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  • 1
    Abstract: Background There is debate about the value of assessing levels of C-reactive protein (CRP) and other biomarkers of inflammation for the prediction of first cardiovascular events. Methods We analyzed data from 52 prospective studies that included 246,669 participants without a history of cardiovascular disease to investigate the value of adding CRP or fibrinogen levels to conventional risk factors for the prediction of cardiovascular risk. We calculated measures of discrimination and reclassification during follow-up and modeled the clinical implications of initiation of statin therapy after the assessment of CRP or fibrinogen. Results The addition of information on high-density lipoprotein cholesterol to a prognostic model for cardiovascular disease that included age, sex, smoking status, blood pressure, history of diabetes, and total cholesterol level increased the C-index, a measure of risk discrimination, by 0.0050. The further addition to this model of information on CRP or fibrinogen increased the C-index by 0.0039 and 0.0027, respectively (P 〈 0.001), and yielded a net reclassification improvement of 1.52% and 0.83%, respectively, for the predicted 10-year risk categories of "low" (〈 10%), " intermediate" (10% to 〈 20%), and "high" (〉= 20%) (P 〈 0.02 for both comparisons). We estimated that among 100,000 adults 40 years of age or older, 15,025 persons would initially be classified as being at intermediate risk for a cardiovascular event if conventional risk factors alone were used to calculate risk. Assuming that statin therapy would be initiated in accordance with Adult Treatment Panel III guidelines (i.e., for persons with a predicted risk of 〉= 20% and for those with certain other risk factors, such as diabetes, irrespective of their 10-year predicted risk), additional targeted assessment of CRP or fibrinogen levels in the 13,199 remaining participants at intermediate risk could help prevent approximately 30 additional cardiovascular events over the course of 10 years. Conclusions In a study of people without known cardiovascular disease, we estimated that under current treatment guidelines, assessment of the CRP or fibrinogen level in people at intermediate risk for a cardiovascular event could help prevent one additional event over a period of 10 years for every 400 to 500 people screened. (Funded by the British Heart Foundation and others.)
    Type of Publication: Journal article published
    PubMed ID: 23034020
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  • 2
    Abstract: Background The extent to which adult height, a biomarker of the interplay of genetic endowment and early-life experiences, is related to risk of chronic diseases in adulthood is uncertain. Methods We calculated hazard ratios (HRs) for height, assessed in increments of 6.5 cm, using individual-participant data on 174 374 deaths or major non-fatal vascular outcomes recorded among 1 085 949 people in 121 prospective studies. Results For people born between 1900 and 1960, mean adult height increased 0.5-1 cm with each successive decade of birth. After adjustment for age, sex, smoking and year of birth, HRs per 6.5 cm greater height were 0.97 (95% confidence interval: 0.96-0.99) for death from any cause, 0.94 (0.93-0.96) for death from vascular causes, 1.04 (1.03-1.06) for death from cancer and 0.92 (0.90-0.94) for death from other causes. Height was negatively associated with death from coronary disease, stroke subtypes, heart failure, stomach and oral cancers, chronic obstructive pulmonary disease, mental disorders, liver disease and external causes. In contrast, height was positively associated with death from ruptured aortic aneurysm, pulmonary embolism, melanoma and cancers of the pancreas, endocrine and nervous systems, ovary, breast, prostate, colorectum, blood and lung. HRs per 6.5 cm greater height ranged from 1.26 (1.12-1.42) for risk of melanoma death to 0.84 (0.80-0.89) for risk of death from chronic obstructive pulmonary disease. HRs were not appreciably altered after further adjustment for adiposity, blood pressure, lipids, inflammation biomarkers, diabetes mellitus, alcohol consumption or socio-economic indicators.
    Type of Publication: Journal article published
    PubMed ID: 22825588
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  • 3
    ISSN: 1540-8183
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Clinical factors and terminal events associated with sudden death in 51 patients were analyzed from among a multicenter experience of 864 recipients of first generation automatic implantable cardioverter defibrillator (AICD™) devices (single zone, committed, monophasic pulse with ≥1 epicardial patch electrode) during the period May 1982—February 1988. For these 51 patients, mean age was 58 years and atherosclerotic heart disease was present in 84%, with a history of ventricular fibrillation (VF) in 61%, and inducible sustained ventricular tachycardia (VT) in 84%; mean left ventricular ejection fraction was 0.26. Nearly 80% experienced one or more appropriate AICDT shocks during the median 9 month (range 0-46 months) period prior to death. Of 30 monitored deaths, the first documented terminal rhythm was VF in 12 (40%), VT in 8 (27%), and asystole or electromechanical dissociation in the remaining 10 (33%). Shocks were documented during terminal events in 21 (66%) of 32 witnessed cases of sudden death with activated devices. The proportion of monitored or witnessed sudden deaths that were known or presumed to be tachyarrhythmic (based on terminal VT, VF, or shocks) ranged from 69% (11/16 cases with activated/nondepleted devices and a defibrillation threshold [DFT] ≤ 20 J) to 81% (29/36 cases on intention-to-treat basis). Of 27 patients with known or presumed sudden tachyarrhythmic death, the AICD™ had been deactivated prior to death in 4 (15%); activated, but depleted in 4 (15%); activated/nondepleted, but with DFT of 25 J in 4 (15%); and activated/nondepleted, but without DFT testing in 4 (15%). The remaining 11 (41%) known or presumed sudden tachyarrhythmic deaths occurred in patients with activated/nondepleted devices and DFT ≤20 J; however, definite or suspected contributory factors (e.g., hematoma under epicardial patch, generator component failure, or drug-induced DFT rise) could be identified in 6 (55%) of 11 cases. Thus, in this first-generation AICD™ experience: 1) most sudden deaths occurred on the basis of a known or presumed tachyarrhythmia; and 2) an understanding of apparent “failure” of ICD therapy could often be gained through an integrated analysis of associated clinical factors and management practices, as well as device “hardware” function. These observations are likely to remain relevant, even with respect to newer generation ICDs.
    Type of Medium: Electronic Resource
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