0401: Which parameters can predict the response to exercise training in cardiac patients?

AimsBenefit effects of exercise training are well known and validated after a cardiac event, but some patients fail to ameliorate their functional capacity. This retrospective study determined which parameters in the initial cardio pulmonary exercise test could predict an improvement of functional capacity after training in cardiac patients.Methods and results292 cardiac patients with a complete training intervention were divided in two groups at the end of their rehabilitation : one group with a gain equal or more than 1 MET (148 patients) and one group with a gain less than 1 MET (144 patients) when the initial and final cardio pulmonary exercise tests were compared. The cardiac event (coronary revascularization 38%, aortic valvular surgery 23%, coronary stenting 18%) was similar in both group. The initial peak VO2 was not different (100 watts vs 110 watts, 15.6ml/kg/min vs 16.1ml/kg/min) neither the ventilator threshold nor the training intervention (19.3 sessions vs 17.9). At the end of the exercise training intervention, the gain of peak VO2 was 4.1ml/kg/min (+28%) in the global population and 6.8ml/kg/min (+46%) in the group ≥1 METS vs 1.29ml/kg/min (9.3%) in the group < 1 MET. Clinical predictor factors for a gain ≥1 MET were: age (58.3 years vs 62**p < 0,05), sex male (92% vs 83%*), ejection fraction (LVEF 52,5% vs 49,9%****p < 0,001). The initial discriminated exercise parameters were the energetic cost per watt (VO2/watt) 11,4 vs 12,2** the ventilatory cost (VE/watt) 0.62 vs 0.67*, the intensity per body kilogram (watts/kg) 1.43 vs 1.31* and the cardiac frequency per 1 liter of VO2 was lower 102 vs 110*.ConclusionThe benefit on functional capacity after exercise training intervention depended more of the initial physical condition than of the cardiac pathology in patients discharged in our cardiac rehabilitation centers. The exercise training should be more directed by the initial excise test

Penetrance estimation of Alzheimer disease in SORL1 loss-of-function variant carriers using a family-based strategy and stratification by APOE genotypes

International audienceAbstract Background Alzheimer disease (AD) is a common complex disorder with a high genetic component. Loss-of-function (LoF) SORL1 variants are one of the strongest AD genetic risk factors. Estimating their age-related penetrance is essential before putative use for genetic counseling or preventive trials. However, relative rarity and co-occurrence with the main AD risk factor, APOE -ε4, make such estimations difficult. Methods We proposed to estimate the age-related penetrance of SORL1 -LoF variants through a survival framework by estimating the conditional instantaneous risk combining (i) a baseline for non-carriers of SORL1- LoF variants, stratified by APOE-ε4 , derived from the Rotterdam study ( N = 12,255), and (ii) an age-dependent proportional hazard effect for SORL1- LoF variants estimated from 27 extended pedigrees (including 307 relatives ≥ 40 years old, 45 of them having genotyping information) recruited from the French reference center for young Alzheimer patients. We embedded this model into an expectation-maximization algorithm to accommodate for missing genotypes. To correct for ascertainment bias, proband phenotypes were omitted. Then, we assessed if our penetrance curves were concordant with age distributions of APOE -ε4-stratified SORL1- LoF variant carriers detected among sequencing data of 13,007 cases and 10,182 controls from European and American case-control study consortia. Results SORL1- LoF variants penetrance curves reached 100% (95% confidence interval [99–100%]) by age 70 among APOE -ε4ε4 carriers only, compared with 56% [40–72%] and 37% [26–51%] in ε4 heterozygous carriers and ε4 non-carriers, respectively. These estimates were fully consistent with observed age distributions of SORL1- LoF variant carriers in case-control study data. Conclusions We conclude that SORL1- LoF variants should be interpreted in light of APOE genotypes for future clinical applications