Serum Gamma Glutamyltransferase (GGT) in Coronary Artery Disease: Exploring the Asian Indian Connection

Background:There is a need to identify novel markers for CAD, independent of traditional CV risk factors. One of these is gamma?glutamyl transferase (GGT), a marker of increased oxidative stress. Given the high prevalence of CAD in Asian Indians, the link of GGT and CAD in them needs to be studied. Aim: To assess GGT in patients with angiographically documented CAD. Methods and Results: Two hundred patients aged 58.1 ± 9.95 years, 73% males, hypertension 56%, diabetes 40% were included. Mean GGT was 63.6 ± 44.33 (10–269 U/L). The levels of GGT progressively increased in those with single/double or triple?vessel CAD (36.5, 61.5, and 87 U/L, respectively, P < 0.001). Using objective criteria of CAD burden (SYNTAX and Gensini scores), we reaffirmed these findings. GGT in patients with SYNTAX tertiles 0–22, 23–32, and 33 was 33, 62, and 97 U/L, respectively and in Gensini tertiles 0–17.65, 17.66–56.65, ?56.66 was 32, 52, and 88 U/L, respectively, all P < 0.001. SYNTAX score 23 was present in only 23% patients in GGT tertile 1 (<41 U/L), whereas60% and 94% in GGT tertiles 2 and 3 had SYNTAX 23. Significant positive correlation was seen between GGT and SYNTAX (r = 0.634) and Gensini score (r = 0.772). Conclusions: In this study, GGT had an independent correlation with angiographic severity of CAD and SYNTAX and Gensini scores. Although the existing evidence seems biologically plausible, more studies are needed to explore the potential role of this inexpensive marker for predicting disease burden in patients with CAD.

Exploring the Association of Fibrinogen and CRP with the Clinical Spectrum of CAD and Periprocedural Outcomes in Patients Undergoing Percutaneous Coronary Interventions

Background:The pathophysiology of an atherosclerotic plaque is mediated by the mechanisms involving thrombus formation and systemic inflammation. While C-reactive protein (CRP) levels are useful in predicting a cardiovascular event in intermediate risk population, the usefulness of routinely measuring fibrinogen in patients with acute coronary syndrome (ACS) is debatable. Also, data on the association of these markers with periprocedural outcomes in patients undergoing percutaneous coronary interventions (PCI) is scarce. Aims: The study aimed to determine whether the levels of fibrinogen and CRP vary across the different spectra of CAD and whether they have any correlation with cardiac Troponin I levels. Materials and Methods: A total of 284 patients with coronary artery disease undergoing percutaneous coronary intervention were included in the study. Complete blood count, serum lipid profile, serum CRP, fibrinogen, and troponin I were measured for all patients. Results: Patients with STEMI had significantly higher levels of CRP as compared to those with unstable angina (USA) and chronic stable angina (CSA). Patients presenting with ACS had significantly higher baseline fibrinogen as compared to those with CSA. A significant positive correlation between CRP and admission Troponin I (r = 0.50; P < 0.05) as well as fibrinogen and admission troponin I (r = 0.30; P < 0.05) was observed. The CRP levels were significantly higher in 15 patients with periprocedural MI as compared to those who did not develop periprocedural MI. Conclusions: The levels of the markers of inflammation and atherothrombosis vary with presentation across varied spectra of CAD with generally higher levels in acute presentation and in those who develop periprocedural MI.

Is Indexed Left Atrial Volume (LAVi) in Indian Patients with Acute Coronary Syndrome (ACS) Undergoing Revascularization a Predictor of Cardiovascular Outcomes?

Background: Left atrial volume indexed to body surface area (LAVi) is the recommended method for LA size quantification. Assessing LAVi in Indian patients undergoing coronary interventions for acute coronary syndrome (STEMI, NSTEMI, and UA) is clinically relevant. Methods and Results: Amongst 190 patients (66.4 yrs, 68.4% males), 29.5%, 40.5%, and 30% respectively had STEMI, NSTEMI and UA. Mean LAVi was 32.29 ± 12.06 ml/m2 and 111 (58.4%) had LAVi ?32 while 79 (41.6%) had LAVi <32. Patients were divided into 2 groups (group 1 LAVi >32 and group 2 LAVi <32). Group 1 patients had higher prevalence of TVD [n = 49 vs n = 5, p = <0.001] and higher mean Syntax score (24.47 vs 14.64, p = <0.001). Despite similar LVEF, those with higher LAVi had had higher incidence of mild MR (50.4 vs 27.8, P = 0.0002) and moderate/severe MR was present only in Group 1 patients (27.9% and 5.4%). Grade I, II, and III diastolic dysfunction was present in 71.2, 17.1, and 9.9% patients in Group 1 vs 45.6%, 0%, and 0% in group 2. Diastolic parameters like septal E/e’ and lateral E/e’ratio were also higher in Group 1. Major adverse cardiovascular events? (MACE) at 30 days was significantly higher in group 1 (20.7 vs 6.3%, P = 0.006). On multivariate analysis, triple vessel disease and LAVi were the only predictors of MACE while LVEF was not. ROC curve analysis for LAVi demonstrated that a cut?off 33.35 ml/m2, predicted 30 day MACE with Area under curve (AUC) 0.775 (95% CI 0.700?0.850); sensitivity and specificity of 86.7% and 61.4%. Inter?quartile analysis of LAVi (<26.3, 26.3?33.35, 33.36?36.3, and >36.3 ml/m2) demonstrated that 30 day MACE increased across quartiles (4.16%, 4.25%, 22.44%, and 28.26%, respectively, P < 0.001). Conclusion: Amongst patients with ACS undergoing revascularization, those with higher LAVi had more severe CAD, diastolic dysfunction and higher 30 day MACE. LAVi provides superior prognostic information as compared to conventional LV systolic and diastolic parameters in patients with ACS and should be incorporated in routine echocardiographic analysis. More studies with larger numbers and longer follow up are required to further elucidate on this.

Incidence and predictors of forearm hematoma during the transradial approach for percutaneous coronary interventions

Background The transradial approach for percutaneous coronary intervention (TRA-PCI) reduces vascular complications compared with the transfemoral approach (TFA). Although hematoma formation is less frequent with the TRA than TFA, it is not uncommon, and its presentation ranges from mild hematoma to compartment syndrome. Incidence and predictors of hematoma have not been well studied. Methods and results The present study was conducted to prospectively evaluate the incidence and predictors of forearm hematoma after TRA-PCI. The study population consisted of consecutive patients undergoing TRA-PCI. Baseline and procedural characteristics and clinical outcomes were prospectively collected. All patients were observed for forearm/arm hematoma immediately after procedure, after band removal, before discharge, and whenever the patient complained of pain/swelling in the limb. Logistic regression analysis was performed to determine the predictors for hematoma formation. A total of 520 patients who had successfully completed TRA-PCI were included in the final analysis. The mean age was 55.2 ± 9.5 years, and 24% patients were women. Hematoma occurred in 53 (10.2%) patients. Hematomas were of grade I, II, III, and IV in 22 (4.2%), 9 (1.7%), 18 (3.5%), and 4 (0.8%) patients, respectively. On multivariate logistic regression analysis, age, body mass index, multiple puncture attempt, glycoprotein IIb/IIIa receptor blocker use, nonclopidogrel agent use for dual antiplatelet therapy, and multiple catheter exchanges emerged as independent predictors for hematoma formation. Conclusions Forearm hematoma following TRA-PCI occurs in about 10% patients. Most hematomas occur near the puncture area. The independent predictors for hematoma formation are age, body mass index, multiple puncture attempts, intensive antiplatelet therapy, and multiple catheter exchanges.

Heart rate manipulation in dilated cardiomyopathy: Assessing the role of Ivabradine

Background Heart rate (HR) reduction is of benefit in chronic heart failure (HF). The effect of heart rate reduction using Ivabradine on various echocardiographic parameters in dilated cardiomyopathy has been less investigated. Methods Of 187 patients with HF (DCM, NYHA II–IV, baseline HR > 70/min), 125 patients were randomized to standard therapy (beta blockers, ACEI, diuretics, n = 62) or add-on Ivabradine (titrated to maximum 7.5 mg BD, n = 63). Beta-blockers were titrated in both the groups. Results At 3 months both groups had improvement in NYHA class, 6 min walk test, Minnesota Living With Heart Failure (MLWHF) scores and fall in BNP, however the magnitude of change was greater in Ivabradine group. Those on Ivabradine also had lower LV volumes, higher LVEF (28.8 ± 3.6 vs 27.2 ± 0.5, p = 0.01) and more favorable LV global strain (11 ± 1.7vs 12.2 ± 1.1, p = <0.001), MPI (0.72 ± 0.1 vs 0.6 ± 0.1, p = <0.001), LV mass (115.2 ± 30 vs 131.4 ± 35, p = 0.007), LV wall stress (219.8 ± 46 vs 238 ± 54) and calculated LV work (366 ± 101 vs 401 ± 102, p = 0.05). The benefit of Ivabradine was sustained at 6 months follow up. The % change in HR was significantly higher in Ivabradine group (−32.2% vs −19.3%, p = 0.001) with no difference in blood pressure. Resting HR < 70/min was achieved in 96.8% vs 27.9%, respectively in the two groups. Conclusion Addition of Ivabradine to standard therapy in patients with DCM and symptomatic HF and targeting a heart rate < 70/min improves symptoms, quality of life and various echocardiographic parameters.

Efficacy of stem cell in improvement of left ventricular function in acute myocardial infarction - MI3 Trial.

Background & objectives: Acute myocardial infarction (AMI) is characterized by irreparable and irreversible loss of cardiac myocytes. Despite major advances in the management of AMI, a large number of patients are left with reduced left ventricular ejection fraction (LVEF), which is a major determinant of short and long term morbidity and mortality. A review of 33 randomized control trials has shown varying improvement in left ventricular (LV) function in patients receiving stem cells compared to standard medical therapy. Most trials had small sample size and were underpowered. This phase III prospective, open labelled, randomized multicenteric trial was undertaken to evaluate the efficacy in improving the LVEF over a period of six months, after injecting a predefined dose of 5-10 × 108 autologous mononuclear cells (MNC) by intra-coronary route, in patients, one to three weeks post ST elevation AMI, in addition to the standard medical therapy. Methods: In this phase III prospective, multicentric trial 250 patients with AMI were included and randomized into stem cell therapy (SCT) and non SCT groups. All patients were followed up for six months. Patients with AMI having left ventricular ejection fraction (LVEF) of 20-50 per cent were included and were randomized to receive intracoronary stem cell infusion after successfully completing percutaneous coronary intervention (PCI). Results: On intention-to-treat analysis the infusion of MNCs had no positive impact on LVEF improvement of ≥ 5 per cent. The improvement in LVEF after six months was 5.17 ± 8.90 per cent in non SCT group and 4.82 ± 10.32 per cent in SCT group. The adverse effects were comparable in both the groups. On post hoc analysis it was noted that the cell dose had a positive impact when infused in the dose of ≥ 5 X 108 (n=71). This benefit was noted upto three weeks post AMI. There were 38 trial deviates in the SCT group which was a limitation of the study. Interpretation & conclusions: Infusion of stem cells was found to have no benefit in ST elevation AMI. However, the procedure was safe. A possible benefit was seen when the predefined cell dose was administered which was noted upto three weeks post AMI, but this was not significant and needs confirmation by larger trials.

Metabolic syndrome & Framingham Risk Score Observations from a coronary angiographic study in Indian patients.

Background & objectives: Metabolic syndrome (MS) is an important determinant of cardiovascular (CV) risk. Framingham Risk Scores (FRS) often underestimate the CV risk in Asians, younger patients and those with MS. Asians often develop coronary artery disease (CAD) at a younger age and also have a high prevalence of MS. Only limited data are available on the relationship between MS and FRS in such patients and the present study was undertaken to report on this aspect in an Indian patient population with angiographically documented CAD. Methods: Two hundred patients undergoing coronary angiography during a three months study period were included. Diagnosis of MS was based on modified south Asian guidelines. Results: Of the 200 patients (age 56.5 ± 8.6 yr) undergoing coronary angiography, MS was diagnosed in 77 per cent n=154; abdominal obesity, low HDL and hypertension were the commonest of the diagnostic criteria of MS, being present in >70 per cent cases. Patients with MS had significantly higher mean FRS than those without MS (15.1 vs 8.65, P<0.0001). Most patients with MS (74%, n=148) had an intermediate to high 10-year CV risk (>10%) as estimated by FRS. The proportion of patients with MS progressively increased in those with low, intermediate and high FRS (61, 87 and 92%, respectively). Though the prevalence of MS was uniformly similar (74-84%) in all age groups (<45, 45-55, 55-65 and > 65 yr, respectively), amongst those <45 yr, none of the patients could be categorized as having high CV risk as estimated by FRS despite having angiographic CAD, highlighting the limitation of age dependence of FRS. Interpretation & conclusions: MS is common in Indian patients with angiographically documented CAD; most patients with MS have 10-year risk of >10 per cent as estimated by FRS. Though MS is uniformly prevalent across all age groups, using the FRS may underestimate the CV risk in Indian patients despite documented CAD. These findings have significant implications for Asian patients with CAD in whom onset of CAD is often at a younger age than their Western counterparts. There should be continued health care emphasis on detection of MS and intensification of targeted preventive strategies.

Premature coronary artery disease in North India: an angiography study of 1971 patients.

BACKGROUND: South Asians, specially Indians, show increased risk for atherosclerosis and have the highest mortality rates due to coronary artery disease amongst all ethnic groups studied so far. We aimed to find out the differences in clinical-biochemical and angiographic profile of young patients versus older patients with angiographically proven atherosclerotic coronary artery disease. METHODS AND RESULTS: Group I (n=828) consisted of patients with age above 55 years (mean age: 63.15 +/- 5.76 years), group II (n=924, mean age: 49.13 +/- 4.25 years) consisted of patients between age 41-55 years and group III (n=219) consisted of patients with age < or = 40 years (mean age: 37.37 +/- 2.92 years). Among the conventional risk factors, smoking was significantly more frequent in group III, while diabetes mellitus and systemic hypertension were more prevalent in groups II and I. Q wave myocardial infarction was more frequently present in groups II and III. Only about one-third of the entire patient population in the myocardial infarction group received thrombolytic therapy. Total cholesterol, low-density lipoprotein cholesterol, and triglyceride levels were significantly higher in younger patients (groups II and III), while high-density lipoprotein cholesterol was significantly low in whole cohort but more so in older patients. Single vessel involvement was more common in group III, while multi-vessel involvement, diffuse disease and fluoroscopic calcium were more common in groups I and II. CONCLUSIONS: Significant differences were observed in the clinical, biochemical and angiographic profile of young patients with coronary artery disease as compared to elderly patients. The younger cohort had more atherogenic lipid profile, higher prevalence of smoking and more frequent single vessel disease. We observed that total cholesterol/high-density lipoprotein cholesterol ratio was a better predictor of coronary artery disease as compared to individual lipid levels.

A tertiary care hospital-based study of conventional risk factors including lipid profile in proven coronary artery disease.

BACKGROUND: The prevalence and mortality rates of coronary artery disease have been known to be higher in the Indian than the Western population. Most data on lipid levels in Indians have been obtained from studies on migrant Asian Indians. There are insufficient data on lipid profile and other conventional risk factors in Indian patients living within India. METHODS AND RESULTS: The study included 2656 consecutive patients who underwent coronary angiography between March 1998 and February 2002. Of these, 2399 subjects had angiographically proven coronary artery disease (group 1) while 257 had normal coronary arteries (group 2). Lipid values were measured in the fasting state on the morning the coronary angiography was done. Patients receiving lipid-lowering agents, those having renal, hepatic or thyroid disorders, patients presenting within 8 weeks after acute myocardial infarction, and patients who were taking noncardiac drugs that affect the lipid profile were excluded from the study. Other conventional risk factors were also recorded. In subjects with coronary artery disease and normal coronary arteries, the levels of mean total cholesterol recorded were 178.5+/-42.1 mg/dl v. 154.1+/-40.2 mg/dl (p<0.001), high-density lipoprotein cholesterol 30.6+/-9 mg/dl v. 27.3+/-6.8 mg/dl (p<0.001), low-density lipoprotein cholesterol 109.8+/-35.4 mg/dl v 93.6+/-33.9 mg/dl (p<0.001), and triglyceride 190.7+/-95.4 mg/dl v. 157.6+/-73.5 mg/dl (p<0.001), respectively. In subgroup analysis by age, the younger coronary artery disease group (< or = 40 years) had significantly higher total and low-density lipoprotein cholesterol levels than the older group (> 40 years), viz. 194.6+/-51.4 mg/dl v. 176.3+/-40.2 mg/dl (p<0.001), and 118.3+/-39.6 mg/dl v. 108.7+/-36.1 mg/dl (p=0.001). Triglyceride levels were not significantly different [211.7+/-105.1 mg/dl v. 187.8+/-93.6 mg/dl (p=ns)], being equally high in both subgroups and, although high-density lipoprotein cholesterol levels were different, this difference was minimal, being equally low in both [32.7+/-9.5 mg/dl v. 30.3+/-9.0 mg/dl (p=ns)]. In the subgroup analysis of those with coronary artery disease, diabetics had significantly lower total cholesterol [174+/-41.1 mg/dl v. 180.4+/-42.4 mg/dl (p<0.001)] and low-density lipoprotein cholesterol levels [105.8+/-34 mg/dl v. 111.5+/-35.8 mg/dl (p<0.001)] than non-diabetics, whereas triglyceride and high-density lipoprotein cholesterol levels were not significantly different, triglycerides being equally high in both [186.2+/-95.5 mg/dl v. 192.5+/-95.2 mg/dl (p=ns)], and high-density lipoprotein equally low in both [30.9+/-9.3 mg/dl v. 30.5+/-9 mg/dl (p=ns)]. The commonest associated conventional risk factor in diabetics was hypertension and, in the younger age group (< or = 40 years), it was smoking and a positive family history of premature coronary artery disease. CONCLUSIONS: We conclude that in north Indians, coronary artery disease occurs at much lower levels of total cholesterol and low-density lipoprotein cholesterol than other populations, and high triglyceride and low high-density lipoprotein levels are more of a universal phenomenon in this population. Younger patients have a more atherogenic lipid profile than the older subgroup with coronary artery disease, and smoking and a family history of premature coronary artery disease are the most common associated risk factors. Total cholesterol levels seem to play a lesser role in the occurrence of coronary artery disease in diabetics, the presence of which is in itself overwhelming for the occurrence of coronary artery disease.

Double right coronary artery with anomalous left main and septal arteries originating from the right coronary sinus.

Anomalies of the coronary artery are often asymptomatic and are uncommon in the general population. We present a case of a double right coronary artery along with anomalous origin of the left main coronary artery and first septal perforator, all originating from the right coronary sinus.