Navigating Cardiovascular Risk and Lipid Management in Indian Patients: Key Messages from the Lipid Association of India 2024 Consensus Statement IV.

Effective lipid management is crucial for preventing atherosclerotic cardiovascular disease (ASCVD). The Western lipid guidelines may not apply to Indian subjects because of the vast differences in cardiovascular (CV) disease epidemiology. To overcome this challenge, the Lipid Association of India (LAI) in 2016 proposed an ASCVD risk stratification algorithm. The appropriate low-density lipoprotein cholesterol (LDL-C) goals for various risk groups were proposed, with an LDL-C target of <50 mg/dL recommended for the first time globally for patients in the very high-risk group. Subsequently, in 2020, an extreme risk group was added because of observations that patients with more severe or extensive ASCVD, along with multiple risk factors and comorbidities, had increased rates of adverse CV events and could benefit from more intensive LDL-C lowering. The extreme risk group was subdivided into categories A and B, with LDL-C targets as low as 30 mg/dL or lower. The availability of further evidence regarding the significance of novel risk factors and the availability of new LDL-C lowering therapies necessitated refining the ASCVD risk assessment algorithm, defining LDL-C targets for subjects with these risk factors, and incorporating recommendations for attaining very low LDL-C levels in a defined, select group of patients. Accordingly, the LAI expert group recently published the Consensus Statement IV, which is a comprehensive document addressing several key issues about risk stratification and dyslipidemia management in Indian subjects. LDL-C and nonhigh-density lipoprotein cholesterol (non-HDL-C) are not only primary and co-primary targets for lipid-lowering therapy but also risk factors for ASCVD risk stratification. Apolipoprotein B is a secondary target. The risk assessment algorithm has been updated to incorporate several nonconventional yet relevant CV risk factors. Additionally, the role of subclinical atherosclerosis has been highlighted. The CV risk due to subclinical atherosclerosis has been considered equivalent to that of established ASCVD, and hence, similar LDL-C targets have been recommended. Furthermore, a new risk category-extreme risk group category C has been added for the small subgroup of patients who continue to experience ASCVD sequelae despite achieving LDL-C levels of 30 mg/dL or lower. An ultralow LDL-C target (10-15 mg/dL) has been recommended along with optimal control of risk factors and guideline-directed management of comorbidities. Dyslipidemia management should be effective with sustained LDL-C lowering. In high-risk situations (e.g., acute coronary syndrome), the LDL-C target should be achieved as early as possible, preferably within the first 2 weeks. The present document summarizes the key messages from the LAI Consensus Statement IV.

Does Adopting Western Low-density Lipoprotein Cholesterol Targets Expose Indians to a Higher Risk of Cardiovascular Events? Expert Opinion From the Lipid Association of India.

Adverse cardiovascular (CV) events have declined in Western countries due at least in part to aggressive risk factor control, including dyslipidemia management. The American and European (Western) dyslipidemia treatment guidelines have contributed significantly to the reduction in atherosclerotic cardiovascular disease (ASCVD) incidence in the respective populations. However, their direct extrapolation to Indian patients does not seem appropriate for the reasons described below. In the US, mean low-density lipoprotein cholesterol (LDL-C) levels have markedly declined over the last 2 decades, correlating with a proportional reduction in CV events. Conversely, poor risk factor control and dyslipidemia management have led to increased CV and coronary artery disease (CAD) mortality rates in India. The population-attributable risk of dyslipidemia is about 50% for myocardial infarction, signifying its major role in CV events. In addition, the pattern of dyslipidemia in Indians differs considerably from that in Western populations, requiring unique strategies for lipid management in Indians and modified treatment targets. The Lipid Association of India (LAI) recognized the need for tailored LDL-C targets for Indians and recommended lower targets compared to Western guidelines. For individuals with established ASCVD or diabetes with additional risk factors, an LDL-C target of <50 mg/dL was recommended, with an optional target of ≤30 mg/dL for individuals at extremely high risk. There are several reasons that necessitate these lower targets. In Indian subjects, CAD develops 10 years earlier than in Western populations and is more malignant. Additionally, Indians experience higher CAD mortality despite having lower basal LDL-C levels, requiring greater LDL-C reduction to achieve a comparable CV event reduction. The Indian Council for Medical Research-India Diabetes study described a high prevalence of dyslipidemia among Indians, characterized by relatively lower LDL-C levels, higher triglyceride levels, and lower high-density lipoprotein cholesterol (HDL-C) levels compared to Western populations. About 30% of Indians have hypertriglyceridemia, aggravating ASCVD risk and complicating dyslipidemia management. The levels of atherogenic triglyceride-rich lipoproteins, including remnant lipoproteins, are increased in hypertriglyceridemia and are predictive of CV events. Hypertriglyceridemia is also associated with higher levels of small, dense LDL particles, which are more atherogenic, and higher levels of apolipoprotein B (Apo B), reflecting a higher burden of circulating atherogenic lipoprotein particles. A high prevalence of low HDL-C, which is often dysfunctional, and elevated lipoprotein(a) [Lp(a)] levels further contribute to the heightened atherogenicity and premature CAD in Indians. Considering the unique characteristics of atherogenic dyslipidemia in Indians, lower LDL-C, non-HDL-C, and Apo B goals compared to Western guidelines are required for effective control of ASCVD risk in Indians. South Asian ancestry is identified as a risk enhancer in the American lipid management guidelines, highlighting the elevated ASCVD risk of Indian and other South Asian individuals, suggesting a need for more aggressive LDL-C lowering in such individuals. Hence, the LDL-C goals recommended by the Western guidelines may be excessively high for Indians and could result in significant residual ASCVD risk attributable to inadequate LDL-C lowering. Further, the results of Mendelian randomization studies have shown that lowering LDL-C by 5-10 mg/dL reduces CV risk by 8-18%. The lower LDL-C targets proposed by LAI can yield these incremental benefits. In conclusion, Western LDL-C targets may not be suitable for Indian subjects, given the earlier presentation of ASCVD at lower LDL-C levels. They may result in greater CV events that could otherwise be prevented with lower LDL-C targets. The atherogenic dyslipidemia in Indian individuals necessitates more aggressive LDL-C and non-HDL-C lowering, as recommended by the LAI, in order to stem the epidemic of ASCVD in India.

Elemental profiling of agricultural soil in Hoshiarpur utilizing analytical techniques.

Our study aimed to assess the soil quality in Punjab's Hoshiarpur district through a meticulous analysis of nutrient and elemental composition. Using a variety of analytical techniques, including Neutron Activation Analysis (NAA), external Particle-induced Gamma-ray Emission (PIGE) an Ion beam analysis Technique, and energy-dispersive X-ray fluorescence (ED-XRF), we delved into soil characterization for 22 agricultural soil samples in the Punjab region. Within the NAA framework, utilizing the Pneumatic Carrier Facility and the self-serve facility at Dhruva reactor in Mumbai, a brief 1-min irradiation procedure identified pivotal elements-Na, Mg, V, Al, Mn, and K. Conversely, an extended neutron irradiation process of approximately 4 h within the self-serve facility enabled the estimation of nearly 12 elements, including Rare Earth Elements (REEs), Transition elements, and other significant elements. The external PIGE technique quantified low Z elements (Na, Mg, Al, and Si), contributing to our analytical arsenal. Rigorously validating both NAA and PIGE methodologies, we compared results meticulously against established geological standard reference materials-specifically USGS RGM-1 and USGS AGV-1.Instrumental in elemental analysis, ED-XRF spectroscopy fortified our investigative endeavors by quick assessment of ten crucial elements. The elemental analysis revealed notable accumulations of Mn and Zn in the soil, surpassing the suggested permissible limits, whereas Co, Cr, and Pb were found to be within the recommended thresholds set by WHO/UNEP. Beyond elemental profiling, our study extended to estimate the accumulation levels of various elements utilizing ecological risk factors such as Contamination Factor, Potential Ecological Risk Index, Pollution Load Index, and Geoaccumulation Factor. Our findings highlighted significant accumulation of REEs including La, Sm and Yb.. This evaluation sheds new light on the interplay between soil composition and environmental health, emphasizing the need for advanced accessible agricultural technologies to prevent and forecast contaminant discharge in arable soil. This commitment aligns with our broader goal of advancing sustainable practices in soil management.

Time-efficient etching of LR-115 SSNTD film for indoor radon, thoron quantification.

LR-115 Solid State Nuclear Track Detector (SSNTD) is commonly utilized for quantifying indoor radon-thoron levels, by tallying the tracks formed in the films by exposure to these gases. Conventionally, sodium hydroxide (NaOH) is used to etch LR-115 films for 90 min at 60°C. However, this study suggests a time-efficient alternative approach utilizing potassium hydroxide (KOH) as the etchant. In an initial investigation, the bulk etch rates of KOH were examined at different normalities and temperatures, revealing that KOH exhibited nearly double the bulk etch rates compared to NaOH. Subsequently, a specially designed controlled experiment was conducted to assess the efficacy of the technique by enumerating the tracks generated in the films. Both etchants demonstrated very similar track counts for identical controlled exposures, indicating the reliability of the method. A consistent behavior was observed in the real-case scenario of LR-115 films exposed indoors to alpha particles from radon and its decay products. In both experiments, the etching with KOH for 45 min gave track densities comparable to standard NaOH etching for 90 min, highlighting the time efficiency of this method. Investigations were carried out into track shape and size features, aspects crucial to the measurement technique, using microscopic imaging of samples treated with both etchants. Strikingly similar track shapes and sizes were observed, affirming the consistency in the track measurement technique. Collectively, these findings suggest that KOH etchant reduces the etching time, presenting itself as a time-efficient method for quantifying radon and thoron track density.

R wave peak time and no reflow following primary percutaneous coronary intervention: Immediate and short-term outcomes.

BACKGROUND: No reflow (NR) remains an important constraint in management of ST elevation myocardial Infarction (STEMI) patients undergoing primary percutaneous coronary intervention (PCI). Most ECG parameters validated till date including ST resolution are postprocedural. R wave peak time (RWPT) is a dynamic parameter and reflects conduction delay in ischaemic myocardium in selected leads supplied by infarct related artery (IRA). The present study was undertaken to see whether preprocedural RWPT per se or RWPT following primary PCI can predict persistence of NR along with immediate and short-term clinical outcome. METHODS: 200 patients were enrolled after exclusion. Clinical, Biochemical, ECG parameters including RPWT and angiographic parameters (pre- and post-procedure) were recorded. ECG papers was analysed using digital image processing software (http://imagej.nih.gov/ij/). All patients were followed up for 6 months. RESULTS: NR was observed in 35% of the patients. Age, Diabetes, symptom to balloon time, higher thrombus burden, peak CPK-MB level (pre and post procedure) were significantly higher in NR group. On ECG analysis, baseline RWPT, QRS duration and pathological Q wave were significantly higher in NR group. On multivariate analysis, age (OR 1.10 CI 1.00-1.21 P = 0.04), thrombus grade ≥ 3 in IRA (OR 12.38 CI 2.08-73.58 P = 0.006), symptom to balloon time (OR 2.18 CI 1.6-3.0 P < 0.001) and baseline RWPT on ECG [OR 1.86 CI 1.24-2.78, P = 0.003] were found to be independent predictors of NR. Increase in RWPT following primary PCI was found to both highly sensitive and specific for diagnosing persistence of NR after primary PCI. Follow up at the end of 6 months has shown that patients with increased RWPT following primary PCI had worse short-term cardiovascular outcomes compared to those with decreased RWPT following primary PCI. CONCLUSION: Baseline RWPT is a significant predictor of NR in patients of STEMI undergoing primary PCI. A persistently increased RWPT following primary PCI is also a highly sensitive and specific ECG marker of persistence of NR which is associated with adverse short-term clinical outcome.

Unmet Need for Further LDL-C Lowering in India despite Statin Therapy: Lipid Association of India Recommendations for the Use of Bempedoic Acid.

Lipid-lowering therapy plays a crucial role in reducing adverse cardiovascular (CV) events in patients with established atherosclerotic cardiovascular disease (ASCVD) and familial hypercholesterolemia. Lifestyle interventions along with high-intensity statin therapy are the first-line management strategy followed by ezetimibe. Only about 20-30% of patients who are on maximally tolerated statins reach recommended low-density lipoprotein cholesterol (LDL-C) goals. Several factors contribute to the problem, including adherence issues, prescription of less than high-intensity statin therapy, and de-escalation of statin dosages, but in patients with very high baseline LDL-C levels, including those with familial hypercholesterolemia and those who are intolerant to statins, it is critical to expand our arsenal of LDL-C-lowering medications. Moreover, in the extreme risk group of patients with an LDL-C goal of ≤30 mg/dL according to the Lipid Association of India (LAI) risk stratification algorithm, there is a significant residual risk requiring the addition of non-statin drugs to achieve LAI recommended targets. This makes bempedoic acid a welcome addition to the existing non-statin therapies such as ezetimibe, bile acid sequestrants, and PCSK9 inhibitors. A low frequency of muscle-related side effects, minimal drug interactions, a significant reduction in high-sensitivity C-reactive protein (hsCRP), and a lower incidence of new-onset or worsening diabetes make it a useful adjunct for LDL-C lowering. However, the CV outcomes trial results are still pending. In this LAI consensus document, we discuss the pharmacology, indications, contraindications, advantages, and evidence-based recommendations for the use of bempedoic acid in clinical practice.

Prevalence and predictors of left atrial appendage inactivity in patients of rheumatic mitral stenosis in sinus rhythm: An observational study.

BACKGROUND: Systemic thromboembolism is a known complication of rheumatic mitral stenosis (RMS) in sinus rhythm (SR). Left atrial appendage (LAA), the commonest site of thrombus formation is usually hypocontractile (inactive) in such patients. We aimed to study the prevalence of LAA inactivity (LAAI) in severe RMS and assess its independent predictors. METHODS: The study population consisted of 100 patients of severe RMS in SR. Transthoracic and transesophageal echocardiography were done to assess LAA contractile function. Patients with LAA-peak emptying velocity < 25 cm/seconds were defined as having LAAI. RESULTS: The mean age of study subjects was 31.66±8.69 years and 56% were females. 73% patients had LAAI (Group A), while remaining 27% had normal LAA function (Group B). Mitral-valve area (MVA) and lateral annulus systolic velocity (Sa-wave) were significantly lower while mitral valve mean gradient (MVMG) and serum fibrinogen were significantly higher (all p-values < 0.001) in group A patients. On multivariate binary logistic regression analysis, MVMG (p < 0.001), Sa-wave (p = 0.02), and serum fibrinogen (p = 0.005) were independent predictors of LAAI. Optimal cut-off values of MVMG, Sa-wave and serum fibrinogen for predicting LAAI were 11.5 mm Hg, 6.8 cm/seconds and 300 mg/dl, respectively. Sixty-Seven (90.55%) patients in group A compared to 13(48.1%) in group B had LA/LAA smoke. LAAI was the only independent predictor of left atrium (LA)/LAA smoke with or without associated thrombus. CONCLUSION: There is high prevalence of LAAI in patients of severe MS in SR. MVMG, Sa-wave, and serum fibrinogen levels are independent predictors of LAAI. LAAI is an independent predictor of LA/LAA smoke with or without associated thrombus.

Role of lymphocyte-to-monocyte ratio as a predictive marker for diabetic coronary artery disease: A cross-sectional study.

BACKGROUND: The lymphocyte to monocyte ratio (LMR) is considered a marker of systemic inflammation in cardiovascular disease and acts as predictor of mortality in coronary artery disease. AIM: To investigate the predictive role of LMR in diabetic coronary artery disease patients. METHODS: This cross-sectional study was conducted at tertiary care super-specialty hospital at New Delhi, India. A total of 200 angiography-proven coronary artery disease (CAD) patients were enrolled and grouped into two categories: Group I [CAD patients with type 2 diabetes mellitus (T2DM) and glycated hemoglobin (HbA1c) levels ≥ 6.5%], and Group II (CAD patients without T2DM and HbA1c levels < 6.5%). Serum lipoproteins, HbA1c, and complete blood count of enrolled patients were analyzed using fully automatic analyzers. RESULTS: The logistic regression analysis showed an odds ratio of 1.48 (95%CI: 1.28-1.72, P < 0.05) for diabetic coronary artery disease patients (Group I) in unadjusted model. After adjusting for age, gender, diet, smoking, and hypertension history, the odds ratio increased to 1.49 (95%CI: 1.29-1.74, P < 0.01) in close association with LMR. Further adjustment for high cholesterol and triglycerides yielded the same odds ratio of 1.49 (95%CI: 1.27-1.75, P < 0.01). Receiver operating characteristic curve analysis revealed 74% sensitivity, 64% specificity, and 0.74 area under the curve (95%CI: 0.67-0.80, P < 0.001), suggesting moderate predictive accuracy for diabetic CAD patients. CONCLUSION: LMR showed positive association with diabetic coronary artery disease, with moderate predictive accuracy. These findings have implications for improving CAD management in diabetics, necessitating further research and targeted interventions.

Discovering hidden patterns: Association rules for cardiovascular diseases in type 2 diabetes mellitus.

BACKGROUND: It is increasingly common to find patients affected by a combination of type 2 diabetes mellitus (T2DM) and coronary artery disease (CAD), and studies are able to correlate their relationships with available biological and clinical evidence. The aim of the current study was to apply association rule mining (ARM) to discover whether there are consistent patterns of clinical features relevant to these diseases. ARM leverages clinical and laboratory data to the meaningful patterns for diabetic CAD by harnessing the power help of data-driven algorithms to optimise the decision-making in patient care. AIM: To reinforce the evidence of the T2DM-CAD interplay and demonstrate the ability of ARM to provide new insights into multivariate pattern discovery. METHODS: This cross-sectional study was conducted at the Department of Biochemistry in a specialized tertiary care centre in Delhi, involving a total of 300 consented subjects categorized into three groups: CAD with diabetes, CAD without diabetes, and healthy controls, with 100 subjects in each group. The participants were enrolled from the Cardiology IPD & OPD for the sample collection. The study employed ARM technique to extract the meaningful patterns and relationships from the clinical data with its original value. RESULTS: The clinical dataset comprised 35 attributes from enrolled subjects. The analysis produced rules with a maximum branching factor of 4 and a rule length of 5, necessitating a 1% probability increase for enhancement. Prominent patterns emerged, highlighting strong links between health indicators and diabetes likelihood, particularly elevated HbA1C and random blood sugar levels. The ARM technique identified individuals with a random blood sugar level > 175 and HbA1C > 6.6 are likely in the "CAD-with-diabetes" group, offering valuable insights into health indicators and influencing factors on disease outcomes. CONCLUSION: The application of this method holds promise for healthcare practitioners to offer valuable insights for enhancing patient treatment targeting specific subtypes of CAD with diabetes. Implying artificial intelligence techniques with medical data, we have shown the potential for personalized healthcare and the development of user-friendly applications aimed at improving cardiovascular health outcomes for this high-risk population to optimise the decision-making in patient care.

Efficacy of nicorandil and ranolazine in prevention of contrast-induced nephropathy in patients with mild-to-moderate renal dysfunction: a randomized controlled trial.

INTRODUCTION: Contrast-induced nephropathy (CIN) is a common complication after percutaneous coronary intervention (PCI). There is conflicting evidence regarding efficacy of nicorandil in CIN prevention. With respect to ranolazine, there is physiological possibility as well as data in animal study regarding its protective effect against CIN; there is, however, no human data till date. AIM AND OBJECTIVES: To assess the efficacy of nicorandil and ranolazine in preventing CIN. The secondary endpoint was to measure difference in postprocedure acute kidney injury (AKI) incidence across groups. Also, patients were followed up till 6 months for major adverse events. MATERIAL AND METHODS: This single-center randomized controlled study included 315 patients of coronary artery disease with mild-to-moderate renal dysfunction undergoing elective PCI. Eligible patients were assigned to either nicorandil (n = 105), ranolazine (n = 105) or control group (n = 105) in 1 : 1 : 1 ratio by block randomization. All enrolled patients were given intravenous sodium chloride at rate of 1.0 mL/kg/h (0.5 mL/kg/h for patients with left ventricular ejection fraction <45%) from 6 h before procedure till 12 h after procedure. Iso-osmolar contrast agent (iodixanol) was used for all patients. In addition to hydration, patients in nicorandil group received oral nicorandil (10 mg, 3 times/d) and those in ranolazine group received oral ranolazine (1000 mg, 2 times/d) 1 day before procedure and for 2 days after PCI. Patients in control group received only hydration. RESULTS: Total number of CIN was 34 (10.7%), which included 19 (18.1%) in control, 8 (7.6%) in nicorandil and 7 (6.6%) in ranolazine group. There was significant association of CIN reduction across groups ( P  = 0.012). On pairwise comparison also, there was significant benefit across control and ranolazine as well as control and nicorandil ( P  < 0.025). There was numerically higher incidence of AKI in controls; the difference, however, did not reach statistical significance after applying Bonferroni correction ( P  = 0.044). Over 6-month follow-up, adverse events were similar across groups. CONCLUSION: While this study adds to existing literature that supports role for nicorandil in CIN prevention, the efficacy of ranolazine in protecting against CIN has been demonstrated in humans for the first time.