ECHOCARDIOGRAPHIC PARAMETERS IN ATHLETES OF DIFFERENT SPORTS

Competitive athletics is often associated with moderate left ventricular (LV) hypertrophy, and it has been hypothesized that training mode and type of exercise modulates long-term cardiac adaptation. The purpose of the study was to compare cardiac structure and function among athletes of various sports and sedentary controls. Standard transthoracic two-dimensional M-mode and Doppler echocardiography was performed at rest in Caucasian male canoe/kayak paddlers (n = 9), long distance runners (LDR, n = 18), middle distance runners (MDR, n = 17), basketball players (BP, n = 31), road cyclists (n = 8), swimmers (n = 10), strength/power athletes (n = 9) of similar age (range, 15 to 31 yrs), training experience (4 to 9 years), and age-matched healthy male sedentary controls (n = 15). Absolute interventricular septum (IVS) thickness and LV wall thickness, but not LV diameter, were greater in athletes than sedentary controls. Left ventricular mass of all athletes but relative wall thickness of only BP, swimmers, cyclists, and strength/power athletes were higher as compared with controls (p < 0.05). Among athletes, smaller IVS thickness was observed in MDR than BP, cyclists, swimmers or strength/power athletes, while LDR had higher body size-adjusted LV diameter as compared to BP, cyclists and strength/power athletes. In conclusion, relative LV diameter was increased in long distance runners as compared with basketball players, cyclists, and strength/power athletes. Basketball, road cycling, strength/power, and swimming training were associated with increased LV concentricity as compared with paddling or distance runnin

Dual endothelin antagonist aprocitentan for resistant hypertension (PRECISION): a multicentre, blinded, randomised, parallel-group, phase 3 trial

Auteurs : the PRECISION investigatorsInternational audienceBackground Resistant hypertension is associated with increased cardiovascular risk. The endothelin pathway has been implicated in the pathogenesis of hypertension, but it is currently not targeted therapeutically, thereby leaving this relevant pathophysiological pathway unopposed with currently available drugs. The aim of the study was to assess the blood pressure lowering efficacy of the dual endothelin antagonist aprocitentan in patients with resistant hypertension. Methods PRECISION was a multicentre, blinded, randomised, parallel-group, phase 3 study, which was done in hospitals or research centres in Europe, North America, Asia, and Australia. Patients were eligible for randomisation if their sitting systolic blood pressure was 140 mm Hg or higher despite taking standardised background therapy consisting of three antihypertensive drugs, including a diuretic. The study consisted of three sequential parts: part 1 was the 4-week double-blind, randomised, and placebo-controlled part, in which patients received aprocitentan 12•5 mg, aprocitentan 25 mg, or placebo in a 1:1:1 ratio; part 2 was a 32-week single (patient)-blind part, in which all patients received aprocitentan 25 mg; and part 3 was a 12-week double-blind, randomised, and placebo-controlled withdrawal part, in which patients were re-randomised to aprocitentan 25 mg or placebo in a 1:1 ratio. The primary and key secondary endpoints were changes in unattended office systolic blood pressure from baseline to week 4 and from withdrawal baseline to week 40, respectively. Secondary endpoints included 24-h ambulatory blood pressure changes. The study is registered on ClinicalTrials.gov, NCT03541174. Findings The PRECISION study was done from June 18, 2018, to April 25, 2022. 1965 individuals were screened and 730 were randomly assigned. Of these 730 patients, 704 (96%) completed part 1 of the study; of these, 613 (87%) completed part 2 and, of these, 577 (94%) completed part 3 of the study. The least square mean (SE) change in office systolic blood pressure at 4 weeks was-15•3 (SE 0•9) mm Hg for aprocitentan 12•5 mg,-15•2 (0•9) mm Hg for aprocitentan 25 mg, and-11•5 (0•9) mm Hg for placebo, for a difference versus placebo of-3•8 (1•3) mm Hg (97•5% CI-6•8 to-0•8, p=0•0042) and-3•7 (1•3) mm Hg (-6•7 to-0•8; p=0•0046), respectively. The respective difference for 24 h ambulatory systolic blood pressure was-4•2 mm Hg (95% CI-6•2 to-2•1) and-5•9 mm Hg (-7•9 to-3•8). After 4 weeks of withdrawal, office systolic blood pressure significantly increased with placebo versus aprocitentan (5•8 mm Hg, 95% CI 3•7 to 7•9, p<0•0001). The most frequent adverse event was mild-to-moderate oedema or fluid retention, occurring in 9%, 18%, and 2% for patients receiving aprocitentan 12•5 mg, 25 mg, and placebo, during the 4-week double-blind part, respectively. This event led to discontinuation in seven patients treated with aprocitentan. During the trial, a total of 11 treatment-emergent deaths occurred, none of which were regarded by the investigators to be related to study treatment. Interpretation In patients with resistant hypertension, aprocitentan was well tolerated and superior to placebo in lowering blood pressure at week 4 with a sustained effect at week 40