Sudden cardiac death risk factor identification in hypertensive patients PH GACON 2, F.PILLON 1, F SUBTIL 3 1 UMR CNRS Service de Pharmacologie Clinique, Université Claude Bernard Lyon1. 2 Service de Cardiologie clinique et interventionnelle – Centre Régional Universitaire Dijon 3 Service de Biostatistiques ACC Genève, 18 Octobre 2014 INTRODUCTION No significant interactions between the study and the treatment treatment group were found. No interaction was observed between the treatment group and the covariates that were significant in the multivariate analysis. A significant quantitative interaction was observed between the study MFRIT and systolic blood pressure: the odds ratio obtained for studies other than MRFIT was found to be 0.86 (95% CI: 0.83, 1.24) and not significant (p = 0.27). Thus, the effect of systolic blood pressure in the MRFIT was different from the effect observed in other studies METHODES Sudden cardiac death is defined as an unexplained death within 24 hours after onset of symptoms or earlier. It is a traumatic event for the patient's family. Ways of acting are limited and prevention is of primary importance. For long, its prevention has been confounded with coronary artery disease prevention. However, recent studies suggest that sudden cardiac death might be a distinct condition, whose occurrence cannot be diminished by using blood pressure lowering medication. Further research for risk factors for sudden cardiac death is necessary to identify situations in which a preventive strategy would be particularly relevant. RESULTS CONCLUSIONS This study shows that in hypertensive patients, the covariates including age, sex, smoking, systolic blood pressure, high cholesterol, which are risk factors for coronary events, are risk factors for sudden cardiac death. The patients (16 058) included were enrolled in five randomized, controlled clinical studies, available through the INDANA research program (COOPE, MRFIT, EWPHE, STOP, SYSTEUR studies). These studies assessed the benefits of antihypertensive treatments against placebo or absence of treatment in hypertensive patients. The endpoint was the occurrence of sudden cardiac death. Various covariates were taken into account, including age, sex, smoking, history of atrial fibrillation, of heart failure, of myocardial infarction and of stroke, systolic blood pressure, diastolic blood pressure, body mass index, blood glucose, cholesterol, creatinine level, potassium level, heart rate. Baseline factors were related to risk of sudden cardiac death by logistic regression, adjusting for trial and treatment group. The model, builds on 2/3 of the patients, was converted to a risk score, validated on the remaining third of patients. In a univariate analysis, the following parameters were significantly linked with the incidence of sudden death: age, the male gender, smoker, myocardial infarction history, diastolic blood pressure, heart failure history and cholesterolemia. In a multivariate analysis, we found that the risk for sudden cardiac death multiplied: - by 1.95 (95% CI: 1.87, 2.03) every 10 years of age (p = 0.001), - by 4.16 (95% CI: 1.45, 11.89) in men compared to women (p = 0.007), - by 1.91 (95% CI: 1.21, 3.00) in smokers compared to non-smokers (p = 0.005). The rise of 1 cmHg in systolic blood pressure multiplied by 1.14 (95% CI: 1.13, 1.16) the risk for sudden cardiac death (p = 0.03), and of 1 mmol / L cholesterol by 1.36 (95% CI: 1.11, 1.67) (p = 0.002). REFERENCES CovariatesβOdds Ratio (95%CI)p-value Age (10 years)-0,240,78 (0,77-0,79)< 0.01 Male sex1,424,16 (2,15-8,02)< 0.01 Smoker0,952,60 (1,72-3,92)< 0.01 History of myocardial infarction0,862,37 (1,14-4,94)0,02 history of stroke-1,360,25 (0,03-1,84)0,17 Systolic blood pressure (10 mm Hg)-0,0670,93 (0,82-1,14)0,12 Diastolic blood pressure (10 mm Hg)-0,310,73 (0,72-0,74)< 0.01 BMI (22-25)-0,370,68 (0,27-1,69)0,41 BMI (> 25)-0,110,88 (0,40-1,93)0,76 Blood glucose (mmol/L)0,0311,03 (0,88-1,20)0,69 Serum creatinine (μmol/L)0,0061,006 (0,99-1,01)0,24 History of heart failure1,384,00 (1,44-11,08)< 0.01 Total cholesterol level(mmol/L)0,251,29 (1,12-1,49)0,00 Heart rate (10 bpm)-0,010,998 (0,992-1)0,64 Serum potassium (mmol/L)0,071,07 (0,68-1,69)0,74 CovariatesCoefficient βOdds-ratio (IC : 95%)p-value Age (10 years)6,70E-011,95 (1,87-2,03)0,001 Male gender1,43E+004,16 (1,45-11,89)0,007 Smoking6,48E-011,91(1,21-3,00)0,005 Systolic blood pressure (10 mmHg) 1,37E-011,14 (1,13-1,16)0,035 Total cholesterol level 3,13E-011,36 (1,11-1,67)0,002 Study Odds-Ratio for MRFIT (95% CI) p-value Odds-Ratio for other studies than MRFIT (95% CI) p-value Systolic blood pressure MRFIT1,46 (1,42-1,51)0,010,86 (0,83-1,24)0,27 1.Mimouni Y, LeDigarcher A, Armanet M, Bejan Angoulvant T, Chevalier P, Gueyffier F. Blood pressure drugs do not decrease the risk of sudden death. European Society of Hypertension, Milan Hadj Sadok S, Clave G, Israel H, Pillon F, Gueyffier F. Do Statins prevent sudden cardiac death in all patients? EuroMeeting March 2012, Copenhagen. 3.Dalhöf B, Lindholm L, Hansson L, Shersten B, Ekbom T, Wester PO. Morbidity and mortality in the Swedish Trial in Old Patient with Hypertension (STOP-Hypertension). Lancet. 1991; 338: Amery A, Birkenhäger W, Brixho P, Bulpitt C, Clément D, Deruyttere M, De Schaepdryver A, Dollery C, Fagard R, Forette F, Forte J, Hamdy R, Henry JF, Joossens JV, Leonetti G, Lund-Johansen P, O’Malley K, Petrie J, Strasser T, Tuomilheto J, Williams B. Mortality and morbidity results from the European Working Party on High Blood Pressure in the Elderly Trial. Lancet. 1985;i: Amery A, Birkenhâger W, Bulpitt C, Clément D, De Leeuw P, Dollery C, Fagard R, Fletcher A, Forette F, Leonetti G, O’Brien O, O’Malley K, Rodicio J, Rosenfeld J, Staessen J, Strasser T, Terzoli L, Thijs L, Tuomilehto J, Webster J. Syst-Eur. A multicentre trial on the treatment of isolated systolic hypertension in the elderly: objectives, protocol, and organization. Aging 1991; 3: Coope J, Warender TS. Randomised trial of treatment of hypertension in elderly patients in primary care. Br Med J 1986; 293: