Aortic aneurysms in a general population cohort: prevalence and risk factors in men and women.

AIMS: The prevalence and difference in risk factors for having thoracic aortic aneurysm (TAA) and abdominal aortic aneurysm (AAA) in men compared with women in the general population is not well described. This study aimed to test the hypotheses that (i) cardiovascular risk factors for TAA and AAA differ and (ii) the prevalence of TAA and AAA is sex specific. METHODS AND RESULTS: Aortic examination using computed tomography angiography was performed in 11 294 individuals (56% women), with a mean age of 62 (range 40-95) years participating in the Copenhagen General Population Study. TAAs were defined as an ascending aortic diameter ≥45 mm and a descending aortic diameter ≥35 mm, while AAAs were defined as an abdominal aortic diameter ≥30 mm. Demographic data were obtained from questionnaires. Overall prevalence of aortic aneurysms (AAs) in the study population included: total population 2.1%, men 4.0% and women 0.7% (P-value men vs. women P < 0.001). AAs were independently associated with male sex, increasing age, and body surface area (BSA). While TAAs were associated with hypertension, odds ratio (OR) = 2.0 [95% confidence interval (CI): 1.5-2.8], AAAs were associated with hypercholesterolaemia and smoking, OR = 2.4 (95% CI: 1.6-3.6) and 3.2 (95% CI: 1.9-5.4). CONCLUSION: Subclinical AAs are four times more prevalent in men than in women. In both sexes, increasing age and BSA are risk factors for AAs of any anatomical location. Whereas arterial hypertension is a risk factor for TAAs, hypercholesterolaemia and smoking are risk factors for AAAs.

Subclinical Coronary Atherosclerosis and Risk for Myocardial Infarction in a Danish Cohort : A Prospective Observational Cohort Study.

BACKGROUND: Coronary atherosclerosis may develop at an early age and remain latent for many years. OBJECTIVE: To define characteristics of subclinical coronary atherosclerosis associated with the development of myocardial infarction. DESIGN: Prospective observational cohort study. SETTING: Copenhagen General Population Study, Denmark. PARTICIPANTS: 9533 asymptomatic persons aged 40 years or older without known ischemic heart disease. MEASUREMENTS: Subclinical coronary atherosclerosis was assessed with coronary computed tomography angiography conducted blinded to treatment and outcomes. Coronary atherosclerosis was characterized according to luminal obstruction (nonobstructive or obstructive [≥50% luminal stenosis]) and extent (nonextensive or extensive [one third or more of the coronary tree]). The primary outcome was myocardial infarction, and the secondary outcome was a composite of death or myocardial infarction. RESULTS: A total of 5114 (54%) persons had no subclinical coronary atherosclerosis, 3483 (36%) had nonobstructive disease, and 936 (10%) had obstructive disease. Within a median follow-up of 3.5 years (range, 0.1 to 8.9 years), 193 persons died and 71 had myocardial infarction. The risk for myocardial infarction was increased in persons with obstructive (adjusted relative risk, 9.19 [95% CI, 4.49 to 18.11]) and extensive (7.65 [CI, 3.53 to 16.57]) disease. The highest risk for myocardial infarction was noted in persons with obstructive-extensive subclinical coronary atherosclerosis (adjusted relative risk, 12.48 [CI, 5.50 to 28.12]) or obstructive-nonextensive (adjusted relative risk, 8.28 [CI, 3.75 to 18.32]). The risk for the composite end point of death or myocardial infarction was increased in persons with extensive disease, regardless of degree of obstruction-for example, nonobstructive-extensive (adjusted relative risk, 2.70 [CI, 1.72 to 4.25]) and obstructive-extensive (adjusted relative risk, 3.15 [CI, 2.05 to 4.83]). LIMITATION: Mostly White persons were studied. CONCLUSION: In asymptomatic persons, subclinical, obstructive coronary atherosclerosis is associated with a more than 8-fold elevated risk for myocardial infarction. PRIMARY FUNDING SOURCE: AP Møller og Hustru Chastine Mc-Kinney Møllers Fond.

Aortic aneurysms and markers of platelet activation, hemostasis, and endothelial disruption in people living with HIV.

Introduction: People living with HIV (PLWH) are at twice the risk of developing cardiovascular diseases and have more than four times higher odds of aortic aneurysm (AA) than the uninfected population. However, biomarkers of AA in PLWH are yet to be discovered. We aimed to investigate whether circulating biomarkers reflecting platelet activation, hemostasis and endothelial disruption, i.e. sCD40L, D-dimer, syndecan-1, and thrombomodulin, were associated with AA in PLWH. Methods: Five hundred seventy one PLWH from the Copenhagen Comorbidity in HIV Infection (COCOMO) study ≥40 years of age with an available contrast-enhanced CT scan as well as available biomarker analyses were included. The biomarkers were analyzed on thawed plasma. For each biomarker, we defined high level as a concentration in the upper quartile and low level as a concentration below the upper quartile. For D-dimer, the cut-off was defined as the lower limit of detection. Using unadjusted and adjusted logistic and linear regression models, we analyzed associations between AA and sCD40L, D-dimer, syndecan-1, and thrombomodulin, respectively in PLWH. Results: PLWH had median (IQR) age 52 years (47-60), 88% were male, median (IQR) time since HIV diagnosis was 15 years (8-23), and 565 (99%) were currently on antiretroviral treatment. High level of sCD40L was associated with lower odds of AA in both unadjusted (odds ratio, OR, 0.23 (95% CI 0.07-0.77; P=0.017)) and adjusted models (adjusted OR, aOR, 0.23 (95% CI 0.07-0.78; P=0.019)). Detectable level of D-dimer was associated with higher odds of AA in both unadjusted (OR 2.76 (95% CI 1.34-5.67; P=0.006)) and adjusted models (aOR 2.22 (95% CI 1.02-4.85; P=0.045)). Conclusions: SCD40L was associated with lower odds of AA whereas D-dimer was independently associated with higher odds of AA in PLWH. This calls for further investigations into specific biomarkers to aid early diagnosis of AA in PLWH.

Structural abnormalities after aortic root replacement with stentless xenograft.

OBJECTIVE: In complex and high-risk aortic root disease, the porcine Freestyle stentless bioprosthesis (Medtronic Inc, Minneapolis, Minn) is an important surgical treatment option. We aimed to determine prevalence and clinical effect of structural and functional abnormalities after full-root Freestyle implantation. METHODS: Our cross-sectional 2-center study combined with clinical follow-up included 253 patients with full-root Freestyle bioprostheses implanted from 1999 to 2017. Patients underwent transthoracic echocardiography (TTE) and contrast-enhanced, electrocardiogram-gated 4-dimensional cardiac computed tomography (4DCT) at median age 70 (interquartile range, 62-75) years. After 4DCT, clinical follow-up continued throughout 2018. Median follow-up was 3.3 years before 4DCT and 1.4 years after. RESULTS: We identified abnormalities in 46% of patients, including pseudoaneurysms (n = 32; 13%), moderate or severe coronary ostial stenosis (n = 54; 21%), and moderate-severe leaflet thickening or reduced leaflet motion (n = 51; 20%). TTE only identified 1 patient with pseudoaneurysm. After 4DCT, the unadjusted hazard ratio for surgical reintervention among patients with abnormal 4DCT was 4.2 (95% confidence interval, 1.2-15.3), in all, 10% required a reintervention. 4DCT abnormalities were associated with a statistically nonsignificant increased risk of death, stroke, or myocardial infarction (hazard ratio obtained using Cox proportional hazards regression analysis, 2.4; 95% confidence interval, 0.7-7.6). In all, 4.0% died, 3.6% had a myocardial infarction, and 2.0% had a stroke. CONCLUSIONS: Structural and functional abnormalities of the aortic root are frequent after Freestyle implantation and TTE appears to be insufficient for follow-up. Abnormalities might be associated with increased risk of reintervention and potentially adverse clinical outcomes. Longer follow-up and larger study populations are needed to further clarify the clinical implications of abnormalities identified with 4DCT.

Coronary artery- and aortic valve calcifications in patients with Philadelphia-negative myeloproliferative neoplasms.

BACKGROUND: Patients with the hematological cancers Philadelphia-negative Myeloproliferative Neoplasms (MPNs) have an increased risk of cardiovascular disease. However, whether MPNs have an increased burden of cardiac calcification has not been thoroughly investigated. Our aim is to investigate whether patients with MPNs have an increased burden of cardiac calcification that could help explain their increased risk of cardiovascular disease. METHODS AND RESULTS: We recruited 161 patients (mean age 65 years, 52% men) with an MPN diagnosis between 2016 and 2018. Coronary artery calcium score (CACS) and aortic valve calcification (AVC) were measured by cardiac computer tomography, and detailed information on cardiovascular risk factors was recorded. MPNs were matched on age and sex, with 805 controls from the Copenhagen General Population Study. A CACS>400 was present in 26% of MPNs and 19% of controls (p = 0.031). AVC was present in 58% of MPNs and 34% of controls (p < 0.0001). After adjustment for cardiovascular risk factors, the odds ratio (OR) of a CACS>400 was 1.9 (95% CI 1.2-3.1, p = 0.008) in MPNs compared to controls, and the OR of AVC was 4.4 (95% CI 2.9-6.9, p < 0.0001) in MPNs compared to controls. CONCLUSION: Patients with MPNs have a significantly higher prevalence of a CACS >400 and AVC, compared to controls from the general population. The association between MPN and a CACS>400 or AVC remains significant after adjustment for cardiovascular risk factors. These novel data support the hypothesis that MPNs have an increased burden of cardiac calcifications, independent of other cardiovascular risk factors.

ECG and CT for the detection of left atrial enlargement in hypertensive individuals-a population-based study.

Left atrial enlargement (LAE) is associated with hypertension and an increased risk of cardiovascular morbidity and mortality. Guidelines for hypertension recommend LAE evaluation. We aimed to estimate the agreement of LAE as assessed by 12-lead electrocardiogram (ECG) and cardiac computed tomography (CT) in both the general population and hypertensive individuals. Cardiac CT and ECG were used to evaluate the presence of LAE in participants in the Copenhagen General Population Study. LAE, is defined as an LA volume above the 97.5% upper confidence limit by cardiac CT, as compared with multiple ECG criteria for LAE. A total of 3507 participants (47% males, age: 60 ± 10 years) were included. The prevalence of CT-defined LAE was 5.9% in the total population and 8.7% in participants with hypertension. In hypertensive individuals, LAE was identified by CT or by ECG in 31% with only a 4% overlap. ECG signs for anatomical LAE by CT had high negative predictive values between 93 and 96% but low sensitivity and positive predictive values. Specificity ranged from 27 to 93%. P-wave duration >120 ms was the best performing criterion, with a sensitivity of 48%, a specificity of 78%, and the highest area under the curve (0.66). We found a discrepancy in LAE prevalence when participants were assessed by CT and ECG, indicating that the two diagnostic modalities reflect different phenotypes of left atrial alterations. The diagnostic performance of ECG criteria for identifying anatomical LAE was poor.

HIV infection is associated with thoracic and abdominal aortic aneurysms: a prospective matched cohort study.

AIMS: Little is known about the prevalence of aortic aneurysms among people living with HIV (PLWH). We investigated whether HIV status is independently associated with having aortic aneurysms. Furthermore, we determined risk factors associated with aortic aneurysms in PLWH. METHODS AND RESULTS: PLWH aged ≥40 years (n = 594) were recruited from the Copenhagen Comorbidity in HIV Infection study and matched for age and sex with uninfected controls (n = 1188) from the Copenhagen General Population Study. Aortic dimensions were assessed using contrast enhanced computed tomography. Aortic aneurysms were defined according to the European Society of Cardiology guidelines, i.e. an aortic dilation of ≥50% or an infrarenal aortic diameter of ≥30 mm. Among PLWH and uninfected controls, the median (interquartile range) age was 52 (47-60) and 52 (48-61) and 88% and 90% were male, respectively. We found 46 aneurysms in 42 (7.1%) PLWH and 31 aneurysms in 29 (2.4%) uninfected controls (P < 0.001). PLWH had a significantly higher prevalence of ascending aortic aneurysms and infrarenal aortic aneurysms. In an adjusted model, HIV was independently associated with aortic aneurysms (adjusted odds ratio; 4.51 [95% confidence interval 2.56-8.08], P < 0.001). Within PLWH, obesity and hepatitis B co-infection were associated with aortic aneurysms. CONCLUSION: PLWH had four-fold higher odds of aortic aneurysms compared to uninfected controls, and HIV status was independently associated with aortic aneurysms. Among PLWH, age, obesity and hepatitis B co-infection were associated with higher odds of aortic aneurysms. Our findings suggest that increased attention to aortic aneurysms in PLWH may be beneficial.

Pulmonary Arterial Enlargement in Well-Treated Persons With Human Immunodeficiency Virus.

BACKGROUND: Pulmonary artery enlargement is a marker of pulmonary hypertension. We aimed to determine the proportion with pulmonary artery enlargement among well-treated persons with human immunodeficiency virus HIV (PWH) and uninfected controls. METHODS: PWH with a chest computed tomography were included from the ongoing Copenhagen Comorbidity in HIV Infection (COCOMO) study. Age and sex-matched uninfected controls were recruited from the Copenhagen General Population Study. Pulmonary artery enlargement was defined as a ratio of >1 between the diameter of the main pulmonary artery (at the level of its bifurcation) and the diameter of the ascending aorta. RESULTS: In total, 900 PWH were included, and 44 (5%) had a pulmonary artery-aorta ratio (PA:A) >1. After adjustment for age, sex, and body mass index, obesity (adjusted odds ratio, 4.33; 95% confidence interval, 1.76-10.65; P = .001) and injection drug use (IDU) (4.90; 1.00-18.46; P = .03) were associated with higher odds of having a PA:A >1, and pulmonary indices and smoking status were not. HIV seropositivity was borderline associated with a PA:A >1 (adjusted odds ratio, 1.89; 95% confidence interval, .92-3.85; P = .08). CONCLUSIONS: A PA:A >1 was common in PWH. Obesity and IDU were independently associated with this finding and HIV serostatus was borderline associated with it, but HIV-related factors were not. Increased awareness may be appropriate in obese PWH and those with IDU.

Prevalence and Risk Factors of Moderate-to-Severe Hepatic Steatosis in Human Immunodeficiency Virus Infection: The Copenhagen Co-morbidity Liver Study.

BACKGROUND: People with human immunodeficiency virus (PWH) may be at risk of nonalcoholic fatty liver disease. We compared the prevalence of moderate-to-severe hepatic steatosis (M-HS) in PWH with human immunodeficiency virus (HIV)-uninfected controls and determined risk factors for M-HS in PWH. METHODS: The Copenhagen Co-Morbidity in HIV Infection study included 453 participants, and the Copenhagen General Population Study included 765 participants. None had prior or current viral hepatitis or excessive alcohol intake. Moderate-to-severe hepatic steatosis was assessed by unenhanced computed tomography liver scan defined by liver attenuation ≤48 Hounsfield units. Adjusted odds ratios (aORs) were computed by adjusted logistic regression. RESULTS: The prevalence of M-HS was lower in PWH compared with uninfected controls (8.6% vs 14.2%, P < .01). In multivariable analyses, HIV (aOR, 0.44; P < .01), female sex (aOR, 0.08; P = .03), physical activity level (aOR, 0.09; very active vs inactive; P < .01), and alcohol (aOR, 0.89 per unit/week; P = .02) were protective factors, whereas body mass index (BMI) (aOR, 1.58 per 1 kg/m2; P < .01), alanine transaminase (ALT) (aOR, 1.76 per 10 U/L; P < .01), and exposure to integrase inhibitors (aOR, 1.28 per year; P = .02) were associated with higher odds of M-HS. CONCLUSIONS: Moderate-to-severe hepatic steatosis is less common in PWH compared with demographically comparable uninfected controls. Besides BMI and ALT, integrase inhibitor exposure was associated with higher prevalence of steatosis in PWH.

Prevalence and risk factors of prolonged QT interval and electrocardiographic abnormalities in persons living with HIV.

OBJECTIVE: Abnormal ECGs are associated with increased risk of arrhythmias and sudden cardiac death. We aimed to investigate the prevalence and associated risk factors of prolonged QTc and major ECG abnormalities, in persons living with HIV (PLWH) and uninfected controls. DESIGN: PLWH aged at least 40 years were recruited from the Copenhagen comorbidity in HIV infection (COCOMO) study and matched on sex and age to uninfected controls from the Copenhagen General Population Study. METHODS: ECGs were categorized according to Minnesota Code Manual of ECG Findings definition of major abnormalities. A QT interval corrected for heart rate (QTc) greater than 440 ms in men and greater than 460 ms in women was considered prolonged. Pathologic Q-waves were defined as presence of major Q-wave abnormalities. RESULTS: ECGs were available for 745 PLWH and 2977 controls. Prolonged QTc was prevalent in 9% of PLWH and 6% of controls, P = 0.052. Pathologic Q-waves were more common in PLWH (6%) than in controls (4%), P = 0.028. There was no difference in prevalence of major ECG abnormalities between PLWH and controls, P = 0.987.In adjusted analyses, HIV was associated with a 3.6 ms (1.8-5.4) longer QTc interval, P < 0.001, and HIV was independently associated with prolonged QTc [adjusted odds ratio: 1.59 (1.14-2.19)], P = 0.005. HIV was borderline associated to pathologic Q-waves after adjusting, P = 0.051. CONCLUSION: HIV was associated with higher odds ratio of prolonged QTc after adjustment for cardiovascular risk factors, but analyses were not adjusted for QT-prolonging medication. Although evidence indicated more pathologic Q-waves in PLWH, the risk seemed to be associated mainly with an adverse risk profile.

Assessment of left ventricular outflow tract and aortic root: comparison of 2D and 3D transthoracic echocardiography with multidetector computed tomography.

AIMS: Accurate echocardiographic assessment of left ventricular outflow tract (LVOT) and the aortic root is necessary for risk stratification and choice of appropriate treatment in patients with pathologies of the aortic valve and aortic root. Conventional 2D transthoracic echocardiographic (TTE) assessment is based on the assumption of a circular shaped LVOT and aortic root, although previous studies have indicated a more ellipsoid shape. 3D TTE and multidetector computed tomography (MDCT) applies planimetry and are not dependent on geometrical assumptions. The aim was to test accuracy, feasibility, and reproducibility of 3D TTE compared to 2D TTE assessment of LVOT and aortic root areas, with MDCT as reference. METHODS AND RESULTS: We examined 51 patients with 2D/3D TTE and MDCT at the same day. All patients were re-examined with 2D/3D TTE on a different day to evaluate 2D and 3D re-test variability. Areas of LVOT, aortic annulus, and sinus were assessed using 2D, 3D TTE, and MDCT. Both 2D/3D TTE underestimated the areas compared to MDCT; however, 3D TTE areas were significantly closer to MDCT-areas. 2D vs. 3D mean MDCT-differences: LVOT 1.61 vs. 1.15 cm2, P = 0.019; aortic annulus 1.96 vs. 1.06 cm2, P < 0.001; aortic sinus 1.66 vs. 1.08 cm2, P = 0.015. Feasibility was 3D 76-79% and 2D 88-90%. LVOT and aortic annulus areas by 3D TTE had lowest variabilities; intraobserver coefficient of variation (CV) 9%, re-test variation CV 18-20%. CONCLUSION: Estimation of LVOT and aortic root areas using 3D TTE is feasible, more precise and more accurate than 2D TTE.

Left ventricular hypertrophy identified by cardiac computed tomography and ECG in hypertensive individuals: a population-based study.

OBJECTIVES: Screening of left ventricular hypertrophy (LVH) is a biomarker of organ damage in hypertensive individuals and associated with increased mortality. Cardiac computed tomography (CT) is widely expanding worldwide; however, the value of CT assessment of LVH is unknown. We aimed to identify individuals with LVH using both cardiac CT and electrocardiograms (ECG) and to explore potential differences between these phenotypical distinct diagnostic modalities. METHODS: Participants in the Copenhagen General Population Study underwent 12-lead ECG and cardiac CT and were evaluated for the presence of LVH. Multiple ECG signs of LVH were compared with LVH by CT. RESULTS: Out of 4942 participants, 1347 had untreated hypertension and in this group, 13% presented with anatomical LVH by CT and 10% by ECG with an overlap of 4%. ECG signs of LVH had negative predictive values between 87 and 89% compared with CT. Using a combination of the Sokolow-Lyon index, the Cornell voltage duration product and/or a Romhilt-Estes score at least 4, lead to an increased C-statistics (P < 0.001) compared with the use of any single ECG sign of LVH. Individuals with solely CT but not ECG signs of LVH had higher SBPs (152 vs. 144 mmHg, P < 0.001) and larger left atria (49 vs. 45 ml/m, P < 0.001) compared with individuals with solely ECG LVH. CONCLUSION: CT and ECG identifies LVH in 19% of hypertensive individuals with only a small diagnostic overlap. Commonly used ECG criteria for LVH cannot safely rule out the presence of anatomical LV organ damage.

The relationship between volumetric thoracic bone mineral density and coronary calcification in men and women - results from the Copenhagen General Population Study.

BACKGROUND: The association between low bone mineral density (BMD) and the presence of coronary artery calcium (CAC) as a marker of atherosclerosis is unclear. The aim of this study was to assess the potential relationship between volumetric thoracic bone mineral density and coronary calcification in a large population of men and women. METHODS: Participants from the Copenhagen General Population Study underwent multidetector computed tomography. Volumetric thoracic BMD and CAC were assessed in the same scan. CAC was measured using calibrated mass score (cMS). cMS was dichotomized as cMS = 0 or cMS > 0. The association between BMD and cMS was analyzed using multiple logistic regression in men, premenopausal and postmenopausal women. The model was adjusted for age, BMI, hypertension, hypercholesterolemia, diabetes, known cardiovascular disease and smoking. RESULTS: Of 2548 eligible participants, 1163 men and 1385 women, mean age 61 ±â€¯10 were included in the study. Mean BMD was 138 ±â€¯46 mg/cm3 for men and 151 ±â€¯49 mg/cm3 women. In 696 men (67%) and 537 women (41%) cMS was found to be above zero. For men, a decrease in BMD of 100 mg/cm3 was associated to an odds ratio of 1.49 for cMS > 0 (95% confidence interval: 1.04-2.13, P = 0.03). In postmenopausal women, a decrease in BMD of 100 mg/cm3 was associated to an odds ratio of 1.47 for MS > 0 (95% confidence interval: 1.04-2.08, P = 0.03). For premenopausal women, no significant association was found between BMD and cMS (odds ratio = 0.74, 95% confidence interval: 0.36-1.52, P = 0.4). CONCLUSION: Bone mineral density and coronary calcification are inversely related in both men and postmenopausal women, supporting the hypothesis that a direct relation between bone loss and development of atherosclerosis exists irrespective of gender.

Prognostic implications of left ventricular asymmetry in patients with asymptomatic aortic valve stenosis.

Aims: Left ventricular (LV) regional hypertrophy in the form of LV asymmetry is a common finding in patients with aortic valve stenosis. The aim of this study was to test the hypothesis that LV asymmetry predicts future symptomatic status and indication for aortic valve replacement (AVR) in patients with asymptomatic aortic valve stenosis. Methods and results: In total, 114 patients with asymptomatic aortic valve stenosis (peak velocity > 2.5 m/s assessed by echocardiographic screening and LV ejection fraction > 50%) were enrolled in the study. LV asymmetry and LV geometry was assessed by multi-detector computed tomography according to previous definitions. Follow-up was conducted using electronic health records. Event-free survival was assessed using Cox proportional hazards models. Patients were followed for a median of 2.2 years (interquartile range 1.6-3.6). Indication for AVR occurred in 46 patients (40%). Patients with LV asymmetry had more than 3 times the risk of AVR (hazard ratio: 3.16; 95% CI: 1.77-5.66; P < 0.001) compared with patients with no LV asymmetry. Multivariate Cox analysis revealed that LV asymmetry was a predictor of future need of AVR (hazard ratio: 3.10; 95% CI: 1.44-6.65; P = 0.004), independent of LV geometry, jet velocity, valvular calcification, and pro-BNP. Conclusions: LV asymmetry is an independent predictor of future need for AVR in patients with asymptomatic aortic valve stenosis. It has incremental prognostic value to LV geometry and may provide a useful method of risk stratification.

Six-minute walking test and long term prognosis in patients with asymptomatic aortic valve stenosis.

BACKGROUND: Management of asymptomatic patients with aortic valve stenosis is challenging due to the elusive relationship between symptomatic status and hemodynamic parameters in addition to the occurrence of cardiovascular death. The 6-minute walking test (6MWT) reflects overall hemodynamic function and could contribute to risk assessment in such patients. METHODS AND RESULTS: One hundred sixteen asymptomatic patients (peak velocity>2.5m/s and left ventricular ejection fraction >50% assessed by echocardiographic screening; 85 males; aged 72±8years) underwent clinical workup, transthoracic echocardiography and a 6MWT. The mean distance covered by patients able to perform the 6MWT (n=107) was 422±90m. Patients were grouped in tertiles according to distance covered in the 6MWT: Short, intermediate and long distance patients. During a median follow-up of 5.5years (IQR 4.5-6.3), 29 (25%) patients died, 10 (9%) from cardiovascular causes. Multivariate analysis revealed that short distance patients (≤390m) were at higher risk of all-cause mortality (HR: 2.44; 95% CI: 1.05-5.67; p=0.04) and cardiovascular mortality (HR: 6.12; 95% CI: 1.18-31.83; p=0.03). For every 100m covered, the risk of all-cause mortality decreased by 35% (HR: 0.65; 95% CI: 0.43-0.99; p=0.04). Long distance patients (>465m) did not experience cardiovascular deaths during follow-up. CONCLUSIONS: In asymptomatic patients with aortic valve stenosis, the 6MWT is an independent predictor of all-cause and cardiovascular mortality. It is of incremental value to the echocardiographic evaluation, suggesting that the 6MWT might be useful to guide clinical follow-up intervals and treatment strategy.

Normal values of regional left ventricular myocardial thickness, mass and distribution-assessed by 320-detector computed tomography angiography in the Copenhagen General Population Study.

Left ventricular (LV) hypertrophy is associated with cardiovascular complications and the geometry is important for prognosis. In some cardiovascular diseases, myocardial hypertrophy or dilation occurs regionally without modifying the global size of the heart. It is therefore relevant to determine regional normal reference values of the left ventricle. The aim of this study was to derive reference values of regional LV myocardial thickness (LVMT) and mass (LVMM) from a healthy study group of the general population using cardiac computed tomography angiography (CCTA). We wanted to introduce LV myocardial distribution (LVMD) as a measure of regional variation of the LVMT. Moreover, we wanted to determine whether these parameters varied between men and women. We studied 568 (181 men; 32%) adults, free of cardiovascular disease and risk factors, who underwent 320-detector CCTA. Mean age was 55 (range 40-84) years. Regional LVMT and LVMM were measured, according to the American Heart Association's 17 segment model, using semi-automatic software. Mean LVMT were 6.6 mm for men and 5.4 mm for women (p < 0.001). The normal LV was thickest in the basal septum (segment 3; men = 8.3 mm; women = 7.2 mm) and thinnest in the mid-ventricular anterior wall (segment 7; men = 5.6 mm; women = 4.5 mm) for both men and women. However, the regional LVMD differed between men and women, with the LV being most heterogenic in women. The normal human LV is morphologically heterogenic, and showed same overall pattern but different regional distribution for men and women. This study introduces LVMD and provides gender specific reference values for regional LVMT, LVMM, and LVMD.

Nocturnal antihypertensive treatment in patients with type 1 diabetes with autonomic neuropathy and non-dipping: a randomised, placebo-controlled, double-blind cross-over trial.

OBJECTIVES: Cardiovascular autonomic neuropathy (CAN) and abnormal circadian blood pressure (BP) rhythm are independent cardiovascular risk factors in patients with diabetes and associations between CAN, non-dipping of nocturnal BP and coronary artery disease have been demonstrated. We aimed to test if bedtime dosing (BD) versus morning dosing (MD) of the ACE inhibitor enalapril would affect the 24-hour BP profile in patients with type 1 diabetes (T1D), CAN and non-dipping. SETTING: Secondary healthcare unit in Copenhagen, Denmark. PARTICIPANTS: 24 normoalbuminuric patients with T1D with CAN and non-dipping were included, consisting of mixed gender and Caucasian origin. Mean±SD age, glycosylated haemoglobin and diabetes duration were 60±7 years, 7.9±0.7% (62±7 mmol/mol) and 36±11 years. INTERVENTIONS: In this randomised, placebo-controlled, double-blind cross-over study, the patients were treated for 12 weeks with either MD (20 mg enalapril in the morning and placebo at bedtime) or BD (placebo in the morning and 20 mg enalapril at bedtime), followed by 12 weeks of switched treatment regimen. PRIMARY AND SECONDARY OUTCOME MEASURES: Primary outcome was altered dipping of nocturnal BP. Secondary outcomes included a measurable effect on other cardiovascular risk factors than BP, including left ventricular function (LVF). RESULTS: Systolic BP dipping increased 2.4% (0.03-4.9%; p=0.048) with BD compared to MD of enalapril. There was no increase in mean arterial pressure dipping (2.2% (-0.1% to 4.5%; p=0.07)). No difference was found on measures of LVF (p≥0.15). No adverse events were registered during the study. CONCLUSIONS: We demonstrated that patients with T1D with CAN and non-dipping can be treated with an ACE inhibitor at night as BD as opposed to MD increased BP dipping, thereby diminishing the abnormal BP profile. The potentially beneficial effect on long-term cardiovascular risk remains to be determined. TRIAL REGISTRATION NUMBER: EudraCT2012-002136-90; Post-results.