Consensus on Current Landscape and Treatment Trends of Obesity in India for Primary Care Physicians.

Objectives: The objective of this consensus article was to form a list of expert recommendations and an easily adaptable algorithm for obesity management in India by primary care physicians (PCPs). Methods: A Delphi-based model was followed to form a list of the consensus recommendations. Consensus statements were created from the results of a literature review that were graded as per the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) criteria. After being evaluated by an expert panel comprising diabetologists, endocrinologists, cardiologists, bariatric surgeons, and gynecologists, the statements were revised and reevaluated by a larger group of practitioners, including PCPs and diabetologists, to arrive at a consensus. Results: The panel opined that obesity is increasing in prevalence in India and is projected to rise in the coming years. Body mass index and waist circumference were both recommended for better identification of people at risk of obesity-related comorbidities than either of them alone. The Edmonton Obesity Staging System (EOSS) was suggested as being most suitable for the assessment (staging) of obesity. A multidisciplinary team was considered invaluable for assessing and managing patients with obesity. The use of once-a-week semaglutide (2.4 mg) via the subcutaneous route was suggested as the first-choice anti-obesity treatment when pharmacotherapy is deemed necessary. An algorithm considering all these aspects was proposed. Conclusion: Obesity needs to be recognized as a significant contributor to other comorbidities. The diagnosis and management of obesity should be comprehensive and consider patient psychology, the presence or absence of comorbidities, available pharmacologic agents, and long-term outcomes. The proposed algorithm could help clinicians in this aspect and improve the overall outcomes. How to cite this article: Deshpande NR, Kapoor N, Dalal JJ, et al. Consensus on Current Landscape and Treatment Trends of Obesity in India for Primary Care Physicians. J Assoc Physicians India 2023;71(10):69-77.

Screening of PCSK9 and LDLR genetic variants in Familial Hypercholesterolemia (FH) patients in India.

Familial Hypercholesterolemia (FH) is an autosomal, dominant, inherited disorder characterized by severely elevated LDL-cholesterol (LDL-C) levels with high risk for Coronary Artery Disease (CAD). There are limited genetic studies especially on genes other than Low Density Lipoprotein receptor (LDLR) conducted in Indian population. Thus, our aim was to screen the entire Proprotein Convertase Subtilisin/Kexin type 9 gene (PCSK9) gene & hotspot exons 3, 4 and 9 of LDLR gene in FH cases and controls. 50 FH cases were categorized into definite, probable and possible cases according to Dutch Lipid Network Criteria (DLNC) who were gender matched with 50 healthy controls. All 12 exons of PCSK9, and hotspot exons 3, 4 & 9 of LDLR gene were screened through High Resolution Melt (HRM) curve analysis. Enzyme linked immunosorbent assay was performed to measure circulating PCSK9 levels. Total cholesterol and LDL-C were significantly high in all three groups of cases. Total 8 nonpathogenic variants in exon 1, 5, 7 and 9 of the PCSK9 gene were detected. In LDLR gene, 3 known pathogenic and 1 benign variant were found in exon 3 & 4. In FH cases, PCSK9 levels were significantly high compared to controls (P = 0.0001), and were directly correlated to LDL-C (P = 0.0001) and Total Cholesterol (P = 0.0001). Our study is first to screen the entire PCSK9 gene in western part of India. Since no pathogenic variants were identified, it is possible that PCSK9 variants are clinically less relevant. However, 3 known pathogenic variants were found in the LDLR gene. These findings support our understanding of the genetic spectrum of FH in India.

Current Perspective on Use of NOAC in Clinical Practice in India.

Oral vitamin K antagonists (VKA) such as warfarin have been the mainstay of therapy for stroke prevention in patients with non valvular atrial fibrillation (NVAF) while low-molecular-weight heparin, fondaparinux and adjusted-dose warfarin or aspirin have been routinely used for thromboembolism (VTE) prophylaxis in patients undergoing total hip or knee replacement. However, VKAs are associated with considerable limitations, including increased risk of bleeding and narrow therapeutic window. Novel oral anticoagulants (NOACs, now referred as Non Vit K dependent oral anticoagulants), including the direct thrombin inhibitor dabigatran and direct Factor Xa inhibitors such as rivaroxaban and apixaban are now approved alternatives to warfarin for prophylaxis of stroke and systemic embolic events (SEE) in patients with NVAF and treatment and prophylaxis of VTE. The efficacy and safety of NOACs have been proven in several clinical trials. The advantages offered by NOACs such as rapid onset and termination of action, predictable anticoagulant effect, less frequent laboratory monitoring make them promising alternatives to warfarin. However, clinicians in India seek more information over the practical aspects that require due consideration to ensure proper use of these drugs. The article addresses some crucial aspects of NOAC therapy such as measurement of anticoagulant effects, transition between different agents, ensuring drug intake compliance, dealing with dosing errors, management of bleeding complications etc based on the guidance offered by the European Heart Rhythm Association in 2013.

Cardiac Biomarkers for Better Management of Acute Coronary Syndromes.

Acute myocardial infarction (AMI) causes significant mortality and morbidity. Timely diagnosis allows clinicians to risk stratify their patients and select appropriate treatment. Biomarkers have been used to diagnose or rule out AMI. An increasing number of novel biomarkers have been identified to predict the outcome following AMI or acute coronary syndrome (ACS). This may facilitate tailoring of appropriate therapy to high-risk patients. This review focuses on a variety of promising biomarkers which provide diagnostic and prognostic information.

Managing dyslipidaemia in young adults.

Indians have early onset atherosclerotic cardiovascular disease and acquire the risk factors at a younger age, and hence we need to aggressively address the management of dyslipidemia in the young. Cholesterol levels early in life will influence the development of atherosclerosis. Young atherosclerotic cardiovascular disease (ASCVD) patients (18-40 yrs) should receive lipid-lowering drugs to reduce LDL-C<55 mg. Due to the asymptomatic nature of dyslipidemia, early screening will enable the implementation of management strategies which will decrease future cardiovascular events. In this review, we will provide insights into identifying and managing dyslipidemia in the 18-40 years age group (young adults). It is suggested that early detection and more aggressive management of dyslipidemia in young adults with or without risk factors like diabetes, hypertension, tobacco and central obesity, might reduce the risk of CV events occurring later in life. Although lifestyle modification is the mainstay of treatment (dietary recommendations, exercise, tobacco cessation, weight reduction, etc.) but in certain young adults we suggest use of statins in low dose or non-statin drugs if they have associated risk factors, LDL-C >160 mg or a high coronary calcium score. Young adults who are carriers of FH gene should receive aggressive lifestyle modification and appropriate antilipidemic therapy.

Lipid Association of India 2023 update on cardiovascular risk assessment and lipid management in Indian patients: Consensus statement IV.

OBJECTIVE: In 2016, the Lipid Association of India (LAI) developed a cardiovascular risk assessment algorithm and defined low-density lipoprotein cholesterol (LDL-C) goals for prevention of atherosclerotic cardiovascular disease (ASCVD) in Indians. The recent refinements in the role of various risk factors and subclinical atherosclerosis in prediction of ASCVD risk necessitated updating the risk algorithm and treatment goals. METHODS: The LAI core committee held twenty-one meetings and webinars from June 2022 to July 2023 with experts across India and critically reviewed the latest evidence regarding the strategies for ASCVD risk prediction and the benefits and modalities for intensive lipid lowering. Based on the expert consensus and extensive review of published data, consensus statement IV was commissioned. RESULTS: The young age of onset and a more aggressive nature of ASCVD in Indians necessitates emphasis on lifetime ASCVD risk instead of the conventional 10-year risk. It also demands early institution of aggressive preventive measures to protect the young population prior to development of ASCVD events. Wide availability and low cost of statins in India enable implementation of effective LDL-C-lowering therapy in individuals at high risk of ASCVD. Subjects with any evidence of subclinical atherosclerosis are likely to benefit the most from early aggressive interventions. CONCLUSIONS: This document presents the updated risk stratification and treatment algorithm and describes the rationale for each modification. The intent of these updated recommendations is to modernize management of dyslipidemia in Indian patients with the goal of reducing the epidemic of ASCVD among Indians in Asia and worldwide.

Platelet polymorphisms: frequency distribution and association with coronary artery disease in an Indian population.

Platelets play a critical role in normal blood hemostasis and thrombus formation in myocardial infarction (MI). Several polymorphisms of genes involved in platelet activation and fibrinolysis have been reported to be associated with MI. The aim of the present study was to determine the frequency distribution and association of polymorphisms in these genes with coronary artery disease (CAD) among Indians. A case-control genetic association study was performed for polymorphisms in platelet glycoprotein receptors (GPIIb/IIIa [HPA1a/1b], GPIb-IX-V [VNTR], and GPIa/IIa [C807T]), fibrinogen ß-chain (BclI), α-chain (Aα312), tissue plasminogen activator (tPA) [I/D] and plasminogen activator inhibitor-I (PAI-1) [4G/5G] in 473 healthy controls and 446 patients with stable and unstable angina. Genotyping was either by PCR-based restriction endonuclease digestion or allele-specific primers. The I allele frequency of the tPA I/D polymorphism was significantly higher in our patients (χ(2)=7.33, P<0.01) and no other polymorphisms varied significantly between patients and controls. Also, none of the polymorphisms seemed to affect the severity of the disease, the only exception being the mutant alleles of ß chain of fibrinogen gene, which were significantly elevated in single vessel disease. This is the first study to evaluate the role of gene polymorphisms in both the thrombotic and fibrinolytic pathway in the Indian population and suggests that tPA I/D polymorphism confers CAD risk in our population.

Therapeutic adherence in hypertension: Current evidence and expert opinion from India.

Hypertension (HTN) is a globally prevalent non-communicable disease contributing significantly to cardiovascular (CV) morbidity and mortality. In achieving control of HTN, therapeutic adherence plays a crucial role. Studies from India identify varying rates of adherence to antihypertensive medications. Multiple factors determine treatment adherence in HTN. In India, factors such as lower socioeconomic status, health literacy, asymptomatic nature of disease, forgetfulness, cost of medications, and duration of HTN determine the adherence. An excellent physician-patient relationship incorporating adequate counseling along with the use of other methods can identify poor adherence. Improving adherence necessitates incorporating a multipronged approach with strategies directed at physicians, patients, and health systems. With innovation in therapeutics, the pharmaceutical sector can contribute significantly to improve adherence. Furthermore, increasing adherence to lifestyle interventions can help achieve better HTN control and improve CV outcomes. In the Indian context, more emphasis is necessary on patient education, enhanced physician-patient relationship and communication, increased access to health care, and affordability in improving therapeutic adherence in HTN.

Consensus Recommendations by the Asian Pacific Society of Cardiology: Optimising Cardiovascular Outcomes in Patients with Type 2 Diabetes.

The Asian Pacific Society of Cardiology convened a consensus statement panel for optimising cardiovascular (CV) outcomes in type 2 diabetes, and reviewed the current literature. Relevant articles were appraised using the Grading of Recommendations, Assessment, Development and Evaluation system, and consensus statements were developed in two meetings and were confirmed through online voting. The consensus statements indicated that lifestyle interventions must be emphasised for patients with prediabetes, and optimal glucose control should be encouraged when possible. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are recommended for patients with chronic kidney disease with adequate renal function, and for patients with heart failure with reduced ejection fraction. In addition to SGLT2i, glucagon-like peptide-1 receptor agonists are recommended for patients at high risk of CV events. A blood pressure target below 140/90 mmHg is generally recommended for patients with type 2 diabetes. Antiplatelet therapy is recommended for secondary prevention in patients with atherosclerotic CV disease.

Infective endocarditis--a tale of two cases and the lessons (re)learned.

Infective endocarditis due to uncommon organisms or at uncommon sites presents a diagnostic challenge. Because signs and symptoms can be nonspecific and vary greatly, a high index of suspicion is necessary. We have recently treated two such cases, one due to HACEK organism (Eikenella corrodens) in a patient with established valvular heart disease and other of right sided endocarditis due to Pseudomonas aeruginosa. This report describes the diagnostic difficulties faced.

Proposed low-density lipoprotein cholesterol goals for secondary prevention and familial hypercholesterolemia in India with focus on PCSK9 inhibitor monoclonal antibodies: Expert consensus statement from Lipid Association of India.

BACKGROUND: Rates of atherosclerotic cardiovascular disease (ASCVD) are strikingly high in India compared to Western countries and are increasing. Moreover, ASCVD events occur at a younger age with only modest hypercholesterolemia, most commonly with low levels of high-density lipoprotein cholesterol. The course of ASCVD also appears to be more fulminant with higher mortality. OBJECTIVE: In light of these issues, the Lipid Association of India (LAI) endeavored to develop revised guidelines with more aggressive low-density lipoprotein cholesterol (LDL-C) goals in secondary prevention and for patients with familial hypercholesterolemia compared to guidelines in the United States and other countries. METHODS: Owing to the paucity of clinical outcomes data in India, it was necessary to place major emphasis on expert opinion as a complement to randomized placebo-controlled data generated mostly in non-Indian cohorts. To facilitate this process, the LAI conducted a series of 19 meetings among 162 lipid specialists in 13 cities throughout India over a period of 11 months before formulating this expert consensus statement. RESULTS: The LAI recommends an LDL-C goal <50 mg/dL in all patients in secondary prevention or very high-risk primary prevention but proposes an optional goal ≤30 mg/dL in category A extreme-risk patients (eg, coronary artery disease + familial hypercholesterolemia) and a recommended goal ≤30 mg/dL in category B extreme-risk patients [coronary artery disease + (1) diabetes and polyvascular disease/≥3 major ASCVD risk factors/end organ damage, or (2) recurrent acute coronary syndrome within 12 months despite LDL-C <50 mg/dL, or (3) homozygous familial hypercholesterolemia]. CONCLUSIONS: More aggressive LDL-C goals are needed for prevention of ASCVD in India, as described in this expert consensus statement. Use of statins and ezetimibe needs to increase in India in combination with improved control of other ASCVD risk factors. Proprotein convertase subtilisin kexin type 9 inhibitors can improve LDL-C goal achievement in patients with refractory hypercholesterolemia.

Trimetazidine in cardiovascular medicine.

Abnormalities of myocardial energy metabolism appear as a common background of the two major cardiac disorders: ischemic heart disease (IHD) and heart failure (HF). Myocardial ischemia has been recently conceived as a multifaceted syndrome that can be precipitated by a number of mechanisms including metabolic abnormalities. HF is a progressive disorder characterised by a complex interaction of haemodynamic, neurohormonal and metabolic disturbances. HF may further promote metabolic changes, generating a vicious cycle. Thus, targeting cardiac metabolism in IHD patients may prevent the deterioration of left ventricular function, stopping the progression to HF. For these reasons, several studies have explored the potential benefits of trimetazidine (TMZ), an inhibitor of free fatty acids oxidation that shifts cardiac and muscle metabolism to glucose utilization. Because of its mechanism of action, TMZ has been found to provide a cardioprotective effect in patients with angina, diabetes mellitus, and left ventricular (LV) dysfunction, and those undergoing revascularization procedures, without relevant side effects. In addition, the lack of interference with heart rate, arterial pressure, and most of frequent comorbidities, makes TMZ an attractive option for patients and clinicians as well. The impact of TMZ on long term mortality and morbidity in ischemic syndromes and in heart failure need to be conclusively confirmed in properly designed RCT.

ST2 elevation in heart failure, predictive of a high early mortality.

BACKGROUND: Soluble suppression of tumorigenicity-2 (sST2) is a novel biomarker shown to be useful for prognostic assessment in heart failure (HF). However, very limited data exists about its prognostic utility in patients with HF in India. METHODS: We studied 150 patients [mean age 67.7 ± 13.3, 93 (62%) males], hospitalized with clinical HF, irrespective of their left ventricular ejection fraction (LVEF). HF was confirmed by N-terminal probrain natriuretic peptide (NT-proBNP) value above 125 ng/L. Primary end point was death or cardiac transplant at 1-year follow-up, with additional telephonic follow-up performed at 2 years. The clinical outcomes were correlated with the sST2 values obtained at the time of initial hospitalization. RESULTS: HF was ischemic in origin in 82.0% patients. The primary outcome occurred in 9.3% patients at the end of 1-year follow-up and in 16.7% patients at the end of 2 years. The patients who had events had significantly higher NT-proBNP and sST2 values, but there was no difference in the clinical characteristics, cause of HF, baseline LVEF, or serum creatinine. The patients with elevated sST2 levels (>35 ng/mL) had substantially higher event rates than those with normal sST2 levels (13.7% vs 0.0% at 1-year, P = 0.005; 22.5% vs 4.2% at 2-years, P = 0.004). On multivariate analysis, sST2 was the strongest predictor of adverse outcomes at both 1-year and 2-year follow-ups. CONCLUSION: In patients hospitalized for HF, elevated sST2 >35 ng/mL at the time of initial hospitalization was associated with significantly high mortality over a 2-year period. The prognostic value of sST2 was incremental to that of NT-proBNP. These findings suggest that a single elevated sST2 value at the time of hospitalization should alert the physicians about the high risk of adverse outcomes and should help facilitate timely intensification of HF treatment.

Modulation of myocardial energetics: An important category of agents in the multimodal treatment of coronary artery disease and heart failure.

The combined and relative contribution of glucose and fatty acid oxidation generates myocardial energy, which regulates the cardiac function and efficiency. Any dysregulation in this metabolic homeostasis can adversely affect the function of heart and contribute to cardiac conditions such as angina and heart failure. Metabolic agents ameliorate this internal metabolic anomaly, by shifting the energy production pathway from free fatty acids to glucose, resulting in a better performance of the heart. Metabolic therapy is relatively a new modality, which functions through optimization of cardiac substrate metabolism. Among the metabolic therapies, trimetazidine and ranolazine are the agents presently available in India. In the present review, we would like to present the metabolic perspective of pathophysiology of coronary artery disease and heart failure, and metabolic therapy by using trimetazidine and ranolazine.

Oral antiplatelet therapy and platelet inhibition: An experience from a tertiary care center.

AIMS AND OBJECTIVES: Although clopidogrel combined with aspirin is the most commonly used dual drug combination to avert thrombotic events in patients with coronary artery disease, the poor responsiveness to clopidogrel remains a concern. The objective of the current study is to assess the extent of resistance to clopidogrel, prasugrel, and ticagrelor in a real life set of patients with coronary artery disease who underwent percutaneous coronary intervention (PCI). MATERIALS AND METHODS: A total of 539 patients, who underwent PCI and were on aspirin and on any of the three drugs, namely, clopidogrel, prasugrel and ticagrelor, were followed up regularly in the outpatient department. After 24h of initiation of antiplatelet medication, response to the treatment in all the patients was assessed using thrombelastography. The average percentage platelet inhibition was assessed along with the resistance and sensitivity to the drug in each patient. Sensitivity and resistance to the specific drug was defined as >50% and <50% of mean platelet inhibition, respectively. RESULTS: About 99.15% of the patients treated with ticagrelor were sensitive to the drug and the difference between ticagrelor, clopidogrel, and prasugrel groups for sensitivity was significant with a p value of 0.00001, in favor of ticagrelor. It was also found that ticagrelor was significantly (p value of 0.001) associated with least resistance as compared with the other drugs assessed in the study. CONCLUSIONS: Use of ticagrelor as dual therapy along with aspirin in patients with coronary artery disease (CAD) and undergoing PCI was associated with a significantly higher mean percentage platelet inhibition, higher sensitivity, and lower resistance as compared with the usage of clopidogrel or prasugrel.

Management standards for stable coronary artery disease in India.

Coronary artery disease (CAD) is one of the important causes of cardiovascular morbidity and mortality globally, giving rise to more than 7 million deaths annually. An increasing burden of CAD in India is a major cause of concern with angina being the leading manifestation. Stable coronary artery disease (SCAD) is characterised by episodes of transient central chest pain (angina pectoris), often triggered by exercise, emotion or other forms of stress, generally triggered by a reversible mismatch between myocardial oxygen demand and supply resulting in myocardial ischemia or hypoxia. A stabilised, frequently asymptomatic phase following an acute coronary syndrome (ACS) is also classified as SCAD. This definition of SCAD also encompasses vasospastic and microvascular angina under the common umbrella.

Time to shift from contemporary to high-sensitivity cardiac troponin in diagnosis of acute coronary syndromes.

Early rule-in and rule-out of non-ST-segment elevation myocardial infarction (NSTEMI) is a challenge. In patients with inconclusive findings on ECG, cardiac biomarkers play a crucial role in the diagnosis. The introduction of the new high-sensitive cardiac troponin test (hs-TnI assay) has changed the landscape of NSTEMI diagnosis. The new hs-TnI assay can detect troponin values at a lower level compared with a contemporary cardiac troponin (cTn) assay. The hs-cTnI assay has a coefficient of variation of ≤10%, well below the 99th percentile value. It reduces the time to diagnose acute myocardial infarction from 6h to 3h. A recent study has demonstrated that hs-cTnI can further reduce the time to 1h in 70% of all patients with chest pain. The European Society of Cardiology 2015 guidelines recommend including a second sample of hs-cTnI within 3h of presentation This increases the sensitivity of the hs-TnI assay from 82.3% (at admission) to 98.2% and negative predictive value from 94.7% (at admission) to 99.4%. Combining the 99th percentile at admission with serial changes in troponin increases the positive predictive value to rule in acute coronary syndrome from 75.1% at admission to 95.8% after 3h. The 2015 ESC Guidelines recommend the use of a rapid rule out protocol (0h and 1h) when hs-cTnI with a validated 0 to1h algorithm is available. Training and displaying the clinical algorithm depicting the role of hs-TnI assay in acute cardiac care units and in EDs are an efficient way to deliver the new standard of care to patients. Compared with contemporary troponin assays, the hs-cTn assay accelerates the diagnostic pathway to 0-1h, thus reducing the time for diagnosis of NSTEMI and hence, its management.

The Indian Consensus Document on cardiac biomarker.

Despite recent advances, the diagnosis and management of heart failure evades the clinicians. The etiology of congestive heart failure (CHF) in the Indian scenario comprises of coronary artery disease, diabetes mellitus and hypertension. With better insights into the pathophysiology of CHF, biomarkers have evolved rapidly and received diagnostic and prognostic value. In CHF biomarkers prove as measures of the extent of pathophysiological derangement; examples include biomarkers of myocyte necrosis, myocardial remodeling, neurohormonal activation, etc. In CHF biomarkers act as indicators for the presence, degree of severity and prognosis of the disease, they may be employed in combination with the present conventional clinical assessments. These make the biomarkers feasible options against the present expensive measurements and may provide clinical benefits.