CYP8A1 gene polymorphisms and left main coronary artery disease

Background: Left main (LM) disease is rare but the most hazardous phenotype of coronary artery disease (CAD). Thus, early detection of participants at high risk of developing left main coronary heart disease (LM-CAD) is crucial. The aim of this study was to identify gene polymorphisms which could distinguish participants who are at high risk of developing LM-CAD. Such a candidate can be the prostaglandin I2 or prostacyclin (PGI2) gene. Methods: The DNA of 254 participants (151 participants with angiographically documented LM-CAD and 103 healthy controls) was analyzed for the frequency of C1117A polymorphism in the gene coding CYP8A1. Results: The genotype distribution was different between the LM-CAD and the control group. Particularly, the CC genotype of CYP8A1 was commoner in the LM-CAD than in the healthy group (P <.001). Allele frequencies were also differently distributed between the 2 groups. C allele frequency was higher in LM-CAD group (P =.016). Conclusions: The CC genotype of C1117A polymorphism is associated with higher risk of LM-CAD, which prospectively may have potential importance in screening high-risk populations. However, further investigations in larger populations are required to confirm these findings. © The Author(s) 2012

Lipoprotein Apheresis and Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitors in Patients With Heterozygous Familial Hypercholesterolemia: A One Center Study

Aim: We evaluated the lipid-lowering (LL) effect of proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) in patients with heterozygous familial hypercholesterolemia (HeFH) treated with LL-drugs and lipoprotein apheresis (LA). Patients and Methods: The PCSK9i treatment (evolocumab 420 mg/4 weeks, alirocumab 150 mg/2 weeks, or alirocumab 75 mg/2 weeks: 9, 6, and 2 patients, respectively) was initiated in patients with HeFH (n = 17; aged 35-69 years, 10 men, previously treated with statins + ezetimibe ± colesevelam and LA sessions for 2-12 years). A lipid profile was obtained before and immediately after the LA session and before, 1 and 2 months after switching to PCSK9i treatment. The duration of PCSK9i therapy ranged from 3 to 18 months. Results: Median total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG) levels before LA were 268, 198, 46, and 126 mg/dL, respectively, and decreased (at the end of the LA session) to 117, 50, 40, and 51 mg/dL, respectively (P <.001 for TC and P =.001 for all other comparisons). The median time-averaged LDL-C levels following LA were 155 (121, 176; median [25th, 75th percentile]) mg/dL. Median TC, LDL-C, and TG levels before PCSK9i therapy were 269, 190, and 127 mg/dL and decreased to 152, 100, and 95 mg/dL, respectively (P =.002, P <.002, and P <.03, respectively). Steady LDL-C levels with PCSK9i treatment were significantly lower compared with time-averaged LDL-C levels following LA (median value: 100 vs 155 mg/dL; P =.008). With PCSK9i, from 13 patients with CHD, 6 (46.1%) patients achieved LDL-C <70 mg/dL, and 2 patients (15.4%) achieved LDL-C <100 mg/dL. Lipoprotein apheresis was discontinued in all patients except for 2 who continued once monthly. Conclusions: PCSK9i can reduce LDL-C more consistently over time compared with a transient decrease following LA in HeFH patients. PCSK9i therapy may reduce the frequency of LA. Larger trials are required to establish the clinical implications of PCSK9i in patients previously on LA. © The Author(s) 2020

The double-edged sword of t1-mapping in systemic sclerosis-a comparison with infectious myocarditis using cardiovascular magnetic resonance

Aims: T1-mapping is considered a surrogate marker of acute myocardial inflammation. However, in diffuse cutaneous systemic sclerosis (dcSSc) this might be confounded by coexisting myocardial fibrosis. We hypothesized that T1-based indices should not by themselves be considered as indicators of myocardial inflammation in dcSSc patients. Methods/Results: A cohort of 59 dcSSc and 34 infectious myocarditis patients was prospectively evaluated using a 1.5-Tesla system for an indication of suspected myocardial inflammation and was compared with 31 healthy controls. Collectively, 33 (97%) and 57 (98%) of myocarditis and dcSSc patients respectively had ≥1 pathologic T2-based index. However, 33 (97%) and 45 (76%) of myocarditis and dcSSc patients respectively had ≥1 pathologic T2-based index. T2-signal ratio was significantly higher in myocarditis patients compared with dcSSc patients (2.5 (0.6) vs. 2.1 (0.4), p < 0.001). Early gadolinium enhancement, late gadolinium enhancement and T2-mapping did not differ significantly between groups. However, both native T1-mapping and extracellular volume fraction were significantly lower in myocarditis compared with dcSSc patients (1051.0 (1027.0, 1099.0) vs. 1120.0 (1065.0, 1170.0), p < 0.001 and 28.0 (26.0, 30.0) vs. 31.5 (30.0, 33.0), p < 0.001, respectively). The original Lake Louise criteria (LLc) were positive in 34 (100%) myocarditis and 40 (69%) dcSSc patients, while the updated LLc were positive in 32 (94%) and 44 (76%) patients, respectively. Both criteria had good agreement with greater but nonsignificant discordance in dcSSc patients. Conclusions: ∼25% of dcSSc patients with suspected myocardial inflammation had no CMR evidence of acute inflammatory processes. T1-based indices should not be used by themselves as surrogates of acute myocardial inflammation in dcSSc patients. © 2020 by the authors. Licensee MDPI, Basel, Switzerland

Mortality after First Myocardial Infarction in Greek Patients: A 4-Year Follow-Up Study

Background: Death associated with coronary heart disease (CHD) depends in part on the time since the myocardial infarction (MI) and modification of risk factors. Methods: This observational, retrospective 4-year follow-up study consisted of 804 patients (628 men). The participants completed a questionnaire reporting diet, demographic factors, personal behavior (smoking, physical activity), anthropometry, prior medical conditions (hypertension, diabetes mellitus), and recent medication. Results: During 48 months of follow-up, 12% of men and 15% of women died. Older age, longer duration of smoking, and frequency of exercise were significantly different between survivors and the deceased (P =.014, P =.014, P =.001, respectively). Multivariate analysis revealed associations with years of smoking (odds ratio, OR: 1.10, P =.025), treatment with nitrates (OR: 4.81, P =.024), and increased frequency of exercise (OR: 0.42, P =.013), adjusting for age and gender. Conclusions: We should emphasize cessation of smoking and increased physical activity in MI survivors. Antismoking programs should start at an early age

Prospects of using cardiovascular magnetic resonance in the identification of arrhythmogenic substrate in autoimmune rheumatic diseases

Sudden cardiac death (SCD) is due to ventricular tachycardia/fibrillation (VT/VF) and may occur with or without any structural or functional heart disease. The presence of myocardial edema, ischemia and/or fibrosis plays a crucial role in the pathogenesis of VT/VF, irrespective of the pathophysiologic background of the disease. Specifically, in autoimmune rheumatic diseases (ARDs), various entities such as myocardial/vascular inflammation, ischemia and fibrosis may lead to VT/VF. Furthermore, autonomic dysfunction, commonly found in ARDs, may also contribute to SCD in these patients. The only non-invasive, radiation-free imaging modality that can perform functional assessment and tissue characterization is cardiovascular magnetic resonance (CMR). Due to its capability to detect and quantify edema, ischemia and fibrosis in parallel with ventricular function assessment, CMR has the great potential to identify ARD patients at high risk for VT/VF, thus influencing both cardiac and anti-rheumatic treatment and modifying perhaps the criteria for implantation of cardioverter defibrillators. © 2018, Springer-Verlag GmbH Germany, part of Springer Nature

Reduced global longitudinal strain at rest and inadequate blood pressure response during exercise treadmill testing in male heterozygous familial hypercholesterolemia patients

Background: Heterozygous familial hypercholesterolemia (heFH) is a genetic disorder leading to premature coronary artery disease (CAD). We hypothesized that the subclinical pathophysiologic consequences of hypercholesterolemia may be detected before the occurrence of clinically overt CAD by stress testing and myocardial strain imaging. Patients-methods: We evaluated the treadmill tests (ETTs) of 46 heFH men without known arterial hypertension/diabetes mellitus/vasculopathy like CAD and of 39 healthy men matched for age, baseline systolic/diastolic blood pressure (BP) and heart rate (HR), using Bruce protocol. Global longitudinal strain (GLS) of the left ventricle (LV) additionally to ejection fraction was obtained. Results: heFH men reached a significantly higher peak systolic and diastolic BP compared to controls (p = 0.002 and p < 0.001, respectively). Mean rate pressure product was significantly higher in heFH patients (p = 0.038). Both duration of the ETT and workload in metabolic equivalents was lower in the heFH group (p < 0.001 and p < 0.001, respectively). Baseline to peak rise of systolic and diastolic BP in heFH men was higher (p = 0.008 and p < 0.001 for systolic and diastolic BP, respectively). Furthermore, heFH men had higher rise of HR from baseline to peak, compared to controls; (p = 0.047). GLS in heHF men was slightly decreased (p = 0.014), although the ejection fraction was similar in both groups. Conclusion: heFH men have a higher rise in systolic/diastolic BP during ETT, which may reflect early, preclinical hypertension. Furthermore, slight impairment of LV GLS is present, despite the absence of apparent myocardial dysfunction in conventional 2D echocardiography. © 2021 The Author