Comparative analysis of Nε-carboxymethyl-lysine and inflammatory markers in diabetic and non-diabetic coronary artery disease patients.

BACKGROUND: Coronary artery disease (CAD) is a major cause of death worldwide, and India contributes to about one-fifth of total CAD deaths. The development of CAD has been linked to the accumulation of Nε-carboxymethyl-lysine (CML) in heart muscle, which correlates with fibrosis. AIM: To assess the impact of CML and inflammatory markers on the biochemical and cardiovascular characteristics of CAD patients with and without diabetes. METHODS: We enrolled 200 consecutive CAD patients who were undergoing coronary angiography and categorized them into two groups based on their serum glycosylated hemoglobin (HbA1c) levels (group I: HbA1c ≥ 6.5; group II: HbA1c < 6.5). We analyzed the levels of lipoproteins, plasma HbA1c levels, CML, interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), and nitric oxide. RESULTS: Group I (81 males and 19 females) patients had a mean age of 54.2 ± 10.2 years, with a mean diabetes duration of 4.9 ± 2.2 years. Group II (89 males and 11 females) patients had a mean age of 53.2 ± 10.3 years. Group I had more severe CAD, with a higher percentage of patients with single vessel disease and greater stenosis severity in the left anterior descending coronary artery compared to group II. Group I also exhibited a larger left atrium diameter. Group I patients exhibited significantly higher levels of CML, TNF-α, and IL-6 and lower levels of nitric oxide as compared with group II patients. Additionally, CML showed a significant positive correlation with IL-6 (r = 0.596, P = 0.001) and TNF-α (r = 0.337, P = 0.001) and a negative correlation with nitric oxide (r=-4.16, P = 0.001). Odds ratio analysis revealed that patients with CML in the third quartile (264.43-364.31 ng/mL) were significantly associated with diabetic CAD at unadjusted and adjusted levels with covariates. CONCLUSION: CML and inflammatory markers may play a significant role in the development of CAD, particularly in diabetic individuals, and may serve as potential biomarkers for the prediction of CAD in both diabetic and non-diabetic patients.

Gender differences in genotypic distribution of endothelin-1 gene and endothelin receptor A gene in pulmonary hypertension associated with rheumatic mitral valve disease.

INTRODUCTION: The female gender is a risk factor for idiopathic pulmonary arterial hypertension. However, it is unknown whether females with rheumatic mitral valve disease are more predisposed to develop pulmonary hypertension compared to males. AIM: We aimed to investigate whether there was a difference in genotypic distribution of endothelin-1 (ET-1) and endothelin receptor A (ETA) genes between female and male patients of pulmonary hypertension associated with rheumatic mitral valve disease (PH-MVD). METHODS: We compared prevalence of ET-1 gene (Lys198Asn) and ETA gene (His323His) polymorphisms according to gender in 123 PH-MVD subjects and 123 healthy controls. RESULTS: The presence of mutant Asn/Asn and either mutant Asn/Asn or heterozygous Lys/Asn genotypes of Lys198Asn polymorphism when compared to Lys/Lys in females showed significant association with higher risk (odds ratio [OR] 4.5; p =0.007 and OR 2.39; p =0.02, respectively). The presence of heterozygous C/T and either mutant T/T or heterozygous C/T genotypes of His323His polymorphism when compared to wild C/C genotype in females showed a significant association with higher risk (OR 1.96; p =0.047 and OR 2.26; p =0.01, respectively). No significant difference was seen in genotypic frequencies in males between PH-MVD subjects and controls. Logistic regression analysis showed that mutant genotype Asn/Asn (p =0.007) and heterozygous genotype Lys/Asn of Lys198Asn polymorphism (p =0.018) were independent predictors of development of PH in females. CONCLUSIONS: ET-1 and ETA gene polymorphisms were more prevalent in females than males in PH-MVD signifying that females with rheumatic heart disease may be more susceptible to develop PH.

Endothelin-1 gene and endothelin receptor A gene polymorphisms in severe pulmonary hypertension associated with rheumatic mitral valve disease.

INTRODUCTION: Endothelin-1 (ET-1) gene polymorphisms are implicated in pathogenesis of idiopathic pulmonary arterial hypertension. METHODS: We studied ET-1 (Lys198Asn and 3A/4A) and endothelin receptor A (ETA) gene (His323His) polymorphisms in 123 subjects with pulmonary hypertension associated with rheumatic mitral valve disease (PH-MVD) and 123 healthy controls. RESULTS: The mutant homozygous Asn/Asn genotype in Lys198Asn and T/T genotype in His323His polymorphism was more prevalent in the PH-MVD group. Presence of Asn/Asn genotype was significantly associated with an increased risk (odds ratio 3.9). CONCLUSIONS: ET-1 and ETA gene polymorphisms are prevalent in the PH-MVD group suggesting that they may predispose to the development of PH.

Left atrial function by two-dimensional speckle tracking echocardiography in patients with severe rheumatic mitral stenosis and pulmonary hypertension.

We studied left atrial (LA) function in severe rheumatic mitral stenosis (MS) patients using two-dimensional speckle tracking echocardiography (STE). Eighty patients with isolated severe MS in sinus rhythm and 40 controls underwent comprehensive echocardiography including STE derived LA strain [reservoir strain (LASr), conduit strain (LAScd) and contractile strain (LASct)]. The mean MVA was 0.93 ± 0.21 cm2. The mean values of LASr (14.73 ± 8.59%), LAScd (-7.61 ± 4.47%) and LASct (-7.16 ± 5.15%) in patients were significantly lower (p < 0.001) vs. controls 44.11 ± 10.44%, -32.45 ± 7.63%, -11.85 ± 6.77% respectively and showed decreasing trend with increasing MS severity and higher NYHA class. In conclusion, LA dysfunction is prevalent in severe MS irrespective of NYHA functional class.

Left and right ventricular deformation in patients with severe mitral stenosis and pulmonary hypertension undergoing percutaneous balloon mitral valvuloplasty: A two dimensional speckle-tracking echocardiographic study.

Seventy-five patients with isolated severe MS (mitral valve area: 1.10 ± 0.15 cm2) and pulmonary hypertension underwent regional and global longitudinal strain (GLS) measurements of left (LV) and right ventricle (RV) at baseline and within 48 h after percutaneous balloon mitral valvuloplasty (PBMV). PBMV resulted in significant improvement in LV GLS (-16.35 ± 1.67% vs -19.98 ± 2.17%) and RV GLS (-10.34 ± 2.38% vs -13.83 ± 2.04%), p < 0.001 for both. Absolute increase in strain of basal segments of LV was more compared to mid and apical segments. We also found significant positive correlation between decrease in mean LA pressure (pre PBMV 28.91 ± 4.21 mm Hg vs post PBMV 10.55 ± 3.04 mm Hg, difference of 16.36 mm Hg; p < 0.001) obtained invasively during PBMV for 62 patients with improvement in LV GLS (r = 0.257, p = 0.048), RV GLS (r = 0.267, p = 0.043), and fall in right ventricular systolic pressure (r = 0.308, p = 0.022) that occurred post PBMV. The LV dysfunction is predominantly because of altered hemodynamics due to restricted LV filling with additional contribution from rheumatic involvement of basal LV myocardial segments. The improvement in LV deformation after PBMV is likely due to increase in preload. RV afterload reduction because of LA pressure decrease improved RV deformation.

Multimarker risk stratification approach and cardiovascular outcomes in patients with stable coronary artery disease undergoing elective percutaneous coronary intervention.

AIMS: We studied the utility of multimarker risk stratification approach to predict cardiovascular outcomes in patients with stable coronary artery disease, undergoing elective percutaneous coronary intervention (PCI). METHODS: We prospectively evaluated 302 consecutive patients with stable coronary artery disease and normal CPK-MB and cardiac troponin T levels, and who underwent elective PCI at our institution. The following cardiac biomarkers were measured before and between 12 and 24h post-procedure: CK-MB, cardiac troponin T, hs-CRP, and NT-ProBNP. Patients were followed up for a minimum of 6 months. RESULTS: Post-PCI, CPK-MB levels were elevated but below myocardial infarction (MI) range in 70 patients (23%), and in the MI range in 6 patients (2%). Troponin T levels were detectable but below the 99th percentile (microleak) in 32 patients (10.6%) and elevated above the 99th percentile (periprocedural MI) in 104 patients (34.4%). At 9 months' follow-up, 1% died, 2% had stable angina, 10.3% had non-fatal MI, and 87.7% remained asymptomatic. There was no significant difference in clinical events among groups stratified by elevation of one biomarker or multiple biomarkers. CONCLUSION: Single or multiple biomarker strategy in patients with normal baseline biomarkers failed to predict major cardiac events after PCI over medium-term follow-up.

Massive Bleeding from Guidewire Perforation of an External Iliac Artery: Treatment with Hand-made Stent-Graft Placement.

We report life-threatening bleeding from an external iliac artery perforation following guidewire manipulation in a patient with atherosclerotic iliac artery disease. This complication was successfully managed by indigenous hand-made stent-graft made from two peripheral stents in the catheterization laboratory.