Abhinav Sharma

Prospective Validation that Vulnerable Plaque Associated with Major Adverse Outcomes Have Larger Plaque Volume, Less Dense Calcium, and More Non-Calcified Plaque by Quantitative, Three-Dimensional Measurements Using Intravascular Ultrasound with Radiofrequency Backscatter Analysis: Results from the ATLANTA I Study

Whether quantitative, two-dimensional, and three-dimensional plaque measurements by intravascular ultrasound with radiofrequency backscatter (IVUS/VH) are different between intermediate lesions with or without major adverse cardiovascular events (MACE) is unknown. IVUS/VH-derived parameters were compared in 60 patients with an intermediate coronary lesion (40–70xa0%) between lesions that did or did not result in MACE over 12xa0months. IVUS/VH measurements were done at the site of the minimal lumen area (MLA) and on a per-plaque basis, defined by 40xa0% plaque burden. Pre-specified, adjudicated MACE events occurred in 5 of 60 patients (8.3xa0%). MACE lesions had larger plaque burden (65xa0% vs. 53xa0%, pu2009=u20090.004), less dense calcium (6.6xa0% vs. 14.7xa0%, pu2009=u20090.05), and more non-calcified plaque, mostly fibrofatty kind (17.6xa0% vs. 10xa0%, pu2009=u20090.02). Intermediate coronary lesions associated with MACE at 12xa0months have more plaque, less dense calcium, and more non-calcified plaque, particularly fibrofatty tissue by IVUS/VH.

A peripheral blood gene expression score is associated with plaque volume and phenotype by intravascular ultrasound with radiofrequency backscatter analysis: results from the ATLANTA study

BACKGROUNDnA composite, peripheral gene expression score based on quantitative RNA-measurements has been validated for detecting stenosis against invasive coronary X-ray angiography. IVUS/VH has been validated for quantitative measurements of coronary plaque volume and composition and has been shown to be predictive of outcomes and treatment effects. The correlation between peripheral gene expression and coronary plaque composition by intravascular ultrasound with radiofrequency backscatter (IVUS/VH) is unknown.nnnMETHODSnPeripheral blood gene expression score (GES) was prospectively measured in 18 patients undergoing IVUS/VH. Plaque volume and composition [fibrous tissue (FI), fibro-fatty tissue (FF), necrotic core (NC) and dense calcium (DC)] were quantified in 3 dimensions in all plaques within the entire pullback. The relationship to GES was assessed by Spearman rank correlation.nnnRESULTSnMean age was 61.1±8.6 years; 67% were male. 1,158 mm of coronary anatomy was imaged by IVUS/VH. Using a validated scale of 1-40, mean GES was 21.6±9.4. GES was associated with plaque volume (R(2)=0.55; P=0.018), NC volume (R(2)=0.56; P=0.015), DC volume (R(2)=0.60; P=0.007), and non-calcified plaque volume (R(2)=0.50; P=0.036) by Spearman rank correlation.nnnCONCLUSIONSnIn this preliminary report, increased GES was associated with higher plaque volume and a more vulnerable plaque phenotype as evidenced by NC and DC. This composite GES is not only associated with obstructive coronary disease, but also with higher plaque volume and vulnerable phenotype.

The M235T single nucleotide polymorphism in the angiotensinogen gene is associated with coronary artery calcium in patients with a family history of coronary artery disease

Little is known about the contribution of genetics and lipoprotein subclasses to the development of coronary artery calcification (CAC) in asymptomatic, first-degree relatives of patients with CAD. We evaluated 100 asymptomatic, non-smoking, lipid-lowering therapy-naïve, first-degree relatives of patients with obstructive CAD through testing for 27 biomarkers, 15 single nucleotide polymorphisms in 12 candidate genes, and CAC and compared them to matched controls without family history. We compared prevalence of CAC in those with and without family history and biomarkers between those with and without CAC. Mean age was 41.6xa0±xa09 years; 58% were female. Significantly more subjects with family history had non-zero CAC (median Agatston: 13, range 1-1107) compared to those without family history (median Agatston: 43; range 1-345) (21% vs. 9%; pxa0=xa00.028). Among subjects with family history, in subjects with positive vs. negative CAC, multivariable analysis showed significantly lower HDL-2A (999xa0±xa0333 vs. 1262xa0±xa0397xa0nmol/L) and higher frequency of a substitution of threonine for methionine at codon 235 in the angiotensinogen gene (AGT M235T) (75% vs. 54%; pxa0<xa00.05; odds ratio of 2.6 for CAC). Population attributable risk of one copy of the risk allele at the AGT locus was 16%, highest of any variable tested. In conclusion, in this population of healthy, low-risk subjects with a family history of CAD, the AGT M235T variant was the most significant predictor of CAC independent of blood pressure, raising the possibility of an alternative biological pathway.

Abnormal Lipoprotein(a) Levels Predict Coronary Artery Calcification in Southeast Asians but Not in Caucasians: Use of Noninvasive Imaging for Evaluation of an Emerging Risk Factor

Subclinical atherosclerosis can be quantified by coronary artery calcium (CAC) scoring. Due to its high specificity for atherosclerosis, CAC is an excellent phenotypic tool for the evaluation of emerging risk markers. Lipoprotein(a) [Lp(a)] is atherogenic due to the presence of apoB and may be thrombogenic through its apo(a) component. Lp(a) has been linked to cardiovascular events in Caucasians; however, its link to atherosclerosis in various ethnicities remains unclear. We evaluated the ability of Lp(a) mass to predict subclinical atherosclerosis in Southeast Asians and Caucasians, as measured by CAC. Traditional lipid measurements, Lp(a) measurements, and CAC by 64-slice multidetector computed tomography was performed in 103 consecutive patients in the USA and in 104 consecutive patients in Jakarta, Indonesia. Proportion of positive CAC and median CAC in Southeast Asians and in Caucasians was 61.5% and 63.1%, and 23.5 (interquartile range, 0–270) and 13 (interquartile range, 0–388), respectively. Significantly higher proportion of Southeast Asians had elevated Lp(a) levels, compared to Caucasians (51.0% vs. 29.2%; pu2009=u20090.005). In Southeast Asians, Lp(a) remained an independent predictor of CAC with an odds ratio of 4.97 (95% confidence interval, 1.56–15.88; pu2009<u20090.0001), but not in Caucasians. Receiver operating characteristic analysis showed an improvement in area under the curve from 0.81 to 0.86 (pu2009=u20090.05) when including Lp(a) in the predictive model in Southeast Asians. This translated to 7% of Southeast Asians reclassified to correct CAC status. Lp(a) measurements may have a role in risk stratification of Southeast Asians. Ethnic variation should be taken into account when considering the use of Lp(a) measurements in risk assessment.

Baseline Very Low-Density Lipoprotein Cholesterol is Associated with the Magnitude of Triglyceride Lowering on Statins, Fenofibric Acid, or Their Combination in Patients with Mixed Dyslipidemia

Fibric acid derivatives like fenofibric acid (FA) decrease hepatic production of very low-density lipoprotein (VLDL)-associated triglycerides (TG). Hepatic VLDL production can be estimated from VLDL-associated cholesterol (VLDL-C). We assessed if the degree of TG reduction observed with FA, statins, or their combination is associated with baseline VLDL-C. Overall, 2,715 patients with mixed dyslipidemia in three randomized, controlled studies were assigned to one of six treatment strategies: FA, low-dose statin (LDS), FAu2009+u2009LDS, moderate-dose statin (MDS), FAu2009+u2009MDS, and high-dose statin (HDS). Patients were dichotomized into low- or high-baseline VLDL-C groups. Pooled data were used to compare the degree of TG reduction in patients with low- vs. high-baseline VLDL-C for each treatment arm, using unpaired, two-sided t test. Additionally, the association between baseline VLDL-C level and percentage TG reduction from baseline was evaluated by linear regression. Diagnostic performance of baseline VLDL-C levels in predicting 5, 10, 15, and 20xa0% TG reduction was assessed by receiver operating characteristics (ROC) analysis. In all treatment groups, following 12xa0weeks of therapy, a significantly greater percent change from baseline in TG was observed in the high-baseline VLDL-C group as compared with the low-baseline VLDL-C group. Linear regression analysis indicated that approximately 6 to 13xa0% of the decrease in TG could be explained by baseline VLDL-C. ROC-derived cut points for baseline VLDL-C were obtained for 5, 10, 15, and 20xa0% TG reduction. Baseline VLDL-C levels are associated with the degree of TG lowering using FA, statins, or their combination, thereof.

The Importance of Global Health Experiences During Clinical Training

We read with great interest the review by Abdalla etxa0al. [(1)][1] on the American College of Cardiology (ACC) International Cardiovascular Exchange Database. Global health experiences can positively affect the development of early-career cardiologists. Yet these experiences can often be

Antihyperglycemic Therapies to Treat Patients With Heart Failure and Diabetes Mellitus

There is increasing recognition of the relationship between diabetes and heart failure (HF). Comorbid diabetes is associated with worse outcomes in patients with HF, and death from HF forms a large burden of mortality among patients with diabetes and atherosclerotic cardiovascular disease. However, there is evidence of harm relating to the risk of HF outcomes from several antihyperglycemic therapies. The absence of well-powered randomized controlled studies has resulted in significant treatment variations in the glycemic management in patients with coexisting diabetes and HF. However, there is emerging evidence from recent clinical trials suggesting that sodium-glucose-co-transporter-2 inhibitors may be used as a therapy to improve HF outcomes. In order to understand the current state of knowledge, we reviewed the evolving evidence of antihyperglycemic therapies and present strategies to optimize these therapies in patients with diabetes and HF. This analysis is based on discussions among scientists, clinical trialists, industry sponsors, and regulatory representatives whoxa0attended the 12th Global Cardiovascular Clinical Trialists Forum, Washington, DC, December 1 to 3,xa02016.

FIRST DEMONSTRATION THAT HEPATIC APOB100 AND INTESTINAL APOB48 CO-LOCALIZE WITH MACROPHAGES IN HUMAN CAROTID ATHEROSCLEROTIC PLAQUES

We previously demonstrated the presence and localization of hepatic apoB100 and intestinal apoB48 in human carotid atherosclerotic plaques by immunoperoxidase, immunofluorescence (IF), immunoelectron microscopy, and western blot; however, co-localization of apoB48 and apoB100 with macrophages has

PROSPECTIVELY TRIGGERED, VOLUMETRIC CARDIAC COMPUTED TOMOGRAPHY ANGIOGRAPHY ON A 320 DETECTOR ROW PLATFORM, REDUCES LENGTH OF STAY AND RADIATION EXPOSURE COMPARED TO RADIONUCLIDE MYOCARDIAL PERFUSION IMAGING IN LOW RISK, SYMPTOMATIC PATIENTS PRESENTING TO THE EMERGENCY ROOM

Retrospectively gated CTA has demonstrated a reduction in length of stay (LOS), hospital cost, and radiation exposure in low risk, symptomatic patients presenting to the ER, compared to myocardial perfusion imaging (MPI). However, the benefits of volumetric CTA have not been evaluated in this