@article {1039, title = {Ankle brachial index combined with Framingham Risk Score to predict cardiovascular events and mortality: a meta-analysis.}, journal = {JAMA}, volume = {300}, year = {2008}, month = {2008 Jul 09}, pages = {197-208}, abstract = {

CONTEXT: Prediction models to identify healthy individuals at high risk of cardiovascular disease have limited accuracy. A low ankle brachial index (ABI) is an indicator of atherosclerosis and has the potential to improve prediction.

OBJECTIVE: To determine if the ABI provides information on the risk of cardiovascular events and mortality independently of the Framingham risk score (FRS) and can improve risk prediction.

DATA SOURCES: Relevant studies were identified. A search of MEDLINE (1950 to February 2008) and EMBASE (1980 to February 2008) was conducted using common text words for the term ankle brachial index combined with text words and Medical Subject Headings to capture prospective cohort designs. Review of reference lists and conference proceedings, and correspondence with experts was conducted to identify additional published and unpublished studies.

STUDY SELECTION: Studies were included if participants were derived from a general population, ABI was measured at baseline, and individuals were followed up to detect total and cardiovascular mortality.

DATA EXTRACTION: Prespecified data on individuals in each selected study were extracted into a combined data set and an individual participant data meta-analysis was conducted on individuals who had no previous history of coronary heart disease.

RESULTS: Sixteen population cohort studies fulfilling the inclusion criteria were included. During 480,325 person-years of follow-up of 24,955 men and 23,339 women, the risk of death by ABI had a reverse J-shaped distribution with a normal (low risk) ABI of 1.11 to 1.40. The 10-year cardiovascular mortality in men with a low ABI (< or = 0.90) was 18.7\% (95\% confidence interval [CI], 13.3\%-24.1\%) and with normal ABI (1.11-1.40) was 4.4\% (95\% CI, 3.2\%-5.7\%) (hazard ratio [HR], 4.2; 95\% CI, 3.3-5.4). Corresponding mortalities in women were 12.6\% (95\% CI, 6.2\%-19.0\%) and 4.1\% (95\% CI, 2.2\%-6.1\%) (HR, 3.5; 95\% CI, 2.4-5.1). The HRs remained elevated after adjusting for FRS (2.9 [95\% CI, 2.3-3.7] for men vs 3.0 [95\% CI, 2.0-4.4] for women). A low ABI (< or = 0.90) was associated with approximately twice the 10-year total mortality, cardiovascular mortality, and major coronary event rate compared with the overall rate in each FRS category. Inclusion of the ABI in cardiovascular risk stratification using the FRS would result in reclassification of the risk category and modification of treatment recommendations in approximately 19\% of men and 36\% of women.

CONCLUSION: Measurement of the ABI may improve the accuracy of cardiovascular risk prediction beyond the FRS.

}, keywords = {Adult, Age Factors, Aged, Aged, 80 and over, Ankle, Atherosclerosis, Blood Pressure, Brachial Artery, Cardiovascular Diseases, Cohort Studies, Confidence Intervals, Female, Global Health, Humans, Male, Middle Aged, Odds Ratio, Predictive Value of Tests, Risk Assessment, Risk Factors, Severity of Illness Index}, issn = {1538-3598}, doi = {10.1001/jama.300.2.197}, author = {Fowkes, F G R and Murray, G D and Butcher, I and Heald, C L and Lee, R J and Chambless, L E and Folsom, A R and Hirsch, A T and Dramaix, M and deBacker, G and Wautrecht, J-C and Kornitzer, M and Newman, A B and Cushman, M and Sutton-Tyrrell, K and Fowkes, F G R and Lee, A J and Price, J F and D{\textquoteright}Agostino, R B and Murabito, J M and Norman, P E and Jamrozik, K and Curb, J D and Masaki, K H and Rodr{\'\i}guez, B L and Dekker, J M and Bouter, L M and Heine, R J and Nijpels, G and Stehouwer, C D A and Ferrucci, L and McDermott, M M and Stoffers, H E and Hooi, J D and Knottnerus, J A and Ogren, M and Hedblad, B and Witteman, J C and Breteler, M M B and Hunink, M G M and Hofman, A and Criqui, M H and Langer, R D and Fronek, A and Hiatt, W R and Hamman, R and Resnick, H E and Guralnik, J and McDermott, M M} } @article {6061, title = {Association of heat shock proteins with all-cause mortality.}, journal = {Age (Dordr)}, volume = {35}, year = {2013}, month = {2013 Aug}, pages = {1367-76}, abstract = {

Experimental mild heat shock is widely known as an intervention that results in extended longevity in various models along the evolutionary lineage. Heat shock proteins (HSPs) are highly upregulated immediately after a heat shock. The elevation in HSP levels was shown to inhibit stress-mediated cell death, and recent experiments indicate a highly versatile role for these proteins as inhibitors of programmed cell death. In this study, we examined common genetic variations in 31 genes encoding all members of the HSP70, small HSP, and heat shock factor (HSF) families for their association with all-cause mortality. Our discovery cohort was the Rotterdam study (RS1) containing 5,974 participants aged 55 years and older (3,174 deaths). We assessed 4,430 single nucleotide polymorphisms (SNPs) using the HumanHap550K Genotyping BeadChip from Illumina. After adjusting for multiple testing by permutation analysis, three SNPs showed evidence for association with all-cause mortality in RS1. These findings were followed in eight independent population-based cohorts, leading to a total of 25,007 participants (8,444 deaths). In the replication phase, only HSF2 (rs1416733) remained significantly associated with all-cause mortality. Rs1416733 is a known cis-eQTL for HSF2. Our findings suggest a role of HSF2 in all-cause mortality.

}, keywords = {Aged, 80 and over, Aging, Cause of Death, Forecasting, Genotype, Heat-Shock Proteins, Humans, Longevity, Promoter Regions, Genetic, Retrospective Studies, Transcription, Genetic, United States}, issn = {1574-4647}, doi = {10.1007/s11357-012-9417-7}, author = {Broer, L and Demerath, E W and Garcia, M E and Homuth, G and Kaplan, R C and Lunetta, K L and Tanaka, T and Tranah, G J and Walter, S and Arnold, A M and Atzmon, G and Harris, T B and Hoffmann, W and Karasik, D and Kiel, D P and Kocher, T and Launer, L J and Lohman, K K and Rotter, J I and Tiemeier, H and Uitterlinden, A G and Wallaschofski, H and Bandinelli, S and D{\"o}rr, M and Ferrucci, L and Franceschini, N and Gudnason, V and Hofman, A and Liu, Y and Murabito, J M and Newman, A B and Oostra, B A and Psaty, B M and Smith, A V and van Duijn, C M} } @article {6803, title = {Development and validation of an ankle brachial index risk model for the prediction of cardiovascular events.}, journal = {Eur J Prev Cardiol}, volume = {21}, year = {2014}, month = {2014 Mar}, pages = {310-20}, abstract = {

BACKGROUND: The ankle brachial index (ABI) is related to risk of cardiovascular events independent of the Framingham risk score (FRS). The aim of this study was to develop and evaluate a risk model for cardiovascular events incorporating the ABI and FRS.

DESIGN: An analysis of participant data from 18 cohorts in which 24,375 men and 20,377 women free of coronary heart disease had ABI measured and were followed up for events.

METHODS: Subjects were divided into a development and internal validation dataset and an external validation dataset. Two models, comprising FRS and FRS + ABI, were fitted for the primary outcome of major coronary events.

RESULTS: In predicting events in the external validation dataset, C-index for the FRS was 0.672 (95\% CI 0.599 to 0.737) in men and 0.578 (95\% CI 0.492 to 0.661) in women. The FRS + ABI led to a small increase in C-index in men to 0.685 (95\% CI 0.612 to 0.749) and large increase in women to 0.690 (95\% CI 0.605 to 0.764) with net reclassification improvement (NRI) of 4.3\% (95\% CI 0.0 to 7.6\%, p = 0.050) and 9.6\% (95\% CI 6.1 to 16.4\%, p < 0.001), respectively. Restricting the FRS + ABI model to those with FRS intermediate 10-year risk of 10 to 19\% resulted in higher NRI of 15.9\% (95\% CI 6.1 to 20.6\%, p < 0.001) in men and 23.3\% (95\% CI 13.8 to 62.5\%, p = 0.002) in women. However, incorporating ABI in an improved newly fitted risk factor model had a nonsignificant effect: NRI 2.0\% (95\% CI 2.3 to 4.2\%, p = 0.567) in men and 1.1\% (95\% CI 1.9 to 4.0\%, p = 0.483) in women.

CONCLUSIONS: An ABI risk model may improve prediction especially in individuals at intermediate risk and when performance of the base risk factor model is modest.

}, keywords = {Adult, Aged, Aged, 80 and over, Ankle Brachial Index, Cardiovascular Diseases, Europe, European Continental Ancestry Group, Female, Humans, Male, Middle Aged, Models, Statistical, Predictive Value of Tests, Prognosis, Reproducibility of Results, Risk Assessment, Risk Factors, Sex Factors, Time Factors, United States, Young Adult}, issn = {2047-4881}, doi = {10.1177/2047487313516564}, author = {Fowkes, F G R and Murray, G D and Butcher, I and Folsom, A R and Hirsch, A T and Couper, D J and deBacker, G and Kornitzer, M and Newman, A B and Sutton-Tyrrell, K C and Cushman, M and Lee, A J and Price, J F and D{\textquoteright}Agostino, R B and Murabito, J M and Norman, Pe and Masaki, K H and Bouter, L M and Heine, R J and Stehouwer, C D A and McDermott, M M and Stoffers, H E J H and Knottnerus, J A and Ogren, M and Hedblad, B and Koenig, W and Meisinger, C and Cauley, J A and Franco, Oh and Hunink, M G M and Hofman, A and Witteman, J C and Criqui, M H and Langer, R D and Hiatt, W R and Hamman, R F} }