@article {1177, title = {Cystatin C and sudden cardiac death risk in the elderly.}, journal = {Circ Cardiovasc Qual Outcomes}, volume = {3}, year = {2010}, month = {2010 Mar}, pages = {159-64}, abstract = {

BACKGROUND: Recent studies have demonstrated an association between moderate kidney dysfunction and sudden cardiac death in people with cardiovascular disease.

METHODS AND RESULTS: The study was a longitudinal analysis among 4465 participants from the Cardiovascular Health Study without prevalent cardiovascular disease at baseline. Cystatin C and creatinine were measured from baseline sera. Sudden cardiac death (SCD) was defined as a sudden pulseless condition from a cardiac origin in a previously stable individual that occurred out of the hospital or in the emergency room. The association between cystatin C tertiles and SCD was determined with multivariate Cox proportional hazards. A similar analysis compared SCD incidence across creatinine-based estimated glomerular filtration rate (eGFR) tertiles. Over a median follow-up of 11.2 years, 91 adjudicated SCD events occurred. The annual incidence of SCD events increased across cystatin C tertiles: 10 events per 10 000 person years in tertile 1, 25 events per 10 000 person years in tertile 2, and 32 events per 10 000 person-years in the highest cystatin C tertile. These associations persisted after multivariate adjustment: hazards ratio=2.72; 95\% confidence interval, 1.44 to 5.16 in tertile 2 and hazards ratio=2.67; 95\% confidence interval, 1.33 to 5.35 in tertile 3. After multivariate adjustment, the rate of SCD also increased in a linear distribution across creatinine-based eGFR tertiles: 15 events per 10 000 person-years in tertile 1, 22 events per 10 000 person-years in tertile 2, and 27 events per 10 000 person-years in tertile 3. No significant associations, however, remained between creatinine-based eGFR and SCD after multivariable adjustment.

CONCLUSIONS: Impaired kidney function, as measured by cystatin C, has an independent association with SCD risk among elderly persons without clinical cardiovascular disease.

}, keywords = {Age Factors, Aged, Biomarkers, Chi-Square Distribution, Creatinine, Cystatin C, Death, Sudden, Cardiac, Female, Glomerular Filtration Rate, Humans, Incidence, Kidney Diseases, Longitudinal Studies, Male, Proportional Hazards Models, Risk Assessment, Risk Factors, Time Factors, United States, Up-Regulation}, issn = {1941-7705}, doi = {10.1161/CIRCOUTCOMES.109.875369}, author = {Deo, Rajat and Sotoodehnia, Nona and Katz, Ronit and Sarnak, Mark J and Fried, Linda F and Chonchol, Michel and Kestenbaum, Bryan and Psaty, Bruce M and Siscovick, David S and Shlipak, Michael G} } @article {1248, title = {European ancestry as a risk factor for atrial fibrillation in African Americans.}, journal = {Circulation}, volume = {122}, year = {2010}, month = {2010 Nov 16}, pages = {2009-15}, abstract = {

BACKGROUND: Despite a higher burden of standard atrial fibrillation (AF) risk factors, African Americans have a lower risk of AF than whites. It is unknown whether the higher risk is due to genetic or environmental factors. Because African Americans have varying degrees of European ancestry, we sought to test the hypothesis that European ancestry is an independent risk factor for AF.

METHODS AND RESULTS: We studied whites (n=4543) and African Americans (n=822) in the Cardiovascular Health Study (CHS) and whites (n=10 902) and African Americans (n=3517) in the Atherosclerosis Risk in Communities (ARIC) Study (n=3517). Percent European ancestry in African Americans was estimated with 1747 ancestry informative markers from the Illumina custom ITMAT-Broad-CARe array. Among African Americans without baseline AF, 120 of 804 CHS participants and 181 of 3517 ARIC participants developed incident AF. A meta-analysis from the 2 studies revealed that every 10\% increase in European ancestry increased the risk of AF by 13\% (hazard ratio, 1.13; 95\% confidence interval, 1.03 to 1.23; P=0.007). After adjustment for potential confounders, European ancestry remained a predictor of incident AF in each cohort alone, with a combined estimated hazard ratio for each 10\% increase in European ancestry of 1.17 (95\% confidence interval, 1.07 to 1.29; P=0.001). A second analysis using 3192 ancestry informative markers from a genome-wide Affymetrix 6.0 array in ARIC African Americans yielded similar results.

CONCLUSIONS: European ancestry predicted risk of incident AF. Our study suggests that investigating genetic variants contributing to differential AF risk in individuals of African versus European ancestry will be informative.

}, keywords = {African Americans, Aged, Atrial Fibrillation, European Continental Ancestry Group, Female, Genome-Wide Association Study, Humans, Male, Middle Aged, Risk Factors}, issn = {1524-4539}, doi = {10.1161/CIRCULATIONAHA.110.958306}, author = {Marcus, Gregory M and Alonso, Alvaro and Peralta, Carmen A and Lettre, Guillaume and Vittinghoff, Eric and Lubitz, Steven A and Fox, Ervin R and Levitzky, Yamini S and Mehra, Reena and Kerr, Kathleen F and Deo, Rajat and Sotoodehnia, Nona and Akylbekova, Meggie and Ellinor, Patrick T and Paltoo, Dina N and Soliman, Elsayed Z and Benjamin, Emelia J and Heckbert, Susan R} } @article {1166, title = {Impaired kidney function and atrial fibrillation in elderly subjects.}, journal = {J Card Fail}, volume = {16}, year = {2010}, month = {2010 Jan}, pages = {55-60}, abstract = {

BACKGROUND: Impaired kidney function is associated with increased risk for cardiovascular events. We evaluated whether kidney function is associated with atrial fibrillation (AF) risk in elderly persons.

METHODS AND RESULTS: Subjects were participants in the Cardiovascular Health Study (CHS), a population-based cohort of ambulatory elderly. Measures of kidney function were cystatin C and creatinine-based estimated glomerular filtration rate (eGFR). Among the 4663 participants, 342 (7\%) had AF at baseline and 579 (13\%) developed incident AF during follow-up (mean 7.4 years). In unadjusted analyses, cystatin C quartiles were strongly associated with prevalent AF with a nearly 3-fold odds in the highest quartile compared with the lowest (HR=1.19, 95\% CI [0.80-1.76] in quartile 2; HR=2.00, 95\% CI [1.38-2.88] in quartile 3; and HR=2.87, 95\% CI [2.03-4.07] in quartile 4). This increased risk for prevalent AF remained significant after multivariate adjustment. The risk for incident AF increased across cystatin C quartiles in the unadjusted analysis (HR=1.37, 95\% CI [1.07-1.75] in quartile 2; HR=1.43, 95\% CI [1.11-1.84] in quartile 3; and HR=1.88, 95\% CI [1.47-2.41] in quartile 4); however, after multivariate adjustment, these findings were no longer significant. An estimated GFR <60 mL.min.1.73m(2) was associated with prevalent and incident AF in unadjusted, but not multivariate analyses.

CONCLUSIONS: Impaired kidney function, as measured by cystatin C, is an independent marker of prevalent AF; however, neither cystatin C nor eGFR are predictors of incident AF.

}, keywords = {Age Factors, Aged, Aged, 80 and over, Atrial Fibrillation, Cohort Studies, Cross-Sectional Studies, Female, Follow-Up Studies, Glomerular Filtration Rate, Humans, Kidney Diseases, Kidney Function Tests, Male}, issn = {1532-8414}, doi = {10.1016/j.cardfail.2009.07.002}, author = {Deo, Rajat and Katz, Ronit and Kestenbaum, Bryan and Fried, Linda and Sarnak, Mark J and Psaty, Bruce M and Siscovick, David S and Shlipak, Michael G} } @article {1316, title = {Large-scale candidate gene analysis in whites and African Americans identifies IL6R polymorphism in relation to atrial fibrillation: the National Heart, Lung, and Blood Institute{\textquoteright}s Candidate Gene Association Resource (CARe) project.}, journal = {Circ Cardiovasc Genet}, volume = {4}, year = {2011}, month = {2011 Oct}, pages = {557-64}, abstract = {

BACKGROUND: The genetic background of atrial fibrillation (AF) in whites and African Americans is largely unknown. Genes in cardiovascular pathways have not been systematically investigated.

METHODS AND RESULTS: We examined a panel of approximately 50,000 common single-nucleotide polymorphisms (SNPs) in 2095 cardiovascular candidate genes and AF in 3 cohorts with participants of European (n=18,524; 2260 cases) or African American descent (n=3662; 263 cases) in the National Heart, Lung, and Blood Institute{\textquoteright}s Candidate Gene Association Resource. Results in whites were followed up in the German Competence Network for AF (n=906, 468 cases). The top result was assessed in relation to incident ischemic stroke in the Cohorts for Heart and Aging Research in Genomic Epidemiology Stroke Consortium (n=19,602 whites, 1544 incident strokes). SNP rs4845625 in the IL6R gene was associated with AF (relative risk [RR] C allele, 0.90; 95\% confidence interval [CI], 0.85-0.95; P=0.0005) in whites but did not reach statistical significance in African Americans (RR, 0.86; 95\% CI, 0.72-1.03; P=0.09). The results were comparable in the German AF Network replication, (RR, 0.71; 95\% CI, 0.57-0.89; P=0.003). No association between rs4845625 and stroke was observed in whites. The known chromosome 4 locus near PITX2 in whites also was associated with AF in African Americans (rs4611994; hazard ratio, 1.40; 95\% CI, 1.16-1.69; P=0.0005).

CONCLUSIONS: In a community-based cohort meta-analysis, we identified genetic association in IL6R with AF in whites. Additionally, we demonstrated that the chromosome 4 locus known from recent genome-wide association studies in whites is associated with AF in African Americans.

}, keywords = {African Americans, Aged, Alleles, Atrial Fibrillation, Chromosomes, Human, Pair 4, Cohort Studies, European Continental Ancestry Group, Female, Humans, Male, Middle Aged, National Heart, Lung, and Blood Institute (U.S.), Polymorphism, Single Nucleotide, Receptors, Interleukin-6, Risk Factors, Stroke, United States}, issn = {1942-3268}, doi = {10.1161/CIRCGENETICS.110.959197}, author = {Schnabel, Renate B and Kerr, Kathleen F and Lubitz, Steven A and Alkylbekova, Ermeg L and Marcus, Gregory M and Sinner, Moritz F and Magnani, Jared W and Wolf, Philip A and Deo, Rajat and Lloyd-Jones, Donald M and Lunetta, Kathryn L and Mehra, Reena and Levy, Daniel and Fox, Ervin R and Arking, Dan E and Mosley, Thomas H and M{\"u}ller-Nurasyid, Martina and Young, Taylor R and Wichmann, H-Erich and Seshadri, Sudha and Farlow, Deborah N and Rotter, Jerome I and Soliman, Elsayed Z and Glazer, Nicole L and Wilson, James G and Breteler, Monique M B and Sotoodehnia, Nona and Newton-Cheh, Christopher and K{\"a}{\"a}b, Stefan and Ellinor, Patrick T and Alonso, Alvaro and Benjamin, Emelia J and Heckbert, Susan R} } @article {1350, title = {Vitamin D, parathyroid hormone, and sudden cardiac death: results from the Cardiovascular Health Study.}, journal = {Hypertension}, volume = {58}, year = {2011}, month = {2011 Dec}, pages = {1021-8}, abstract = {

Recent studies have demonstrated greater risks of cardiovascular events and mortality among persons who have lower 25-hydroxyvitamin D (25-OHD) and higher parathyroid hormone (PTH) levels. We sought to evaluate the association between markers of mineral metabolism and sudden cardiac death (SCD) among the 2312 participants from the Cardiovascular Health Study who were free of clinical cardiovascular disease at baseline. We estimated associations of baseline 25-OHD and PTH concentrations individually and in combination with SCD using Cox proportional hazards models after adjustment for demographics, cardiovascular risk factors, and kidney function. During a median follow-up of 14 years, there were 73 adjudicated SCD events. The annual incidence of SCD was greater among subjects who had lower 25-OHD concentrations, 2 events per 1000 for 25-OHD >=20 ng/mL and 4 events per 1000 for 25-OHD <20 ng/mL. Similarly, SCD incidence was greater among subjects who had higher PTH concentrations, 2 events per 1000 for PTH <65 pg/mL and 4 events per 1000 for PTH >=65 pg/mL. Multivariate adjustment attenuated associations of 25-OHD and PTH with SCD. Finally, 267 participants (11.7\% of the cohort) had high PTH and low 25-OHD concentrations. This combination was associated with a >2-fold risk of SCD after adjustment (hazard ratio: 2.19 [95\% CI: 1.17-4.10]; P=0.017) compared with participants with normal levels of PTH and 25-OHD. The combination of lower 25-OHD and higher PTH concentrations appears to be associated independently with SCD risk among older adults without cardiovascular disease.

}, keywords = {Aged, Cardiovascular Diseases, Comorbidity, Death, Sudden, Cardiac, Diabetes Mellitus, Female, Follow-Up Studies, Humans, Hypertension, Incidence, Kidney, Male, Middle Aged, Minerals, Parathyroid Hormone, Proportional Hazards Models, Risk Factors, Socioeconomic Factors, United States, Vitamin D}, issn = {1524-4563}, doi = {10.1161/HYPERTENSIONAHA.111.179135}, author = {Deo, Rajat and Katz, Ronit and Shlipak, Michael G and Sotoodehnia, Nona and Psaty, Bruce M and Sarnak, Mark J and Fried, Linda F and Chonchol, Michel and de Boer, Ian H and Enquobahrie, Daniel and Siscovick, David and Kestenbaum, Bryan} } @article {6084, title = {Novel loci associated with PR interval in a genome-wide association study of 10 African American cohorts.}, journal = {Circ Cardiovasc Genet}, volume = {5}, year = {2012}, month = {2012 Dec}, pages = {639-46}, abstract = {

BACKGROUND: The PR interval, as measured by the resting, standard 12-lead ECG, reflects the duration of atrial/atrioventricular nodal depolarization. Substantial evidence exists for a genetic contribution to PR, including genome-wide association studies that have identified common genetic variants at 9 loci influencing PR in populations of European and Asian descent. However, few studies have examined loci associated with PR in African Americans.

METHODS AND RESULTS: We present results from the largest genome-wide association study to date of PR in 13 415 adults of African descent from 10 cohorts. We tested for association between PR (ms) and ≈2.8 million genotyped and imputed single-nucleotide polymorphisms. Imputation was performed using HapMap 2 YRI and CEU panels. Study-specific results, adjusted for global ancestry and clinical correlates of PR, were meta-analyzed using the inverse variance method. Variation in genome-wide test statistic distributions was noted within studies (λ range: 0.9-1.1), although not after genomic control correction was applied to the overall meta-analysis (λ: 1.008). In addition to generalizing previously reported associations with MEIS1, SCN5A, ARHGAP24, CAV1, and TBX5 to African American populations at the genome-wide significance level (P<5.0 {\texttimes} 10(-8)), we also identified a novel locus: ITGA9, located in a region previously implicated in SCN5A expression. The 3p21 region harboring SCN5A also contained 2 additional independent secondary signals influencing PR (P<5.0 {\texttimes} 10(-8)).

CONCLUSIONS: This study demonstrates the ability to map novel loci in African Americans as well as the generalizability of loci associated with PR across populations of African, European, and Asian descent.

}, keywords = {Adult, African Americans, Cohort Studies, Electrocardiography, Female, Genetic Loci, Genome-Wide Association Study, Humans, Male, Meta-Analysis as Topic, Middle Aged, Polymorphism, Single Nucleotide}, issn = {1942-3268}, doi = {10.1161/CIRCGENETICS.112.963991}, author = {Butler, Anne M and Yin, Xiaoyan and Evans, Daniel S and Nalls, Michael A and Smith, Erin N and Tanaka, Toshiko and Li, Guo and Buxbaum, Sarah G and Whitsel, Eric A and Alonso, Alvaro and Arking, Dan E and Benjamin, Emelia J and Berenson, Gerald S and Bis, Josh C and Chen, Wei and Deo, Rajat and Ellinor, Patrick T and Heckbert, Susan R and Heiss, Gerardo and Hsueh, Wen-Chi and Keating, Brendan J and Kerr, Kathleen F and Li, Yun and Limacher, Marian C and Liu, Yongmei and Lubitz, Steven A and Marciante, Kristin D and Mehra, Reena and Meng, Yan A and Newman, Anne B and Newton-Cheh, Christopher and North, Kari E and Palmer, Cameron D and Psaty, Bruce M and Quibrera, P Miguel and Redline, Susan and Reiner, Alex P and Rotter, Jerome I and Schnabel, Renate B and Schork, Nicholas J and Singleton, Andrew B and Smith, J Gustav and Soliman, Elsayed Z and Srinivasan, Sathanur R and Zhang, Zhu-Ming and Zonderman, Alan B and Ferrucci, Luigi and Murray, Sarah S and Evans, Michele K and Sotoodehnia, Nona and Magnani, Jared W and Avery, Christy L} } @article {6071, title = {Cardiomyocyte injury assessed by a highly sensitive troponin assay and sudden cardiac death in the community: the Cardiovascular Health Study.}, journal = {J Am Coll Cardiol}, volume = {62}, year = {2013}, month = {2013 Dec 03}, pages = {2112-20}, abstract = {

OBJECTIVES: This study sought to determine the association between markers of cardiomyocyte injury in ambulatory subjects and sudden cardiac death (SCD).

BACKGROUND: The pathophysiology of SCD is complex but is believed to be associated with an abnormal cardiac substrate in most cases. The association between biomarkers of cardiomyocyte injury in ambulatory subjects and SCD has not been investigated.

METHODS: Levels of cardiac troponin T, a biomarker of cardiomyocyte injury, were measured by a highly sensitive assay (hsTnT) in 4,431 ambulatory participants in the Cardiovascular Health Study, a longitudinal community-based prospective cohort study. Serial measures were obtained in 3,089 subjects. All deaths, including SCD, were adjudicated by a central events committee.

RESULTS: Over a median follow-up of 13.1 years, 246 participants had SCD. Baseline levels of hsTnT were significantly associated with SCD (hazard ratio [HR] for +1 log(hsTnT): 2.04, 95\% confidence interval [CI]: 1.78 to 2.34]. This association persisted in covariate-adjusted Cox analyses accounting for baseline risk factors (HR: 1.30, 95\% CI: 1.05 to 1.62), as well as for incident heart failure and myocardial infarction (HR: 1.26, 95\% CI: 1.01 to 1.57). The population was also categorized into 3 groups based on baseline hsTnT levels and SCD risk [fully adjusted HR: 1.89 vs. 1.55 vs. 1 (reference group) for hsTnT >=12.10 vs. 5.01 to 12.09 vs. <= 5.00 pg/ml, respectively; p trend = 0.005]. On serial measurements, change in hsTnT levels was also associated with SCD risk (fully adjusted HR for +1 pg/ml per year increase from baseline: 1.03, 95\% CI: 1.01 to 1.06).

CONCLUSIONS: The findings suggest an association between cardiomyocyte injury in ambulatory subjects and SCD risk beyond that of traditional risk factors.

}, keywords = {Aged, Ambulatory Care, Biomarkers, Death, Sudden, Cardiac, Female, Heart Arrest, Humans, Longitudinal Studies, Male, Middle Aged, Myocardium, Myocytes, Cardiac, Proportional Hazards Models, Risk Assessment, Troponin T}, issn = {1558-3597}, doi = {10.1016/j.jacc.2013.07.049}, author = {Hussein, Ayman A and Gottdiener, John S and Bartz, Traci M and Sotoodehnia, Nona and DeFilippi, Christopher and Dickfeld, Timm and Deo, Rajat and Siscovick, David and Stein, Phyllis K and Lloyd-Jones, Donald} } @article {5993, title = {Inflammation and sudden cardiac death in a community-based population of older adults: the Cardiovascular Health Study.}, journal = {Heart Rhythm}, volume = {10}, year = {2013}, month = {2013 Oct}, pages = {1425-32}, abstract = {

BACKGROUND: Inflammation is linked to adverse cardiovascular events, but its association with sudden cardiac death (SCD) has been controversial. Older subjects, who are at particular risk for SCD, were underrepresented in previous studies addressing this issue.

OBJECTIVE: The purpose of this study was to study the association between inflammation and SCD in a community-based population of older adults.

METHODS: In the Cardiovascular Health Study, 5806 and 5382 participants had measurements of C-reactive protein (CRP) and interleukin-6 (IL6), respectively, and were followed for up to 17 years. SCD risk as a function of baseline IL-6 and CRP was assessed in the overall population and in a group of participants without known prevalent cardiac disease.

RESULTS: In univariate analyses, both IL-6 (hazard ratio [HR] 1.79 for 1+ log IL-6, 95\% confidence interval [CI] 1.50-2.13; 5th vs 1st quintile HR 3.36, 95\% CI 2.24-5.05) and CRP (HR 1.31 for 1+ log CRP, 95\% CI 1.18-1.45; 5th vs 1st quintile HR 2.00, 95\% CI 1.40-2.87) were associated with SCD risk. In covariate-adjusted analyses, accounting for baseline risk factors, incident myocardial infarction, and heart failure, the association with SCD risk persisted for IL-6 (HR 1.26 for 1+ log IL-6, 95\% CI 1.02-1.56; 5th vs 1st quintile HR 1.63, 95\% CI 1.03-2.56) but was significantly attenuated for CRP (HR 1.13 for 1+ log CRP, 95\% CI 1.00-1.28; 5th vs 1st quintile HR 1.34, 95\% CI 0.88-2.05). Similar findings were observed in participants without prevalent cardiac disease.

CONCLUSION: Greater burden of inflammation, assessed by IL-6 levels, is associated with SCD risk beyond traditional risk factors, incident myocardial infarction, and heart failure.

}, keywords = {Age Factors, Aged, Aged, 80 and over, Biomarkers, C-Reactive Protein, Case-Control Studies, Cohort Studies, Death, Sudden, Cardiac, Female, Humans, Inflammation, Interleukin-6, Male, Risk Factors}, issn = {1556-3871}, doi = {10.1016/j.hrthm.2013.07.004}, author = {Hussein, Ayman A and Gottdiener, John S and Bartz, Traci M and Sotoodehnia, Nona and DeFilippi, Christopher and See, Vincent and Deo, Rajat and Siscovick, David and Stein, Phyllis K and Lloyd-Jones, Donald} } @article {6399, title = {Fibroblast growth factor-23 and incident atrial fibrillation: the Multi-Ethnic Study of Atherosclerosis (MESA) and the Cardiovascular Health Study (CHS).}, journal = {Circulation}, volume = {130}, year = {2014}, month = {2014 Jul 22}, pages = {298-307}, abstract = {

BACKGROUND: Fibroblast growth factor-23 (FGF-23) is a hormone that promotes urinary phosphate excretion and regulates vitamin D metabolism. Circulating FGF-23 concentrations increase markedly in chronic kidney disease and are associated with increased risk of clinical cardiovascular events. FGF-23 may promote atrial fibrillation (AF) by inducing left ventricular hypertrophy and diastolic and left atrial dysfunction.

METHODS AND RESULTS: We tested the associations of circulating FGF-23 concentration with incident AF among 6398 participants in the Multi-Ethnic Study of Atherosclerosis (MESA) and 1350 participants in the Cardiovascular Health Study (CHS), all free of clinical cardiovascular disease at baseline. Over a median of 7.7 and 8.0 years of follow-up, we observed 291 and 229 incident AF events in MESA and CHS, respectively. In multivariable Cox proportional hazards models, each 2-fold-higher FGF-23 concentration was associated with a 41\% higher risk of incident AF in MESA (hazard ratio, 1.41; 95\% confidence interval, 1.13-1.76; P=0.003) and a 30\% higher risk of incident AF in CHS (hazard ratio, 1.30; 95\% confidence interval, 1.05-1.61; P=0.016) after adjustment for potential confounding characteristics, including kidney disease. Serum phosphate concentration was significantly associated with incident AF in MESA (hazard ratio, 1.15 per 0.5 mg/dL; 95\% confidence interval, 1.02-1.31; P=0.023) but not CHS. In MESA, an association of low estimated glomerular filtration rate with incident AF was partially attenuated by adjustment for FGF-23.

CONCLUSION: Higher circulating FGF-23 concentration is associated with incident AF and may, in part, explain the link between chronic kidney disease and AF.

}, keywords = {Aged, Aged, 80 and over, Atrial Fibrillation, Comorbidity, Ethnic Groups, Female, Fibroblast Growth Factor 3, Follow-Up Studies, Glomerular Filtration Rate, Heart Failure, Humans, Hypertrophy, Left Ventricular, Male, Middle Aged, Phosphates, Proportional Hazards Models, Renal Insufficiency, Chronic, Risk Factors, United States, Ventricular Dysfunction, Left, Ventricular Remodeling, Vitamin D}, issn = {1524-4539}, doi = {10.1161/CIRCULATIONAHA.113.005499}, author = {Mathew, Jehu S and Sachs, Michael C and Katz, Ronit and Patton, Kristen K and Heckbert, Susan R and Hoofnagle, Andrew N and Alonso, Alvaro and Chonchol, Michel and Deo, Rajat and Ix, Joachim H and Siscovick, David S and Kestenbaum, Bryan and de Boer, Ian H} } @article {6662, title = {Fibroblast growth factor 23 and sudden versus non-sudden cardiac death: the Cardiovascular Health Study.}, journal = {Am J Kidney Dis}, volume = {66}, year = {2015}, month = {2015 Jul}, pages = {40-6}, abstract = {

BACKGROUND: Elevated fibroblast growth factor 23 (FGF-23) concentrations are associated with greater risk of cardiovascular events and mortality, especially among people with chronic kidney disease (CKD). Because individuals with CKD are at an increased risk of sudden cardiac death (SCD), we sought to understand whether FGF-23 level is a stronger risk factor for SCD versus non-SCD.

STUDY DESIGN: Cohort study.

SETTING \& PARTICIPANTS: 3,244 participants 65 years or older in the community-based Cardiovascular Health Study.

PREDICTOR: Plasma FGF-23 concentrations.

OUTCOMES: We assessed SCD and non-SCD in these analyses. SCD was adjudicated rigorously and was defined as a sudden pulseless condition of cardiac origin in a previously stable person occurring out of hospital or in the emergency department.

MEASUREMENTS: We estimated associations of baseline FGF-23 concentrations with SCD and non-SCD using Cox proportional hazards models after adjustment for demographics, cardiovascular risk factors, comorbid conditions, and kidney function. We also tested whether associations differed by CKD status.

RESULTS: During a median follow-up of 8.1 years, there were 118 adjudicated SCD and 570 non-SCD events. After multivariable adjustment for demographics, cardiovascular risk factors, comorbid conditions, and parameters of kidney function, higher FGF-23 concentrations were an independent risk factor for non-SCD (HR [per doubling], 1.17; 95\% CI, 1.06-1.30). However, elevated FGF-23 concentrations were not associated independently with SCD (HR [per doubling], 1.07; 95\% CI, 0.85-1.35). In stratified analysis by CKD status (36.5\% of cohort), doubling of FGF-23 concentrations was associated independently with non-SCD (adjusted HR, 1.26; 95\% CI, 1.10-1.45). A similar magnitude of association was observed between FGF-23 level and SCD in the CKD subgroup; however, it was not significant (HR, 1.20; 95\% CI, 0.89-1.62).

LIMITATIONS: Limited power to detect moderate-sized effects between FGF-23 level and SCD in both the primary and stratified analyses.

CONCLUSIONS: In this population-based study, FGF-23 level elevations were associated independently with non-SCD. Among individuals with CKD, the associations between FGF-23 level and SCD and non-SCD were similar.

}, keywords = {Aged, Aged, 80 and over, Biomarkers, Comorbidity, Death, Sudden, Cardiac, Electrocardiography, Female, Fibroblast Growth Factors, Follow-Up Studies, Heart Arrest, Heart Diseases, Humans, Kaplan-Meier Estimate, Male, Prospective Studies, Renal Insufficiency, Chronic, Risk Factors, Sympathetic Nervous System, United States}, issn = {1523-6838}, doi = {10.1053/j.ajkd.2014.10.025}, author = {Deo, Rajat and Katz, Ronit and de Boer, Ian H and Sotoodehnia, Nona and Kestenbaum, Bryan and Mukamal, Kenneth J and Chonchol, Michel and Sarnak, Mark J and Siscovick, David and Shlipak, Michael G and Ix, Joachim H} }