@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 {942, title = {Frailty and risk of venous thromboembolism in older adults.}, journal = {J Gerontol A Biol Sci Med Sci}, volume = {62}, year = {2007}, month = {2007 Jan}, pages = {79-82}, abstract = {

BACKGROUND: Frailty is a common risk factor for morbidity and mortality in elderly persons. Recent evidence links frailty to activation of coagulation and inflammatory pathways. We aimed to determine whether frailty in community-dwelling older adults is a risk factor for venous thromboembolism (VTE).

METHODS: We conducted a prospective cohort study in four U.S. communities involving 4859 participants 65 years old and older. At baseline, in 1989-1993, we assessed frailty based on weight loss, grip strength, feelings of exhaustion, walk time, and physical activity. Incident VTE (deep vein thrombosis or pulmonary embolus) through 2002 was identified by review of hospital records.

RESULTS: Fifty-two percent of the sample was classified as having intermediate or definite frailty. After adjustment for age, race, sex, body mass index, and diabetes, the relative risk of total VTE (n = 150) for people who were frail compared with no frailty was 1.31 (95\% confidence interval [CI], 0.93-1.84). The comparably adjusted relative risk for idiopathic VTE (n = 58) was 1.79 (95\% CI, 1.02-3.13).

CONCLUSIONS: The incidence rates of idiopathic VTE was higher in community-dwelling older adults with baseline frailty compared with no frailty. Further studies of the clotting process in frailty may allow the development of an improved strategy to determine VTE risk in this vulnerable subset of older adults.

}, keywords = {Age Factors, Aged, Aged, 80 and over, Female, Follow-Up Studies, Frail Elderly, Humans, Male, Morbidity, Motor Activity, Prospective Studies, Risk Factors, Thromboembolism, United States, Venous Thrombosis}, issn = {1079-5006}, doi = {10.1093/gerona/62.1.79}, author = {Folsom, Aaron R and Boland, Lori L and Cushman, Mary and Heckbert, Susan R and Rosamond, Wayne D and Walston, Jeremy D} } @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 {1036, title = {Hemostatic and inflammatory risk factors for intracerebral hemorrhage in a pooled cohort.}, journal = {Stroke}, volume = {39}, year = {2008}, month = {2008 Aug}, pages = {2268-73}, abstract = {

BACKGROUND AND PURPOSE: The purpose of this study was to identify novel risk factors for intracerebral hemorrhagic stroke (ICH).

METHODS: Risk factors were assessed at baseline in a pooled cohort of the Atherosclerosis Risk in Communities Study (ARIC) and the Cardiovascular Health Study (CHS) involving 21,680 adults aged 45 or over. Over 263,489 person-years of follow-up, we identified 135 incident ICH events.

RESULTS: In multivariable models, for each SD higher baseline level of fibrinogen, the relative rate of incident ICH increased 35\% (95\% CI, 17\% to 55\%). Fibrinogen was more strongly related to ICH in ARIC than in CHS. In multivariable models, those with von Willebrand factor levels above the median were 1.72 (95\% CI, 0.97 to 3.03) times more likely to have an incident ICH as those below the median. Factor VIII was significantly positively related to ICH in ARIC (relative rate per standard deviation of 1.31; 95\% CI, 1.07 to 1.62), but not in CHS. There was no relation in multivariable models between lipoprotein (a), Factor VII, white blood cell count, or C-reactive protein and ICH.

CONCLUSIONS: Greater plasma fibrinogen and, to some degree, von Willebrand factor were associated with increased rates of ICH in these prospective studies, whereas Factor VIII was related to ICH in younger ARIC study participants only.

}, keywords = {Age Distribution, Aged, Biomarkers, C-Reactive Protein, Cerebral Hemorrhage, Cohort Studies, Factor VIII, Female, Fibrinogen, Follow-Up Studies, Humans, Leukocyte Count, Lipoprotein(a), Male, Middle Aged, Multivariate Analysis, Prevalence, Risk Factors, Stroke, United States, Vasculitis, von Willebrand Factor}, issn = {1524-4628}, doi = {10.1161/STROKEAHA.107.505800}, author = {Sturgeon, Jared D and Folsom, Aaron R and Longstreth, W T and Shahar, Eyal and Rosamond, Wayne D and Cushman, Mary} } @article {1184, title = {Serum albumin and risk of venous thromboembolism.}, journal = {Thromb Haemost}, volume = {104}, year = {2010}, month = {2010 Jul}, pages = {100-4}, abstract = {

The incidence of venous thromboembolism (VTE) is increased in patients with albuminuria. However, whether a low serum albumin concentration is associated with increased risk of VTE has been a matter of controversy. We determined the association of serum albumin with VTE incidence in two large, prospective, population-based cohorts: the Atherosclerosis Risk in Communities (ARIC) Study (n = 15,300) and the Cardiovascular Health Study (CHS) (n = 5,400). Validated VTE occurrence (n = 462 in ARIC and n = 174 in CHS) was ascertained during follow-up. In both studies, after adjustment for age, sex, race, use of hormone replacement therapy, estimated glomerular filtration rate, history of cancer, and diabetes, serum albumin tended to be associated inversely with VTE. The adjusted hazard ratio per standard deviation lower albumin was 1.18 (95\% confidence interval [CI] = 1.08, 1.31) in ARIC and 1.10 (95\% CI = 0.94, 1.29) in CHS. The hazard ratio for albumin below (vs. above) the fifth percentile was 1.28 (95\% CI = 0.90, 1.84) in ARIC and 1.80 (95\% CI = 1.11, 2.93) in CHS. In conclusion, low serum albumin was a modest marker of increased VTE risk. The observed association likely does not reflect cause and effect, but rather that low serum albumin reflects a hyperinflammatory or hypercoagulable state. Whether this association has clinical relevance warrants further study.

}, keywords = {Aged, Biomarkers, Female, Follow-Up Studies, Humans, Incidence, Male, Middle Aged, Risk Factors, Serum Albumin, United States, Venous Thromboembolism}, issn = {2567-689X}, doi = {10.1160/TH09-12-0856}, author = {Folsom, Aaron R and Lutsey, Pamela L and Heckbert, Susan R and Cushman, Mary} } @article {1331, title = {Carotid intima-media thickness, electrocardiographic left ventricular hypertrophy, and incidence of intracerebral hemorrhage.}, journal = {Stroke}, volume = {42}, year = {2011}, month = {2011 Nov}, pages = {3075-9}, abstract = {

BACKGROUND AND PURPOSE: Carotid intima-media thickness and electrocardiographic left ventricular hypertrophy are 2 subclinical cardiovascular disease measures associated with increased risk of total and ischemic strokes. Increased intima-media thickness and electrocardiographic left ventricular hypertrophy also may reflect end-organ hypertensive effects. Information is scant on the associations of these subclinical measures with intracerebral hemorrhage (ICH). We hypothesized that greater carotid intima-media thickness and the presence of electrocardiographic left ventricular hypertrophy would be independently associated with increased ICH incidence.

METHODS: Among 18,155 participants initially free of stroke in the Atherosclerosis Risk in Communities Study (ARIC) and the Cardiovascular Health Study (CHS), we assessed carotid intima-media thickness, carotid plaque, and electrocardiographic left ventricular hypertrophy. Over a median of 18 years of follow-up, 162 incident ICH events occurred.

RESULTS: After adjustment for other ICH risk factors, carotid intima-media thickness was associated positively with incidence of ICH in both ARIC and CHS. The risk was lowest in study-specific Quartile 1, elevated 1.6- to 2.6-fold in Quartiles 2 to 3, and elevated 2.5 to 3.7-fold in Quartile 4 (P<0.05 for both studies). In CHS, having a carotid plaque was associated with a 2-fold (95\% CI, 1.1-3.4) greater ICH risk than having no plaque, but only 1.2-fold (95\% CI, 0.76-2.0) greater ICH risk in ARIC. Electrocardiographic left ventricular hypertrophy carried a hazard ratio of ICH of 1.7 (95\% CI, 0.77-3.7) in CHS and 2.8 (95\% CI, 1.2-6.4) in ARIC.

CONCLUSIONS: Our data suggest that people with carotid atherosclerosis and possibly left ventricular hypertrophy are at increased risk not only of ischemic stroke, but also of ICH.

}, keywords = {Carotid Intima-Media Thickness, Cerebral Hemorrhage, Cohort Studies, Electrocardiography, Female, Follow-Up Studies, Humans, Hypertrophy, Left Ventricular, Incidence, Male, Middle Aged, Prospective Studies, Risk Factors}, issn = {1524-4628}, doi = {10.1161/STROKEAHA.111.623157}, author = {Folsom, Aaron R and Yatsuya, Hiroshi and Psaty, Bruce M and Shahar, Eyal and Longstreth, W T} } @article {1295, title = {Longer legs are associated with greater risk of incident venous thromboembolism independent of total body height. The Longitudinal Study of Thromboembolism Etiology (LITE).}, journal = {Thromb Haemost}, volume = {106}, year = {2011}, month = {2011 Jul}, pages = {113-20}, abstract = {

Several studies have reported that taller individuals are at greater risk of venous thromboembolism (VTE). We hypothesised that longer leg length would be positively associated with incident VTE, and would explain the height association. LITE ascertained VTE in a prospective population-based sample of 21,860 individuals aged 45 and older. Leg length was measured as standing height minus torso length. Cox regression models were adjusted for age, race, sex, waist circumference, diabetes, and factor VIII. To evaluate whether leg length was associated with VTE risk independent of height, we standardised leg length and height per 1 standard deviation (SD), and then included them simultaneously in Cox regression models. A total of 641 incident VTE cases accrued over a median follow-up of 16 years. Participants in the highest quintile of leg length were at 59\% (95\% CI: 22\%-108\%) greater risk of VTE, relative to the lowest quintile. For height, risk was 45\% (12\%-88\%) greater for those in the highest quintile, compared to the lowest. When leg length and height were modelled simultaneously leg length remained associated with VTE risk (HR per 1 SD: 1.21 (1.04-1.40) while height was unrelated (HR per 1 SD: 1.00 (0.86-1.16). To conclude, participants with longer legs were at greater risk of incident VTE, and leg length explained the relation of height to VTE. It remains to be established whether this finding is due to greater venous surface area, a larger number of venous valves, or greater hydrostatic pressure among individuals with longer legs.

}, keywords = {Adult, Aged, Anthropometry, Body Height, Female, Follow-Up Studies, Humans, Leg, Male, Middle Aged, Population Groups, Prospective Studies, Risk Factors, United States, Venous Thromboembolism}, issn = {2567-689X}, doi = {10.1160/TH11-02-0100}, author = {Lutsey, Pamela L and Cushman, Mary and Heckbert, Susan R and Tang, Weihong and Folsom, Aaron R} } @article {6193, title = {Epidemiology and long-term clinical and biologic risk factors for pneumonia in community-dwelling older Americans: analysis of three cohorts.}, journal = {Chest}, volume = {144}, year = {2013}, month = {2013 Sep}, pages = {1008-1017}, abstract = {

BACKGROUND: Preventing pneumonia requires better understanding of incidence, mortality, and long-term clinical and biologic risk factors, particularly in younger individuals.

METHODS: This was a cohort study in three population-based cohorts of community-dwelling individuals. A derivation cohort (n = 16,260) was used to determine incidence and survival and develop a risk prediction model. The prediction model was validated in two cohorts (n = 8,495). The primary outcome was 10-year risk of pneumonia hospitalization.

RESULTS: The crude and age-adjusted incidences of pneumonia were 6.71 and 9.43 cases/1,000 person-years (10-year risk was 6.15\%). The 30-day and 1-year mortality were 16.5\% and 31.5\%. Although age was the most important risk factor (range of crude incidence rates, 1.69-39.13 cases/1,000 person-years for each 5-year increment from 45-85 years), 38\% of pneumonia cases occurred in adults \< 65 years of age. The 30-day and 1-year mortality were 12.5\% and 25.7\% in those \< 65 years of age. Although most comorbidities were associated with higher risk of pneumonia, reduced lung function was the most important risk factor (relative risk = 6.61 for severe reduction based on FEV1 by spirometry). A clinical risk prediction model based on age, smoking, and lung function predicted 10-year risk (area under curve [AUC] = 0.77 and Hosmer-Lemeshow [HL] C statistic = 0.12). Model discrimination and calibration were similar in the internal validation cohort (AUC = 0.77; HL C statistic, 0.65) but lower in the external validation cohort (AUC = 0.62; HL C statistic, 0.45). The model also calibrated well in blacks and younger adults. C-reactive protein and IL-6 were associated with higher pneumonia risk but did not improve model performance.

CONCLUSIONS: Pneumonia hospitalization is common and associated with high mortality, even in younger healthy adults. Long-term risk of pneumonia can be predicted in community-dwelling adults with a simple clinical risk prediction model.

}, keywords = {Age Factors, Aged, Aged, 80 and over, Community-Acquired Infections, Comorbidity, Female, Follow-Up Studies, Hospitalization, Humans, Incidence, Male, Middle Aged, Pneumonia, Prognosis, Prospective Studies, Risk Assessment, Risk Factors, Survival Rate, Time Factors}, issn = {1931-3543}, doi = {10.1378/chest.12-2818}, author = {Yende, Sachin and Alvarez, Karina and Loehr, Laura and Folsom, Aaron R and Newman, Anne B and Weissfeld, Lisa A and Wunderink, Richard G and Kritchevsky, Stephen B and Mukamal, Kenneth J and London, Stephanie J and Harris, Tamara B and Bauer, Doug C and Angus, Derek C} } @article {6572, title = {Incidence of and risk factors for sick sinus~syndrome in the general population.}, journal = {J Am Coll Cardiol}, volume = {64}, year = {2014}, month = {2014 Aug 12}, pages = {531-8}, abstract = {

BACKGROUND: Little is known about the incidence of and risk factors for sick sinus syndrome (SSS), a common indication for pacemaker implantation.

OBJECTIVES: This study sought to describe the epidemiology of SSS.

METHODS: This analysis included 20,572 participants (mean baseline age 59 years, 43\% male) in the ARIC (Atherosclerosis Risk In Communities) study and the CHS (Cardiovascular Health Study), who at baseline were free of prevalent atrial fibrillation and pacemaker therapy, had a heart rate of >= 50 beats/min unless using beta blockers, and were identified as of white or black race. Incident SSS cases were identified by hospital discharge International Classification of Disease-revision 9-Clinical Modification code 427.81 and validated by medical record review.

RESULTS: During an average 17 years of follow-up, 291 incident SSS cases were identified (unadjusted rate 0.8 per 1,000 person-years). Incidence increased with age (hazard ratio [HR]: 1.73; 95\% confidence interval [CI]: 1.47 to 2.05 per 5-year increment), and blacks had a 41\% lower risk of SSS than whites (HR: 0.59; 95\% CI: 0.37 to 0.98). Incident SSS was associated with greater baseline body mass index, height, N-terminal pro-B-type natriuretic peptide, and cystatin C, with longer QRS interval, with lower heart rate, and with prevalent hypertension, right bundle branch block, and cardiovascular disease. We project that the annual number of new SSS cases in the United States will increase from 78,000 in 2012 to 172,000 in 2060.

CONCLUSIONS: Blacks have a lower risk of SSS than whites, and several cardiovascular risk factors were associated with incident SSS. With the aging of the population, the number of Americans with SSS will increase dramatically over the next 50 years.

}, keywords = {African Continental Ancestry Group, Aged, Aged, 80 and over, Cohort Studies, European Continental Ancestry Group, Female, Follow-Up Studies, Humans, Incidence, Male, Middle Aged, Population Surveillance, Prospective Studies, Risk Factors, Sick Sinus Syndrome}, issn = {1558-3597}, doi = {10.1016/j.jacc.2014.03.056}, author = {Jensen, Paul N and Gronroos, Noelle N and Chen, Lin Y and Folsom, Aaron R and deFilippi, Chris and Heckbert, Susan R and Alonso, Alvaro} } @article {6577, title = {Whole-exome sequencing identifies rare and low-frequency coding variants associated with LDL cholesterol.}, journal = {Am J Hum Genet}, volume = {94}, year = {2014}, month = {2014 Feb 06}, pages = {233-45}, abstract = {

Elevated low-density lipoprotein cholesterol (LDL-C) is a treatable, heritable risk factor for cardiovascular disease. Genome-wide association studies (GWASs) have identified 157 variants associated with lipid levels but are not well suited to assess the impact of rare and low-frequency variants. To determine whether rare or low-frequency coding variants are associated with LDL-C, we exome sequenced 2,005 individuals, including 554 individuals selected for extreme LDL-C (>98(th) or <2(nd) percentile). Follow-up analyses included sequencing of 1,302 additional individuals and genotype-based analysis of 52,221 individuals. We observed significant evidence of association between LDL-C and the burden of rare or low-frequency variants in PNPLA5, encoding a phospholipase-domain-containing protein, and both known and previously unidentified variants in PCSK9, LDLR and APOB, three known lipid-related genes. The effect sizes for the burden of rare variants for each associated gene were substantially higher than those observed for individual SNPs identified from GWASs. We replicated the PNPLA5 signal in an independent large-scale sequencing study of 2,084 individuals. In conclusion, this large whole-exome-sequencing study for LDL-C identified a gene not known to be implicated in LDL-C and provides unique insight into the design and analysis of similar experiments.

}, keywords = {Adult, Aged, Apolipoproteins E, Cholesterol, LDL, Cohort Studies, Dyslipidemias, Exome, Female, Follow-Up Studies, Gene Frequency, Genetic Code, Genome-Wide Association Study, Genotype, Humans, Lipase, Male, Middle Aged, Phenotype, Polymorphism, Single Nucleotide, Proprotein Convertase 9, Proprotein Convertases, Receptors, LDL, Sequence Analysis, DNA, Serine Endopeptidases}, issn = {1537-6605}, doi = {10.1016/j.ajhg.2014.01.010}, author = {Lange, Leslie A and Hu, Youna and Zhang, He and Xue, Chenyi and Schmidt, Ellen M and Tang, Zheng-Zheng and Bizon, Chris and Lange, Ethan M and Smith, Joshua D and Turner, Emily H and Jun, Goo and Kang, Hyun Min and Peloso, Gina and Auer, Paul and Li, Kuo-Ping and Flannick, Jason and Zhang, Ji and Fuchsberger, Christian and Gaulton, Kyle and Lindgren, Cecilia and Locke, Adam and Manning, Alisa and Sim, Xueling and Rivas, Manuel A and Holmen, Oddgeir L and Gottesman, Omri and Lu, Yingchang and Ruderfer, Douglas and Stahl, Eli A and Duan, Qing and Li, Yun and Durda, Peter and Jiao, Shuo and Isaacs, Aaron and Hofman, Albert and Bis, Joshua C and Correa, Adolfo and Griswold, Michael E and Jakobsdottir, Johanna and Smith, Albert V and Schreiner, Pamela J and Feitosa, Mary F and Zhang, Qunyuan and Huffman, Jennifer E and Crosby, Jacy and Wassel, Christina L and Do, Ron and Franceschini, Nora and Martin, Lisa W and Robinson, Jennifer G and Assimes, Themistocles L and Crosslin, David R and Rosenthal, Elisabeth A and Tsai, Michael and Rieder, Mark J and Farlow, Deborah N and Folsom, Aaron R and Lumley, Thomas and Fox, Ervin R and Carlson, Christopher S and Peters, Ulrike and Jackson, Rebecca D and van Duijn, Cornelia M and Uitterlinden, Andr{\'e} G and Levy, Daniel and Rotter, Jerome I and Taylor, Herman A and Gudnason, Vilmundur and Siscovick, David S and Fornage, Myriam and Borecki, Ingrid B and Hayward, Caroline and Rudan, Igor and Chen, Y Eugene and Bottinger, Erwin P and Loos, Ruth J F and S{\ae}trom, P{\r a}l and Hveem, Kristian and Boehnke, Michael and Groop, Leif and McCarthy, Mark and Meitinger, Thomas and Ballantyne, Christie M and Gabriel, Stacey B and O{\textquoteright}Donnell, Christopher J and Post, Wendy S and North, Kari E and Reiner, Alexander P and Boerwinkle, Eric and Psaty, Bruce M and Altshuler, David and Kathiresan, Sekar and Lin, Dan-Yu and Jarvik, Gail P and Cupples, L Adrienne and Kooperberg, Charles and Wilson, James G and Nickerson, Deborah A and Abecasis, Goncalo R and Rich, Stephen S and Tracy, Russell P and Willer, Cristen J} } @article {6906, title = {Lifetime Risk of Venous Thromboembolism in Two Cohort Studies.}, journal = {Am J Med}, volume = {129}, year = {2016}, month = {2016 Mar}, pages = {339.e19-26}, abstract = {

BACKGROUND: Greater public awareness of venous thromboembolism may be an important next step for optimizing venous thromboembolism prevention and treatment. "Lifetime risk" is an easily interpretable way of presenting risk information. Therefore, we sought to calculate the lifetime risk of venous thromboembolism (deep vein thrombosis or pulmonary embolism) using data from 2 large, prospective cohort studies: the Cardiovascular Health Study (CHS) and the Atherosclerosis Risk in Communities (ARIC) study.

METHODS: We followed participants aged 45-64 years in ARIC (n = 14,185) and >=65 in CHS (n = 5414) at baseline visits (1987-1989 in ARIC, 1989-1990 and 1992-1993 in CHS) for incident venous thromboembolism (n = 728 in ARIC through 2011 and n = 172 in CHS through 2001). We estimated lifetime risks and 95\% confidence intervals of incident venous thromboembolism using a modified Kaplan-Meier method, accounting for the competing risk of death from other causes.

RESULTS: At age 45 years, the remaining lifetime risk of venous thromboembolism in ARIC was 8.1\% (95\% confidence interval, 7.1-8.7). High-risk groups were African Americans (11.5\% lifetime risk), those with obesity (10.9\%), heterozygous for the factor V Leiden (17.1\%), or with sickle cell trait or disease (18.2\%). Lifetime risk estimates differed by cohort; these differences were explained by differences in time period of venous thromboembolism ascertainment.

CONCLUSIONS: At least 1 in 12 middle-aged adults will develop venous thromboembolism in their remaining lifetime. This estimate of lifetime risk may be useful to promote awareness of venous thromboembolism and guide decisions at both clinical and policy levels.

}, keywords = {African Continental Ancestry Group, Aged, Anemia, Sickle Cell, Cohort Studies, Factor V, Follow-Up Studies, Heterozygote, Humans, Kaplan-Meier Estimate, Middle Aged, Obesity, Risk, Sickle Cell Trait, United States, Venous Thromboembolism}, issn = {1555-7162}, doi = {10.1016/j.amjmed.2015.10.014}, author = {Bell, Elizabeth J and Lutsey, Pamela L and Basu, Saonli and Cushman, Mary and Heckbert, Susan R and Lloyd-Jones, Donald M and Folsom, Aaron R} } @article {8402, title = {Lung function decline in former smokers and low-intensity current smokers: a secondary data analysis of the NHLBI Pooled Cohorts Study.}, journal = {Lancet Respir Med}, volume = {8}, year = {2020}, month = {2020 01}, pages = {34-44}, abstract = {

BACKGROUND: Former smokers now outnumber current smokers in many developed countries, and current smokers are smoking fewer cigarettes per day. Some data suggest that lung function decline normalises with smoking cessation; however, mechanistic studies suggest that lung function decline could continue. We hypothesised that former smokers and low-intensity current smokers have accelerated lung function decline compared with never-smokers, including among those without prevalent lung disease.

METHODS: We used data on six US population-based cohorts included in the NHLBI Pooled Cohort Study. We restricted the sample to participants with valid spirometry at two or more exams. Two cohorts recruited younger adults (>=17 years), two recruited middle-aged and older adults (>=45 years), and two recruited only elderly adults (>=65 years) with examinations done between 1983 and 2014. FEV decline in sustained former smokers and current smokers was compared to that of never-smokers by use of mixed models adjusted for sociodemographic and anthropometric factors. Differential FEV decline was also evaluated according to duration of smoking cessation and cumulative (number of pack-years) and current (number of cigarettes per day) cigarette consumption.

FINDINGS: 25 352 participants (ages 17-93 years) completed 70 228 valid spirometry exams. Over a median follow-up of 7 years (IQR 3-20), FEV decline at the median age (57 years) was 31{\textperiodcentered}01 mL per year (95\% CI 30{\textperiodcentered}66-31{\textperiodcentered}37) in sustained never-smokers, 34{\textperiodcentered}97 mL per year (34{\textperiodcentered}36-35{\textperiodcentered}57) in former smokers, and 39{\textperiodcentered}92 mL per year (38{\textperiodcentered}92-40{\textperiodcentered}92) in current smokers. With adjustment, former smokers showed an accelerated FEV decline of 1{\textperiodcentered}82 mL per year (95\% CI 1{\textperiodcentered}24-2{\textperiodcentered}40) compared to never-smokers, which was approximately 20\% of the effect estimate for current smokers (9{\textperiodcentered}21 mL per year; 95\% CI 8{\textperiodcentered}35-10{\textperiodcentered}08). Compared to never-smokers, accelerated FEV decline was observed in former smokers for decades after smoking cessation and in current smokers with low cumulative cigarette consumption (<10 pack-years). With respect to current cigarette consumption, the effect estimate for FEV decline in current smokers consuming less than five cigarettes per day (7{\textperiodcentered}65 mL per year; 95\% CI 6{\textperiodcentered}21-9{\textperiodcentered}09) was 68\% of that in current smokers consuming 30 or more cigarettes per day (11{\textperiodcentered}24 mL per year; 9{\textperiodcentered}86-12{\textperiodcentered}62), and around five times greater than in former smokers (1{\textperiodcentered}57 mL per year; 1{\textperiodcentered}00-2{\textperiodcentered}14). Among participants without prevalent lung disease, associations were attenuated but were consistent with the main results.

INTERPRETATION: Former smokers and low-intensity current smokers have accelerated lung function decline compared with never-smokers. These results suggest that all levels of smoking exposure are likely to be associated with lasting and progressive lung damage.

FUNDING: National Institutes of Health, National Heart Lung and Blood Institute, and US Environmental Protection Agency.

}, keywords = {Adult, Aged, Case-Control Studies, Ex-Smokers, Female, Follow-Up Studies, Humans, Lung, Male, Middle Aged, National Heart, Lung, and Blood Institute (U.S.), Non-Smokers, Respiratory Physiological Phenomena, Smokers, Smoking, Spirometry, United States, Young Adult}, issn = {2213-2619}, doi = {10.1016/S2213-2600(19)30276-0}, author = {Oelsner, Elizabeth C and Balte, Pallavi P and Bhatt, Surya P and Cassano, Patricia A and Couper, David and Folsom, Aaron R and Freedman, Neal D and Jacobs, David R and Kalhan, Ravi and Mathew, Amanda R and Kronmal, Richard A and Loehr, Laura R and London, Stephanie J and Newman, Anne B and O{\textquoteright}Connor, George T and Schwartz, Joseph E and Smith, Lewis J and White, Wendy B and Yende, Sachin} }