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

BACKGROUND AND AIMS: The prevalence and difference in risk factors for having thoracic and abdominal aortic aneurysms in men compared to women in the general population is not well-described. This study aimed to test the hypotheses i) that cardiovascular risk factors for thoracic and abdominal aortic aneurysms differ and ii) that the prevalence of thoracic and abdominal aortic aneurysms is sex specific. METHODS: 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. Thoracic aortic aneurysms were defined as ascending aortic diameter ≥45 mm and descending aortic diameter ≥35 mm, abdominal aortic aneurysms were defined as abdominal aortic diameter ≥30 mm. Demographic data were obtained from questionnaires. RESULTS: Overall prevalence of aortic aneurysms in the study population included: total population 2.1%, men 4.0% and women 0.7% (p-test men vs. women p<0.001). Aortic aneurysms were independently associated with male sex, increasing age, and body surface area. While thoracic aortic aneurysms were associated with hypertension, odds ratio=2.0[95%CI:1.5-2.8], abdominal aortic aneurysms were associated with hypercholesterolemia and smoking, odds ratios=2.4[95%CI:1.6-3.6] and 3.2[95%CI:1.9-5.4]. CONCLUSIONS: Subclinical aortic aneurysms are four times more prevalent in men than women. In both sexes, increasing age and body surface area are risk factors for aortic aneurysms of any anatomical location. Whereas arterial hypertension is a risk factor for thoracic aortic aneurysms, hypercholesterolemia and smoking are risk factors for abdominal aortic aneurysms.

Clinical characteristics and lipid lowering treatment of patients initiated on proprotein convertase subtilisin-kexin type 9 inhibitors: a nationwide cohort study.

OBJECTIVES: Given the novelty of proprotein convertase subtilisin-kexin type 9 inhibitors (PCSK9i), little is known regarding overall implementation or clinical characteristics among patients who initiate treatment. We aimed to assess the total number of patients initiated on PCSK9i along with a description of the clinical characteristics and lipid lowering treatment (LLT) of such patients. SETTING: A register-based descriptive cohort study of patients receiving a PCSK9i in the time period from 01 January 2016 to 31 March 2017 using a cross linkage between three nationwide Danish registers. Information regarding PCSK9i prescriptions, patient demographics, concurrent pharmacotherapy, comorbidities and previous coronary procedures was identified. RESULTS: Overall, 137 patients initiated treatment with PCSK9i in the study period from 11 in the first quarter of 2016 to 40 in the first quarter of 2017. The majority had a history of ischaemic heart disease (IHD) (67.9%) with ischaemic stroke and diabetes mellitus being present in 7.3% and 16.8% of patients, respectively. All patients initiated on PCSK9i had been previously prescribed statin treatment with atorvastatin and simvastatin being most frequently prescribed in 53% and 36% of patients, respectively. The majority of patients had received both statins and ezetimibe (94.9%) and approximately half of these patients had also received bile acid sequestrant (45.3%). Clinical characteristics mainly differed in patients receiving triple LLT compared with patients not receiving triple LLT in the regards of heart failure. CONCLUSION: Patients treated with PCSK9i were rare, characterised by having IHD and had received various and intensive conventional LLT prior to PCSK9i initiation in agreement with current international guidelines.

Right Ventricular Dysfunction and the Effect of Defibrillator Implantation in Patients With Nonischemic Systolic Heart Failure.

Background Patients with nonischemic systolic heart failure are at an increased risk of sudden cardiac death, but more discriminating tools are needed to identify those patients likely to benefit from implantable cardioverter-defibrillator (ICD) implantation. Whether right ventricular (RV) ejection fraction (RVEF) can identify patients with nonischemic systolic heart failure more likely to benefit from ICD implantation is not yet known. Methods In this post hoc analysis of the DANISH trial (Danish Study to Assess the Efficacy of ICDs in Patients with Nonischemic Systolic Heart Failure on Mortality), patients with nonischemic systolic heart failure randomized to ICD or control underwent cardiovascular magnetic resonance. RV systolic dysfunction was defined as RVEF ≤45%. Cox regression assessed the effects of RV function and ICD implantation on all-cause mortality, sudden cardiac death, and cardiovascular death. Results Overall, 239 patients had interpretable images of RV volume. Median RVEF was 51%, RV systolic dysfunction was present in 75 (31%) patients, and 55 (23%) patients died. RVEF was an independent predictor of all-cause mortality, hazards ratio 1.34 per 10% absolute decrease in RVEF (95% CI, 1.05-1.70), P=0.02. There was a statistically significant interaction between RVEF and the effect of ICD implantation ( P=0.001). ICD implantation significantly reduced all-cause mortality in patients with RV systolic dysfunction, hazards ratio 0.41 (95% CI, 0.17-0.97), P=0.04 but not in patients without RV systolic dysfunction, hazards ratio 1.87 (95% CI, 0.85-3.92), P=0.12, ( P=0.01 for the difference in effect of ICD between RV groups). Conclusions In this post hoc analysis of the DANISH trial, ICD therapy was associated with survival benefit in patients with biventricular heart failure. These findings need confirmation in a prospective study. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier: NCT00542945.

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.

Volume and dimensions of angiographically normal coronary arteries assessed by multidetector computed tomography.

BACKGROUND: The objective of this study was to determine normal values for coronary artery volume (CAV) and individual vasculature and segment dimensions. METHODS: We examined 200 healthy volunteers with an Agatston score of 0 and a normal, high quality coronary CTA. Using 320 slice multidetector row CT and designated vessel tracing software with border detection algorithm, the main coronary arteries and branches were delineated and total and segmental dimensions calculated. RESULTS: 2931 segments (98.9%) could be adequately delineated. Of the 173 subjects with adequate coronary delineations, 140 subjects (81%) received nitroglycerin (NTG) prior to the scan. CAV was 4.33 ml (95% CI: 2.27-6.39) in subjects with NTG and 2.55 ml (95% CI: 0.34-4.76) in subjects without NTG (p < 0.0001). Left ventricular mass (LVM) was strongly correlated with CAV (p < 0.0001) independently of body surface area and gender, whereas gender was not independently correlated with CAV. From right, balanced to left coronary dominance, the left anterior descending artery vasculature mean contribution to CAV increased slightly (37%, 40% and 43%, p = 0.002), and the mean contributions of right coronary artery (RCA) and left circumflex artery (LCX) vasculature was inversely related - from right, balanced to left 46%, 32% and 16% for RCA (p < 0.0001); and 16%, 27% and 38% for LCX (p < 0.0001). CONCLUSION: Normal values for coronary artery volume as assessed by coronary CTA are reported. They strongly correlate with NTG administration and left ventricular mass. The respective contribution of the left and right coronary vascularture is influenced by coronary dominance.