@article {759, title = {Lp(a) lipoprotein, vascular disease, and mortality in the elderly.}, journal = {N Engl J Med}, volume = {349}, year = {2003}, month = {2003 Nov 27}, pages = {2108-15}, abstract = {

BACKGROUND: As compared with what is known about predictors of vascular events in middle-aged persons, less is known about these events in the elderly. Lp(a) lipoprotein, which plays an important part in atherothrombogenesis, has been associated with an increased risk of vascular disease. We investigated this relation among older U.S. adults.

METHODS: In a prospective study of 5888 community-dwelling older adults (65 years of age or older) in the United States, 2375 women and 1597 men who were free of vascular disease provided base-line serum samples for analysis for levels of Lp(a) lipoprotein. These 3972 subjects were followed for a median of 7.4 years to evaluate the development of stroke and to track deaths from vascular causes and all causes. The men and women were divided into quintile groups according to the Lp(a) lipoprotein level at base line.

RESULTS: Using Cox proportional-hazards models, we determined the risk associated with each quintile level of Lp(a) lipoprotein, with the lowest quintile serving as the reference group. As compared with those in the lowest quintile, men in the highest quintile had three times the unadjusted risk of stroke (relative risk, 3.00; 95 percent confidence interval, 1.59 to 5.65), almost three times the risk of death associated with vascular events (relative risk, 2.54; 95 percent confidence interval, 1.59 to 4.08), and nearly twice the risk of death from all causes (relative risk, 1.76; 95 percent confidence interval, 1.31 to 2.36). Adjustment for age; sex; the levels of total cholesterol, low-density lipoprotein cholesterol, and triglycerides; carotid-wall thickness; smoking status; the presence or absence of diabetes and systolic and diastolic hypertension; body-mass index; and other traditional risk factors had little effect on the final assessments. Similar analyses for women, which also included adjustment for estrogen use or nonuse, revealed no such relation.

CONCLUSIONS: Among older adults in the United States, an elevated level of Lp(a) lipoprotein is an independent predictor of stroke, death from vascular disease, and death from any cause in men but not in women. These data support the use of Lp(a) lipoprotein levels in predicting the risk of these events in older men.

}, keywords = {Aged, Coronary Disease, Female, Humans, Incidence, Lipoprotein(a), Male, Mortality, Proportional Hazards Models, Prospective Studies, Risk Factors, Sex Factors, Stroke, Survival Analysis, United States, Vascular Diseases}, issn = {1533-4406}, doi = {10.1056/NEJMoa001066}, author = {Ariyo, Abraham A and Thach, Chau and Tracy, Russell} } @article {826, title = {Cardiovascular risk factors for retinal vein occlusion and arteriolar emboli: the Atherosclerosis Risk in Communities \& Cardiovascular Health studies.}, journal = {Ophthalmology}, volume = {112}, year = {2005}, month = {2005 Apr}, pages = {540-7}, abstract = {

OBJECTIVE: To examine the associations of retinal vein occlusion and arteriolar emboli with cardiovascular disease.

DESIGN: Population-based cross-sectional study.

PARTICIPANTS: Pooled from the Atherosclerosis Risk in Communities Study (n = 12,642; mean age, 60 years) and the Cardiovascular Health Study (n = 2824; mean age, 79 years).

METHODS: Retinal vein occlusion and arteriolar emboli were identified from a single nonmydriatic retinal photograph using a standardized protocol. Photographs were also graded for arteriovenous nicking and focal arteriolar narrowing. All participants had a comprehensive systemic evaluation, including standardized carotid ultrasonography.

MAIN OUTCOME MEASURES: Retinal vein occlusion and arteriolar emboli.

RESULTS: Prevalences of retinal vein occlusion and arteriolar emboli were 0.3\% (n = 39 cases) and 0.2\% (n = 34 cases), respectively. After adjusting for age, retinal vein occlusion was associated with hypertension (odds ratio [OR], 2.96; 95\% confidence interval [CI], 1.43-6.14), systolic blood pressure (BP) (OR, 4.12; 95\% CI, 1.40-12.16; highest quartile vs. lowest), diastolic BP (OR, 2.64; 95\% CI, 1.07-6.46; highest quartile vs. lowest), carotid artery plaque (OR, 5.62; 95\% CI, 2.60-12.16), body mass index (OR, 3.88; 95\% CI, 1.23-12.18; highest quartile vs. lowest), plasma fibrinogen (OR, 3.29; 95\% CI, 1.08-10.02; highest quartile vs. lowest), arteriovenous nicking (OR, 4.09; 95\% CI, 2.00-8.36), and focal arteriolar narrowing (OR, 5.17; 95\% CI, 2.59-10.29). After adjusting for age, retinal arteriolar emboli were associated with hypertension (OR, 3.14; 95\% CI, 1.44-6.84), systolic BP (OR, 3.46; 95\% CI, 1.13-10.65; highest quartile vs. lowest), prevalent coronary heart disease (OR, 2.33; 95\% CI, 1.01-5.42), carotid artery plaque (OR, 4.62; 95\% CI, 1.85-11.57), plasma lipoprotein (a) (OR, 3.69; 95\% CI, 1.20-11.41; highest quartile vs. lowest), plasma fibrinogen (OR, 3.09; 95\% CI, 0.98-9.76; highest quartile vs. lowest), and current cigarette smoking (OR, 3.08; 95\% CI, 1.47-6.47). Approximately a quarter of participants with retinal vein occlusion and arteriolar emboli had evidence of carotid artery plaque as defined from ultrasound.

CONCLUSIONS: Retinal vein occlusion and retinal arteriolar emboli are associated with carotid artery disease, hypertension, and other cardiovascular risk factors.

}, keywords = {Aged, Aged, 80 and over, Arterioles, Blood Pressure, Cardiovascular Diseases, Carotid Stenosis, Coronary Artery Disease, Cross-Sectional Studies, Embolism, Female, Fibrinogen, Humans, Hypertension, Lipoprotein(a), Male, Meta-Analysis as Topic, Middle Aged, Retinal Artery, Retinal Vein Occlusion, Risk Factors}, issn = {1549-4713}, doi = {10.1016/j.ophtha.2004.10.039}, author = {Wong, Tien Yin and Larsen, Emily K Marino and Klein, Ronald and Mitchell, Paul and Couper, David J and Klein, Barbara E K and Hubbard, Larry D and Siscovick, David S and Sharrett, A Richey} } @article {950, title = {Inflammation and hemostasis biomarkers and cardiovascular risk in the elderly: the Cardiovascular Health Study.}, journal = {J Thromb Haemost}, volume = {5}, year = {2007}, month = {2007 Jun}, pages = {1128-35}, abstract = {

BACKGROUND: There are few studies of inflammation and hemostasis biomarkers and cardiovascular disease risk (CVD) in older adults.

OBJECTIVES: To assess multiple biomarkers simultaneously and in combinations for CVD risk assessment in older individuals.

PATIENTS/METHODS: Thirteen biomarkers, interleukin-6 (IL-6), C-reactive protein (CRP), D-dimer, fibrinogen, factor VII, factor VIII, leukocyte count (WBC), platelet count, lipoprotein(a), soluble intercellular adhesion molecule-1 (sICAM-1), albumin, homocysteine and uric acid, were correlated with incident CVD in 4510 individuals in the Cardiovascular Health Study. Baseline biomarkers were analyzed as gender-specific SD increments and quintiles in proportional hazards models adjusted for demographics, CVD risk factors and medications.

RESULTS: Over 9 years with 1700 CVD events, seven biomarkers were associated with CVD. Adjusted hazard ratios (HRs, 95\% CI) per SD increment were 1.16 (1.09, 1.23) for IL-6, 1.16 (1.09, 1.23) for CRP, 1.13 (1.05, 1.21) for D-dimer, 1.17 (1.09, 1.25) for homocysteine, 1.06 (1.00, 1.12) for WBC, 1.06 (1.00, 1.12) for factor VIII, and 1.07 (1.00, 1.13) for lipoprotein(a). Fibrinogen was associated with CVD in men only (HR 1.12, 95\% CI 1.04, 1.22) and sICAM-1 in women only (HR 1.16, 95\% CI 1.05, 1.27). IL-6 and CRP remained associated with CVD when modeled with WBC. Participants were classified by all combinations of two biomarkers being high or low (IL-6, CRP, WBC, factor VIII, cholesterol/HDL). All were associated with CVD when cholesterol/HDL was low and none when CRP was low.

CONCLUSIONS: Seven biomarkers were associated with CVD in older adults, with CRP having some advantages compared with others. Even larger studies are needed to better characterize these associations.

}, keywords = {Aged, Aging, Biomarkers, C-Reactive Protein, Cardiovascular Diseases, Cholesterol, Cohort Studies, Factor VIII, Female, Fibrinogen, Hemostasis, Homocysteine, Humans, Inflammation Mediators, Interleukin-6, Leukocyte Count, Lipoprotein(a), Male, Prospective Studies, Risk Factors}, issn = {1538-7933}, doi = {10.1111/j.1538-7836.2007.02528.x}, author = {Zakai, N A and Katz, R and Jenny, N S and Psaty, B M and Reiner, A P and Schwartz, S M and Cushman, M} } @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 {1116, title = {Lipoprotein(a) concentration and the risk of coronary heart disease, stroke, and nonvascular mortality.}, journal = {JAMA}, volume = {302}, year = {2009}, month = {2009 Jul 22}, pages = {412-23}, abstract = {

CONTEXT: Circulating concentration of lipoprotein(a) (Lp[a]), a large glycoprotein attached to a low-density lipoprotein-like particle, may be associated with risk of coronary heart disease (CHD) and stroke.

OBJECTIVE: To assess the relationship of Lp(a) concentration with risk of major vascular and nonvascular outcomes.

STUDY SELECTION: Long-term prospective studies that recorded Lp(a) concentration and subsequent major vascular morbidity and/or cause-specific mortality published between January 1970 and March 2009 were identified through electronic searches of MEDLINE and other databases, manual searches of reference lists, and discussion with collaborators.

DATA EXTRACTION: Individual records were provided for each of 126,634 participants in 36 prospective studies. During 1.3 million person-years of follow-up, 22,076 first-ever fatal or nonfatal vascular disease outcomes or nonvascular deaths were recorded, including 9336 CHD outcomes, 1903 ischemic strokes, 338 hemorrhagic strokes, 751 unclassified strokes, 1091 other vascular deaths, 8114 nonvascular deaths, and 242 deaths of unknown cause. Within-study regression analyses were adjusted for within-person variation and combined using meta-analysis. Analyses excluded participants with known preexisting CHD or stroke at baseline.

DATA SYNTHESIS: Lipoprotein(a) concentration was weakly correlated with several conventional vascular risk factors and it was highly consistent within individuals over several years. Associations of Lp(a) with CHD risk were broadly continuous in shape. In the 24 cohort studies, the rates of CHD in the top and bottom thirds of baseline Lp(a) distributions, respectively, were 5.6 (95\% confidence interval [CI], 5.4-5.9) per 1000 person-years and 4.4 (95\% CI, 4.2-4.6) per 1000 person-years. The risk ratio for CHD, adjusted for age and sex only, was 1.16 (95\% CI, 1.11-1.22) per 3.5-fold higher usual Lp(a) concentration (ie, per 1 SD), and it was 1.13 (95\% CI, 1.09-1.18) following further adjustment for lipids and other conventional risk factors. The corresponding adjusted risk ratios were 1.10 (95\% CI, 1.02-1.18) for ischemic stroke, 1.01 (95\% CI, 0.98-1.05) for the aggregate of nonvascular mortality, 1.00 (95\% CI, 0.97-1.04) for cancer deaths, and 1.00 (95\% CI, 0.95-1.06) for nonvascular deaths other than cancer.

CONCLUSION: Under a wide range of circumstances, there are continuous, independent, and modest associations of Lp(a) concentration with risk of CHD and stroke that appear exclusive to vascular outcomes.

}, keywords = {Cause of Death, Coronary Disease, Humans, Lipoprotein(a), Risk Factors, Stroke}, issn = {1538-3598}, doi = {10.1001/jama.2009.1063}, author = {Erqou, Sebhat and Kaptoge, Stephen and Perry, Philip L and Di Angelantonio, Emanuele and Thompson, Alexander and White, Ian R and Marcovina, Santica M and Collins, Rory and Thompson, Simon G and Danesh, John} }