Impact of plaque burden and composition on coronary slow flow in ST-segment elevation myocardial infarction undergoing percutaneous coronary intervention: intravascular ultrasound and virtual histology analysis.

AIM: Coronary slow flow (SF) is an important complication of percutaneous coronary intervention (PCI) associated with poor prognosis. The aim was to assess grey-scale intravascular ultrasound (IVUS) and virtual histology (VH-IVUS) characteristics of culprit lesion in ST-elevation myocardial infarction (STEMI). METHODS: A total of 295 consecutive patients with STEMI underwent coronary angiogram and IVUS. Following PCI, patients divided into two groups; SF (thrombolysis in myocardial infarction [TIMI] flow ≤ 2, n = 74) and normal flow (NF) (TIMI flow >2, n = 221). Coronary plaque burden and its composition in relation to SF were evaluated. RESULTS: On grey-scale IVUS, the plaque area (12.3 mm2 vs. 11.5 mm2, p = .01), plaque volume (110.7 mm3 vs. 99.8 mm3, p < .001), lesion external elastic membrane (EEM) cross-sectional area (14.9 mm2 vs. 14.0 mm2, p = .011) and remodelling index (1.3 vs. 1.2, p = .043) were significantly higher in SF group. On VH-IVUS, absolute fibrous volume (48.1 mm3 vs. 41.5 mm3, p ≤ .001), fibrofatty volume (23.8 mm3 vs. 18.6 mm3, p = .015), necrotic core volume (8.3 mm3 vs. 5.5 mm3, p < .001), dense calcium volume (1.2 mm3 vs. 0.6 mm3, p = .003) and thin cap fibroatheroma either single (30.1% vs. 16.1%, p < .001) or multiple (9.6% vs. 1.8%, p < .001) were higher in SF arm. In multivariable analysis, absolute necrotic core volume (odds ratio = 1.159; 95% CI 1.030-1.305, p = .015) was the only independent predictor of SF. CONCLUSIONS: Higher necrotic core volume as detected by VH-IVUS may be a potential risk factor for the development of coronary SF phenomenon in patients with STEMI after PCI.

Association of culprit lesion plaque characteristics with flow restoration post-fibrinolysis in ST-segment elevation myocardial infarction: an intravascular ultrasound-virtual histology study.

BACKGROUND: Not every patient achieves normal coronary flow following fibrinolysis in STEMI (ST-segment elevation myocardial infarction). The culprit lesion plaque characteristics play a prominent role in the coronary flow before and during percutaneous coronary intervention. The main purpose was to determine the culprit lesion plaque features by virtual histology-intravascular ultrasound (VH-IVUS) in patients with STEMI following fibrinolysis in relation to baseline coronary angiogram TIMI (thrombolysis in myocardial infarction) flow. Pre-intervention IVUS was undertaken in 61 patients with STEMI after successful fibrinolysis. After the coronary angiogram, they were separated into the TIMI1-2 flow group (n = 31) and TIMI 3 flow group (n = 30). Culprit lesion plaque composition was evaluated by VH-IVUS. RESULTS: On gray-scale IVUS, the lesion external elastic membrane cross-sectional area (EEM CSA) was significantly higher in the TIMI 1-2 groups as compared to the TIMI 3 group (15.71 ± 3.73 mm2 vs 13.91 ± 2.94 mm2, p = 0.041) with no significant difference in plaque burden (82.42% vs. 81.65%, p = 0.306) and plaque volume (108.3 mm3 vs. 94.3 mm3, p = 0.194). On VH-IVUS, at the minimal luminal area site (MLS), the fibrous area (5.83 mm2 vs. 4.37 mm2, p = 0.024), necrotic core (NC) area (0.95 mm2 vs. 0.59 mm2, p < 0.001), and NC percentage (11% vs. 7.1%, p = 0.024) were higher in the TIMI 1-2 groups in contrast to the TIMI 3 group. The absolute necrotic core (NC) volume (8.3 mm3 vs. 3.65 mm3, p < 0.001) and NC percentage (9.3% vs. 6.0%, p = 0.007) were significantly higher in the TIMI 1-2 groups as compared to the TIMI 3 group. Absolute dense calcium (DC) volume was higher in TIMI 1-2 groups with a trend towards significance (1.0 mm3 vs.0.75 mm3, p = 0.051). In multivariate analysis, absolute NC volume was the only independent predictor of TIMI 1-2 flow (odds ratio = 1.561; 95% CI 1.202-2.026, p = 0.001). Receiver operating characteristic curves showed absolute NC volume has best diagnostic accuracy (AUC = 0.816, p < 0.001) to predict TIMI 1-2 flow with an optimal cutoff value of 4.5 mm3 with sensitivity and specificity of 79% and 61%, respectively. CONCLUSIONS: This study exemplifies that the necrotic core component of the culprit lesion plaque in STEMI is associated with the coronary flow after fibrinolysis. The absolute necrotic core volume is a key determinant of flow restoration post-fibrinolysis and aids in prognostication of less than TIMI 3 flow.

Comparison of Intravascular Ultrasound Virtual Histology Parameters in Diabetes versus Non-Diabetes with Acute Coronary Syndrome.

INTRODUCTION: The progression and pattern of coronary atherosclerosis in diabetes mellitus (DM) is different from non-DM, leading to a higher rate of vascular complications in DM. OBJECTIVE: This study aims to assess and compare the high-risk plaque characteristics in the culprit artery of DM and non-DM patients with acute coronary syndrome (ACS) using virtual histology intravascular ultrasound (VH-IVUS). METHODS: A total of 158 ACS patients were included, 63 of whom were known to have DM. IVUS analysis was done in the de novo target vessel and culprit lesion for which percutaneous coronary intervention was planned. Culprit lesions with a visual-estimate angiographic stenosis of <70% were excluded. RESULTS: The mean age of patients was 52.4 ± 11.6 years. The study group comprised 82% men, 31% with hypertension, and 39.87% with DM. No significant difference was observed between the DM and non-DM groups in relation to quantitative IVUS parameters like lesion length, minimal lumen area, and plaque area. However, there was a significant difference in VH-IVUS parameters like higher necrotic core and dense calcium in the DM patients than in the non-DM patients (p < 0.01). The occurrence of VH-derived thin-cap fibroatheroma (VH-TCFA) in the culprit vessel was significantly higher in the DM group than in the non-DM group (25.3 vs. 5.2%; p < 0.01). Positive vessel-wall remodeling was noted in both groups without any significant difference (p = 0.74). CONCLUSION: The DM patients had high-risk plaque composition features like a higher necrotic core, which is a marker of plaque vulnerability. Thus, aggressive medical therapy targeting vascular inflammation using high-dose statins would help in the stabilization of unstable plaque morphology and the reduction of major cardiovascular events.

ANRIL rs1333049 C/G polymorphism and coronary artery disease in a North Indian population - Gender and age specific associations.

Many studies conducted worldwide substantiate a role of genetic polymorphisms in non-coding regions linked with coronary artery disease (CAD). One such single nucleotide polymorphism (SNP) of a non-coding RNA in the INK4 locus (ANRIL) i.e. rs1333049 C/G in the vicinity of cell cycle regulating genes is documented to have a role in CAD risk. In this study we aimed to determine the association of ANRIL rs1333049 C/G with CAD in a North Indian population. Five hundred disease free controls and 500 CAD patients were genotyped using allele specific ARMS-PCR method. High risk association of rs1333049 was seen in both heterozygous and mutant genotypes (OR=2.883, 95% CI=1.475-5.638 and p=0.002 and OR=6.717, 95% CI=3.444-13.102 and p < 0.001 respectively). Gender stratified analysis revealed risk association in both heterozygous and mutant genotypes in males. However, risk association in the mutant genotype and females was documented. Similarly, risk association was seen in subjects above 40 years of age in heterozygous and mutant genotypes. Similarly, risk association was reported in obese, sedentary lifestyle, positive family history and smoking in the heterozygous and mutant genotype and with diabetes in the mutant GG genotype. The study revealed high risk association of ANRIL rs1333049 with CAD and other risk factors.

Association of IL-8-251 A/T rs4073 and IL-10 rs1800872 -592C/A Polymorphisms and Coronary Artery Disease in North Indian Population.

CAD (Coronary Artery Disease) morbidity is becoming an endemic worldwide. Recently, the role of pro- and anti-inflammatory cytokines in the development of atherosclerotic plaques has been explored, but the association of their genetic polymorphisms and CAD has yet not been established. The present study aimed to investigate the association of IL-8-251A/T (rs4073) and IL-10 -592C/A (rs1800872) polymorphisms and the risk of CAD in North Indian population. 1000 subjects (500 angiographically confirmed CAD patients and 500 controls) were genotyped by ARMS-PCR. Results revealed a significant risk association of both the polymorphisms with CAD. The heterozygous and the mutant genotypes of IL-8 rs4073 were both found to be associated with the risk of disease after adjusting for the confounders (padj < 0.001, ORadj 3.121, 95% CI 1.926-5.056 and padj < 0.001, ORadj 3.116, 95% CI 1.952-4.973, respectively), but only the mutant AA genotype of IL-10 rs1800872 correlated with risk of disease with padj < 0.001, ORadj 4.106, 95% CI 2.160-7.806). Stratifying the samples on the basis of gender revealed CAD in heterozygous and mutant in males (padj < 0.001, ORadj 3.693, 95% CI 2.031-6.716; padj < 0.001, ORadj 3.288, 95% CI 1.848-5.851, respectively) and only the mutant to be associated with risk of disease in females (padj = 0.010, ORadj 2.867, 95% CI 1.284-6.404) for IL-8 rs4073, whereas only the mutant genotype AA of IL-10 rs1800872 associated with CAD risk in males (padj < 0.001, ORadj 5.821, 95% CI 2.831-11.970). Stratified analysis based on age showed a significant higher risk in the heterozygous and mutant genotype in subjects below 40 years of age (padj = 0.039, ORadj 5.052, 95% CI 1.081-23.602; and padj = 0.025, ORadj 5.533, 95% CI 1.239-24.704, respectively) compared with the heterozygous and mutant genotype association of the risk of disease in subjects above 40 years of age (padj < 0.000, ORadj 2.964, 95% CI 1.747-5.027; and padj < 0.000, ORadj 2.859, 95% CI 1.716-4.762, respectively) in IL-8 rs4073. For IL-10 rs1800872, risk association was seen only in subjects above 40 years of age (padj < 0.001, ORadj 5.049, and 95% CI 2.414-10.561). The present study exhibited associations of IL-8-251A/T (rs4073) and IL-10 -592C/A (rs1800872) with CAD in the North Indian population and also that the associations are gender and age dependent.

Coronary artery size in North Indian population - Intravascular ultrasound-based study.

OBJECTIVE: The coronary artery dimensions have important diagnostic and therapeutic implications in management of coronary artery disease (CAD). There is paucity of data on the coronary artery size in the Indian population as measured by intravascular ultrasound (IVUS). METHODS: A total of 303 patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI) with intravascular ultrasound underwent analysis along with quantitative coronary angiography (QCA). Of the 492 proximal coronary segments; 221 relating to left main (LM), 164 to left anterior descending artery (LAD), 45 to left circumflex artery (LCX), and 62 to right coronary artery (RCA) were considered. RESULTS: Patient's mean age was 53.37 ± 3.5 years; men 80%; hypertension 35% and diabetes 24.8%. On IVUS, mean minimal lumen diameter as compared to QCA in LM (4.60 mm versus 4.50 mm, p < 0.001), LAD (3.71 mm versus 3.45 mm, p < 0.001), LCX (3.55 mm versus 3.16 mm, p < 0.001) and RCA (3.85 mm versus 3.27 mm, p < 0.001) were significantly larger. Lumen and external elastic membrane (EEM) cross-sectional area (CSA) were larger in males as compared to females with statistical significance for lumen CSA in LM (p = 0.04); RCA (p = 0.02) and EEM CSA in LM (p = 0.03); RCA (p = 0.006) but no significance for adjusted body surface area (BSA). In multivariate models, BSA and age were independent predictors of LM and LAD diameters and areas, but age was an independent predictor indexed to BSA. CONCLUSION: The coronary artery dimensions by IVUS are significantly larger than QCA. No gender difference in coronary artery size. Age was an independent predictor of coronary artery size in left main and LAD. The coronary artery size may not be a risk factor for acute coronary syndrome.

A novel study to examine the association of PCSK9 rs505151 polymorphism and coronary artery disease in north Indian population.

There is a drastic increase in the number of people suffering from coronary artery disease (CAD) worldwide with Indians being no exception. Being a developing country and experiencing a dramatic shift in lifestyle and eating habits, urbanization and industrialization, all these factors have collectively predisposed the Indian population towards CAD and the prevalence data arequite alarming. Genetic studies have disclosed the role of genes in CAD susceptibility and severity. One such gene is proprotein convertase subtilisin/kexin type 9 (PCSK9) which is sought to modulate the cholesterol levels and hence, has implications in CAD. We aim to explore the association of PCSK9 A/G (rs505151) polymorphism and hence, the susceptibility towards CAD in the north Indian population. Five-hundred angiographically confirmed CAD patients and 500 healthy individuals as control were genotyped by polymerase chain reaction-restriction fragment length polymorphism. Statistical analysis revealed a significant association with the G allele with odds ratio (OR)=1.50, 95% confidence interval (CI)=1.22-1.85 and P=0.000. Also, a strong association was observedfor CAD risk with OR=1.590, 95% CI=1.106-2.284 and P=0.012. However, the homozygous GG mutant genotype was found to be completely absent from our population. Analysis of the dominant model also revealed an association with CAD risk. Our work demonstrated for the first time the association of PCSK9 A/G (rs505151) polymorphism with CAD risk in the north Indian population.

Interaction between ALOX15 polymorphisms and coronary artery disease in North Indian population.

BACKGROUND: Coronary artery disease (CAD) is major cause of death and morbidity worldwide. Arachidonate 12/15-lipoxygenase (ALOX) is a member of the lipid peroxidizing enzyme family and implicated in the pathogenesis of atherosclerosis, but with contradicting results. AIM: The present study aimed to investigate the association of two polymorphisms in ALOX15 (rs2619112 and rs7217186) and the risk of CAD in North Indian population. METHODS: A total of 500 angiographically confirmed CAD patients and 500 control subjects of North Indian population were recruited in the case-control study and genotyped by PCR-RFLP. RESULTS: The data showed a significant association between the two polymorphisms and CAD. Multiple logistic regression revealed heterozygous genotype of both the polymorphisms viz. GA of rs2619112 and CT of rs7217186 to be associated with significant high risk of CAD after adjustment for confounders (p = 0.034, OR = 2.274, 95% CI (1.062-4.870) and p = 0.000, OR = 3.407, 95% CI (2.092-5.548) respectively). Stratified analysis based on gender showed GA and AA of rs2619112 each significantly increased the risk of CAD in females (p = 0.001, OR = 13.120, CI = 2.780-61.928; p = 0.028, OR = 5.393, CI = 1.196-24.316 respectively) whereas only GA increased CAD risk in males (p = 0.005, OR = 2.277, CI = 1.290-4.020). In case of rs7217186, CT and TT showed a significant high risk of CAD in males (p = 0.000, OR = 4.048, CI = 2.678-6.119; p = 0.000, OR = 2.861, CI = 1.928-4.245). CONCLUSION: The present study shows that rs7217186:C > T and rs2619112:G > A of ALOX15 are associated with increased risk of CAD in the North Indian population.