Determination of Sample Size for Different Clinical Study Designs.

AIM: This study illustrates parameters, procedures, and calculations for the statistical determination of sample size for different clinical study designs. MATERIALS AND METHODS: In any research process, the sample size is an important consideration for the implementation of the planned study. From time to time, literature on sample size has been documented in the medical literature. However, the situations covered under them lack comprehensiveness in terms of different study designs, demonstration of calculations, and overreliance on statistical software. RESULTS: The present study provides various facets of sample size determination, such as prerequisite parameters, mathematical formulation, and calculations for clinical study designs [descriptive studies, randomized controlled trials (RCT), correlational studies, comparison of multiple outcomes, survival analysis, sensitivity, and specificity], which will be quite useful. CONCLUSION: This communication will be a good education and learning source for medical professionals to pick and choose a specific scenario and estimate the sample size.

Coronary artery disease and its vascular associates in patients with chronic nonsurgical hypoparathyroidism.

OBJECTIVE: Patients with chronic hypoparathyroidism (cHypoPT) are prone to intracranial-calcification, cataract and nephrocalcinosis. In this study, we systematically investigated the possibility of increased coronary artery calcification (CAC) and coronary artery disease (CAD) in them. DESIGN: Cross-sectional. PATIENTS AND MEASUREMENTS: Ninety-four nonsurgical cHypoPT (M:F = 50:44; age = 45 ± 15 years) with 18.6 ± 9.3 years of illness were assessed. Those with dyspnoea, angina, syncope, abnormal electrocardiogram, echocardiography or significant CAC underwent coronary angiography or myocardial-perfusion-stress imaging. Their lipid parameters and high-sensitivity C-reactive protein (hsCRP) were compared with age-matched healthy controls (Group A, n = 101). The prevalence of CAC in cHypoPT was compared with that of subjects referred from cardiology-clinics (Group B, n = 148, age = 52 ± 11 years). RESULTS: One of 94 cHypoPT had known CAD. On screening, 17 cHypoPT required evaluation for CAD. Two of 17 had severe coronary stenosis, and 12 showed subclinical CAD. CAC and aortic-valve calcification occurred in 21.5% and 11.8%. Clinical and subclinical CAD, CAC and aortic-valve calcification in cHypoPT ≥50 years of age was 8.1%, 27.0%, 52.8% and 27.8%, respectively. Frequency of age-adjusted CAC was comparable between cHypoPT and control Group B (30.2% vs. 30.7%, p = .93). Elevated hsCRP was higher in cHypoPT than in controls A (52% vs. 32%, p < .01). Factors associated with CAD in cHypoPT were CAC and hypertension. However, CAD and CAC showed no association with long-term calcemic or phosphatemic control and intracranial-calcification in cHypoPT. CONCLUSIONS: Clinical and subclinical CAD was observed in 3.2% and 12.8% of cHypoPT patients. The increased prevalence of CAD, CAC and aortic-valve calcification in cHypoPT above 50 years of age suggested their careful cardiac evaluation during follow-up.

Cardiopulmonary Outcomes in Covid-19 Patients Discharged From a Tertiary Care Center: A Prospective Study.

To determine the cardiopulmonary changes in the survivors of acute COVID-19 infection at 3-6 month and 6-12 month. We followed up 53 patients out of which 28 (52%) had mild COVID-19 and 25 (48%) had severe COVID-19. The first follow-up was between 3 month after diagnosis up to 6 month and second follow-up between 6 and 12 month from the date of diagnosis of acute COVID-19. They were monitored using vital parameters, pulmonary function tests, echocardiography and a chest computed tomography (CT) scan. We found improvement in diffusing capacity for carbon monoxide (DLCO) with a median of 52% of predicted and 80% of predicted at the first and second follow-up, respectively. There was improvement in the CTSS in severe group from 22 (18-24) to 12 (10-18; p-0.001). Multivariable logistic regression revealed increased odds of past severe disease with higher CTSS at follow-up (OR-1.7 [CI 1.14-2.77]; P = 0.01). Correlation was found between CTSS and DLCO at second follow-up (r2 = 0.36; p < 0.01). Most of patients recovered from COVID-19 but a subgroup of patients continued to have persistent radiological and pulmonary function abnormalities necessitating a structured follow-up.

Delayed presentation of aorto-pulmonary window, double outlet right ventricle with pulmonary arterial hypertension: Illustration of uncommon association on dual-energy CT.

We present a case of a 26-year-old female with double outlet right ventricle and proximal aorto-pulmonary window (APW). The case highlights the role of computed tomography angiography in the diagnosis and characterization of APW defects, which are difficult to be diagnosed on transthoracic echocardiography.

Impact of bariatric surgery on carotid intima-medial thickness and cardiovascular risk: results of a prospective study.

BACKGROUND: The impact of bariatric surgery on atherosclerosis is a relatively less studied subject. Obesity has been identified as an independent risk factor for cardiovascular disease (CVD). Carotid intima-media thickness (CIMT), a surrogate marker for atherosclerosis and risk of CVD, has been found to be associated with obesity. Recent literature has shown that there is significant reduction in CIMT following bariatric surgery. The aim of this study was to evaluate the impact of bariatric surgery on CIMT and risk of CVD in an Indian population. METHODS: This is a prospective study conducted in a tertiary referral centre in India. Patients undergoing bariatric surgery from December 2017 to September 2019 were included. CIMT measurements and American College of Cardiology/American Heart Association (ACC/AHA)-pooled cohort CVD risk scores were done before and at 6 months and 12 months after surgery. RESULTS: Fifty-four patients were enrolled, of which 70% were females. Mean age was 40.8 ± 10.7 years. Mean pre-operative weight and mean BMI were 115.2 ± 21.9 kg and 45.9 ± 6.5 kg/m2, respectively. Patients who completed 12-month follow-up were considered for analysis of outcomes. There was significant reduction in BMI to 33.1 ± 5.7 kg/m2 at 12 months after surgery (p < 0.0001). Mean CIMT reduced significantly from 0.58 ± 0.08 mm at baseline to 0.52 ± 0.10 mm at 12 months. Lipid profile, fasting blood sugar and HbA1C also improved, which resulted in reduction of lifetime and 10-year CVD risk from 42.3 to 26% and 4 to 1.5%, respectively, at 12 months after surgery. CONCLUSIONS: Bariatric surgery results in significant reduction in CIMT and CVD risk in patients with morbid obesity.

Utility of HEART Pathway in Identifying Low-Risk Chest Pain in Emergency Department.

BACKGROUND: Chest pain is a common presenting symptom in the emergency department (ED). The HEART (history, electroencephalogram [ECG], age, risk factors, and troponin I) score, with addition of troponin at 3 h, helps to determine appropriate risk stratification of the patients. OBJECTIVE: This study evaluated the utility of the HEART pathway as a decision aid designed for risk stratification of patients with acute-onset chest pain for early and safe disposition. METHODS: This was a prospective observational study done in a tertiary care center. Focused history, 12-lead ECG, and baseline troponin I level on arrival and at hour 3 were recorded. Subjects were classified as low risk (HEART score 0-3) or high risk (HEART score ≥ 4). Patients with a HEART score of 0-3 with negative troponin I at 3 h were discharged and were followed up for major adverse cardiac events (MACEs) within 30 days of ED presentation. RESULTS: A total of 250 patients were screened for the study, of which 151 were included for the final analysis. One hundred and two patients (68%) were male and 54% of patients were younger than 45 years. HEART scores of 0 (n = 16), 1 (n = 43), 2 (n = 44), and 3 (n = 48) were observed. There was only 1 MACE (0.7%) in 30 days after ED discharge in the study population. The mean length of ED stay in the low-risk group was 4.5 h. CONCLUSIONS: Low-risk patients, as per the HEART pathway, can be discharged safely from the ED, which reduces ED stay and health care resource use.

Characteristics of Children with Acute Rheumatic Carditis from a High-Incidence Region: Importance of Unexplained Worsening of Functional Class.

BACKGROUND: Acute rheumatic fever (ARF) and acute rheumatic carditis (ARC) continue to be a major public health problem in developing countries. OBJECTIVE: To study the characteristics of children with ARC being treated at a tertiary centre. METHODS AND RESULTS: We studied 126 children (mean age 10.4 ± 2.3 years, range 5-15 years, 60% males) diagnosed with ARC by treating cardiologists. Most had lower socio-economic status. Fifty of 126 (40%) presented with a first episode of ARC. Joint symptoms were present in 29% and fever in 25%. Only 2.4% had subcutaneous nodules and none had erythema marginatum or chorea. Fifty-one percent presented in NYHA class II and 29% in NYHA class III or IV. Tachycardia and heart failure were present in 53% and 21%, respectively. Recent worsening of NYHA class (dyspnoea) was the commonest feature (48%). Laboratory investigations showed raised antistreptolysin O titres (>333 units) in only 36.7% of patients. Raised C-reactive protein (CRP) was present in 70%, while raised erythrocyte sedimentation rate was found in only 37% of patients. On the basis of above findings, the modified Jones criteria (2015) for the diagnosis of ARF were satisfied only in 46% of children. Echocardiography showed mitral valve thickening in 77% and small nodules on the tip of the leaflets in 43% (27 and 8%, respectively for aortic valve). Left ventricular ejection fraction was <50% in only 3 patients. The dominant valve lesion was mitral regurgitation (MR) (present in 95% of patients; severe in 78%, moderate in 15%), while aortic regurgitation was present in 44% (severe in 14%). CONCLUSIONS: The criteria are often not satisfied by patients being treated for ARC. Recent unexplained worsening of dyspnoea, young age, significant MR, echocardiographic nodules, and elevated CRP are important indicators.

Effect of slow breathing on autonomic tone & baroreflex sensitivity in yoga practitioners.

BACKGROUND & OBJECTIVES: Slow breathing increases parasympathetic activity and baroreflex sensitivity (BRS) in healthy individuals, also similarly observed in yoga practitioners. Pranayama which is an important component of yoga when practiced at a slow pace was at a respiratory frequency of around 0.1 Hz (6 breaths/min). Therefore, it was hypothesized that yoga practitioners might have adapted to slow breathing. This study was aimed to decipher the role of yoga on cardiovascular variability during slow breathing (0.1 Hz) in yoga practitioners. METHODS: A cross-sectional study was undertaken in naïve-to-yoga individuals (n=40) and yoga practitioners (n=40) with an average age of 31.08 ± 7.31 and 29.93 ± 7.57 yr, respectively. The analysis of heart rate variability, blood pressure variability (BPV) and BRS during spontaneous and slow breathing was compared between the two groups. RESULTS: During slow breathing, the heart rate (P<0.01) was lower, respiratory rate interval (P<0.05) and pNN50 per cent (P=0.01) were higher, mean systolic BP (SBP) (P<0.05) and SDSD (Standard deviation of successive beat to beat systolic blood pressure differences) (P<0.01) of SBP variability were lower with sequence BRS (P<0.001) and α low frequency (P<0.01) and α high frequency (P<0.001) of spectral BRS were higher in yoga practitioners. INTERPRETATION & CONCLUSIONS: The present study indicated higher parasympathetic activity and BRS with lower SBP variability at rest and during slow breathing in yoga practitioners compared to naive group. Findings indicate that the short-term practice of slow breathing complements the augmented parasympathetic activity and BRS in the yoga group.

E-selectin gene in essential hypertension: a case-control study.

BACKGROUND: Hypertension is associated with endothelial cell dysfunction. E-selectin, an endothelial cell adhesion molecule, is specific for endothelial cell activation. Polymorphism in E-selectin gene has recently been identified among which Leu554Phe E-selectin gene polymorphism is least investigated in essential hypertension. This study reports the association of E-selectin gene Leu554Phe polymorphism and the expression of E-selectin gene in patients with essential hypertension. MATERIALS AND METHODS: We analysed the Leu554Phe polymorphism and expression of E-selectin gene in 250 patients with essential hypertension and 250 normal healthy controls. Genotyping of Leu554Phe polymorphism was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), and the expression of E-selectin gene at mRNA and protein levels were carried out by real-time PCR and Western blot, respectively. RESULTS: A significant association of E-selectin genotypes (CT + TT) with essential hypertension (P < .0001, Odds ratio = 2.2 [1.58-3.24] at 95% CI) was observed. The expression of mRNA for E-selectin gene in patients with essential hypertension was ~12-fold higher as compared to control. We observed an elevated level of E-selectin protein expression (up to 1.9 times) in patients as compared to controls. CONCLUSIONS: A significant association of E-selectin (Leu554Phe) gene and increased expression of E-selectin gene at mRNA and protein levels in patients might be related to the genetic predisposition to develop essential hypertension.

Clinical significance of cathepsin L and cathepsin B in dilated cardiomyopathy.

Dysregulated expression of lysosomal cysteine cathepsins is associated with adverse cardiac remodeling, a characteristic of several cardiovascular diseases. However, the information regarding the role of cysteine cathepsin L (CTSL) and cathepsin B (CTSB) in dilated cardiomyopathy (DCM) is limited. The present study was aimed to investigate the expression of CTSL and CTSB in animal model of doxorubicin (doxo)-induced cardiomyopathy as well as in peripheral blood samples of DCM patients. Cardiac tissue sections from doxo-treated and control rats were used to study the expression of CTSL and CTSB by enzyme assay and immunohistochemistry (IHC). Peripheral blood mononuclear cells (PBMCs) isolated from DCM patients (n = 29) along with age-matched healthy controls (n = 28) were used to assay enzymatic activity of these cathepsins. Activities of these proteases were further correlated with echocardiographic parameters of DCM patients. A significant increase in CTSL activity and protein expression was observed with no changes in CTSB levels in doxo-treated rats as compared to controls. We also observed a drastic increase in the functional activity of cathepsin L+cathepsin B (CTSL+B), CTSL, and CTSB in DCM patients compared to controls (p ≤ 0.001). Increased levels of these proteases exhibited a statistically significant correlation with reduced left ventricular ejection fraction (LVEF) in DCM patients (ρ = -0.58, p = 0.01). For the first time, this study demonstrates a correlation between increased expression of CTSL and CTSB in PBMCs with severity of left ventricular dysfunction in DCM patients. Thus, these proteases may serve as blood-based biomarker of DCM and prove useful in its management.

Does perfusion pattern influence stress-induced changes in left ventricular mechanical dyssynchrony on thallium-201-gated SPECT myocardial perfusion imaging?

BACKGROUND: The relationship between perfusion pattern and stress-induced changes in left ventricular mechanical dyssynchrony (LVMD) on stress-rest thallium-201-gated SPECT myocardial perfusion imaging (Tl-201 SPECT MPI) is not clear. The aim of the study is to assess the relation of perfusion pattern with stress-induced changes in LVMD on Tl-201 MPI. METHODS: Data of 194 patients who underwent exercise-rest Tl-201 MPI between January to December 2012 at our institute was retrospectively evaluated. Institute Ethical committee approval was obtained. Fifty patients who underwent Tl-201 MPI for suspected CAD and had normal LV perfusion and function on MPI were taken as normal group. Patients with perfusion abnormalities (n = 144) were divided into three groups: ischemia (n = 66), infarct (n = 32), and mixed group (n = 46; ischemia and infarct both). Summed stress score, summed rest score, summed difference score (SDS), and LV ejection fraction (EF) were evaluated. Two LVMD parameters, phase standard deviation (PSD) and phase histogram bandwidth (PHB), were assessed in post-stress and rest MPI images. ΔPSD (post-stress PSD - rest PSD) and ΔPHB (post-stress PHB - rest PHB) were calculated to measure stress-induced changes in LVMD. RESULTS: In all the groups, mean post-stress LVMD parameters were lower as compared to LVMD parameters at rest. Post-stress PSD was significantly lower than rest PSD in all groups. Similar trend was noted with PHB values also, but it was statistically significant in the normal and ischemia group only. Post-stress worsening of at least one of the LVMD parameters was noted in 28 patients and all these patients had perfusion abnormalities. But on subgroup analysis, no difference was found in proportion of patients showing post-stress worsening of LVMD between ischemia (13.6%), infarct (25%), and mixed (23.6%) groups. No significant correlation was found between ΔPSD/ΔPHB and ΔLVEF/SDS in any group. CONCLUSION: LV mechanical dyssynchrony parameters are smaller in post-exercise stress as compared to rest on Tl-201 MPI, regardless of perfusion pattern. Stress-induced worsening of LV dyssynchrony was observed only in patients with perfusion abnormalities, but this is not related to the type of perfusion abnormality.

Expression of angiotensin-converting enzyme gene in whole blood in patients with essential hypertension.

OBJECTIVE: The present study aims to investigate the correlation of the angiotensin-converting enzyme (ACE) gene expression and protein expression in patients with essential hypertension in whole blood. METHODS: ACE gene expression was analyzed by Real Time PCR and western blot in 52 patients with essential hypertension and 42 healthy controls. RESULTS: We observed a significant increase in Delta threshold cycle (ΔCT) values in the circulating ACE gene and ACE protein expression in patients as compared to controls. CONCLUSIONS: The up-regulation in relative expression of circulating Angiotensin converting enzyme mRNA and protein in patients with respect to controls might be correlated with high blood pressure in patients with essential hypertension.

Diagnostic potential of SORT1 gene in coronary artery disease.

BACKGROUND: Genome-wide association studies identify SORT1 gene associated with risk of coronary artery disease (CAD). Sortilin protein enhances LDL absorption, form cell development, and atherosclerosis in macrophages. AIM: We therefore explored SORT1 expression in CAD patients and its gene expression's predictive usefulness for the severity of the disease. METHODOLOGY: This is a case control study and Quantitative real-time PCR; Sandwich ELISA and western blotting were used to determine the expression of SORT1 gene at the mRNA and protein level in two hundred healthy controls and two hundred patients with various CAD syndromes. RESULTS: CAD patients exhibit higher SORT1 gene expression in CAD patients, a higher concentration of sortilin in their plasma, and distinct expression patterns in various CAD syndromes. The study reveals a positive correlation between gene expression and the severity of coronary artery stenosis, the number of diseased vessels, and the presence of diabetes. ROC curve analysis of SORT1 gene expression both at mRNA and protein level showed strong discrimination between significant CAD and control subjects. CONCLUSION: Therefore, elevated SORT1 gene expression in various CAD syndromes may be a potential biomarker for the disease.

Retrospective Analysis of Hospital Acquired Infection and Antibiotic Resistance in Coronary Care Unit (CCU), Adult, and Pediatric Cardiology Wards.

BACKGROUND: Antibiotics resistance is an paramount threat affecting the whole world but nowhere situation is as gloomy as in India. No study till date regarding epidemiology of hospital acquired infections in coronary care units(CCU) and cardiology wards from India. From Indian perspective it is the first observational study to analyse microbiological profile and antibiotic resistance in CCU. The purpose of this observational study is to explore the epidemiology and importance of infections in CCU patients. METHODOLOGY: After ethics committee approval, the records of all patients who were admitted in coronary care units, adult and pediatric cardiology wards surgery between January 2020 and December 2021 were reviewed retrospectively. The type of organism,source of infection ,age wise distribution and seasonal variability among patients who developed hospital acquired infection (HAI) were determined. RESULTS: 271 patients developed microbiologically documented HAI during from January 2020 to December 2021. Maximum number of organisms(78/271 28.78%) are isolated from urinary samples ,followed by blood stream(60/271 22.14%) and Endotracheal tube (54/271 19.92%). Acinetobacter baumanii (53/271, 19.5%) being the most common isolate among all the samples taken . Acinetobacter was the most frequent pathogens isolated in patients with LRTI and blood stream infection while E. coli was from urinary tract infection . In the adult population, infection with E. coli(24.6%) is the most common followed by Klebsiella pneumoniae (12.8%) and Acinetobacter baumanii (10.1%). In the pediatric population Acinetobacter baumanii (38.6%%) is the most common followed by Klebsiella pneumoniae (20.5%) and Methicillin Resistant Staphylococcus aureus, MRSA (6.8%). Commonly used antibiotics eg ciprofloxacin,ceftazidime and amikacin were found to be resistant against the top three isolates. CONCLUSION: Urinary tract was the most common site of infection and Gram-negative bacilli, the most common pathogens in adult as well as pediatric population. Antibiotic resistance was maximum with commonly isolated microorganisms.

Significance of QTc interval in chronic hypoparathyroidism and its correlates.

CONTEXT: Hypocalcemia predisposes patients with chronic hypoparathyroidism (cHypoPT) to an increased risk of QTc prolongation and life-threatening arrhythmias. Information on clinical and biochemical correlates of QTc in cHypoPT is limited. DESIGN AND SETTING: Observational cohort study at tertiary-care-center. SUBJECTS AND METHODS: Eighty-eight non-surgical cHypoPT (mean age 44.1 ± 15.4 years, 45 males) were assessed for QTc interval and its possible correlates including arrhythmic symptoms (palpitation/giddiness/syncope), serum total-calcium, phosphate, 25(OH)D and iPTH. RESULTS: The mean QTc in HypoPT cohort was 428 ± 34 ms with 13.6% having prolonged QTc. There was a significant inverse correlation between QTc interval and serum total-calcium measured on the same day (r = -0.43, p < 0.001). The mean serum total-calcium was significantly lower in patients with prolonged QTc (7.05 ± 1.94 vs. 8.49 ± 1.01 mg/dL, p = 0.02). 21.6% of cHypoPT patients had arrhythmic symptoms. They had significantly higher mean QTc (p = 0.02) and also tended to have lower mean serum total-calcium during follow-up (p = 0.06). In multivariable regression, female gender, higher current-age, higher BMI, and low serum total-calcium showed significant association with prolonged QTc. For every mg/dL decrease in serum total-calcium, QTc increased by 13 ms. Receiver-operating-characteristic analysis revealed serum total-calcium at cut-off of 8.3 mg/dL discriminated prolonged QTc with area-under-curve being 0.72 [95% CI: 0.51,0.93]. CONCLUSION: One-fifth of cHypoPT had arrhythmic symptoms and a significant proportion had prolonged QTc. This highlights the need for close monitoring of cHypoPT patients for arrhythmic symptoms and QTc prolongation. The serum total-calcium should be maintained to at least 8.3 mg/dL to minimize the risk of potentially life-threatening arrhythmia in cHypoPT.

South African flag sign to a giant coronary artery aneurysm.

Background: Coronary arteritis leading to aneurysm is one of the unusual presentations of IgG4-related disease. Acute myocardial infarction as a complication of IgG4-related giant coronary artery aneurysm is even rarer. Case summary: We describe the case of a 56-year-old gentleman who presented to our institute with Canadian Cardiovascular Society (CCS) class III angina. His symptoms were persistent even with high-dose antianginal medications. He had an acute coronary syndrome two weeks back for which he was treated conservatively in a peripheral health centre. His 12-lead electrocardiogram at the time of the event was suggestive of high lateral ST-segment elevation myocardial infarction (South African flag sign). His transthoracic echocardiography showed mild left ventricular dysfunction and a large echogenic mass lateral to the left ventricle. Coronary angiography followed by cardiac computed tomography revealed a giant pseudoaneurysm of the proximal and mid-left anterior descending coronary artery. FDG-PET scan showed significant metabolic activity in the aneurysm wall and mediastinal lymph nodes suggesting active inflammation. IgG4-related coronary arteritis was suspected, and the patient underwent aneurysmectomy and coronary artery bypass (CABG) surgery. The histopathology of the resected segment showed diffuse IgG4-secreting plasma cells confirming the diagnosis. Discussion: Atherosclerosis is the most common cause of coronary aneurysms in adults. However, cardiologists should be aware of atypical causes like IgG4-related disease that can even present with acute coronary syndrome. Although multimodality imaging is beneficial during early evaluation, histopathological analysis is the cornerstone for the diagnosis of IgG4-related disease. The management involves both immunosuppressive medication and endovascular or surgical repair.

Cardioprotective effect of root extract of Picrorhiza kurroa (Royle Ex Benth) against isoproterenol-induced cardiotoxicity in rats.

Normal rats pre-treated with P. kurroa (200 mg/kg) alone did not showed significant change, however, isoproterenol (ISP) administration resulted in hemodynamic and left ventricular dysfunction, oxidative stress, and lipid peroxidation. Such cardiac dysfunction was significantly prevented by P. kurroa root extract pre-treatment. Pre-treatment significantly attenuated the ISP-induced oxidative stress by restoring myocardial superoxide dismutase, catalase, and glutathione peroxidase enzymes except reduced glutathione content. P. kurroa pre-treatment markedly attenuated the ISP-induced rise in lipid peroxidation, thereby prevented leakage of myocyte creatine kinase-MB and lactate dehydrogenase enzymes. The results suggest that P. kurroa root extract possesses significant cardioprotective effect, which may be attributed to its antioxidant, anti-peroxidative, and myocardial preservative properties.

Differential role of central and peripheral arterial stiffness in determining brachial artery resting retrograde flow in patients with ischemic heart disease vs healthy subjects.

Retrograde flow in endothelial cell cultures has been shown to induce a pro-atherogenic phenotype. Despite its potential role as a pathophysiological link between cardiovascular risk factors and atherosclerotic disease, resting retrograde flows between patients with cardiovascular disease and healthy subjects have not been compared. Further, the vascular characteristics governing retrograde flow in human arteries have not been systematically investigated. Association of central and peripheral vascular characteristics with retrograde flow profile was investigated in 32 healthy subjects and 47 patients with ischemic heart disease. Endothelial dysfunction was assessed by brachial ultrasound-based calculation of flow-mediated dilation (FMD) and sub-clinical atherosclerosis was estimated from carotid-intima media thickness (CIMT). Retrograde blood flow velocity (RBFV) and shear rate were comparable between the two groups (RBFV 1.82(0.97-3.32) vs 1.78(1.24-2.65) cm/s p = 0.79). Augmentation index was a significant determinant of retrograde flow in both patients and healthy subjects. Carotid artery incremental elastic modulus was an independent determinant of retrograde flow patterns in healthy subjects while ejection fraction, cf/cr PWV ratio and forearm vascular conductance emerged as independent determinants in patients. Retrograde flow patterns were also associated with FMD (RBFV r = -0.43, p = 0.004) and CIMT (r = 0.30, p = 0.041) in patients. The results of the study suggest a difference in the determinants of retrograde flow in patients and healthy subjects, with central arterial stiffness being a major contributor in healthy subjects while interaction between central, peripheral, and cardio-arterial factors influence retrograde flow in patients with ischemic heart disease.

Association of angiotensinogen (M235T) gene polymorphism with blood pressure lowering response to angiotensin converting enzyme inhibitor (Enalapril).

PURPOSE: It has been suggested that genetic backgrounds, which have an association with essential hypertension, may also determine the responsiveness to ACE inhibitor. We determined the association of angiotensinogen (M235T) gene polymorphism with essential hypertension and the relationship between polymorphism in the angiotensinogen (M235T) gene and blood pressure response to ACE inhibitor (Enalapril) in patients with essential hypertension from northern Indian subjects. METHODS: 250 patients with essential hypertension and 250 normal healthy controls from Delhi and surrounding areas were recruited for the investigation. Blood pressure was recorded before and after 6 weeks of treatment with ACE inhibitors, Enalapril. Genotyping were carried out by polymerase chain reaction and Restriction fragment length polymorphism technique. RESULTS: Statistically significant association of T allele was observed with essential hypertension [x2 = 14.67, p = 0.00013, Odds ratio = 1.76 (1.3-2.32) at 95% CI], the relative risk at 95% CI being 1.28 (1.2-1.54). The decrease in systolic blood pressure and diastolic blood pressure after six weeks of treatment of the patients carrying TT genotype (SBP = 26 ± 17.4 mmHg, DBP = 14.83 ± 7.6 mmHg) were greater than the groups carrying MT (SBP = 3.0 ± 7.8 mmHg, DBP = 6.2 ± 3.0 mmHg) and MM genotypes (SBP = 1.2 ± 0.8 mmHg, DBP = 0.10 ± 12.1 mm Hg. CONCLUSIONS: The angiotensinogen (M235T) gene polymorphism is significantly associated with essential hypertension. Patients carrying TT genotype had higher blood pressure lowering response when treated with ACE inhibitor, Enalapril than those carrying MM and MT genotypes suggesting that the T allele may be a possible genetic marker for essential hypertension.