CSI clinical practice guidelines for dyslipidemia management: Executive summary.

Dyslipidemias are the most important coronary artery disease (CAD) risk factor. Proper management of dyslipidemia is crucial to control the epidemic of premature CAD in India. Cardiological Society of India strived to develop consensus-based guidelines for better lipid management for CAD prevention and treatment. The executive summary provides a bird's eye-view of the 'CSI: Clinical Practice Guidelines for Dyslipidemia Management' published in this issue of the Indian Heart Journal. The summary is focused on the busy clinician and encourages evidence-based management of patients and high-risk individuals. The summary has serialized various aspects of lipid management including epidemiology and categorization of CAD risk. The focus is on management of specific dyslipidemias relevant to India-raised low density lipoprotein (LDL) cholesterol, non-high density lipoprotein cholesterol (non-HDL-C), apolipoproteins, triglycerides and lipoprotein(a). Drug therapies for lipid lowering (statins, non-statin drugs and other pharmaceutical agents) and lifestyle management (dietary interventions, physical activity and yoga) are summarized. Management of dyslipidemias in oft-neglected patient phenotypes-the elderly, young and children, and patients with comorbidities-stroke, peripheral arterial disease, kidney failure, posttransplant, HIV (Human immunodeficiency virus), Covid-19 and familial hypercholesterolemia is also presented. This consensus statement is based on major international guidelines (mainly European) and expert opinion of lipid management leaders from India with focus on the dictum: earlier the better, lower the better, longer the better and together the better. These consensus guidelines cannot replace the individual clinician judgement who remains the sole arbiter in management of the patient.

Management of triglycerides, non-high density lipoprotein cholesterol and high density lipoprotein cholesterol.

Dyslipidaemia characterised by elevated total cholesterol/LDL-C, triglyceride or both or decreased HDL-C is an important risk factor for the development of ASCVD. Atherogenic dyslipidaemia characterised by high TG, low HDL-C and elevated small dense LDL (sdLDL) is more prevalent in Asian Indians. Normal level of TG is generally considered as <150 mg/dl. Hypertriglyceridemia is closely associated with obesity, metabolic syndrome and diabetes mellitus. Goals of management of hypertriglyceridemia are to lower the risk of atherosclerotic cardiovascular events and reduce the risk of pancreatitis. Lifestyle modification is important. In severe hypertriglyceridemia, TG lowering pharmacotherapy is important to prevent pancreatitis. In mild to moderate hypertriglyceridemia, pharmacotherapy is employed only if associated with ASCVD or high risk factors and not controlled with lifestyle modifications and statins. Non-High Density Lipoprotein Cholesterol which estimates the cholesterol content of the atherogenic apoB containing lipoproteins, measured as total cholesterol minus HDL-C is equivalent to LDL-C in ASCVD risk assessment and superior to it in those with mild to moderate hypertriglyceridemia. Some international guidelines, have included measurement of non-HDL-C as primary therapeutic target for patients with ASCVD. Low HDL cholesterol is common in Indians. Despite evidence of inverse relationship between HDL-C and cardiovascular events, HDL-C as a causative factor for development of atherosclerosis is unproven. Therapeutic strategies directed at increasing HDL-C levels have not been shown to have cardiovascular benefits and hence HDL-C is currently not a target for drug-based treatment.

Pharmacogenetic variants influence vitamin K anticoagulant dosing in patients with mechanical prosthetic heart valves.

Background: Vitamin K antagonists (VKAs) are class I oral anticoagulants that are widely prescribed following surgical heart valve implantation. The objective of this study was to quantify the relative effects of VKORC1, CYP2C9 and CYP4F2 genotypes in predicting VKA dosing. Materials & methods: A total of 506 South Indian patients with mechanical prosthetic heart valves who were prescribed oral VKAs, such as warfarin or acenocoumarol, were genotyped. The discriminatory ability of mutant genotypes to predict dose categories and bleeding events was assessed using regression analysis. Results: The VKORC1 rs9923231, CYP2C9*3 and CYP4F2*3 mutant genotypes significantly influenced VKA-dose requirements and explained 27.47% of the observed dose variation. Conclusion: These results support pharmacogenetic screening for initial VKA dosing among South Indian patients with mechanical prosthetic heart valves.

Machine learning based model for risk prediction after ST-Elevation myocardial infarction: Insights from the North India ST elevation myocardial infarction (NORIN-STEMI) registry.

BACKGROUND: Risk prediction following ST-Elevation Myocardial Infarction (STEMI) in resource limited countries is critical to identify patients at an increased risk of mortality who might benefit from intensive management. METHODS: North India ST-Elevation Myocardial Infarction (NORIN-STEMI) is an ongoing registry that has prospectively enrolled 3,635 STEMI patients. Of these, 3191 patients with first STEMI were included. Patients were divided into two groups: development (n=2668) and validation (unseen) dataset (n=523). Various ML strategies were used to train and tune the model based on validation dataset results that included 31 clinical characteristics. These models were compared in sensitivity, specificity, F1-score, receiver operating characteristic area under the curve (AUC), and overall accuracy to predict mortality at 30 days. ML model decision making was analyzed using the Shapley Additive exPlanations (ShAP) summary plot. RESULTS: At 30 days, the mortality was 7.7%. On the validation dataset, Extra Tree ML model had the best predictive ability with sensitivity: 85%, AUC: 79.7%, and Accuracy: 75%. ShAP interpretable summary plot determined delay in time to revascularization, baseline cardiogenic shock, left ventricular ejection fraction <30%, age, serum creatinine, heart failure on presentation, female sex, and moderate-severe mitral regurgitation to be major predictors of all-cause mortality at 30 days (P<0.001 for all). CONCLUSION: ML models lead to an improved mortality prediction following STEMI. ShAP summary plot for the interpretability of the AI model helps to understand the model's decision in identifying high-risk individuals who may benefit from intensified follow-up and close monitoring.

Changing pattern of admissions for acute myocardial infarction in India during the COVID-19 pandemic.

AIM: Studies on the changes in the presentation and management of acute myocardial infarction (AMI) during the COVID-19 pandemic from low- and middle-income countries are limited. We sought to determine the changes in the number of admissions, management practices, and outcomes of AMI during the pandemic period in India. METHODS & RESULTS: In this two-timepoint cross-sectional study involving 187 hospitals across India, patients admitted with AMI between 15th March to 15th June in 2020 were compared with those admitted during the corresponding period of 2019. We included 41,832 consecutive adults with AMI. Admissions during the pandemic period (n = 16414) decreased by 35·4% as compared to the corresponding period in 2019 (n = 25418). We observed significant heterogeneity in this decline across India. The weekly average decrease in AMI admissions in 2020 correlated negatively with the number of COVID cases (r = -0·48; r2 = 0·2), but strongly correlated with the stringency of lockdown index (r = 0·95; r2 = 0·90). On a multi-level logistic regression, admissions were lower in 2020 with older age categories, tier 1 cities, and centers with high patient volume. Adjusted utilization rate of coronary angiography, and percutaneous coronary intervention decreased by 11·3%, and 5·9% respectively. CONCLUSIONS: The magnitude of reduction in AMI admissions across India was not uniform. The nature, time course, and the patient demographics were different compared to reports from other countries, suggesting a significant impact due to the lockdown. These findings have important implications in managing AMI during the pandemic.

One-year clinical outcome of patients with nonvalvular atrial fibrillation: Insights from KERALA-AF registry.

BACKGROUND: We report patient characteristics, treatment pattern and one-year clinical outcome of nonvalvular atrial fibrillation (NVAF) from Kerala, India. This cohort forms part of Kerala Atrial Fibrillation (KERALA-AF) registry which is an ongoing large prospective study. METHODS: KERALA-AF registry collected data of adults with previously or newly diagnosed atrial fibrillation (AF) during April 2016 to April 2017. A total of 3421 patients were recruited from 53 hospitals across Kerala state. We analysed one-year follow-up outcome of 2507 patients with NVAF. RESULTS: Mean age at recruitment was 67.2 years (range 18-98) and 54.8% were males. Main co-morbidities were hypertension (61.2%), hyperlipidaemia (46.2%) and diabetes mellitus (37.2%). Major co-existing diseases were chronic kidney disease (42.1%), coronary artery disease (41.6%), and chronic heart failure (26.4%). Mean CHA2DS2-VASc score was 3.18 (SD ± 1.7) and HAS-BLED score, 1.84 (SD ± 1.3). At baseline, use of oral anticoagulants (OAC) was 38.6% and antiplatelets 32.7%. On one-month follow-up use of OAC increased to 65.8% and antiplatelets to 48.3%. One-year all-cause mortality was 16.48 and hospitalization 20.65 per 100 person years. The main causes of death were cardiovascular (75.0%), stroke (13.1%) and others (11.9%). The major causes of hospitalizations were acute coronary syndrome (35.0%), followed by arrhythmia (29.5%) and heart failure (8.4%). CONCLUSIONS: Despite high risk profile of patients in this registry, use of OAC was suboptimal, whereas antiplatelets were used in nearly half of patients. A relatively high rate of annual mortality and hospitalization was observed in patients with NVAF in Kerala AF Registry.

Pattern of acute MI admissions in India during COVID-19 era: A Cardiological Society of India study - Rationale and design.

BACKGROUND: COVID-19 pandemic has affected around 20million patients worldwide and 2.0 million cases from India. The lockdown was employed to delay the pandemic. However, it had an unintentional impact on acute cardiovascular care, especially acute myocardial infarction (AMI). Observational studies have shown a decrease in hospital admissions for AMI in several developed countries during the pandemic period. We aimed to evaluate the impact of COVID-19 on the AMI admissions patterns across India. METHODS: In this multicentric, retrospective, cross-sectional study, we included all AMI cases admitted to participating hospitals during the study period 15th March to 15th June 2020 and compared them using a historical control of all cases of AMI admitted during the corresponding period in the year 2019. Major objective of the study is to analyze the changes inthe number of hospital admissions for AMI in hospitals across India. In addition, we intend to evaluate the impact of COVID-19 on the weekly AMI admission rates, and other performance measures like rates of thrombolysis/primary percutaneous interventions (PCI), window period, door to balloon time, and door to needle time. Other objectives include evaluation of changes in the major complications and mortality rates of AMI and its predictors during COVID-19 pandemic. CONCLUSIONS: This CSI-AMI study will provide scientific evidence about the impact of COVID-19 on AMI care in India. Based on this study, we may be able to suggest appropriate changes to the existing MI guidelines and to educate the public regarding emergency care for AMI during COVID-19 pandemic.

Family history of cardiovascular disease and risk of premature coronary heart disease: A matched case-control study.

Background: Self-reported family history of cardiovascular disease (CVD) is an independent risk factor for future coronary heart disease (CHD) events. However, inclusion of family history of CVD in the traditional risk scores failed to improve risk prediction of CHD. It is proposed that family history of CVD may substantially increase the risk of CHD among younger individuals. Methods: We conducted a matched case-control study with 170 hospital-based premature CHD patients (<55 years in men and <65 years in women) from a tertiary care centre in Thiruvananthapuram, Kerala and age and sex matched community-based controls in 1:1 ratio. Conditional logistic regression analysis was conducted to assess the independent association of family history of cardiovascular disease (CVD) and premature CHD. We estimated McNemar's odds ratios and their 95 percent confidence intervals. Results: The prevalence of any family history of CVD and CHD in the control population was 24% and 21%, respectively. The family history of CVD was independently associated with premature CHD (odds ratio (OR) = 9.0; 95% confidence interval (CI) 4.7-17.3). There was a dose-response relationship between family history and premature CHD as the risk increased linearly with increase in number of affected family members. Conclusions: Family history of CVD is an independent risk factor for premature CHD. The risk of premature CHD increases linearly with increase in number of affected family members. Collecting family history beyond parental history of CVD is important for risk stratification. Targeting young individuals with family history of CVD for intensive risk reduction interventions may help to prevent future events.

Impact of the 2017 ACC/AHA guidelines on the prevalence of hypertension among Indian adults: Results from a cross-sectional survey.

BACKGROUND: The impact of the 2017 American College of Cardiology (ACC)/American Heart Association (AHA) guidelines for diagnosis and management of hypertension on the prevalence of hypertension in India is unknown. METHODS: We analyzed data from the Cardiac Prevent 2015 survey to estimate the change in the prevalence of hypertension. The JNC8 guidelines defined hypertension as a systolic blood pressure of ≥140 â€‹mmHg or diastolic blood pressure of ≥90 â€‹mmHg. The 2017 ACC/AHA guidelines define hypertension as a systolic blood pressure of ≥130 â€‹mmHg or diastolic blood pressure of ≥80 â€‹mmHg. We standardized the prevalence as per the 2011 census population of India. We also calculated the prevalence as per the World Health Organization (WHO) World Standard Population (2000-2025). RESULTS: Among 180,335 participants (33.2% women), the mean age was 40.6 â€‹± â€‹14.9 years (41.1 â€‹± â€‹15.0 and 39.7 â€‹± â€‹14.7 years in men and women, respectively). Among them, 8,898 (4.9%), 99,791 (55.3%), 35,694 (11.9%), 23,084 (12.8%), 9,989 (5.5%) and 2,878 (1.6%) participants belonged to age group 18-19, 20-44, 45-54, 55-64, 65-74 and â€‹≥ â€‹75 years respectively. The prevalence of hypertension according to the JNC8 and 2017 ACC/AHA guidelines was 29.7% and 63.8%, respectively- an increase of 115%. With the 2011 census population of India, this suggests that currently, 486 million Indian adults have hypertension according to the 2017 ACC/AHA guidelines, an addition of 260 million as compared to the JNC8 guidelines. CONCLUSION: According to the 2017 ACC/AHA guidelines, 3 in every 5 Indian adults have hypertension.

Prevalence of hypertension among Indian adults: Results from the great India blood pressure survey.

OBJECTIVE: Hypertension is the most important risk factor for cardiovascular morbidity and mortality. There is limited data on hypertension prevalence in India. This study was conducted to estimate the prevalence of hypertension among Indian adults. METHODS: A national level survey was conducted with fixed one-day blood pressure measurement camps across 24 states and union territories of India. Hypertension was defined as systolic blood pressure (BP) ≥140 mmHg or a diastolic BP ≥90 mmHg or on treatment for hypertension. The prevalence was age- and gender-standardized according to the 2011 census population of India. RESULTS: Blood pressure was recorded for 180,335 participants (33.2% women; mean age 40.6 ± 14.9 years). Among them, 8,898 (4.9%), 99,791 (55.3%), 35,694 (11.9%), 23,084 (12.8%), 9,989 (5.5%), and 2,878 (1.6%) participants were of the age group 18-19, 20-44, 45-54, 55-64, 65-74, and ≥ 75 years, respectively. Overall prevalence of hypertension was 30.7% (95% confidence interval [CI]: 30.5, 30.9) and the prevalence among women was 23.7% (95% CI: 23.3, 24). Prevalence adjusted for 2011 census population and the WHO reference population was 29.7% and 32.8%, respectively. CONCLUSION: There is a high prevalence of hypertension, with almost one in every three Indian adult affected.

Kerala Atrial Fibrillation Registry: a prospective observational study on clinical characteristics, treatment pattern and outcome of atrial fibrillation in Kerala, India, cohort profile.

PURPOSE: Limited published data exist on the clinical epidemiology of atrial fibrillation (AF) in South Asia including India. Most of the published data are from the Western countries and the Far East. The Kerala AF registry was initiated to collect systematic, prospective data on clinical characteristics, risk factors, treatment pattern and outcomes of consecutive AF patients who consulted cardiologists across the state of Kerala, India. PARTICIPANTS: All newly diagnosed and previously reported patients aged ≥18 years with documented evidence of AF on ECG were included. Patients with transient AF due to infection, acute myocardial infarction, alcohol intoxication, metabolic abnormalities and AF seen in postoperative cases and critically ill patients with life expectancy less than 30 days were excluded. FINDINGS TO DATE: A total of 3421 patients were recruited from 53 hospitals across Kerala from April 2016 to April 2017. There were 51% (n=1744) women. The median age of the cohort was 65 (IQR 56-74) years. Hypertension, diabetes mellitus and dyslipidaemia were present in 53.8%, 34.5% and 42.2% patients, respectively. Chronic kidney disease was observed in 46.6%, coronary artery disease in 34.8% and heart failure (HF) in 26.5% of patients. Mean CHA2DS2-VASc score of the cohort was 2.9, and HAS-BLED score was 1.7. Detailed information of antithrombotic and antiarrhythmic drugs was collected at baseline and on follow-up. During 1-year follow-up, 443 deaths (12.9%) occurred of which 332 (9.7%) were cardiac death and 63 (1.8%) were due to stroke. There were 578 (16.8%) hospitalisations mainly due to acute coronary syndrome, arrythmias and HF. FUTURE PLANS: Currently, this is the largest prospective study on AF patients from India, and the cohort will be followed for 5 years to observe the treatment patterns and clinical outcomes. The investigators encourage collaborations with national and international AF researchers. TRIAL REGISTRATION NUMBER: CTRI/2017/10/010097.

A Kerala model for cardiovascular research?

India's contribution to cardiovascular research has been dismal with a share of only 1% of total number of papers published in the world during the period 1999-2008. Based on two recent studies published from Kerala, the Kerala ACS Registry and the CSI Kerala CRP Study and four other studies being undertaken in Kerala, we think that a Kerala model for cardiovascular research can be conceptualized. This model which consists of funding by professional organization of cardiologists with wide participation of cardiologists, physicians, health workers, nurses, and in some situations general public, logistics looked after by a central coordinator and study design by panel of experts or institutions of repute in the region and carried out at low cost can be considered for implementation in rest of India. Studies based on such a model may change practice pattern of cardiovascular diseases in India.

Effect of Smoking on Metalloproteinases (MMPs) Activity in Patients with Acute Myocardial Infarction (AMI).

INTRODUCTION: Many risk factors are involved in the course and pathogenesis of Acute Myocardial Infarction (AMI). Smoking can significantly increase the AMI mortality and morbidity. Matrix metalloproteinases (MMPs), a class of Zn containing enzymes, are involved in the erosion of the fibrous cap and rupture of the plaque which leads to AMI. AIM: To evaluate the activity of MMP2 and MMP9 in AMI patients, with or without the habit of smoking. MATERIALS AND METHODS: The study group consists of 300 AMI patients and 100 sex and age matched control subjects with and without the habit of smoking. MMP2 and MMP9 activities were measured in the blood samples of these patients and controls by sandwich enzyme immunoassay and the values were noted and compared. RESULTS: Both MMP2 and MMP9 were found to be significantly elevated in all the AMI patients when compared to the normal controls subjects irrespective of the habit of smoking. However MMP9 showed a significant elevation when compared to MMP2 in patients with the habit of smoking. CONCLUSION: The results of the present study shows increased concentration of both MMPs in AMI patients. However, concentration of MMP9 was found to be more in patients with the habit of smoking when compared to MMP2, indicating that smoking can increase the activity of MMP9 in these patients. Hence apart from producing the free radicals, the smoke can increase the activities of matrix degrading enzymes which in turn contribute to the vulnerability of plaque.

Prevalence of coronary artery disease and coronary risk factors in Kerala, South India: a population survey - design and methods.

BACKGROUND: There is paucity of reliable contemporary data on prevalence of coronary artery disease (CAD) and risk factors in Indians. Only a few studies on prevalence of CAD have been conducted in Kerala, a Southern Indian state. The main objective of the Cardiological Society of India Kerala Chapter Coronary Artery Disease and Its Risk Factors Prevalence Study (CSI Kerala CRP Study) was to determine the prevalence of CAD and risk factors of CAD in men and women aged 20-79 years in urban and rural settings of three geographical areas of Kerala. METHODS: The design of the study was cross-sectional population survey. We estimated the sample size based on an anticipated prevalence of 7.4% of CAD for rural and 11% for urban Kerala. The derived sample sizes for rural and urban areas were 3000 and 2400, respectively. The urban areas for sampling constituted one ward each from three municipal corporations at different parts of the state. The rural sample was drawn from two panchayats each in the same districts as the urban sample. One adult from each household in the age group of 20-59 years was selected using Kish method. All subjects between 60 and 79 years were included from each household. A detailed questionnaire was administered to assess the risk factors, history of CAD, family history, educational status, socioeconomic status, dietary habits, physical activity and treatment for CAD; anthropometric measurements, blood pressure, electrocardiogram and fasting blood levels of glucose and lipids were recorded.

Presentation, management, and outcomes of 25 748 acute coronary syndrome admissions in Kerala, India: results from the Kerala ACS Registry.

AIMS: There are limited contemporary data on the presentation, management, and outcomes of acute coronary syndrome (ACS) admissions in India. We aimed to develop a prospective registry to address treatment and health systems gaps in the management of ACSs in Kerala, India. METHODS AND RESULTS: We prospectively collected data on 25 748 consecutive ACS admissions from 2007 to 2009 in 125 hospitals in Kerala. We evaluated data on presentation, management, and in-hospital mortality and major adverse cardiovascular events (MACE). We created random-effects multivariate regression models to evaluate predictors of outcomes while accounting for confounders. Mean (SD) age at presentation was 60 (12) years and did not differ among ACS types [ST-segment myocardial infarction (STEMI) = 37%; non-STEMI = 31%; unstable angina = 32%]. In-hospital anti-platelet use was high (>90%). Thrombolytics were used in 41% of STEMI, 19% of non-STEMI, and 11% of unstable angina admissions. Percutaneous coronary intervention rates were marginally higher in STEMI admissions. Discharge medication rates were variable and generally suboptimal (<80%). In-hospital mortality and MACE rates were highest for STEMI (8.2 and 10.3%, respectively). After adjustment, STEMI diagnosis (vs. unstable angina) [odds ratio (OR) (95% confidence interval = 4.06 (2.36, 7.00)], symptom-to-door time >6 h [OR = 2.29 (1.73, 3.02)], and inappropriate use of thrombolysis [OR = 1.33 (0.92, 1.91)] were associated with higher risk of in-hospital mortality and door-to-needle time <30 min [OR = 0.44 (0.27, 0.72)] was associated with lower mortality. Similar trends were seen for risk of MACE. CONCLUSION: These data represent the largest ACS registry in India and demonstrate opportunities for improving ACS care.