We acknowledge the value of CT in quantitative assessment of valvular macrocalcifications. in men (all p 0.01). In Cox regression analyses, moderate/severe AVC at baseline was associated with a 2.5-fold (95%?CI 1.64 to 3.80) higher hazard rate of major cardiovascular events in women, and a 2.2-fold higher hazard rate in men (95%?CI 1.54 to 3.17) (both p 0.001), after adjustment for age, hypertension, study treatment, aortic compliance, left ventricular (LV) mass and systolic function, AS severity and hs-CRP. Moderate/severe AVC at baseline also predicted a 1.8-fold higher hazard rate of all-cause mortality in men (95%?CI 1.04 to 3.06, p 0.05) Rilpivirine (R 278474, TMC 278) independent of age, AS severity, LV mass and aortic compliance, but not in women. Conclusion In conclusion, AVC scored by echocardiography has sex-specific characteristics in AS. Moderate/severe AVC is associated with higher cardiovascular morbidity in both sexes, and with higher all-cause mortality in men. Trial registration number ClinicalTrials.gov identifier: “type”:”clinical-trial”,”attrs”:”text”:”NCT00092677″,”term_id”:”NCT00092677″NCT00092677 that women have significantly lower aortic valve calcification (AVC) load than men independent of the severity of AS.3 From this, sex-specific cut-off values for Agatston score indicating severe AS were developed and validated.3 4 Although cardiac CT more accurately measures AVC in AS and may help identify severe AS in asymptomatic patients with discordantly graded AS by conventional echocardiographic measures, it is not recommended by current guidelines as a routine test in patients with AS.5 While CT primarily quantifies areas of valvular macrocalcification, recent studies by positron emission tomography have revealed that AVC also includes inflammation and microcalcification. 6 7 Since different processes involved Rilpivirine (R 278474, TMC 278) in AVC are reflected by echocardiography and CT, AVC by echocardiography is not synonymous with AVC assessed by CT.8 The association of AVC scored by echocardiography with higher rates of combined aortic valve replacement and death has previously been documented in two studies by Rosenhek em et al. /em 9 10 However, sex-specific risk factors and prognostic implications of AVC scored by echocardiography have not been published from a large, prospective study. This was the aim of the present study. Methods Study population The present analysis of the SEAS study included the 1725 men and women (92% of the total study population) that had images available for AVC scoring on the baseline echocardiogram. Compared with ineligible patients, the patients selected for the present analysis did not differ in age, sex, prevalence of hypertension or severity of AS (all p 0.05). The SEAS study protocol, baseline characteristics and outcome have been previously published.11 12 In short, 1873 asymptomatic patients with mostly moderate AS and without known diabetes, cardiovascular or renal disease were randomised to double-blind, placebo-controlled treatment with combined ezetimibe 10?mg and simvastatin 40? mg daily for 4 years.12 Hypertension was defined as history of hypertension, use of antihypertensive drug treatment or blood pressure 140/90?mm?Hg at the clinic baseline visit. Echocardiographic measurements Echocardiography was performed using a standardised protocol in 173 study centres in seven European countries.13 14 All echocardiograms were analysed at the echocardiographic core laboratory at Haukeland University Hospital, Bergen, Norway, and 94% were proofread by the same experienced reader. Quantitative echocardiography for assessment of AS and LV structure and function was performed following current guidelines.5 15 16 Previous analyses from the SEAS trial have shown excellent reproducibility for measurements of LV dimensions.17 Aortic valve area adjusted for pressure recovery in the aortic root (energy loss index (ELI)) was used as the primary measure of AS severity, given the superior prognostic value previously demonstrated. 18 Aortic and mitral regurgitation were graded by colour Doppler. AVC was graded as none (no calcification), mild (isolated small spots), moderate (multiple bigger spots) and severe (extensive calcification of all cusps).9 LV mass was calculated using an autopsy validated formula.19 LV hypertrophy was considered present if LV mass/height2.7 was 49.2?g/m2.7 in men and 46.7?g/m2.7 in women.20 LV systolic function was assessed by biplane Simpsons ejection fraction and by midwall shortening adjusted for circumferential end-systolic stress taking the mean transaortic valve gradient into account (stress-corrected midwall shortening (scMWS)).21 22 Aortic compliance was assessed from LV stroke volume/pulse pressure ratio.23 Study outcomes The primary outcome of the SEAS study was major cardiovascular events, a composite endpoint consisting Rilpivirine (R 278474, TMC 278) of aortic valve-related events (combined aortic valve replacement, congestive heart failure due to AS and cardiovascular death) and ischaemic cardiovascular events (combined non-fatal myocardial infarction, non-haemorrhagic stroke, coronary revascularisation, hospitalisation for unstable angina pectoris and cardiovascular death).12 Secondary outcomes included aortic valve events and ischaemic cardiovascular events analysed separately. All-cause mortality was a tertiary endpoint. All outcomes were classified by an independent endpoint classification committee blinded to study-group assignment.11 Ethics approval The SEAS study was approved by ethics committees in all participating study centres, and.We acknowledge the value of CT in quantitative assessment of valvular macrocalcifications. study treatment, aortic compliance, left ventricular (LV) mass and systolic function, AS severity and hs-CRP. Moderate/severe AVC at baseline also predicted a 1.8-fold higher hazard rate of all-cause mortality in men (95%?CI 1.04 to 3.06, p 0.05) independent of age, AS severity, LV mass and aortic compliance, but not in women. Conclusion In conclusion, AVC scored by echocardiography has sex-specific characteristics in AS. Moderate/severe AVC is associated with higher cardiovascular morbidity in both sexes, and with higher all-cause mortality in men. Trial registration number ClinicalTrials.gov identifier: “type”:”clinical-trial”,”attrs”:”text”:”NCT00092677″,”term_id”:”NCT00092677″NCT00092677 that women have significantly lower aortic valve calcification (AVC) load than men independent of the severity of AS.3 From this, sex-specific cut-off values for Agatston score indicating severe AS were developed and validated.3 4 Although cardiac CT more accurately measures AVC in AS and may help identify severe AS in asymptomatic patients with discordantly graded AS by conventional echocardiographic measures, it is not recommended by current guidelines as a routine test in patients with AS.5 While CT primarily quantifies areas of valvular macrocalcification, recent studies by positron emission tomography have revealed that AVC also includes inflammation and microcalcification.6 7 Since different processes involved in AVC are reflected by echocardiography and CT, AVC by echocardiography is not synonymous with AVC assessed by CT.8 The association of AVC scored by echocardiography with higher rates of combined aortic valve replacement and death has previously been documented in Rabbit Polyclonal to MUC7 two studies by Rosenhek em et al. /em 9 10 However, sex-specific risk factors and prognostic implications of AVC scored by echocardiography have not been published from a large, prospective study. This was the aim of the present study. Methods Study population The present analysis of the SEAS study included the 1725 men and women (92% of the total study population) that had images available for AVC scoring on the baseline echocardiogram. Compared with ineligible patients, the patients selected for the present analysis did not differ in age, sex, prevalence of hypertension or severity of AS (all p 0.05). The SEAS study protocol, baseline characteristics and outcome have been previously published.11 12 In short, 1873 asymptomatic patients with mostly moderate AS and without known diabetes, cardiovascular or renal disease were randomised to double-blind, placebo-controlled treatment with combined ezetimibe 10?mg and simvastatin 40?mg daily for 4 years.12 Hypertension was defined as history of hypertension, use of antihypertensive drug treatment or blood pressure 140/90?mm?Hg at the clinic baseline visit. Echocardiographic measurements Echocardiography was performed using a standardised protocol in 173 study centres in seven European countries.13 14 All echocardiograms were analysed at the echocardiographic core laboratory at Haukeland University Hospital, Bergen, Norway, and 94% were proofread by the same experienced reader. Quantitative echocardiography for assessment of AS and LV structure and function was performed following current guidelines.5 15 16 Previous analyses from the SEAS trial have shown excellent reproducibility for measurements of LV dimensions.17 Aortic valve area adjusted for pressure recovery in the aortic root (energy loss index (ELI)) was used as the primary measure of AS severity, given the superior prognostic value previously demonstrated.18 Aortic and mitral regurgitation were graded by colour Doppler. AVC was graded as none (no calcification), mild (isolated small spots), moderate (multiple bigger spots) and severe (extensive calcification of all cusps).9 LV mass was calculated using an autopsy validated formula.19 LV hypertrophy was considered present if LV mass/height2.7 was 49.2?g/m2.7 in men and 46.7?g/m2.7 in women.20 LV systolic function was assessed by biplane Simpsons ejection fraction and by midwall shortening adjusted for circumferential end-systolic stress taking the mean transaortic valve gradient into account (stress-corrected midwall shortening (scMWS)).21 22 Aortic compliance was assessed from LV stroke volume/pulse.