Non-physician health workers for improving adherence to medications and healthy lifestyle following acute coronary syndrome: 24-month follow-up study.

OBJECTIVE: To evaluate usefulness of non-physician health workers (NPHW) to improve adherence to medications and lifestyles following acute coronary syndrome (ACS). METHODS: We randomized 100 patients at hospital discharge following ACS to NPHW intervention (n=50) or standard care (n=50) in an open label study. NPHW was trained for interventions to improve adherence to medicines - antiplatelets, ß-blockers, renin-angiotensin system (RAS) blockers and statins and healthy lifestyles. Intervention lasted 12 months with passive follow-up for another 12. Both groups were assessed for adherence using a standardized questionnaire. RESULTS: ST elevation myocardial infarction (STEMI) was in 49 and non-STEMI in 51, mean age was 59.0±11 years. 57% STEMI were thrombolyzed. On admission majority were physically inactive (71%), consumed unhealthy diets (high fat 77%, high salt 58%, low fiber 57%) and 21% were smokers/tobacco users. Coronary revascularization was performed in 90% (percutaneous intervention 79%, bypass surgery 11%). Drugs at discharge were antiplatelets 100%, ß-blockers 71%, RAS blockers 71% and statins 99%. Intervention and control groups had similar characteristics. At 12 and 24 months, respectively, in intervention vs control groups adherence (>80%) was: anti platelets 92.0% vs 77.1% and 83.3% vs 40.9%, ß blockers 97.2% vs 90.3% and 84.8% vs 45.0%), RAS blockers 95.1% vs 82.3% and 89.5% vs 46.1%, and statins 94.0% vs 70.8% and 87.5% vs 29.5%; smoking rates were 0.0% vs 12.5% and 4.2% vs 20.5%, regular physical activity 96.0% vs 50.0%, and 37.5% vs 34.1%, and healthy diet score 5.0 vs 3.0, and 4.0 vs 2.0 (p<0.01 for all). Intervention vs standard group at 12 months had significantly lower mean systolic BP, heart rate, body mass index, waist:hip ratio, total cholesterol, triglyceride, and LDL cholesterol (p<0.01). CONCLUSIONS: NPHW-led educational intervention for 12 months improved adherence to evidence based medicines and healthy lifestyles. Efficacy continued for 24 months with attrition.

Study of differences in presentation, risk factors and management in diabetic and nondiabetic patients with acute coronary syndrome.

OBJECTIVES: To compare clinical characteristics, treatment, and utilization of evidence-based medicines at discharge from hospital in acute coronary syndrome (ACS) patients with or without diabetes at a tertiary care cardiac center in India. METHODS: We performed an observational study in consecutive patients discharged following management of ACS. We obtained demographic details, comorbid conditions, and cardiovascular risk factors, physical and biochemical parameters, and management. Descriptive statistics are reported. RESULTS: We enrolled 100 patients (diabetics = 28) with mean age of 59.0 ± 10.8 years (diabetics 59.3 ± 11.6, nondiabetics 58.9 ± 8.5). Forty-nine patients had ST-elevation myocardial infarction (STEMI) (diabetics = 14, 28.7%) while 51 had nonSTEMI/unstable angina (diabetics = 14, 27.4%) (P = nonsignificant). Among diabetics versus nondiabetics there was greater prevalence (%) of hypertension (78.6% vs. 44.4%), obesity (25.0% vs. 8.3%), abdominal obesity (85.7% vs. 69.4%) and sedentary activity (89.2% vs. 77.8%), and lower prevalence of smoking/tobacco use (10.7% vs. 25.0%) (P < 0.05). In STEMI patients 28 (57.1%) were thrombolysed (diabetes 17.8% vs. 31.9%), percutaneous coronary interventions (PCI) was in 67.8% diabetics versus 84.7% nondiabetics and coronary bypass surgery in 21.4% versus 8.3%. At discharge, in diabetics versus nondiabetics, there was similar use of angiotensin converting enzyme inhibitors (67.9% vs. 69.4%) and statins (100.0% vs. 98.6%) while use of dual antiplatelet therapy (85.7% vs. 95.8%) and beta-blockers (64.3% vs. 73.6%) was lower (P < 0.05). CONCLUSIONS: Diabetic patients with ACS have greater prevalence of cardiometabolic risk factors (obesity, abdominal obesity, and hypertension) as compared to nondiabetic patients. Less diabetic patients undergo PCIs and receive lesser dual anti-platelet therapy and beta-blockers.

Epidemiology of cardioprotective pharmacological agent use in stable coronary heart disease.

OBJECTIVE: To determine use of class and type of cardioprotective pharmacological agents in patients with stable coronary heart disease (CHD) we performed a prescription audit. METHODS: A cross sectional survey was conducted in major districts of Rajasthan in years 2008-09. We evaluated prescription for classes (anti-platelets, ß-blockers, angiotensin converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARB), calcium channel blockers (CCB) and statins) and specific pharmacological agents at clinics of physicians in tertiary (n = 18), secondary (n = 69) and primary care (n = 43). Descriptive statistics are reported. RESULTS: Prescriptions of 2290 stable CHD patients were audited. Anti-platelet use was in 2031 (88.7%), ß-blockers 1494 (65.2%), ACE inhibitors 1196 (52.2%), ARBs 712 (31.1%), ACE inhibitors - ARB combinations 19 (0.8%), either ACE inhibitors or ARBs 1908 (83.3%), CCBs 1023 (44.7%), statins 1457 (63.6%) and other lipid lowering agents in 170 (7.4%). Among anti-platelets aspirin-clopidogrel combination was used in 88.5%. Top three molecules in ß-blockers were atenolol (37.8%), metoprolol (26.4%) and carvedilol (11.9%); ACE inhibitors ramipril (42.1%), lisinopril (20.3%) and perindopril (10.9%); ARB's losartan (47.7%), valsartan (22.3%) and telmisartan (14.9%); CCBs amlodipine (46.7%), diltiazem (29.1%) and verapamil (9.5%) and statins were atorvastatin (49.8%), simvastatin (28.9%) and rosuvastatin (18.3%). Use of metoprolol, ramipril, valsartan, diltiazem and atorvastatin was more at tertiary care, and atenolol, lisinopril, losartan, amlodipine and simvasatin in primary care (p < 0.01). CONCLUSIONS: There is low use of ß-blockers, ACE inhibitors, ARBs and statins in stable CHD patients among physicians in Rajasthan. Significant differences in use of specific molecules at primary, secondary and tertiary healthcare are observed.

Primary pioglitazone failure in Asian Indian diabetics is not related to common Pro12Ala polymorph of PPAR-gamma gene.

To determine the various factors influencing glycemic response to pioglitazone monotherapy in newly diagnosed Asian Indian T2DM patients. Thirty T2DM patients (age 53.23 +/- 8.067 yrs, M: F ratio 14:16) were treated with pioglitazone for at least 14 weeks. Relationship between its glucose lowering effect and following patient parameters was studied: BMI, W:H ratio, HOMA-R, HOMA-beta and Pro12Ala polymorph of PPAR-gamma gene. Glycemic targets could be achieved in 20 (66.67%) subjects. All the parameters were comparable among responders and non-responders at the start of therapy. All the participants were homozygous for Pro allele of Pro12Ala polymorph of PPAR-gamma gene. There was a significant positive association between glycemic response to pioglitazone and W: H ratio (beta = 0.426, P = 0.034) and HOMA-R (beta = 0.563, P = 0.008). Primary pioglitazone failure cannot be explained on the basis of body fat and its distribution, insulin resistance and secretory function and Pro12Ala polymorph of PPAR-gamma gene. Among responders central obesity and high insulin resistance were associated with better glycemic response.

PSF-TFE3 oncoprotein in papillary renal cell carcinoma inactivates TFE3 and p53 through cytoplasmic sequestration.

Papillary renal cell carcinomas are associated with chromosomal translocations involving the helix-loop-helix leucine-zipper region of the TFE3 gene on the X chromosome. These translocations lead to the expression of TFE3 chimeras of PRCC, RCC17, NonO and PSF (PTB-associated splicing factor). In this study, we explored the role of PSF-TFE3 fusion protein in mediating cell transformation. Unlike wild-type TFE3 or PSF, which are nuclear proteins, PSF-TFE3 is not a nuclear protein and is targeted to the endosomal compartment. Although PSF-TFE3 has no effect on the nuclear localization of wild-type PSF, it sequesters wild-type TFE3 as well as p53 in the extranuclear compartment leading to functionally null p53 and TFE3 cells. In UOK-145 papillary renal carcinoma cells, which endogenously express PSF-TFE3, siRNA complementary to the PSF-TFE3 fusion junction leads to a reduction in PSF-TFE3 and redistribution of endogenous TFE3 and p53 from the cytoplasmic compartment to the nucleus. Our results indicate that PSF-TFE3 acts through a novel mechanism, and exports TFE3, p53 and possibly other factors from the nucleus to the cytoplasm for degradation leading to the transformed phenotype. Thus, PSF-TFE3 is a promising target for the treatment for a subset of renal cell carcinomas.