@article {675, title = {Fasting and 2-hour postchallenge serum glucose measures and risk of incident cardiovascular events in the elderly: the Cardiovascular Health Study.}, journal = {Arch Intern Med}, volume = {162}, year = {2002}, month = {2002 Jan 28}, pages = {209-16}, abstract = {

BACKGROUND: The contributions of fasting and 2-hour postchallenge glucose level to cardiovascular events remain ill-defined, especially for nondiabetic adults. This study examined the relative predictive power of fasting and 2-hour glucose level on cardiovascular event risk.

METHODS: A total of 4014 community-dwelling adults 65 years or older who participated in the baseline visit of the Cardiovascular Health Study and who were without treated diabetes or previous myocardial infarction or stroke were eligible for analyses. Participants with treated diabetes at baseline were excluded. Incident myocardial infarction or stroke, or coronary death, was the outcome of interest. Age-, sex-, and race-adjusted proportional hazards regression models described individual and joint associations between baseline measures of fasting and 2-hour postchallenge glucose level and event risk.

RESULTS: There were 764 incident cardiovascular events during 8.5 years of follow-up. Fasting glucose level of 115 mg/dL (6.4 mmol/L) or more was associated with an increased cardiovascular risk (hazard ratio [HR], 1.66 [95\% confidence interval (CI), 1.39-1.98]) in adjusted analyses compared with fasting glucose level less than 115 mg/dL. Two-hour glucose level was associated with a linear risk (HR, 1.02 [95\% CI, 1.00-1.04] per 10 mg/dL [0.6 mmol/L]) that included an additional increase in risk for 2-hour glucose level of 154 mg/dL (8.5 mmol/L) or more (HR, 1.29 [95\% CI, 1.04-1.59]) in adjusted analyses. In joint fasting and 2-hour glucose models, only 2-hour glucose level remained predictive of event risk.

CONCLUSIONS: Two-hour glucose level was better than fasting glucose level alone at identifying older adults at increased risk of major incident cardiovascular events.

}, keywords = {Aged, Blood Glucose, Cardiovascular Diseases, Fasting, Female, Glucose Tolerance Test, Humans, Male, Myocardial Infarction, Predictive Value of Tests, Proportional Hazards Models, Risk Assessment, Stroke}, issn = {0003-9926}, doi = {10.1001/archinte.162.2.209}, author = {Smith, Nicholas L and Barzilay, Joshua I and Shaffer, Douglas and Savage, Peter J and Heckbert, Susan R and Kuller, Lewis H and Kronmal, Richard A and Resnick, Helaine E and Psaty, Bruce M} } @article {730, title = {Cardiac benefits of fish consumption may depend on the type of fish meal consumed: the Cardiovascular Health Study.}, journal = {Circulation}, volume = {107}, year = {2003}, month = {2003 Mar 18}, pages = {1372-7}, abstract = {

BACKGROUND: Few studies have examined associations of fish consumption with ischemic heart disease (IHD) risk among older adults or how different types of fish meals relate to IHD risk.

METHODS AND RESULTS: In a population-based prospective cohort study, usual fish consumption was ascertained at baseline among 3910 adults aged > or =65 years and free of known cardiovascular disease in 1989 and 1990. Consumption of tuna and other broiled or baked fish correlated with plasma phospholipid long-chain n-3 fatty acids, whereas consumption of fried fish or fish sandwiches (fish burgers) did not. Over 9.3 years{\textquoteright} mean follow-up, there were 247 IHD deaths (including 148 arrhythmic deaths) and 363 incident nonfatal myocardial infarctions (MIs). After adjustment for potential confounders, consumption of tuna or other broiled or baked fish was associated with lower risk of total IHD death (P for trend=0.001) and arrhythmic IHD death (P=0.001) but not nonfatal MI (P=0.44), with 49\% lower risk of total IHD death and 58\% lower risk of arrhythmic IHD death among persons consuming tuna/other fish 3 or more times per week compared with less than once per month. In similar analyses, fried fish/fish sandwich consumption was not associated with lower risk of total IHD death, arrhythmic IHD death, or nonfatal MI but rather with trends toward higher risk.

CONCLUSIONS: Among adults aged > or =65 years, modest consumption of tuna or other broiled or baked fish, but not fried fish or fish sandwiches, is associated with lower risk of IHD death, especially arrhythmic IHD death. Cardiac benefits of fish consumption may vary depending on the type of fish meal consumed.

}, keywords = {Aged, Animals, Arrhythmias, Cardiac, Diet, Eating, Fatty Acids, Omega-3, Female, Fishes, Humans, Male, Myocardial Infarction, Myocardial Ischemia, Prospective Studies, Risk, Tuna}, issn = {1524-4539}, doi = {10.1161/01.cir.0000055315.79177.16}, author = {Mozaffarian, Dariush and Lemaitre, Rozenn N and Kuller, Lewis H and Burke, Gregory L and Tracy, Russell P and Siscovick, David S} } @article {722, title = {n-3 Polyunsaturated fatty acids, fatal ischemic heart disease, and nonfatal myocardial infarction in older adults: the Cardiovascular Health Study.}, journal = {Am J Clin Nutr}, volume = {77}, year = {2003}, month = {2003 Feb}, pages = {319-25}, abstract = {

BACKGROUND: Little is known about the relation of the dietary intake of n-3 polyunsaturated fatty acids, ie, docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) from fatty fish and alpha-linolenic acid from vegetable oils, with ischemic heart disease among older adults.

OBJECTIVE: We investigated the associations of plasma phospholipid concentrations of DHA, EPA, and alpha-linolenic acid as biomarkers of intake with the risk of incident fatal ischemic heart disease and incident nonfatal myocardial infarction in older adults.

DESIGN: We conducted a case-control study nested in the Cardiovascular Health Study, a cohort study of adults aged > or = 65 y. Cases experienced incident fatal myocardial infarction and other ischemic heart disease death (n = 54) and incident nonfatal myocardial infarction (n = 125). Matched controls were randomly selected (n = 179). We measured plasma phospholipid concentrations of n-3 polyunsaturated fatty acids in blood samples drawn approximately 2 y before the event.

RESULTS: A higher concentration of combined DHA and EPA was associated with a lower risk of fatal ischemic heart disease, and a higher concentration of alpha-linolenic acid with a tendency to lower risk, after adjustment for risk factors [odds ratio: 0.32 (95\% CI: 0.13, 0.78; P = 0.01) and 0.52 (0.24, 1.15; P = 0.1), respectively]. In contrast, n-3 polyunsaturated fatty acids were not associated with nonfatal myocardial infarction.

CONCLUSIONS: Higher combined dietary intake of DHA and EPA, and possibly alpha-linolenic acid, may lower the risk of fatal ischemic heart disease in older adults. The association of n-3 polyunsaturated fatty acids with fatal ischemic heart disease, but not with nonfatal myocardial infarction, is consistent with possible antiarrhythmic effects of these fatty acids.

}, keywords = {Aged, alpha-Linolenic Acid, Biomarkers, Case-Control Studies, Cohort Studies, Coronary Disease, Dietary Supplements, Docosahexaenoic Acids, Eicosapentaenoic Acid, Fatty Acids, Omega-3, Female, Fish Oils, Humans, Incidence, Male, Myocardial Infarction, Odds Ratio, Phospholipids, Prevalence, Prospective Studies, Risk Factors}, issn = {0002-9165}, doi = {10.1093/ajcn/77.2.319}, author = {Lemaitre, Rozenn N and King, Irena B and Mozaffarian, Dariush and Kuller, Lewis H and Tracy, Russell P and Siscovick, David S} } @article {850, title = {Alcohol use and risk of ischemic stroke among older adults: the cardiovascular health study.}, journal = {Stroke}, volume = {36}, year = {2005}, month = {2005 Sep}, pages = {1830-4}, abstract = {

BACKGROUND AND PURPOSE: The association of light to moderate alcohol consumption with risk of ischemic stroke remains uncertain, as are the roles of potentially mediating factors and modification by apolipoprotein E (apoE) genotype.

METHODS: We studied the prospective association of alcohol consumption and risk of ischemic stroke among 4410 participants free of cardiovascular disease at baseline in the Cardiovascular Health Study, a population-based cohort study of older adults from 4 US communities. Participants reported their consumption of alcoholic beverages yearly.

RESULTS: During an average follow-up period of 9.2 years, 434 cases of incident ischemic stroke occurred. Compared with long-term abstainers, the multivariate relative risks of ischemic stroke were 0.85 (95\% CI, 0.63 to 1.13), 0.75 (95\% CI, 0.53 to 1.06), 0.82 (95\% CI, 0.51 to 1.30), and 1.03 (95\% CI, 0.68 to 1.57) among consumers of <1, 1 to 6, 7 to 13, and > or =14 drinks per week (P quadratic trend 0.06). ApoE genotype appeared to modify the alcohol-ischemic stroke relationship (P interaction 0.08), with generally lower risks among drinkers than abstainers in apoE4-negative participants but higher risks among drinkers than abstainers among apoE4-positive participants. We could not identify candidate mediators among lipid, inflammatory, and prothrombotic factors.

CONCLUSIONS: In this study of older adults, the association of alcohol use and risk of ischemic stroke was U-shaped, with modestly lower risk among consumers of 1 to 6 drinks per week. However, apoE genotype may modify this association, and even moderate alcohol intake may be associated with an increased risk of ischemic stroke among apoE4-positive older adults.

}, keywords = {Aged, Alcohol Drinking, Apolipoproteins E, Brain Infarction, Brain Ischemia, Cohort Studies, Female, Follow-Up Studies, Genetic Predisposition to Disease, Genotype, Humans, Hypertension, Inflammation, Ischemia, Lipids, Male, Middle Aged, Multivariate Analysis, Myocardial Infarction, Prospective Studies, Risk, Risk Factors, Stroke, Substance-Related Disorders, Thrombosis, Time Factors, Vascular Diseases}, issn = {1524-4628}, doi = {10.1161/01.STR.0000177587.76846.89}, author = {Mukamal, Kenneth J and Chung, Hyoju and Jenny, Nancy S and Kuller, Lewis H and Longstreth, W T and Mittleman, Murray A and Burke, Gregory L and Cushman, Mary and Beauchamp, Norman J and Siscovick, David S} } @article {845, title = {C-reactive protein and the 10-year incidence of coronary heart disease in older men and women: the cardiovascular health study.}, journal = {Circulation}, volume = {112}, year = {2005}, month = {2005 Jul 05}, pages = {25-31}, abstract = {

BACKGROUND: High C-reactive protein (CRP) is associated with increased coronary heart disease risk. Few long-term data in the elderly are available.

METHODS AND RESULTS: Baseline CRP was measured in 3971 men and women > or =65 years of age without prior vascular diseases; 26\% had elevated concentrations (>3 mg/L). With 10 years of follow-up, 547 participants developed coronary heart disease (CHD; defined as myocardial infarction or coronary death). With elevated CRP, the 10-year cumulative CHD incidences were 33\% in men and 17\% in women. The age-, ethnicity-, and sex-adjusted relative risk of CHD for CRP >3 mg/L compared with <1 mg/L was 1.82 (95\% CI, 1.46 to 2.28). Adjusting for conventional risk factors reduced the relative risk to 1.45 (95\% CI, 1.14 to 1.86). The population-attributable risk of CHD for elevated CRP was 11\%. Risk relationships did not differ in subgroups defined by baseline risk factors. We assessed whether CRP improved prediction by the Framingham Risk Score. Among men with a 10-year Framingham-predicted risk of 10\% to 20\%, the observed CHD incidence was 32\% for elevated CRP. Among women, CRP discriminated best among those with a 10-year predicted risk >20\%; the incidences were 31\% and 10\% for elevated and normal CRP levels, respectively.

CONCLUSIONS: In older men and women, elevated CRP was associated with increased 10-year risk of CHD, regardless of the presence or absence of cardiac risk factors. A single CRP measurement provided information beyond conventional risk assessment, especially in intermediate-Framingham-risk men and high-Framingham-risk women.

}, keywords = {Age Factors, Aged, Aged, 80 and over, Biomarkers, C-Reactive Protein, Coronary Disease, Female, Humans, Incidence, Inflammation, Male, Myocardial Infarction, Predictive Value of Tests, Risk Factors}, issn = {1524-4539}, doi = {10.1161/CIRCULATIONAHA.104.504159}, author = {Cushman, Mary and Arnold, Alice M and Psaty, Bruce M and Manolio, Teri A and Kuller, Lewis H and Burke, Gregory L and Polak, Joseph F and Tracy, Russell P} } @article {932, title = {Association of polymorphisms in the CRP gene with circulating C-reactive protein levels and cardiovascular events.}, journal = {JAMA}, volume = {296}, year = {2006}, month = {2006 Dec 13}, pages = {2703-11}, abstract = {

CONTEXT: C-reactive protein (CRP) is an inflammation protein that may play a role in the pathogenesis of cardiovascular disease (CVD).

OBJECTIVE: To assess whether polymorphisms in the CRP gene are associated with plasma CRP, carotid intima-media thickness (CIMT), and CVD events.

DESIGN, SETTING, AND PARTICIPANTS: In the prospective, population-based Cardiovascular Health Study, 4 tag single-nucleotide polymorphisms (SNPs) (1919A/T, 2667G/C, 3872G/A, 5237A/G) were genotyped in 3941 white (European American) participants and 5 tag SNPs (addition of 790A/T) were genotyped in 700 black (African American) participants, aged 65 years or older, all of whom were without myocardial infarction (MI) or stroke before study entry. Median follow-up was 13 years (1989-2003).

MAIN OUTCOME MEASURES: Baseline CIMT; occurrence of MI, stroke, and CVD mortality during follow-up.

RESULTS: In white participants, 461 incident MIs, 491 incident strokes, and 490 CVD-related deaths occurred; in black participants, 67 incident MIs, 78 incident strokes, and 75 CVD-related deaths occurred. The 1919T and 790T alleles were associated with higher CRP levels in white and black participants, respectively. The 3872A allele was associated with lower CRP levels in both populations, and the 2667C allele was associated with lower CRP levels in white participants only. There was no association between CIMT and any CRP gene polymorphism in either population. In white participants, the 1919T allele was associated with increased risk of stroke for TT vs AA (hazard ratio [HR], 1.40; 95\% confidence interval [CI], 1.06-1.87) and for CVD mortality (HR, 1.40; 95\% CI, 1.10-1.90). In black participants, homozygosity for the 790T allele was associated with a 4-fold increased risk of MI compared with homozygosity for the 790A allele (95\% CI, 1.58-10.53). The minor alleles of the 2 SNPs associated with lower plasma CRP concentration in white participants (2667C and 3872A) were associated with decreased risk of CVD mortality.

CONCLUSIONS: Genetic variation in the CRP gene is associated with plasma CRP levels and CVD risk in older adults.

}, keywords = {African Continental Ancestry Group, Aged, C-Reactive Protein, Cardiovascular Diseases, Carotid Arteries, European Continental Ancestry Group, Female, Genotype, Humans, Male, Myocardial Infarction, Polymorphism, Single Nucleotide, Proportional Hazards Models, Risk, Stroke, Tunica Intima}, issn = {1538-3598}, doi = {10.1001/jama.296.22.2703}, author = {Lange, Leslie A and Carlson, Christopher S and Hindorff, Lucia A and Lange, Ethan M and Walston, Jeremy and Durda, J Peter and Cushman, Mary and Bis, Joshua C and Zeng, Donglin and Lin, Danyu and Kuller, Lewis H and Nickerson, Deborah A and Psaty, Bruce M and Tracy, Russell P and Reiner, Alexander P} } @article {967, title = {Association of carotid artery intima-media thickness, plaques, and C-reactive protein with future cardiovascular disease and all-cause mortality: the Cardiovascular Health Study.}, journal = {Circulation}, volume = {116}, year = {2007}, month = {2007 Jul 03}, pages = {32-8}, abstract = {

BACKGROUND: Carotid atherosclerosis, measured as carotid intima-media thickness or as characteristics of plaques, has been linked to cardiovascular disease (CVD) and to C-reactive protein (CRP) levels. We investigated the relationship between carotid atherosclerosis and CRP and their joint roles in CVD prediction.

METHODS AND RESULTS: Of 5888 participants in the Cardiovascular Health Study, an observational study of adults aged > or = 65 years, 5020 without baseline CVD were included in the analysis. They were followed up for as long as 12 years for CVD incidence and all-cause mortality after baseline ultrasound and CRP measurement. When CRP was elevated (> 3 mg/L) among those with detectable atherosclerosis on ultrasound, there was a 72\% (95\% CI, 1.46 to 2.01) increased risk for CVD death and a 52\% (95\% CI, 1.37 to 1.68) increased risk for all-cause mortality. Elevated CRP in the absence of atherosclerosis did not increase CVD or all-cause mortality risk. The proportion of excess risk attributable to the interaction of high CRP and atherosclerosis was 54\% for CVD death and 79\% for all-cause mortality. Addition of CRP or carotid atherosclerosis to conventional risk factors modestly increased in the ability to predict CVD, as measured by the c statistic.

CONCLUSIONS: In older adults, elevated CRP was associated with increased risk for CVD and all-cause mortality only in those with detectable atherosclerosis based on carotid ultrasound. Despite the significant associations of CRP and carotid atherosclerosis with CVD, these measures modestly improve the prediction of CVD outcomes after one accounts for the conventional risk factors.

}, keywords = {African Americans, Aged, Biomarkers, C-Reactive Protein, Cardiovascular Diseases, Carotid Artery Diseases, Cohort Studies, Comorbidity, Diabetes Mellitus, European Continental Ancestry Group, Female, Follow-Up Studies, Humans, Hyperlipidemias, Hypertension, Incidence, Inflammation, Kaplan-Meier Estimate, Male, Mass Screening, Mortality, Myocardial Infarction, Obesity, Predictive Value of Tests, Proportional Hazards Models, Prospective Studies, Risk Assessment, Risk Factors, ROC Curve, Smoking, Stroke, Survival Analysis, Tunica Intima, Tunica Media, Ultrasonography, United States}, issn = {1524-4539}, doi = {10.1161/CIRCULATIONAHA.106.645606}, author = {Cao, Jie J and Arnold, Alice M and Manolio, Teri A and Polak, Joseph F and Psaty, Bruce M and Hirsch, Calvin H and Kuller, Lewis H and Cushman, Mary} } @article {930, title = {Serum amyloid P and cardiovascular disease in older men and women: results from the Cardiovascular Health Study.}, journal = {Arterioscler Thromb Vasc Biol}, volume = {27}, year = {2007}, month = {2007 Feb}, pages = {352-8}, abstract = {

OBJECTIVE: Serum amyloid P (SAP), a pentraxin like C-reactive protein (CRP), functions in innate immunity. However, associations of SAP with cardiovascular disease (CVD) are unknown.

METHODS AND RESULTS: We examined these associations in the Cardiovascular Health Study using a case-cohort design. Nonexclusive case groups were incident angina (n=523), myocardial infarction (MI; n=308), stroke (n=323), and CVD death (n=288). 786 participants had no events. SAP was correlated with CRP, CVD risk factors (obesity, blood pressure, lipids), common and internal carotid wall thickness, and ankle-brachial index (all P<0.02). In Cox regression models adjusted for age, sex, and ethnicity, a standard deviation increase in SAP (9.8 mg/L) was associated with angina (hazard ratio; 95\% confidence interval 1.3; 1.2 to 1.5) and MI (1.3; 1.1 to 1.5), but not stroke (1.1; 0.9 to 1.3) or CVD death (1.1; 0.9 to 1.3). Adding CRP to the models had no significant effect on associations. Adjusting for CVD risk factors slightly attenuated SAP associations with CVD events; however, associations with angina and MI remained significant.

CONCLUSIONS: Although both are pentraxins, SAP and CRP may represent different facets of inflammation. The association of SAP with CVD in these older adults further supports the role of innate immunity in atherosclerosis.

}, keywords = {Aged, Aged, 80 and over, Aging, Angina, Unstable, Atherosclerosis, C-Reactive Protein, Cardiovascular Diseases, Case-Control Studies, Female, Humans, Hypertension, Immunity, Innate, Male, Myocardial Infarction, Obesity, Prevalence, Proportional Hazards Models, Risk Factors, Serum Amyloid P-Component}, issn = {1524-4636}, doi = {10.1161/01.ATV.0000254150.97741.fe}, author = {Jenny, Nancy Swords and Arnold, Alice M and Kuller, Lewis H and Tracy, Russell P and Psaty, Bruce M} } @article {6811, title = {Association of Cardiometabolic Multimorbidity With Mortality.}, journal = {JAMA}, volume = {314}, year = {2015}, month = {2015 Jul 7}, pages = {52-60}, abstract = {

IMPORTANCE: The prevalence of cardiometabolic multimorbidity is increasing.

OBJECTIVE: To estimate reductions in life expectancy associated with cardiometabolic multimorbidity.

DESIGN, SETTING, AND PARTICIPANTS: Age- and sex-adjusted mortality rates and hazard ratios (HRs) were calculated using individual participant data from the Emerging Risk Factors Collaboration (689,300 participants; 91 cohorts; years of baseline surveys: 1960-2007; latest mortality follow-up: April 2013; 128,843 deaths). The HRs from the Emerging Risk Factors Collaboration were compared with those from the UK Biobank (499,808 participants; years of baseline surveys: 2006-2010; latest mortality follow-up: November 2013; 7995 deaths). Cumulative survival was estimated by applying calculated age-specific HRs for mortality to contemporary US age-specific death rates.

EXPOSURES: A history of 2 or more of the following: diabetes mellitus, stroke, myocardial infarction (MI).

MAIN OUTCOMES AND MEASURES: All-cause mortality and estimated reductions in life expectancy.

RESULTS: In participants in the Emerging Risk Factors Collaboration without a history of diabetes, stroke, or MI at baseline (reference group), the all-cause mortality rate adjusted to the age of 60 years was 6.8 per 1000 person-years. Mortality rates per 1000 person-years were 15.6 in participants with a history of diabetes, 16.1 in those with stroke, 16.8 in those with MI, 32.0 in those with both diabetes and MI, 32.5 in those with both diabetes and stroke, 32.8 in those with both stroke and MI, and 59.5 in those with diabetes, stroke, and MI. Compared with the reference group, the HRs for all-cause mortality were 1.9 (95\% CI, 1.8-2.0) in participants with a history of diabetes, 2.1 (95\% CI, 2.0-2.2) in those with stroke, 2.0 (95\% CI, 1.9-2.2) in those with MI, 3.7 (95\% CI, 3.3-4.1) in those with both diabetes and MI, 3.8 (95\% CI, 3.5-4.2) in those with both diabetes and stroke, 3.5 (95\% CI, 3.1-4.0) in those with both stroke and MI, and 6.9 (95\% CI, 5.7-8.3) in those with diabetes, stroke, and MI. The HRs from the Emerging Risk Factors Collaboration were similar to those from the more recently recruited UK Biobank. The HRs were little changed after further adjustment for markers of established intermediate pathways (eg, levels of lipids and blood pressure) and lifestyle factors (eg, smoking, diet). At the age of 60 years, a history of any 2 of these conditions was associated with 12 years of reduced life expectancy and a history of all 3 of these conditions was associated with 15 years of reduced life expectancy.

CONCLUSIONS AND RELEVANCE: Mortality associated with a history of diabetes, stroke, or MI was similar for each condition. Because any combination of these conditions was associated with multiplicative mortality risk, life expectancy was substantially lower in people with multimorbidity.

}, keywords = {Adult, Aged, Comorbidity, Diabetes Mellitus, Female, Humans, Life Expectancy, Male, Middle Aged, Mortality, Myocardial Infarction, Risk Factors, Stroke}, issn = {1538-3598}, doi = {10.1001/jama.2015.7008}, author = {Di Angelantonio, Emanuele and Kaptoge, Stephen and Wormser, David and Willeit, Peter and Butterworth, Adam S and Bansal, Narinder and O{\textquoteright}Keeffe, Linda M and Gao, Pei and Wood, Angela M and Burgess, Stephen and Freitag, Daniel F and Pennells, Lisa and Peters, Sanne A and Hart, Carole L and H{\r a}heim, Lise Lund and Gillum, Richard F and Nordestgaard, B{\o}rge G and Psaty, Bruce M and Yeap, Bu B and Knuiman, Matthew W and Nietert, Paul J and Kauhanen, Jussi and Salonen, Jukka T and Kuller, Lewis H and Simons, Leon A and van der Schouw, Yvonne T and Barrett-Connor, Elizabeth and Selmer, Randi and Crespo, Carlos J and Rodriguez, Beatriz and Verschuren, W M Monique and Salomaa, Veikko and Sv{\"a}rdsudd, Kurt and van der Harst, Pim and Bj{\"o}rkelund, Cecilia and Wilhelmsen, Lars and Wallace, Robert B and Brenner, Hermann and Amouyel, Philippe and Barr, Elizabeth L M and Iso, Hiroyasu and Onat, Altan and Trevisan, Maurizio and D{\textquoteright}Agostino, Ralph B and Cooper, Cyrus and Kavousi, Maryam and Welin, Lennart and Roussel, Ronan and Hu, Frank B and Sato, Shinichi and Davidson, Karina W and Howard, Barbara V and Leening, Maarten J G and Leening, Maarten and Rosengren, Annika and D{\"o}rr, Marcus and Deeg, Dorly J H and Kiechl, Stefan and Stehouwer, Coen D A and Nissinen, Aulikki and Giampaoli, Simona and Donfrancesco, Chiara and Kromhout, Daan and Price, Jackie F and Peters, Annette and Meade, Tom W and Casiglia, Edoardo and Lawlor, Debbie A and Gallacher, John and Nagel, Dorothea and Franco, Oscar H and Assmann, Gerd and Dagenais, Gilles R and Jukema, J Wouter and Sundstr{\"o}m, Johan and Woodward, Mark and Brunner, Eric J and Khaw, Kay-Tee and Wareham, Nicholas J and Whitsel, Eric A and Nj{\o}lstad, Inger and Hedblad, Bo and Wassertheil-Smoller, Sylvia and Engstr{\"o}m, Gunnar and Rosamond, Wayne D and Selvin, Elizabeth and Sattar, Naveed and Thompson, Simon G and Danesh, John} } @article {6878, title = {Prognostic Significance of High-Sensitivity Cardiac Troponin T Concentrations between the Limit of Blank and Limit of Detection in Community-Dwelling Adults: A Metaanalysis.}, journal = {Clin Chem}, volume = {61}, year = {2015}, month = {2015 Dec}, pages = {1524-31}, abstract = {

BACKGROUND: There is controversy regarding whether to report concentrations of high-sensitivity cardiac troponin T (hs-cTnT) to the limit of blank (LOB) (3 ng/L) or the limit of detection (LOD) (5 ng/L) of the assay in community-based cohorts. We hypothesized that hs-cTnT concentrations between the LOB and LOD would be associated with poorer cardiovascular outcomes compared to concentrations below the LOB.

METHODS: hs-cTnT was analyzed in a total of 10 723 participants from the Cardiovascular Health Study (CHS), Atherosclerosis Risk in Communities (ARIC) study, and Dallas Heart Study (DHS). Participants were divided into 2 groups, those with hs-cTnT concentrations below the limit of blank (LOB) (<3 ng/L) and those with hs-cTnT between the LOB and limit of detection (LOD) (3-4.99 ng/L). Cross-sectional associations with traditional cardiovascular risk factors and cardiac structural measurements, and longitudinal associations with long-term cardiovascular outcomes of incident heart failure and cardiovascular death, were determined.

RESULTS: Participants with hs-cTnT between the LOB and LOD for all 3 cohorts were older, more likely to be male, and have a higher burden of cardiovascular risk factors and structural pathology. A metaanalysis of the 3 cohorts showed participants with hs-cTnT between the LOB and LOD were at increased risk of new-onset heart failure (hazard ratio, 1.18; 95\% CI, 1.02-1.38) and cardiovascular mortality (hazard ratio, 1.29; 95\% CI, 1.06-1.57).

CONCLUSIONS: hs-cTnT concentrations between the LOB and LOD (3-4.99 ng/L) are associated with a higher prevalence of traditional risk factors, more cardiac pathology, and worse outcomes than concentrations below the LOB (<3 ng/L).

}, keywords = {Aged, Atherosclerosis, Biomarkers, Cross-Sectional Studies, Female, Heart Failure, Humans, Independent Living, Limit of Detection, Longitudinal Studies, Male, Middle Aged, Myocardial Infarction, Prognosis, Risk Assessment, Risk Factors, Sex Factors, Troponin T}, issn = {1530-8561}, doi = {10.1373/clinchem.2015.244160}, author = {Parikh, Ravi H and Seliger, Stephen L and de Lemos, James and Nambi, Vijay and Christenson, Robert and Ayers, Colby and Sun, Wensheng and Gottdiener, John S and Kuller, Lewis H and Ballantyne, Christie and deFilippi, Christopher R} } @article {6931, title = {APOL1 Genotype, Kidney and Cardiovascular Disease, and Death in Older Adults.}, journal = {Arterioscler Thromb Vasc Biol}, volume = {36}, year = {2016}, month = {2016 Feb}, pages = {398-403}, abstract = {

OBJECTIVE: We sought to evaluate the cardiovascular impact of coding variants in the apolipoprotein L1 gene APOL1 that protect against trypanosome infection but have been associated with kidney disease among African Americans.

APPROACH AND RESULTS: As part of the Cardiovascular Health Study, a population-based cohort of Americans aged >=65 years, we genotyped APOL1 polymorphisms rs73885319 and rs71785153 and examined kidney function, subclinical atherosclerosis, and incident cardiovascular disease and death over 13 years of follow-up among 91 African Americans with 2 risk alleles, 707 other African Americans, and 4964 white participants. The high-risk genotype with 2 risk alleles was associated with 2-fold higher levels of albuminuria and lower ankle-brachial indices but similar carotid intima-media thickness among African Americans. Median survival among high-risk African Americans was 9.9 years (95\% confidence interval [CI], 8.7-11.9), compared with 13.6 years (95\% CI, 12.5-14.3) among other African Americans and 13.3 years (95\% CI, 13.0-13.6) among whites (P=0.03). The high-risk genotype was also associated with increased risk for incident myocardial infarction (adjusted hazard ratio 1.8; 95\% CI, 1.1-3.0) and mortality (adjusted hazard ratio 1.3; 95\% CI 1.0-1.7). Albuminuria and risk for myocardial infarction and mortality were nearly identical between African Americans with 0 to 1 risk alleles and whites.

CONCLUSIONS: APOL1 genotype is associated with albuminuria, subclinical atherosclerosis, incident myocardial infarction, and mortality in older African Americans. African Americans without 2 risk alleles do not differ significantly in risk of myocardial infarction or mortality from whites. APOL1 trypanolytic variants may account for a substantial proportion of the excess risk of chronic disease in African Americans.

}, keywords = {African Americans, Age Factors, Aged, Albuminuria, Apolipoproteins, Atherosclerosis, Cardiovascular Diseases, Cause of Death, European Continental Ancestry Group, Female, Gene Frequency, Genetic Predisposition to Disease, Health Status Disparities, Heterozygote, Homozygote, Humans, Incidence, Kaplan-Meier Estimate, Kidney Diseases, Lipoproteins, HDL, Male, Myocardial Infarction, Phenotype, Proportional Hazards Models, Prospective Studies, Risk Assessment, Risk Factors, Time Factors, United States}, issn = {1524-4636}, doi = {10.1161/ATVBAHA.115.305970}, author = {Mukamal, Kenneth J and Tremaglio, Joseph and Friedman, David J and Ix, Joachim H and Kuller, Lewis H and Tracy, Russell P and Pollak, Martin R} }