Coronary artery disease among asymptomatic diabetic and nondiabetic patients undergoing coronary computed tomography angiography

OBJECTIVES: The aim of this study was to determine the prevalence and severity of coronary artery disease (CAD) and the plaque composition in asymptomatic diabetic and nondiabetic patients undergoing coronary computed tomography angiography (CCTA). BACKGROUND: CAD is the major cause of death among patients with diabetes. The true prevalence of CAD in asymptomatic diabetic patients, however, remains unknown. MATERIALS AND METHODS: A total of 328 consecutive patients (each with at least one risk factor or abnormal stress-test results) were referred for cardiac evaluation, 42 with diabetes and 286 without diabetes, all asymptomatic for cardiac-related symptoms. Groups were matched for age, sex, and CAD risk factors. CAD was defined as coronary atherosclerosis, with obstructive or nonobstructive lesions. CCTA was performed and findings compared between patients with diabetes and those without. RESULTS: CAD was present in 39 (93%) diabetic patients and in 211 (73%) nondiabetic patients (P=0.006). Obstructive CAD was more common in diabetic patients than in nondiabetic patients (29 vs. 6.6%, respectively; P<0.0001). In diabetic patients, more coronary segments with atherosclerosis per patient were detected (5.5 segments/patient vs. 2.8 segments/patient in nondiabetics; P<0.0001). The total Agatston score was significantly higher in diabetic patients vs. nondiabetic patients (370+/-96 and 79.9+/-16, respectively; P<0.0001). CONCLUSION: Our results indicate a high prevalence (93%) of CAD in asymptomatic diabetic patients with either nonobstructive or obstructive lesions. CCTA may be a useful imaging modality for selecting patients at high risk who would benefit most from further evaluation for subclinical ischemia.     

Ca2+ influx through T- and L-type Ca2+ channels have different effects on myocyte contractility and induce unique cardiac phenotypes

T-type Ca(2+) channels (TTCCs) are expressed in the developing heart, are not present in the adult ventricle, and are reexpressed in cardiac diseases involving cardiac dysfunction and premature, arrhythmogenic death. The goal of this study was to determine the functional role of increased Ca(2+) influx through reexpressed TTCCs in the adult heart. A mouse line with cardiac-specific, conditional expression of the alpha1G-TTCC was used to increase Ca(2+) influx through TTCCs. alpha1G hearts had mild increases in contractility but no cardiac histopathology or premature death. This contrasts with the pathological phenotype of a previously studied mouse with increased Ca(2+) influx through the L-type Ca(2+) channel (LTCC) secondary to overexpression of its beta2a subunit. Although alpha1G and beta2a myocytes had similar increases in Ca(2+) influx, alpha1G myocytes had smaller increases in contraction magnitude, and, unlike beta2a myocytes, there were no increases in sarcoplasmic reticulum Ca(2+) loading. Ca(2+) influx through TTCCs also did not induce normal sarcoplasmic reticulum Ca(2+) release. alpha1G myocytes had changes in LTCC, SERCA2a, and phospholamban abundance, which appear to be adaptations that help maintain Ca(2+) homeostasis. Immunostaining suggested that the majority of alpha1G-TTCCs were on the surface membrane. Osmotic shock, which selectively eliminates T-tubules, induced a greater reduction in L- versus TTCC currents. These studies suggest that T- and LTCCs are in different portions of the sarcolemma (surface membrane versus T-tubules) and that Ca(2+) influx through these channels induce different effects on myocyte contractility and lead to distinct cardiac phenotypes.     

Addressing the link between paraoxonase-1 gene variants and the incidence of early onset myocardial infarction

Introduction

The enzyme paraoxonase-1 (PON1) represents an endogenous defense mechanism against vascular oxidative stress, thereby contributing to the prevention of atherosclerosis. Several polymorphisms have been reported in the PON1 gene, including Q192R. PON1 phenotype is commonly expressed as the paraoxonase/arylesterase ratio (PON/ARE). The major aim of this study was to investigate the association between PON1 Q192R polymorphism, PON1 phenotypes and the incidence of early-onset acute myocardial infarction (AMI) in Egyptians.

Material and methods

The study subjects consisted of 102 AMI patients and 72 age-matched healthy controls. Genotyping and enzyme activities were determined using PCR-RFLP and kinetic spectrophotometric assays, respectively.

Results

The genotype distribution for the PON1 gene was significantly different between AMI patients (QQ = 38.24%, QR = 49.02%, RR = 12.75%) and controls (QQ = 66.67%, QR = 25%, RR = 8.33%). Allele frequencies were also significantly different between patients (Q = 62.75%, R = 37.25%) and controls (Q = 79.17%, R = 20.83%). The genotypes QR and RR showed higher risk for AMI compared to the homozygous QQ (odds ratio (OR) = 3.231, p < 0.001). The average PON/ARE ratio in MI patients (1.187 ±0.1) did not differ significantly from controls (1.118 ±0.26). However, it showed a significant difference among different genotypes in both AMI patients (QQ = 0.91 ±0.11, QR = 1.09 ±0.11 and RR = 2.65 ±0.4) (p = 0.0002) and controls (QQ = 0.68 ±0.1, QR = 1.07 ±0.11 and RR = 4.89 ±2.84) (p < 0.0001).

Conclusions

PON1 192R allele represents an independent risk factor for early-onset AMI in Egyptians, and PON1 Q192R polymorphism modulates the paraoxonase phenotype.     

Predictors of repeat transarterial chemoembolization in the treatment of hepatocellular carcinoma

ObjectivesRepeat transarterial chemoembolization (TACE) is a common intervention performed for hepatocellular carcinoma (HCC). The aim of this study was to identify predictors of the need for repeat TACE.MethodsBetween 2008 and 2012, data on patient and tumour variables were collected for 262 patients treated with a first TACE procedure for HCC. The decision to perform repeat TACE procedures was made at the completion of the first TACE or after follow-up imaging demonstrated the subtotal treatment of HCC tumours.ResultsRepeat TACE was performed in 67 of 262 (25.6%) patients. Necrosis of HCC, measured after the first TACE, was lower in patients who subsequently received repeat TACE (P = 0.042). On multivariable analysis, total tumour diameter of >5 cm [odds ratio (OR) 2.76, 95% confidence interval (CI) 1.45–5.25; P = 0.002] and increasing age (OR 1.04/year, 95% CI 1.00–1.07; P = 0.030) were predictive of the need for repeat TACE. Measures of liver function and TACE approach (selective versus non-selective) were not predictive of repeat TACE. Median survival did not differ significantly between patients who did (median survival: 21.1 months) and did not (median survival: 26.1 months) receive a repeat TACE procedure (P = 0.574).ConclusionsThe requirement for repeat TACE is associated with older age, increased HCC tumour burden and subtotal TACE-induced HCC necrosis. Importantly, repeat TACE was not associated with reduced survival.