@article {689, title = {Calcium channel blocker use and gastrointestinal tract bleeding among older adults.}, journal = {Age Ageing}, volume = {31}, year = {2002}, month = {2002 May}, pages = {217-8}, keywords = {Aged, Antihypertensive Agents, Calcium Channel Blockers, Gastrointestinal Hemorrhage, Geriatric Assessment, Health Services for the Aged, Humans, Hypertension, Prospective Studies, Risk Factors}, issn = {0002-0729}, doi = {10.1093/ageing/31.3.217}, author = {Kaplan, Robert C and Heckbert, Susan R and Koepsell, Thomas D and Rosendaal, Frits R and Furberg, Curt D and Cooper, Lawton S and Psaty, Bruce M} } @article {697, title = {Cardiovascular disease risk status in elderly persons with renal insufficiency.}, journal = {Kidney Int}, volume = {62}, year = {2002}, month = {2002 Sep}, pages = {997-1004}, abstract = {

BACKGROUND: Renal insufficiency has been independently associated with incident cardiovascular disease events in some, but not all, prospective studies. We determined the prevalence of elevated cardiovascular disease risk status among elderly persons with renal insufficiency.

METHODS: This study is a cross-sectional analysis using data collected at the baseline visit of the Cardiovascular Health Study, which enrolled 5888 community dwelling adults aged 65 years or older from four clinical centers in the United States. Renal insufficiency was defined as a serum creatinine level > or =1.3 mg/dL in women and > or =1.5 mg/dL in men. The outcomes of this study included prevalent cardiovascular disease [prior coronary heart disease (CHD) or stroke], subclinical cardiovascular disease (abnormal values of ankle-arm index, carotid ultrasound, and echocardiography) and elevated cardiovascular risk based upon a diagnosis of diabetes and the Framingham equations. The association between renal insufficiency and cardiovascular risk status was estimated with and without adjustment for other cardiovascular predictors.

RESULTS: Among the 5808 participants with creatinine levels measured at entry, 15.9\% of men (N = 394), and 7.6\% of women (N = 254) had renal insufficiency. The prevalence of either clinical or subclinical cardiovascular disease was 64\% in persons with renal insufficiency compared with 43\% in those without it [odds ratio (OR) 2.34; 95\% confidence interval (95\% CI), 1.96, 2.80]. After adjustment for other cardiovascular risk factors, renal insufficiency remained significantly associated with clinical and subclinical cardiovascular disease (adjusted OR 1.43; 95\% CI, 1.18, 1.75), but the magnitude of association was substantially reduced. After combining clinical and subclinical cardiovascular disease, diabetes, and an estimated risk>20\% by the Framingham equations, 78\% of men and 61\% of women with renal insufficiency had elevated cardiovascular risk status.

CONCLUSIONS: Renal insufficiency is a marker for elevated cardiovascular disease risk in community dwelling elderly adults.

}, keywords = {Age Distribution, Aged, Cholesterol, HDL, Cholesterol, LDL, Coronary Disease, Creatinine, Cross-Sectional Studies, Female, Humans, Kidney Failure, Chronic, Male, Prevalence, Prospective Studies, Risk Factors}, issn = {0085-2538}, doi = {10.1046/j.1523-1755.2002.00522.x}, author = {Shlipak, Michael G and Fried, Linda F and Crump, Casey and Bleyer, Anthony J and Manolio, Teri A and Tracy, Russell P and Furberg, Curt D and Psaty, Bruce M} } @article {703, title = {Incidence, manifestations, and predictors of brain infarcts defined by serial cranial magnetic resonance imaging in the elderly: the Cardiovascular Health Study.}, journal = {Stroke}, volume = {33}, year = {2002}, month = {2002 Oct}, pages = {2376-82}, abstract = {

BACKGROUND AND PURPOSE: MRI-defined infarcts are common in the elderly. We sought to explore incidence, manifestations, and predictors of such infarcts.

METHODS: The Cardiovascular Health Study (CHS) is a population-based, longitudinal study of 5888 people aged > or =65 years. Participants have had extensive baseline and follow-up evaluations; 1433 participants underwent 2 MRI scans separated by 5 years and had no infarcts on initial MRI.

RESULTS: On follow-up MRI, 254 participants (17.7\%) had 1 or more infarcts. Most were single (75.6\%), subcortical (79.9\%), and small (3 to 20 mm in 87.0\%). Only 11.4\% of those with infarcts experienced a documented transient ischemic attack or stroke between the scans. Although participants were similar at initial MRI, those with MRI-defined infarcts on follow-up experienced greater decline than those without infarcts on the Modified Mini-Mental State Examination and Digit-Symbol Substitution test (both P<0.01). Severity of white matter changes on initial MRI was the strongest predictor of incident infarcts. When it was excluded from stepwise multivariable models, predictors were serum creatinine, age, and ankle-arm index.

CONCLUSIONS: Incident MRI-defined infarcts commonly affect the elderly. Most are small, subcortical, and not associated with acute symptoms recognized as a transient ischemic attack or stroke. Nonetheless, they cannot be considered silent because of their association with subtle cognitive deficits. These covert infarcts are associated with white matter changes, which may share a common pathophysiology. Whether control of vascular risk factors, such as blood pressure, would reduce the risk of developing these infarcts and associated cognitive decline deserves further investigation.

}, keywords = {Aged, Brain Infarction, California, Cohort Studies, Creatinine, Follow-Up Studies, Humans, Incidence, Longitudinal Studies, Magnetic Resonance Imaging, Maryland, Multivariate Analysis, Neuropsychological Tests, North Carolina, Odds Ratio, Pennsylvania, Predictive Value of Tests, Risk Factors}, issn = {1524-4628}, doi = {10.1161/01.str.0000032241.58727.49}, author = {Longstreth, W T and Dulberg, Corinne and Manolio, Teri A and Lewis, Michael R and Beauchamp, Norman J and O{\textquoteright}Leary, Daniel and Carr, Jeff and Furberg, Curt D} } @article {705, title = {Outcome of congestive heart failure in elderly persons: influence of left ventricular systolic function. The Cardiovascular Health Study.}, journal = {Ann Intern Med}, volume = {137}, year = {2002}, month = {2002 Oct 15}, pages = {631-9}, abstract = {

BACKGROUND: Most persons with congestive heart failure are elderly, and many elderly persons with congestive heart failure have normal left ventricular systolic function.

OBJECTIVE: To evaluate the relationship between left ventricular systolic function and outcome of congestive heart failure in elderly persons.

DESIGN: Population-based longitudinal study of coronary heart disease and stroke.

SETTING: Four U.S. sites: Forsyth County, North Carolina; Sacramento County, California; Allegheny County, Pennsylvania; and Washington County, Maryland.

PARTICIPANTS: 5888 persons who were at least 65 years of age and were recruited from the community.

MEASUREMENTS: Total mortality and cardiovascular morbidity and mortality.

RESULTS: Of 5532 participants, 269 (4.9\%) had congestive heart failure. Among these, left ventricular function was normal in 63\%, borderline decreased in 15\%, and overtly impaired in 22\%. The mortality rate was 25 deaths per 1000 person-years in the reference group (no congestive heart failure and normal left ventricular function at baseline); 154 deaths per 1000 person-years in participants with congestive heart failure and impaired left ventricular systolic function; 87 and 115 deaths per 1000 person-years in participants with congestive heart failure and normal or borderline systolic function, respectively; and 89 deaths per 1000 person-years in persons with impaired left ventricular function but no congestive heart failure. Although the risk for death from congestive heart failure was lower in persons with normal systolic function than in those with impaired function, more deaths were associated with normal systolic function because more persons with heart failure fall into this category.

CONCLUSIONS: Community-dwelling elderly persons, especially those with impaired left ventricular function, have a substantial risk for death from congestive heart failure. However, more deaths occur from heart failure in persons with normal systolic function because left ventricular function is more often normal than impaired in elderly persons with heart failure.

}, keywords = {Aged, Cause of Death, Echocardiography, Female, Heart Failure, Humans, Longitudinal Studies, Male, Myocardial Infarction, Prevalence, Prognosis, Risk Factors, Stroke, Ventricular Dysfunction, Right, Ventricular Function, Left}, issn = {1539-3704}, doi = {10.7326/0003-4819-137-8-200210150-00006}, author = {Gottdiener, John S and McClelland, Robyn L and Marshall, Robert and Shemanski, Lynn and Furberg, Curt D and Kitzman, Dalane W and Cushman, Mary and Polak, Joseph and Gardin, Julius M and Gersh, Bernard J and Aurigemma, Gerard P and Manolio, Teri A} } @article {708, title = {Time trends in high blood pressure control and the use of antihypertensive medications in older adults: the Cardiovascular Health Study.}, journal = {Arch Intern Med}, volume = {162}, year = {2002}, month = {2002 Nov 11}, pages = {2325-32}, abstract = {

BACKGROUND: Control of high blood pressure (BP) in older adults is an important part of public health efforts at prevention.

OBJECTIVE: To assess recent time trends in the awareness, treatment, and control of high BP and in the use of medications to treat high BP.

METHODS: In the Cardiovascular Health Study, 5888 adults 65 years and older were recruited from 4 US centers. At baseline, participants underwent an extensive examination that included the measurement of BP, use of medications, and other risk factors. Participants were followed up with annual visits that assessed BP and medication use from baseline in 1989-1990 through the examination in 1998-1999. The primary outcome measures were control of BP to levels lower than than 140/90 mm Hg and the prevalence of use of various classes of antihypertensive medications.

RESULTS: The awareness, treatment, and control of high BP improved during the 1990s. The proportions aware and treated were higher among blacks than whites, though control prevalences were similar. For both groups combined, the control of high BP to lower than 140/90 mm Hg increased from 37\% at baseline to 49\% in 1999. The 51\% whose BP was not controlled generally had isolated mild to moderate elevations in systolic BP. Among treated persons, the improvement in control was achieved in part by a mean increase of 0.2 antihypertensive medications per person over the course of 9 years. Improved control was also achieved by increasing the proportion of the entire Cardiovascular Health Study population that was treated for hypertension, from 34.5\% in 1990 to 51.1\% in 1999. Time trends in antihypertensive drug use were pronounced. Among those without coronary disease, the use of low-dose diuretics and beta-blockers decreased, while the use of newer agents, such as calcium channel blockers, angiotensin-converting enzyme inhibitors, and alpha-blockers increased.

CONCLUSIONS: While control of high BP improved in the 1990s, about half the participants with hypertension had uncontrolled BP, primarily mild to moderate elevations in systolic BP. Low-dose diuretics and beta-blockers--the preferred agents since 1993 according to the recommendations of the Joint National Committee on the Detection, Evaluation and Treatment of High Blood Pressure--remained underused. More widespread use of these agents will be an important intervention to prevent the devastating complications of hypertension, including stroke, myocardial infarction, and heart failure.

}, keywords = {Age Factors, Aged, Antihypertensive Agents, Awareness, Cohort Studies, Drug Therapy, Female, Health Knowledge, Attitudes, Practice, Humans, Hypertension, Male, Prospective Studies, Time Factors}, issn = {0003-9926}, doi = {10.1001/archinte.162.20.2325}, author = {Psaty, Bruce M and Manolio, Teri A and Smith, Nicholas L and Heckbert, Susan R and Gottdiener, John S and Burke, Gregory L and Weissfeld, Joel and Enright, Paul and Lumley, Thomas and Powe, Neil and Furberg, Curt D} } @article {719, title = {Elevations of inflammatory and procoagulant biomarkers in elderly persons with renal insufficiency.}, journal = {Circulation}, volume = {107}, year = {2003}, month = {2003 Jan 07}, pages = {87-92}, abstract = {

BACKGROUND: Renal insufficiency has been associated with cardiovascular disease events and mortality in several prospective studies, but the mechanisms for the elevated risk are not clear. Little is known about the association of renal insufficiency with inflammatory and procoagulant markers, which are potential mediators for the cardiovascular risk of kidney disease.

METHODS AND RESULTS: The cross-sectional association of renal insufficiency with 8 inflammatory and procoagulant factors was evaluated using baseline data from the Cardiovascular Health Study, a population-based cohort study of 5888 subjects aged > or =65 years. C-reactive protein, fibrinogen, factor VIIc, and factor VIIIc levels were measured in nearly all participants; interleukin-6, intercellular adhesion molecule-1, plasmin-antiplasmin complex, and D-dimer levels were measured in nearly half of participants. Renal insufficiency was defined as a serum creatinine level > or =1.3 mg/dL in women and > or =1.5 mg/dL in men. Multivariate linear regression was used to compare adjusted mean levels of each biomarker in persons with and without renal insufficiency after adjustment for other baseline characteristics. Renal insufficiency was present in 647 (11\%) of Cardiovascular Health Study participants. After adjustment for baseline differences, levels of C-reactive protein, fibrinogen, interleukin-6, factor VIIc, factor VIIIc, plasmin-antiplasmin complex, and D-dimer were significantly greater among persons with renal insufficiency (P<0.001). In participants with clinical, subclinical, and no cardiovascular disease at baseline, the positive associations of renal insufficiency with these inflammatory and procoagulant markers were similar.

CONCLUSION: Renal insufficiency was independently associated with elevations in inflammatory and procoagulant biomarkers. These pathways may be important mediators leading to the increased cardiovascular risk of persons with kidney disease.

}, keywords = {Aged, alpha-2-Antiplasmin, Biomarkers, Blood Coagulation Factors, C-Reactive Protein, Cardiovascular Diseases, Cohort Studies, Creatinine, Cross-Sectional Studies, Female, Fibrin Fibrinogen Degradation Products, Fibrinogen, Fibrinolysin, Humans, Inflammation, Interleukin-6, Male, Prospective Studies, Renal Insufficiency, Risk Factors}, issn = {1524-4539}, doi = {10.1161/01.cir.0000042700.48769.59}, author = {Shlipak, Michael G and Fried, Linda F and Crump, Casey and Bleyer, Anthony J and Manolio, Teri A and Tracy, Russell P and Furberg, Curt D and Psaty, Bruce M} } @article {803, title = {The association between lipid levels and the risks of incident myocardial infarction, stroke, and total mortality: The Cardiovascular Health Study.}, journal = {J Am Geriatr Soc}, volume = {52}, year = {2004}, month = {2004 Oct}, pages = {1639-47}, abstract = {

OBJECTIVES: To assess the association between lipid levels and cardiovascular events in older adults.

DESIGN: A prospective population-based study.

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

PARTICIPANTS: A total of 5,201 adults aged 65 and older living in U.S. communities, plus a recruitment of 687 African Americans 3 years later.

MEASUREMENTS: Fasting lipid measures included low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), total cholesterol, and triglycerides.

RESULTS: At baseline, 1,954 men and 2,931 women were at risk for an incident myocardial infarction (MI) or stroke. During an average 7.5-year follow-up, 436 subjects had a coronary event, 332 had an ischemic stroke, 104 a hemorrhagic stroke, and 1,096 died. After adjustment, lipid measures were not major predictors of the outcomes of MI, ischemic stroke, hemorrhagic stroke, and total mortality. For total cholesterol and LDL-C, the associations with MI and ischemic stroke were only marginally significant. HDL-C was inversely associated with MI risk (hazard ratio=0.85 per standard deviation of 15.7 mg/dL, 95\% confidence interval=0.76-0.96). For the outcome of ischemic stroke, high levels of HDL-C were associated with a decreased risk in men but not women. Lipid measures were generally only weakly associated with the risks of hemorrhagic stroke or total mortality.

CONCLUSION: In this population-based study of older adults, most lipid measures were weakly associated with cardiovascular events. The association between low HDL-C and increased MI risk was nonetheless strong and consistent.

}, keywords = {African Americans, African Continental Ancestry Group, Aged, Female, Health Surveys, Humans, Incidence, Lipids, Male, Mortality, Myocardial Infarction, Population Surveillance, Prospective Studies, Risk Factors, Stroke, United States}, issn = {0002-8614}, doi = {10.1111/j.1532-5415.2004.52455.x}, author = {Psaty, Bruce M and Anderson, Melissa and Kronmal, Richard A and Tracy, Russell P and Orchard, Trevor and Fried, Linda P and Lumley, Thomas and Robbins, John and Burke, Greg and Newman, Anne B and Furberg, Curt D} } @article {780, title = {Medications and cardiovascular health in older adults: room for improvement in prevention and treatment.}, journal = {Am J Geriatr Cardiol}, volume = {13}, year = {2004}, month = {2004 May-Jun}, pages = {161-7}, keywords = {Aged, Antihypertensive Agents, Atrial Fibrillation, Cardiovascular Diseases, Diabetes Mellitus, Health Knowledge, Attitudes, Practice, Heart Failure, Humans, Hyperlipidemias, Hypertension, Hypolipidemic Agents, Risk Factors}, issn = {1076-7460}, doi = {10.1111/j.1076-7460.2004.02124.x}, author = {Rhoads, Caroline S and Psaty, Bruce M and Olson, Jean L and Furberg, Curt D} } @article {804, title = {Risk of congestive heart failure in an elderly population treated with peripheral alpha-1 antagonists.}, journal = {J Am Geriatr Soc}, volume = {52}, year = {2004}, month = {2004 Oct}, pages = {1648-54}, abstract = {

OBJECTIVES: To compare the risk of congestive heart failure (CHF) in elderly individuals treated with any peripheral alpha-1 antagonist for hypertension with any thiazide, test whether the risk persists in subjects without cardiovascular disease (CVD) at baseline, and examine CHF risk in normotensive men with prostatism treated with alpha antagonists.

DESIGN: Prospective cohort study.

SETTING: Four U.S. sites: Washington County, Maryland; Allegheny County, Pennsylvania; Sacramento County, California; and Forsyth County, North Carolina.

PARTICIPANTS: A total of 5,888 community-dwelling subjects aged 65 and older.

MEASUREMENTS: Adjudicated incident CHF.

RESULTS: The 3,105 participants with treated hypertension were at risk for CHF; 22\% of men and 8\% of women took alpha antagonists during follow-up. The age-adjusted risk of CHF in those receiving monotherapy treated with alpha antagonists was 1.90 (95\% confidence interval=1.03-3.50) compared with thiazides. In subjects without CVD at baseline receiving monotherapy, women taking an alpha antagonist had a 3.6 times greater age-adjusted risk of CHF, whereas men had no difference in risk. Adjustment for systolic blood pressure attenuated statistical differences in risk. There were 930 men without hypertension at risk for CHF; 5\% used alpha antagonists during follow-up, with no observed increase in CHF risk.

CONCLUSION: Subjects receiving alpha antagonist monotherapy for hypertension had a two to three times greater risk of incident CHF, also seen in lower-risk subjects, but differences in blood pressure control partly explained this.

}, keywords = {Adrenergic alpha-Antagonists, Aged, Antihypertensive Agents, Benzothiadiazines, Blood Pressure, Cohort Studies, Diuretics, Female, Heart Failure, Humans, Hypertension, Male, Risk Factors, Sodium Chloride Symporter Inhibitors, United States}, issn = {0002-8614}, doi = {10.1111/j.1532-5415.2004.52456.x}, author = {Bryson, Chris L and Smith, Nicholas L and Kuller, Lewis H and Chaves, Paulo H M and Manolio, Teri A and Lewis, William and Boyko, Edward J and Furberg, Curt D and Psaty, Bruce M} } @article {856, title = {Association of beta-blocker use with mortality among patients with congestive heart failure in the Cardiovascular Health Study (CHS).}, journal = {Am Heart J}, volume = {150}, year = {2005}, month = {2005 Sep}, pages = {464-70}, abstract = {

BACKGROUND: In clinical trials, beta-blocker therapy reduces all-cause mortality among people with congestive heart failure (CHF) characterized by depressed systolic function, but few trials included large numbers of elderly participants. This study assessed the association between beta-blocker therapy and mortality among community-dwelling older adults with CHF.

METHODS: The Cardiovascular Health Study (CHS) is a longitudinal, population-based study of adults aged > or = 65 years. Recruitment began in 1989 with follow-up extending through June 2000 or death. Cox proportional hazard regression models were used to assess the association between beta-blocker therapy and all-cause mortality among 950 participants who developed new-onset CHF.

RESULTS: beta-Blocker users (n = 157) were more likely than nonusers (n = 793) to have treated hypertension, clinical coronary artery disease, and valvular disease at the time of CHF diagnosis. Death occurred in 67 users and 446 nonusers during a median follow-up of 2.3 years. Compared with nonuse, use of beta-blockers was associated with a multivariable adjusted hazard ratio (HR) of 0.74 (95\% CI 0.56-0.98) for all-cause mortality. Among the 520 participants who had left ventricular ejection fraction assessed within 90 days after CHF diagnosis, the risk for all cause mortality associated with beta-blocker use did not differ significantly between those with ejection fraction of < 40\% and those with ejection fraction of > or = 40\% (HR 0.56, 95\% CI 0.27-1.13; HR 0.82, 95\% CI 0.56-1.22, respectively; interaction P = .34).

CONCLUSIONS: This observational study suggests that beta-blocker treatment is associated with a reduced risk of all-cause mortality among community-dwelling older adults with CHF.

}, keywords = {Adrenergic beta-Antagonists, Age Factors, Aged, Aged, 80 and over, Female, Follow-Up Studies, Heart Failure, Humans, Male}, issn = {1097-6744}, doi = {10.1016/j.ahj.2004.12.022}, author = {Chan, Jeannie D and Rea, Thomas D and Smith, Nicholas L and Siscovick, David and Heckbert, Susan R and Lumley, Thomas and Chaves, Paulo and Furberg, Curt D and Kuller, Lewis and Psaty, Bruce M} } @article {812, title = {Incidence, manifestations, and predictors of worsening white matter on serial cranial magnetic resonance imaging in the elderly: the Cardiovascular Health Study.}, journal = {Stroke}, volume = {36}, year = {2005}, month = {2005 Jan}, pages = {56-61}, abstract = {

BACKGROUND AND PURPOSE: Magnetic resonance imaging (MRI) scans in the elderly commonly show white matter findings that may raise concerns. We sought to document incidence, manifestations, and predictors of worsening white matter grade on serial imaging.

METHODS: The Cardiovascular Health Study is a population-based, longitudinal study of 5888 people aged 65 years and older, of whom 1919 have had extensive initial and follow-up evaluations, including 2 MRI scans separated by 5 years. Scans were read without clinical information in standard side-by-side fashion to determine worsening white matter grade.

RESULTS: Worsening was evident in 538 participants (28\%), mostly (85\%) by 1 grade. Although similar at initial scan, participants with worsening white matter grade, compared with those without, experienced greater decline on modified Mini-Mental State examination and Digit-Symbol Substitution test (both P< or =0.001) after controlling for potential confounding factors, including occurrence of transient ischemic attack or stroke between scans. Independent predictors of worsening white matter grade included cigarette smoking before initial scan and infarct on initial scan. Otherwise, predictors differed according to white matter grade on initial scan. For low initial grade, increased age, increased diastolic blood pressure, increased high-density lipoprotein cholesterol, and decreased low-density lipoprotein cholesterol were associated with increased risk of worsening. For high initial grade, any cardiovascular disease and low ankle-arm index were associated with decreased risk of worsening, whereas use of diuretics and statins were associated with increased risk.

CONCLUSIONS: Worsening white matter grade on serial MRI scans in elderly is common, is associated with cognitive decline, and has complex relations with cardiovascular risk factors.

}, keywords = {Aged, Brain, Cardiovascular Diseases, Cognition Disorders, Female, Humans, Incidence, Leukoaraiosis, Longitudinal Studies, Magnetic Resonance Imaging, Male, Risk Factors, Stroke}, issn = {1524-4628}, doi = {10.1161/01.STR.0000149625.99732.69}, author = {Longstreth, W T and Arnold, Alice M and Beauchamp, Norman J and Manolio, Teri A and Lefkowitz, David and Jungreis, Charles and Hirsch, Calvin H and O{\textquoteright}Leary, Daniel H and Furberg, Curt D} } @article {868, title = {Weight loss, muscle strength, and angiotensin-converting enzyme inhibitors in older adults with congestive heart failure or hypertension.}, journal = {J Am Geriatr Soc}, volume = {53}, year = {2005}, month = {2005 Nov}, pages = {1996-2000}, abstract = {

OBJECTIVES: To determine whether angiotensin-converting enzyme (ACE) inhibitor use may be associated with weight maintenance and sustained muscle strength (measured by grip strength) in older adults.

DESIGN: Data from the Cardiovascular Health Study (CHS), a community-based prospective cohort study of 5,888 older adults, were used.

SETTING: Subjects were recruited from four U.S. sites beginning in 1989; this analysis included data through 2001.

PARTICIPANTS: CHS participants with congestive heart failure (CHF) or treated hypertension.

MEASUREMENTS: The exposure, current ACE inhibitor use, was ascertained by medication inventory at annual clinic visits; the outcomes were weight change and grip-strength change during the following year. Multivariate linear regression was used, accounting for correlations between observations on the same participant over time.

RESULTS: The average annual weight change was -0.38 kg in 2,834 participants (14,443 person-years) with treated hypertension and -0.62 kg in 342 participants (980 person-years) with CHF. ACE inhibitor use was associated with less annual weight loss after adjustment for potential confounders: a difference of 0.17 kg (95\% confidence interval (CI)=0.05-0.29) in those with treated hypertension and 0.29 kg (95\% CI=-0.25-0.83) in those with CHF. There was no evidence of association between ACE inhibitor use and grip-strength change.

CONCLUSION: ACE inhibitor use may be associated with weight maintenance, but not maintenance of muscle strength, in older adults with treated hypertension.

}, keywords = {Aged, Aged, 80 and over, Angiotensin-Converting Enzyme Inhibitors, Female, Hand Strength, Heart Failure, Humans, Hypertension, Male, Multivariate Analysis, Outcome Assessment, Health Care, Prospective Studies, Statistics as Topic, United States, Weight Loss}, issn = {0002-8614}, doi = {10.1111/j.1532-5415.2005.53568.x}, author = {Schellenbaum, Gina D and Smith, Nicholas L and Heckbert, Susan R and Lumley, Thomas and Rea, Thomas D and Furberg, Curt D and Lyles, Mary F and Psaty, Bruce M} } @article {896, title = {Characteristics and baseline clinical predictors of future fatal versus nonfatal coronary heart disease events in older adults: the Cardiovascular Health Study.}, journal = {Circulation}, volume = {113}, year = {2006}, month = {2006 May 09}, pages = {2177-85}, abstract = {

BACKGROUND: Although >80\% of annual coronary heart disease (CHD) deaths occur in adults aged >65 years and the population is aging rapidly, CHD event fatality and its predictors in the elderly have not been well described.

METHODS AND RESULTS: The first myocardial infarction (MI) or CHD death among the 5888 adults aged > or =65 years occurring during enrollment in the Cardiovascular Health Study during 1989-2001 was identified and adjudicated. Characteristics measured at examinations before the event were examined for associations with case fatality (death before hospitalization or hospital discharge) and for differences in predictors by demographics or clinical history. During a median follow-up of 8.2 years, 985 CHD events occurred, of which 30\% were fatal. Case fatality decreased slightly over time, ranging from 28\% to 30\% per year in the early 1990s versus 23\% by 2000-2001; with adjustment for age at MI and gender, there was a 6\% lower odds of fatality with each successive year (odds ratio [OR], 0.94; 95\% confidence interval [CI], 0.90 to 0.98). Case fatality was similar by race and gender but higher with age and prior CHD (MI, angina, or revascularization). When considered alone, many subclinical disease measures, such as common carotid intima-media thickness, ankle-arm index, left ventricular mass by ECG, and a major ECG abnormality, and traditional risk factors, such as diabetes and hypertension, were associated with fatality. In multivariable analysis, independent predictors of fatality were prior congestive heart failure (OR, 3.20; 95\% CI, 2.32 to 4.41), prior CHD rather than only history of MI (OR, 2.51; 95\% CI, 1.84 to 3.43), diabetes (OR, 1.66; 95\% CI, 1.10 to 2.31), and age (OR, 1.21 per 5 years; 95\% CI, 1.07 to 1.37), adjusted for gender and each other. Prior congestive heart failure, regardless of left ventricular systolic function, age, gender, or prior CHD, conferred a > or =3-fold increased risk of fatality in almost all subgroups.

CONCLUSIONS: Among community-dwelling older adults, CHD case fatality remains substantial, with easily identifiable risk factors that may be different from those that predict incident disease. In the elderly in whom the risk/benefit of therapies may be influenced by multiple competing comorbidities and care needs, risk stratification possibly may be improved further by focusing more aggressive care on specific patients, especially those with a history of congestive heart failure or prior CHD.

}, keywords = {Age Factors, Aged, Aged, 80 and over, Carotid Artery, Common, Cohort Studies, Comorbidity, Coronary Disease, Diabetes Mellitus, Electrocardiography, Female, Follow-Up Studies, Forecasting, Heart Failure, Heart Ventricles, Hospitalization, Humans, Hyperlipidemias, Hypertension, Male, Multivariate Analysis, Myocardial Infarction, Organ Size, Predictive Value of Tests, Risk Factors, Sampling Studies, Tunica Intima, Tunica Media, United States}, issn = {1524-4539}, doi = {10.1161/CIRCULATIONAHA.105.610352}, author = {Pearte, Camille A and Furberg, Curt D and O{\textquoteright}Meara, Ellen S and Psaty, Bruce M and Kuller, Lewis and Powe, Neil R and Manolio, Teri} } @article {887, title = {Comparison of mortality risk for electrocardiographic abnormalities in men and women with and without coronary heart disease (from the Cardiovascular Health Study).}, journal = {Am J Cardiol}, volume = {97}, year = {2006}, month = {2006 Feb 01}, pages = {309-15}, abstract = {

Mortality risk associated with electrocardiographic (ECG) abnormalities has been commonly reported to be lower in women than in men. We compared coronary heart disease (CHD) and all-cause mortality risk for ECG variables during a mean 9.1-year follow-up in 4,912 participants in the Cardiovascular Health Study who were > or = 65 years of age. The hypothesis was that mortality risk for ECG abnormalities is not lower in women than in men. Five ECG variables were significant mortality predictors in Cox regression models that were adjusted for demographic, clinical, and medication variables. Gender differences were significant and mortality risk was higher in women for ECG estimates of left ventricular mass for both end points and for nondipolar QRS voltage for all-cause mortality. When evaluated simultaneously in multiple ECG variable risk models in subgroups that were stratified by baseline CHD status, no gender difference was significant. In the latter models, ST depression was a strong predictor of CHD mortality in groups with and without previous CHD. Other significant ECG predictors were previous myocardial infarction in the previous CHD group and nondipolar QRS voltage in the CHD-free group. Four ECG abnormalities were significant predictors of all-cause mortality in the CHD-free group, with risk increases of 18\% to 50\%. The risk of all-cause mortality in the previous CHD group was significantly increased for ST depression (by 64\%), the ECG estimate of left ventricular mass (by 48\%), and previous myocardial infarction (by 34\%). In conclusion, we found no evidence that the relative risk of mortality for ECG abnormalities is lower in women than in men.

}, keywords = {Aged, Coronary Disease, Electrocardiography, Female, Humans, Male, Risk}, issn = {0002-9149}, doi = {10.1016/j.amjcard.2005.08.046}, author = {Rautaharju, Pentti M and Ge, Sijian and Nelson, Jennifer C and Marino Larsen, Emily K and Psaty, Bruce M and Furberg, Curt D and Zhang, Zhu-Ming and Robbins, John and Gottdiener, John S and Chaves, Paulo H M} } @article {939, title = {Alcohol consumption and risk and prognosis of atrial fibrillation among older adults: the Cardiovascular Health Study.}, journal = {Am Heart J}, volume = {153}, year = {2007}, month = {2007 Feb}, pages = {260-6}, abstract = {

BACKGROUND: The relationship of alcohol consumption with risk of atrial fibrillation (AF) is inconsistent in previous studies, and its relationship with prognosis of AF is undetermined.

METHODS: As part of the Cardiovascular Health Study, a population-based cohort of adults 65 years and older from 4 US communities, 5609 participants reported their use of beer, wine, and spirits yearly. We identified cases of AF with routine study electrocardiograms and validated discharge diagnoses from hospitalizations.

RESULTS: A total of 1232 cases of AF were documented during a mean of 9.1 years of follow-up. Compared with long-term abstainers, the multivariable-adjusted hazard ratios were 1.25 (95\% CI, 1.02-1.54) among former drinkers, 1.09 (95\% CI, 0.94-1.28) among consumers of less than 1 drink per week, 1.00 (95\% CI, 0.84-1.19) among consumers of 1 to 6 drinks per week, 1.06 (95\% CI, 0.82-1.37) among consumers of 7 to 13 drinks per week, and 1.09 (95\% CI, 0.88-1.37) among consumers of 14 or more drinks per week (P trend = 0.64). In analyses of mortality among participants with AF, the hazard ratios were 1.27 (95\% CI, 1.06-1.52) among former drinkers, 0.94 (95\% CI, 0.76-1.18) among consumers of less than 1 drink per week, 0.98 (95\% CI, 0.78-1.23) among consumers of 1 to 6 drinks per week, 0.73 (95\% CI, 0.51-1.03) among consumers of 7 to 13 drinks per week, and 0.81 (95\% CI, 0.59-1.11) among consumers of 14 or more drinks per week (P trend = 0.12).

CONCLUSIONS: Current moderate alcohol consumption is not associated with risk of AF or with risk of death after diagnosis of AF, but former drinking identifies individuals at higher risk.

}, keywords = {Aged, Alcohol Drinking, Atrial Fibrillation, Female, Follow-Up Studies, Humans, Incidence, Longitudinal Studies, Male, Prognosis, Risk Factors}, issn = {1097-6744}, doi = {10.1016/j.ahj.2006.10.039}, author = {Mukamal, Kenneth J and Psaty, Bruce M and Rautaharju, Pentti M and Furberg, Curt D and Kuller, Lewis H and Mittleman, Murray A and Gottdiener, John S and Siscovick, David S} } @article {1022, title = {Distribution and correlates of lipoprotein-associated phospholipase A2 in an elderly cohort: the Cardiovascular Health Study.}, journal = {J Am Geriatr Soc}, volume = {56}, year = {2008}, month = {2008 May}, pages = {792-9}, abstract = {

OBJECTIVES: To determine whether high levels of lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) are associated with prevalent cardiovascular disease (CVD) and to evaluate factors most influencing Lp-PLA(2) levels in a community-based cohort of older adults.

DESIGN: Cross-sectional.

SETTING: The Cardiovascular Health Study (CHS), a population-based cohort study of men and women aged 65 and older.

PARTICIPANTS: Five thousand five hundred thirty-one CHS participants.

MEASUREMENTS: Levels of Lp-PLA(2) activity were determined using stored blood samples from the baseline examination.

RESULTS: Mean Lp-PLA(2) was higher in participants with electrocardiographically determined ventricular conduction defect and major Q-wave abnormality and was positively correlated with left ventricular (LV) mass. It was high in those with echocardiographically determined abnormal LV ejection fraction, which persisted after adjustment. Mean Lp-PLA(2) was also higher in participants with mild renal insufficiency and kidney disease. After multivariable adjustment, there was a modest but significant 27\% greater risk of prevalent CHF per standard deviation increment of Lp-PLA(2) and a modest but significant 12\% greater risk of prevalent myocardial infarction. Lp-PLA(2) was weakly but mainly most strongly correlated with cholesterol and lipoproteins, but those correlations were not especially strong. Lp-PLA(2) was weakly positively correlated with soluble intercellular adhesion molecule-1 but not interleukin-6. In total, all factors considered could explain only 29\% of Lp-PLA(2) activity.

CONCLUSION: Novel findings in the study are the associations, in those aged 65 and older, between Lp-PLA(2) activity and LV dysfunction, CHF, and renal disease. CVD risk factors only minimally explain levels of Lp-PLA(2).

}, keywords = {1-Alkyl-2-acetylglycerophosphocholine Esterase, Aged, Atherosclerosis, Body Mass Index, Cardiac Output, Low, Cardiovascular Diseases, Cholesterol, HDL, Cholesterol, LDL, Cohort Studies, Cross-Sectional Studies, Electrocardiography, Female, Heart Failure, Humans, Hypertrophy, Left Ventricular, Long QT Syndrome, Male, Reference Values, Renal Insufficiency, Risk Factors, Statistics as Topic, Triglycerides}, issn = {1532-5415}, doi = {10.1111/j.1532-5415.2008.01667.x}, author = {Furberg, Curt D and Nelson, Jeanenne J and Solomon, Cam and Cushman, Mary and Jenny, Nancy Swords and Psaty, Bruce M} } @article {1023, title = {Lipoprotein-associated phospholipase A2 and risk of venous thrombosis in older adults.}, journal = {Am J Hematol}, volume = {83}, year = {2008}, month = {2008 Jul}, pages = {524-7}, abstract = {

Lipoprotein-associated phospholipase A2 (Lp-PLA2) is an enzyme involved in inflammation and platelet function. Inherited deficiency and elevated levels are associated with atherosclerosis. Given potential common etiologies of atherosclerosis and venous thrombosis (VT), we hypothesized that low and high Lp-PLA2 would be associated with VT risk. Lp-PLA(2) mass and activity were measured in baseline samples of Cardiovascular Health Study participants (5,888 men and women age > or =65), excluding 354 reporting pre-baseline VT. The study endpoint was VT unrelated to cancer after 11.6 years follow-up. Hazard ratios were estimated using Cox proportional hazard models, adjusting for age, race, sex, and body-mass index. With 129 cases of VT, there was no association of Lp-PLA2 activity with risk. Adjusted hazard ratios were 1.19 (CI 0.62, 2.29) and 0.87 (CI 0.43, 1.76) for the lowest and highest decile, respectively, compared to the 10-25th percentile. Corresponding hazard ratios for Lp-PLA2 mass were 1.63 (CI 0.79, 3.34) and 1.33 (CI 0.61, 2.87). Results were robust to several definitions of low or high Lp-PLA2. While the association of Lp-PLA(2) levels with arterial disease events implies a role for this enzyme in atherogenesis, our findings suggest that it is not prothrombotic.

}, keywords = {1-Alkyl-2-acetylglycerophosphocholine Esterase, Aged, Female, Humans, Male, Risk Factors, Venous Thrombosis}, issn = {1096-8652}, doi = {10.1002/ajh.21182}, author = {Olson, Nels and O{\textquoteright}Meara, Ellen S and Jenny, Nancy S and Folsom, Aaron R and Bovill, Edwin G and Furberg, Curt D and Heckbert, Susan R and Psaty, Bruce M and Cushman, Mary} } @article {1045, title = {Physical activity and incidence of atrial fibrillation in older adults: the cardiovascular health study.}, journal = {Circulation}, volume = {118}, year = {2008}, month = {2008 Aug 19}, pages = {800-7}, abstract = {

BACKGROUND: Vigorous exertion and endurance training have been reported to increase atrial fibrillation (AF). Associations of habitual light or moderate activity with AF incidence have not been evaluated.

METHODS AND RESULTS: We prospectively investigated associations of leisure-time activity, exercise intensity, and walking habits, assessed at baseline and updated during follow-up visits, with incident AF, diagnosed by annual 12-lead ECGs and hospital discharge records, from 1989 to 2001 among 5446 adults > or =65 years of age in the Cardiovascular Health Study. During 47 280 person-years of follow-up, 1061 new AF cases occurred (incidence 22.4/1000 person-years). In multivariable-adjusted analyses, leisure-time activity was associated with lower AF incidence in a graded manner, with 25\% (hazard ratio [HR] 0.75, 95\% confidence interval [CI] 0.61 to 0.90), 22\% (HR 0.78, 95\% CI 0.65 to 0.95), and 36\% (HR 0.64, 95\% CI 0.52 to 0.79) lower risk in quintiles 3, 4, and 5 versus quintile 1 (P for trend <0.001). Exercise intensity had a U-shaped relationship with AF (quadratic P=0.02): Versus no exercise, AF incidence was lower with moderate-intensity exercise (HR 0.72, 95\% CI 0.58 to 0.89) but not with high-intensity exercise (HR 0.87, 95\% CI 0.64 to 1.19). Walking distance and pace were each associated with lower AF risk in a graded manner (P for trend <0.001); when we assessed the combined effects of distance and pace, individuals in quartiles 2, 3, and 4 had 25\% (HR 0.75, 95\% CI 0.56 to 0.99), 32\% (HR 0.68, 95\% CI 0.50 to 0.92), and 44\% (HR 0.56, 95\% CI 0.38 to 0.82) lower AF incidence than individuals in quartile 1. Findings appeared unrelated to confounding by comorbidity or indication. After evaluation of cut points of moderate leisure-time activity (approximately 600 kcal/week), walking distance (12 blocks per week), and pace (2 mph), 26\% of all new AF cases (95\% CI 7\% to 43\%) appeared attributable to absence of these activities.

CONCLUSIONS: Light to moderate physical activities, particularly leisure-time activity and walking, are associated with significantly lower AF incidence in older adults.

}, keywords = {Aged, Aged, 80 and over, Atrial Fibrillation, Exercise, Female, Humans, Incidence, Leisure Activities, Male, Motor Activity, Prospective Studies, Walking}, issn = {1524-4539}, doi = {10.1161/CIRCULATIONAHA.108.785626}, author = {Mozaffarian, Dariush and Furberg, Curt D and Psaty, Bruce M and Siscovick, David} } @article {1066, title = {Prevalence, prognosis, and implications of isolated minor nonspecific ST-segment and T-wave abnormalities in older adults: Cardiovascular Health Study.}, journal = {Circulation}, volume = {118}, year = {2008}, month = {2008 Dec 16}, pages = {2790-6}, abstract = {

BACKGROUND: The prevalence and prognostic significance of isolated minor nonspecific ST-segment and T-wave abnormalities (NSSTTAs) in older adults are poorly understood.

METHODS AND RESULTS: Cardiovascular Health Study participants free of both clinical cardiovascular disease and major ECG abnormalities were included. We examined the prospective association of isolated minor NSSTTAs (defined by Minnesota Codes 4-3, 4-4, 5-3, and 5-4) with total, cardiovascular, and coronary mortality and incident nonfatal myocardial infarction. Among 3224 participants (61.9\% women; mean age, 72 years), 233 (7.2\%) had isolated NSSTTAs at baseline. Covariates associated with isolated NSSTTAs included older age, nonwhite race (20.5\% of blacks versus 4.8\% of whites; P<0.001), diabetes, and higher blood pressure and body mass index but not the presence of subclinical cardiovascular disease. After 39 518 person-years of follow-up, the presence of isolated NSSTTAs was associated with significantly increased risk for coronary heart disease mortality (multivariable-adjusted hazards ratio, 1.76; 95\% CI, 1.18 to 2.61) but not with incident nonfatal myocardial infarction (multivariable-adjusted hazards ratio, 0.71; 95\% CI, 0.43 to 1.17). The association of isolated NSSTTAs with coronary death was independent of subclinical atherosclerosis and left ventricular mass measures. In secondary analyses, among those with cardiac death, there was a significantly higher rate of primary arrhythmic death (32.3\% versus 15.4\%; P=0.02) in participants with isolated NSSTTAs versus those without NSSTTAs.

CONCLUSIONS: Isolated NSSTTAs are common in older Americans and are associated with significantly increased risk for coronary death. However, isolated NSSTTAs are not associated with incident nonfatal myocardial infarction, suggesting that they are associated particularly with increased risk for primary arrhythmic death.

}, keywords = {Age Factors, Aged, Arrhythmias, Cardiac, Cardiovascular Diseases, Cohort Studies, Electrocardiography, Female, Health Status, Humans, Male, Middle Aged, Prevalence, Prognosis, Prospective Studies}, issn = {1524-4539}, doi = {10.1161/CIRCULATIONAHA.108.772541}, author = {Kumar, Anita and Prineas, Ronald J and Arnold, Alice M and Psaty, Bruce M and Furberg, Curt D and Robbins, John and Lloyd-Jones, Donald M} } @article {1133, title = {Lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) and risk of cardiovascular disease in older adults: results from the Cardiovascular Health Study.}, journal = {Atherosclerosis}, volume = {209}, year = {2010}, month = {2010 Apr}, pages = {528-32}, abstract = {

OBJECTIVE: To examine associations between lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) antigen level (mass) and enzymatic activity (activity) and cardiovascular disease (CVD) in older adults.

METHODS: We examined associations of Lp-PLA(2) mass and activity with incident myocardial infarction (MI; n=508), stroke (n=565) and CVD death (n=665) using Cox regressions adjusted for age, sex, ethnicity and CVD risk factors in 3949 older adults, aged > or =65 years at baseline, from the Cardiovascular Health Study (CHS).

RESULTS: Lp-PLA(2) was associated with incident CVD events in these older adults. Hazard ratios (95\% confidence intervals) for highest versus lowest tertiles of Lp-PLA(2) mass were 1.49 (1.19-1.85) for MI, 1.21 (0.98-1.49) for stroke and 1.11 (0.92-1.33) for CVD death. The highest tertile of Lp-PLA(2) activity was associated with MI (1.36; 1.09-1.70) and CVD death (1.23; 1.02-1.50). Combined Lp-PLA(2) tertile 3 and CRP>3mg/l, compared to Lp-PLA(2) tertile 1 and CRP<1mg/l, was associated with MI (2.29; 1.49-3.52) for Lp-PLA(2) mass and MI (1.66; 1.10-2.51) and CVD death (1.57; 1.08-2.26) for activity. For MI, both mass and activity added excess risk to elevated CRP alone ( approximately 20\% excess risk) and activity added excess risk for CVD death ( approximately 12\%).

CONCLUSION: Lp-PLA(2) mass and activity were associated with incident CVD events in older adults in CHS. Lp-PLA(2) and CRP were independent and additive in prediction of events. While associations were modest, these results support further exploration of Lp-PLA(2) to identify older individuals at risk for CVD.

}, keywords = {1-Alkyl-2-acetylglycerophosphocholine Esterase, Aged, C-Reactive Protein, Cardiovascular Diseases, Female, Humans, Myocardial Infarction, Population Surveillance, Prospective Studies, Risk, Stroke}, issn = {1879-1484}, doi = {10.1016/j.atherosclerosis.2009.09.021}, author = {Jenny, Nancy Swords and Solomon, Cam and Cushman, Mary and Tracy, Russell P and Nelson, Jeanenne J and Psaty, Bruce M and Furberg, Curt D} } @article {1285, title = {Mineral metabolism markers and the long-term risk of hip fracture: the cardiovascular health study.}, journal = {J Clin Endocrinol Metab}, volume = {96}, year = {2011}, month = {2011 Jul}, pages = {2186-93}, abstract = {

CONTEXT: Disturbances in mineral metabolism are associated with lower bone mineral density and fracture; however, previous human studies have assessed individual mineral metabolism markers in isolation.

OBJECTIVE: We assessed serum concentrations of 25-hydroxyvitamin D (25-OHD), PTH, and bone-specific alkaline phosphatase (BAP) concentrations individually, and in combination, in association with the long-term risk of hip fracture among a general population of older adults.

DESIGN AND SETTING: We studied 2294 participants from the Cardiovascular Health Study (mean age 74 yr) who were ambulatory and free of hip fracture and known cardiovascular disease at baseline. We used proportional hazards models to evaluate associations of baseline serum 25-OHD, PTH, and BAP concentrations with the time to first hospitalized hip fracture.

RESULTS: During a median of 13 yr of follow-up, 242 participants (10.6\%) developed an incident hip fracture. Serum 25-OHD concentrations less than 15 ng/ml were associated with a 61\% greater adjusted risk of fracture (95\% confidence interval 12-132\% greater). In contrast, neither serum PTH nor BAP concentrations were significantly associated with fracture risk. The association of 25-OHD deficiency with hip fracture was not significantly altered by either PTH or BAP concentrations.

CONCLUSIONS: Serum concentrations of 25-OHD, but not PTH or BAP, are associated with long-term hip fracture risk among ambulatory older adults. These data suggest that 25-OHD is the most relevant mineral metabolism marker of fracture risk among older people.

}, keywords = {Aged, Aged, 80 and over, Alkaline Phosphatase, Biomarkers, Bone Density, Female, Hip Fractures, Humans, Male, Parathyroid Hormone, Risk, Vitamin D}, issn = {1945-7197}, doi = {10.1210/jc.2010-2878}, author = {Robinson-Cohen, Cassianne and Katz, Ronit and Hoofnagle, Andrew N and Cauley, Jane A and Furberg, Curt D and Robbins, John A and Chen, Zhao and Siscovick, David S and de Boer, Ian H and Kestenbaum, Bryan} } @article {6996, title = {Lipoprotein-Associated Phospholipase A2 and Incident Peripheral Arterial Disease in Older Adults: The Cardiovascular Health Study.}, journal = {Arterioscler Thromb Vasc Biol}, volume = {36}, year = {2016}, month = {2016 Apr}, pages = {750-6}, abstract = {

OBJECTIVE: Although prior studies report a relationship between elevated lipoprotein-associated phospholipase A2 (Lp-PLA2) and incident cardiovascular disease, the prospective association of Lp-PLA2 with incident peripheral arterial disease (PAD) has not been studied. We investigated the association between Lp-PLA2 mass and activity and the risk of developing clinical PAD and low ankle-brachial index (ABI).

APPROACH AND RESULTS: Among Cardiovascular Health Study participants, a population-based cohort of 5888 adults aged >=65 years enrolled in 1989 to 1990, Lp-PLA2 mass and activity were measured in 4537 individuals without baseline PAD. Clinical PAD, defined as leg artery revascularization or diagnosed claudication, was ascertained through 2011. Incident low ABI, defined as ABI <0.9 and decline of >=0.15, was assessed among 3537 individuals who had an ABI >0.9 at baseline and a second ABI measurement 3 or 6 years later. Analyses were adjusted for demographics, cholesterol, smoking, comorbidities, and C-reactive protein. Each standard deviation increment in Lp-PLA2 mass (117 ng/mL) was associated with a higher risk of developing clinical PAD (hazard ratio 1.28; 95\% confidence interval 1.13, 1.45) and incident low ABI (odds ratio 1.16; 95\% confidence interval 1.00, 1.33). Results per standard deviation increment in Lp-PLA2 activity (13 nmol/min per mL) were similar for clinical PAD (hazard ratio 1.24; 95\% confidence interval 1.07, 1.44) and low ABI (odds ratio 1.28; 95\% confidence interval 1.09, 1.50).

CONCLUSIONS: Higher Lp-PLA2 mass and activity were associated with development of both incident clinical PAD and low ABI. Future studies are needed to determine whether pharmacological inhibition of Lp-PLA2 reduces the incidence of PAD.

}, keywords = {1-Alkyl-2-acetylglycerophosphocholine Esterase, Age Factors, Aged, Aging, Ankle Brachial Index, Biomarkers, Chi-Square Distribution, Female, Humans, Incidence, Inflammation Mediators, Logistic Models, Male, Odds Ratio, Peripheral Arterial Disease, Prognosis, Proportional Hazards Models, Risk Assessment, Risk Factors, Time Factors, United States, Up-Regulation}, issn = {1524-4636}, doi = {10.1161/ATVBAHA.115.306647}, author = {Garg, Parveen K and Arnold, Alice M and Hinckley Stukovsky, Karen D and Koro, Carol and Jenny, Nancy S and Mukamal, Kenneth J and Criqui, Michael H and Furberg, Curt D and Newman, Anne B and Cushman, Mary} }