeded genome-wide significance. The findings merit replication in other community-based settings of incident HF.

}, keywords = {African Americans, Aged, Aged, 80 and over, Cohort Studies, Endopeptidases, European Continental Ancestry Group, Female, Genome-Wide Association Study, Heart Failure, Humans, Incidence, Male, Middle Aged, Polymorphism, Single Nucleotide, Risk, Ubiquitin-Specific Proteases}, issn = {1942-3268}, doi = {10.1161/CIRCGENETICS.109.895763}, author = {Smith, Nicholas L and Felix, Janine F and Morrison, Alanna C and Demissie, Serkalem and Glazer, Nicole L and Loehr, Laura R and Cupples, L Adrienne and Dehghan, Abbas and Lumley, Thomas and Rosamond, Wayne D and Lieb, Wolfgang and Rivadeneira, Fernando and Bis, Joshua C and Folsom, Aaron R and Benjamin, Emelia and Aulchenko, Yurii S and Haritunians, Talin and Couper, David and Murabito, Joanne and Wang, Ying A and Stricker, Bruno H and Gottdiener, John S and Chang, Patricia P and Wang, Thomas J and Rice, Kenneth M and Hofman, Albert and Heckbert, Susan R and Fox, Ervin R and O{\textquoteright}Donnell, Christopher J and Uitterlinden, Andr{\'e} G and Rotter, Jerome I and Willerson, James T and Levy, Daniel and van Duijn, Cornelia M and Psaty, Bruce M and Witteman, Jacqueline C M and Boerwinkle, Eric and Vasan, Ramachandran S} }