@article {1042, title = {Novel measures of heart rate variability predict cardiovascular mortality in older adults independent of traditional cardiovascular risk factors: the Cardiovascular Health Study (CHS).}, journal = {J Cardiovasc Electrophysiol}, volume = {19}, year = {2008}, month = {2008 Nov}, pages = {1169-74}, abstract = {

UNLABELLED: Novel HRV Predicts CV Mortality in the Elderly.

BACKGROUND: It is unknown whether abnormal heart rate turbulence (HRT) and abnormal fractal properties of heart rate variability identify older adults at increased risk of cardiovascular death (CVdth).

METHODS: Data from 1,172 community-dwelling adults, ages 72 +/- 5 (65-93) years, who participated in the Cardiovascular Health Study (CHS), a study of risk factors for CV disease in people >or=65 years. HRT and the short-term fractal scaling exponent (DFA1) derived from 24-hour Holter recordings. HRT categorized as: normal (turbulence slope [TS] and turbulence onset [TO] normal) or abnormal (TS and/or TO abnormal). DFA1 categorized as low (1). Cox regression analyses stratified by Framingham Risk Score (FRS) strata (low = <10, mid = 10-20, and high >20) and adjusted for prevalent clinical cardiovascular disease (CVD), diabetes, and quartiles of ventricular premature beat counts (VPCs).

RESULTS: CVdths (N = 172) occurred over a median follow-up of 12.3 years. Within each FRS stratum, low DFA1 + abnormal HRT predicted risk of CVdth (RR = 7.7 for low FRS; 3.6, mid FRS; 2.8, high FRS). Among high FRS stratum participants, low DFA1 alone also predicted CVdth (RR = 2.0). VPCs in the highest quartile predicted CVdth, but only in the high FRS group. Clinical CV disease predicted CVdth at each FRS stratum (RR = 2.9, low; 2.6, mid; and 1.9, high). Diabetes predicted CVdth in the highest FRS group only (RR = 2.2).

CONCLUSIONS: The combination of low DFA1 + abnormal HRT is a strong risk factor for CVdth among older adults even after adjustment for conventional CVD risk measures and the presence of CVD.

}, keywords = {Aged, Aged, 80 and over, Arrhythmias, Cardiac, Death, Sudden, Cardiac, Electrocardiography, Ambulatory, Female, Heart Rate, Humans, Male, Maryland, Reproducibility of Results, Risk Assessment, Risk Factors, Sensitivity and Specificity, Survival Analysis, Survival Rate}, issn = {1540-8167}, doi = {10.1111/j.1540-8167.2008.01232.x}, author = {Stein, Phyllis K and Barzilay, Joshua I and Chaves, Paulo H M and Mistretta, Stephanie Q and Domitrovich, Peter P and Gottdiener, John S and Rich, Michael W and Kleiger, Robert E} } @article {1138, title = {N-terminal pro-B-type natriuretic peptide is a major predictor of the development of atrial fibrillation: the Cardiovascular Health Study.}, journal = {Circulation}, volume = {120}, year = {2009}, month = {2009 Nov 03}, pages = {1768-74}, abstract = {

BACKGROUND: Atrial fibrillation (AF), the most common cardiac rhythm abnormality, is associated with significant morbidity, mortality, and healthcare expenditures. Elevated B-type natriuretic peptide levels have been associated with the risk of heart failure, AF, and mortality.

METHODS AND RESULTS: The relation between N-terminal pro-B-type natriuretic peptide (NT-proBNP) and AF was studied in 5445 Cardiovascular Health Study participants with the use of relative risk regression for predicting prevalent AF and Cox proportional hazards for predicting incident AF. NT-proBNP levels were strongly associated with prevalent AF, with an unadjusted prevalence ratio of 128 for the highest quintile (95\% confidence interval, 17.9 to 913.3; P<0.001) and adjusted prevalence ratio of 147 for the highest quintile (95\% confidence interval, 20.4 to 1064.3; P<0.001) compared with the lowest. After a median follow-up of 10 years (maximum of 16 years), there were 1126 cases of incident AF (a rate of 2.2 per 100 person-years). NT-proBNP was highly predictive of incident AF, with an unadjusted hazard ratio of 5.2 (95\% confidence interval, 4.3 to 6.4; P<0.001) for the development of AF for the highest quintile compared with the lowest; for the same contrast, NT-proBNP remained the strongest predictor of incident AF after adjustment for an extensive number of covariates, including age, sex, medication use, blood pressure, echocardiographic parameters, diabetes mellitus, and heart failure, with an adjusted hazard ratio of 4.0 (95\% confidence interval, 3.2 to 5.0; P<0.001).

CONCLUSIONS: In a community-based population of older adults, NT-proBNP was a remarkable predictor of incident AF, independent of any other previously described risk factor.

}, keywords = {Aged, Aged, 80 and over, Atrial Fibrillation, Female, Humans, Immunoassay, Longitudinal Studies, Male, Natriuretic Peptide, Brain, Peptide Fragments, Predictive Value of Tests, Prevalence, Proportional Hazards Models, Risk Factors}, issn = {1524-4539}, doi = {10.1161/CIRCULATIONAHA.109.873265}, author = {Patton, Kristen K and Ellinor, Patrick T and Heckbert, Susan R and Christenson, Robert H and DeFilippi, Christopher and Gottdiener, John S and Kronmal, Richard A} } @article {1242, title = {N-terminal pro-B-type natriuretic peptide is associated with sudden cardiac death risk: the Cardiovascular Health Study.}, journal = {Heart Rhythm}, volume = {8}, year = {2011}, month = {2011 Feb}, pages = {228-33}, abstract = {

BACKGROUND: Sudden cardiac death (SCD), the cause of 250,000-450,000 deaths per year, is a major public health problem. The majority of those affected do not have a prior cardiovascular diagnosis. Elevated B-type natriuretic peptide levels have been associated with the risk of heart failure and mortality as well as with sudden death in women.

OBJECTIVE: The purpose of this study was to examine the relationship between N-terminal pro-B-type natriuretic peptide (NT-proBNP) and SCD in the Cardiovascular Health Study population.

METHODS: The risk of SCD associated with baseline NT-proBNP was examined in 5,447 participants. Covariate-adjusted Cox model regressions were used to estimate the hazard ratios of developing SCD as a function of baseline NT-proBNP.

RESULTS: Over a median follow-up of 12.5 years (maximum 16), there were 289 cases of SCD. Higher NT-proBNP levels were strongly associated with SCD, with an unadjusted hazard ratio of 4.2 (95\% confidence interval [2.9, 6.1]; P <.001) in the highest quintile compared with in the lowest. NT-proBNP remained associated with SCD even after adjustment for numerous clinical characteristics and risk factors (age, sex, race, and other associated conditions), with an adjusted hazard ratio for the fifth versus the first quintile of 2.5 (95\% confidence interval [1.6, 3.8]; P <.001).

CONCLUSION: NT-proBNP provides information regarding the risk of SCD in a community-based population of older adults, beyond other traditional risk factors. This biomarker may ultimately prove useful in targeting the population at risk with aggressive medical management of comorbid conditions.

}, keywords = {Age Distribution, Aged, Biomarkers, Cardiovascular Diseases, Cohort Studies, Confidence Intervals, Death, Sudden, Cardiac, Female, Humans, Incidence, Kaplan-Meier Estimate, Male, Middle Aged, Natriuretic Peptide, Brain, Peptide Fragments, Predictive Value of Tests, Proportional Hazards Models, Retrospective Studies, Risk Assessment, Sex Distribution, Time Factors, United States}, issn = {1556-3871}, doi = {10.1016/j.hrthm.2010.10.038}, author = {Patton, Kristen K and Sotoodehnia, Nona and DeFilippi, Christopher and Siscovick, David S and Gottdiener, John S and Kronmal, Richard A} } @article {8008, title = {NT -pro BNP as a Mediator of the Racial Difference in Incident Atrial Fibrillation and Heart Failure.}, journal = {J Am Heart Assoc}, volume = {8}, year = {2019}, month = {2019 Apr 02}, pages = {e010868}, abstract = {

Background Blacks harbor more cardiovascular risk factors than whites, but experience less atrial fibrillation ( AF ). Conversely, whites may have a lower risk of heart failure ( CHF ). N-terminal pro-B-type natriuretic peptide ( NT -pro BNP) levels are higher in whites, predict incident AF , and have diuretic effects in the setting of increased ventricular diastolic pressures, potentially providing a unifying explanation for these racial differences. Methods and Results We used data from the CHS (Cardiovascular Health Study) to determine the degree to which baseline NT -pro BNP levels mediate the relationships between race and incident AF and CHF by comparing beta estimates between models with and without NT -pro BNP . The ARIC (Atherosclerosis Risk in Communities) study was used to assess reproducibility. Among 4731 CHS (770 black) and 12~418 ARIC (3091 black) participants, there were 1277 and 1253 incident AF events, respectively. Whites had higher baseline NT -pro BNP ( CHS : 40\% higher than blacks; 95\% CI , 29-53; ARIC : 39\% higher; 95\% CI , 33-46) and had a greater risk of incident AF compared with blacks ( CHS : adjusted hazard ratio, 1.60; 95\% CI , 1.31-1.93; ARIC : hazard ratio, 1.93; 95\% CI , 1.57-2.27). NT -pro BNP levels explained a significant proportion of the racial difference in AF risk ( CHS : 36.2\%; 95\% CI , 23.2-69.2\%; ARIC : 24.6\%; 95\% CI , 14.8-39.6\%). Contrary to our hypothesis, given an increased risk of CHF among whites in CHS (adjusted hazard ratio, 1.20; 95\% CI , 1.05-1.47) and the absence of a significant association between race and CHF in ARIC (adjusted hazard ratio, 1.07; 95\% CI , 0.94-1.23), CHF -related mediation analyses were not performed. Conclusions A substantial portion of the relationship between race and AF was statistically explained by baseline NT -pro BNP levels. No consistent relationship between race and CHF was observed.

}, issn = {2047-9980}, doi = {10.1161/JAHA.118.010868}, author = {Whitman, Isaac R and Vittinghoff, Eric and deFilippi, Christopher R and Gottdiener, John S and Alonso, Alvaro and Psaty, Bruce M and Heckbert, Susan R and Hoogeveen, Ron C and Arking, Dan E and Selvin, Elizabeth and Chen, Lin Y and Dewland, Thomas A and Marcus, Gregory M} }