Indian Heart Journal
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Item Lipid clinical trials with special reference to Indian population(Elsevier, 2024-03) Basha, Aseem; Ramakrishnan, SivasubramanianIndians have a pattern of atherogenic dyslipidaemia characterised by not so high LDL-C but elevated small, dense LDL-C, elevated triglyceride levels and low HDL-C levels. In addition, different lipid-lowering drugs exhibit pharmacokinetic variability in Indians, which may have implications on the optimum doses required to achieve the desired LDL-C levels. Currently the management of dyslipidaemia in Indians are based on the landmark trials, which largely included western population. This review focusses on major clinical trials of lipid lowering drugs with special reference to the Indian population.Item Lipoprotein a Lp(a)(Elsevier, 2024-03) Ghose, TapanLp(a) is a genetically determined, heritable, independent and causal risk factor for ASCVD. About 1 in 5 people worldwide have elevated Lp(a) (>50 mg/dL or >125 nmol/L) whereas in Indians it is 25 %. Epidemiological, genome-wide association and mendelian randomization studies have demonstrated an association between elevated Lp(a) levels and increased incidence of myocardial infarction, aortic valve stenosis, ischemic stroke, heart failure, CV and all-cause mortality. The increased Lp(a)-mediated CV risk is mediated by pro-inflammatory, pro-thrombotic and pro-atherogenic processes, leading to progression of atherosclerosis and increased risk of thrombosis. Lp(a) level reaches peak by 5 years of age and remains stable over time. Levels are not much influenced by dietary and environmental factors but it can vary in certain clinical situations like thyroid diseases, chronic kidney disease, inflammation and sepsis. It should be measured at least once in life time. Cascade testing for high Lp(a) is recommended in the settings of FH, family history of (very) high Lp(a), and personal or family history of ASCVD. In the absence of specific Lp(a)-lowering therapies, comprehensive risk factor management is recommended as per guidelines for individuals with elevated Lp(a). PCSK9 inhibitors and Inclisiran reduce Lp(a) by 25%. Pelacarsen is an antisense oligonucleotide and is found to reduce Lp(a) by 80%. In a recent Indian study of 1,021 CAD patients, presence of elevated Lp(a) (>50 mg/dL) correlated with severe angiographic disease. 37% of ACS patients exhibited elevated Lp(a) and it was higher in young CAD patients with FH (43%).Item Apolipoprotein B - An ideal biomarker for atherosclerosis?(Elsevier, 2024-03) Singh, Kavita; Prabhakaran, DorairajThis review article describes the pathophysiological mechanisms linking Apolipoprotein B (Apo-B) and athero- sclerosis, summarizes the existing evidence on Apo B as a predictor of atherosclerotic cardiovascular disease and recommendations of (inter)national treatment guidelines regarding Apo B in dyslipidemia management. A single Apo B molecule is present in every particle of very low-density lipoprotein, intermediate density lipoprotein, low density lipoprotein, and lipoprotein(a). This unique single Apo B per particle ratio makes plasma Apo B con- centration a direct measure of the number of circulating atherogenic lipoproteins. This review of global evidence on Apo B as a biomarker for atherosclerosis confirms that Apo B is a single atherogenic lipid marker present in all lipids sub-fractions except HDL-C, and thus, Apo B integrates and extends the information from triglycerides and cholesterol, which could simplify and improve care for atherosclerotic cardiovascular disease.Item Overview of a collaborative global effort to address the burden of familial hypercholesterolaemia(Elsevier, 2024-03) Lyons, Alexander R.M.; Stevens, Christophe A.T.; Dharmayat, Kanika I.; Vallejo-Vaz, Antonio J.; Ray, Kausik K.This is an overview of the EAS Familial Hypercholesterolaemia (FH) Studies Collaboration (FHSC) global con- sortium and registry (established 2015), which broadly addresses the global burden of FH. Eighty-seven National Lead Investigators from 74 countries form this expanding global consortium, and this global registry currently includes pooled data on 70,000 participants from participating countries to facilitate FH surveillance. Published first results from this global registry concluded that FH is diagnosed late, and management of LDL-cholesterol falls below guideline recommendations, and therefore earlier detection of FH and wider use of combination therapy is required. Further FHSC studies will follow on updated data including new countries, participants and variables, and non-DNA genetic information, and on the remaining cohorts in the registry. FHSC cross-sectional collaborative global studies are expected to promote FH detection earlier in life to subsequently initiate early lipid lowering therapy to reduce lifelong exposure to cumulative LDL-cholesterol thus reducing cardiovascular disease risk.Item Familial hypercholesterolemia(Elsevier, 2024-03) Sawhney, J.P.S.; Madan, KushalFamilial hypercholesterolemia is a common genetic disorder of autosomal inheritance associated with elevated LDL-cholesterol. It is estimated to affect 1:250 individuals in general population roughly estimated to be 5 million in India. The prevalence of FH is higher in young CAD patients (<55 years in men; <60 years in women). FH is underdiagnosed and undertreated. Screening during childhood and Cascade screening of family members of known FH patients is of utmost importance in order to prevent the burden of CAD. Early identification of FH patients and early initiation of the lifelong lipid lowering therapy is the most effective strategy for managing FH. FH management includes pharmaceutical agents (statins and non statin drugs) and lifestyle modification. Inspite of maximum dose of statin with or without Ezetimibe, if target levels of LDL-C are not achieved, Bempedoic acid, proprotein convertase subtilisin/kexin type 9 (PCSK9) Inhibitors/Inclisiran can be added.Item Pediatric hyperlipidemia(Elsevier, 2024-03) Garg, Ankit; Radhakrishnan, S.The leading cause of mortality worldwide is atherosclerotic cardiovascular disease. Atherosclerotic plaques are well known to originate early in the childhood. Identifying hyperlipidemia in early childhood creates an op- portunity to prevent major cardiovascular events in adults. Children with identified risk factors are at an increased risk of developing cardiovascular incidents in later life. This article emphasizes the diagnosis and management of pediatric hyperlipidemia with reference to the recent guidelines. In terms of etiology pediatric hyperlipidemia are divided into primary and secondary causes. The mainstay of management includes high-risk target screening, early risk factor identification and lifestyle modifications in vulnerable population. Drug therapy is recommended in primary hyperlipidemia and in children with no response to lifestyle changes.Item Managing dyslipidaemia in young adults(Elsevier, 2024-03) Dalal, Jamshed J.; Khan, TabassumIndians 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 (1840 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 1840 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.Item Dyslipidaemia in endocrine disorders(Elsevier, 2024-03) Sridharan, Kalyani; Kalra, SanjayLipid disorders are common in several endocrine conditions. Diabetes mellitus, hypothyroidism and Cushing's syndrome are the common endocrine disorders with dyslipidemia. Dyslipidemia has a significant impact on endocrine and metabolic health and the risk of atherosclerotic cardiovascular disease. In most cases of dyslipidemia, the suspicion of endocrine diseases must be based on clinical symptoms and signs. Optimal management of the dyslipidemia requires treatment of the underlying endocrine condition. Lipid lowering therapy is a useful adjunct or a requirement in many cases. The Indian guidelines provide a pragmatic and practical approach to the management of lipid disorders in endocrine disease, as well as endocrine vigilance with lipid therapy.Item Management of dyslipidemia in special groups(Elsevier, 2024-03) P B, Jayagopal; Kerkar, Prafulla G.Dyslipidemia management in situations like pregnancy, in diseases like rheumatoid arthritis, human immuno- deficiency virus (HIV) disease, chronic liver disease, and in the elderly are challenging scenarios. Pregnancy is a contraindication for many drugs. The interaction of various drugs used in HIV infection and rheumatoid arthritis makes it even more difficult to treat with conventional and approved drugs for dyslipidemia. Elderly and chronic renal failure patients often do not tolerate the drugs very well and the data of dyslipidemia management is very different. Lastly, COVID-19 is a unique scenario where clear information is yet to be provided. In this manuscript, the current understanding and available data on the treatment of dyslipidemia in these special situations are discussed.Item Coronary artery disease in patients with rheumatic valvular heart disease- An analysis from eastern India(Elsevier, 2024-02) Karak, Avik; Deb, Novonil; Khanra, Dibbendu; Guha, Santanu; Mukherjee, AnindyaIntroduction: There is insufficient information on the angiographic characteristics of individuals with rheumatic valvular heart disease (VHD) from eastern India. The objective of this research is to gather important data in this area to aid the best surgical outcomes for patients with rheumatic VHD. Materials and methods: 978 consecutive patients with rheumatic VHD, scheduled for surgical intervention, were recruited. Result and conclusion: Mitral valve involvement was observed in 66.1 %, aortic valve in 7.3 % and both valves in 26.6 %. Patients with CAD had significantly higher proportions of severe aortic stenosis (AS). Therefore, addressing the risk factors for CAD is crucial in patients with rheumatic VHD.Item Managing dyslipidemia in solid organ transplant patients(Elsevier, 2024-03) Mehta, AshwaniSolid organ transplant recipients face an increased risk of dyslipidemia, which contributes to cardiovascular complications. Commonly used drugs such as ciclosporin and tacrolimus can aggravate and cause dyslipidemia. Immunosuppressive drugs particularly ciclosporin and tacrolimus are also known to worsen dyslipidemia in transplant recipients. Mammalian target of rapamycin (mTOR) inhibitors like sirolimus and everolimus also alter lipid metabolism. Lifestyle and dietary modifications should be encouraged. Careful consideration of immuno- suppressant choices is also vital to control dyslipidemia. Statins are recommended as first-line agents for lipid- lowering therapy, with consideration for potential drug interactions. Other options, such as ezetimibe and nicotinic acid, may be considered as alternatives. The management of dyslipidemia in renal transplant patients mainly involves statin therapy, although the clinical effectiveness in this population is not well-documented. Lifestyle modifications, careful drug selection, and statin therapy are key components in managing dyslipide- mia in solid organ transplant patients.Item Dyslipidemia and peripheral arterial disease(Elsevier, 2024-03) Yadav, Ajay; Sawant, Vivek; Bedi, Varinder Singh; Yadav, KanupriyaPeripheral arterial disease (PAD) affects 12 % of adult population and is increasing globally and in India. Pe- ripheral arterial disease when associated with atherosclerosis in two or more other arterial beds such as coronary artery disease (CAD), mesenteric/renal artery and cerebrovascular disease (CVD), is known as polyvascular disease. The Reduction of Atherothrombosis for Continued Health (REACH) registry reported that 1 out of 6 patients had multi-vascular bed involvement. Progression of PAD to critical limb ischaemia (CLI) is seen in 1 % of affected patients per year, but patients who progress to CLI may have a 10- to 15-fold increased risk of car- diovascular death. The 2019 ECS/EAS guidelines for the management of dyslipidaemias have suggested that for primary or secondary prevention in very high risk, patients should follow a therapeutic regimen that achieves >50 % LDL-C reduction from baseline and an LDL-C goal of <55 mg/dl. High Intensity Statin is mainstay of treatment but optimal management is inadequate. Statin treatment reduces all-cause mortality by 39 %, CV death by 41 %, CV outcomes by 34 %, ischaemic stroke by 28 %, acute limb ischaemia by 30 % and amputations by 35 %. Ezetimibe when added to statins in IMPROVE-IT trial, showed significant reduction of MACE. PCSK9 inhibitor (FOURIER TRIAL) showed reduction in primary end point in PAD vs Non PAD patients (3.5 % vs 1.6 %). There is a critical need for an Indian multi-disciplinary task force for research on the direct impact of lipid- lowering agents on limb salvage rates and major limb-related events in PAD patients.Item Managing dyslipidaemia in patients with chronic kidney disease(Elsevier, 2024-03) Mehta, AshwaniPatients with CKD are at increased risk for cardiovascular events. Clinical studies suggest statins reduce all-cause mortality and cardiovascular events in patients with CKD. Lipid lowering therapy with statin with or without ezetemibe is recommended for most of the patients in patients with eGFR <60 mL/min and also in those who have an increased urinary albumin-to-creatinine ratio (?3 mg/mmol) for at least 3 months. Evidence suggests that it should not be started for hemodialysis patients without evidence of ASCVD. Patients who were already taking statins or statin/ezetimibe combination at the time of dialysis should consider continuing these medi- cations, especially if they have ASCVD. Fibrates should not be used in conjunction with statins in patients with CKD, and ezetimibe monotherapy is also not recommended. The role of PCSK9 inhibitors is evolving suggests that it is effective in lowering LDL cholesterol without affecting the renal outcomes.Item Dyslipidemia in diabetes(Elsevier, 2024-03) Kalra, Sanjay; Raizada, NishantDiabetes mellitus is a metabolic disorder that often predisposes to cardiovascular diseases (CVD). CVD is an important cause of morbidity and mortality in diabetes. The typical diabetic dyslipidaemia is characterized by low HDL cholesterol, high triglycerides with mildly increased or even normal LDL. This attenuated rise in LDL is due to the more atherogenic small dense LDL particles. Genetic factors, obesity, lack of physical activity, alcohol abuse, poorly controlled glucose levels are some of the common risk factors for dyslipidaemia. Non- pharmacological management of dyslipidaemia is important and includes modification in the diet, increase in physical activity and efforts to reduce weight. Statins remain the mainstay of pharmacotherapy for dyslipidaemia in diabetes. Due to the small dense LDL, even patients with diabetes who have normal LDL cholesterol, achieve reduction in cardiovascular risk with statin therapy. Those patients who do not achieve acceptable LDL re- ductions with statin alone can be treated with combination therapy of ezetimibe with statins. Many novel therapies have also emerged such as bempedoic acid and proprotein convertase subtilisin/kexin 9 (PCSK9) in- hibitors. The targets for LDL cholesterol depend upon the patients underlying cardiovascular risk category. The use of pharmacotherapy for lowering triglycerides in patients with mild to moderate hypertriglyceridemia and diabetes is still a matter of debate. Proper management of dyslipidaemia is critical component of treatment of diabetes mellitus.Item Dyslipidaemia in elderly and stroke patients(Elsevier, 2024-03) Kahali, DhimanLowering of cholesterol containing atherogenic particles through lipid lowering therapies is of outmost important in both in the elderly age group and younger age group in reducing the cardiovascular risk. This chapter sum- marizes the current existing knowledge regarding the factors which affects the key decision-making process in patients with older age, and also in special circumstance where the direct evidence of benefit for cholesterol lowering is lacking. Effort has been made to briefly summarize the recommendations to the patient and his/her family based on risk stratification of atherosclerotic versus non-atherosclerotic cardiovascular disease, comor- bidity burden, quality of life, survival prognosis, lifestyle/socioeconomic status and presence of frailty. Here in this chapter, we have collated and presented the available robust clinical trial evidence which is very much necessary for the assessment of risk versus benefit for hypolipidemic drugs in the elderly age group. While plethora of pharmacological interventions has evolved including statins, ezetimibe, bempedoic acid, PCSK9 inhibitors, Inclisiran etc., but it is essential to establish lipid-lowering therapy goals based on the stroke subtype and the presence of comorbidities. Here in this section we have reviewed the collated clinical evidences for optimal drug regimen recommendation for elderly stroke patients for both primary and secondary prevention.Item Dietary management of dyslipidemia(Elsevier, 2024-03) Chopra, Arun K.The rising burden of cardiovascular disease (CVD) has made the achievement of optimal lipoprotein levels a major public health priority. As nearly a fifth of global mortality is associated with dietary factors, and rec- ommendations have been mired in controversy, a fresh look on the available data is attempted. Well established concepts regarding nutrition and cardiometabolic health, role of macronutrients, calories, and controversial foods are discussed followed by recommendations in the Indian context. A healthy dietary pattern rather than individual foods or nutrients is emphasized, and this is generally plant based with optional consumption of dairy, eggs, and meats within the suggested limits. Suggestions/recommendations are given for consumption of indi- vidual foods, remembering that choosing appropriate replacement foods is as important as restricting unhealthy foods.Item Exercise and lipids(Elsevier, 2024-03) Madan, Kushal; Sawhney, J.P.S.Evidence from the existing literature suggests that exercise has positive effects for prevention and treatment of cardiovascular diseases by reducing risk factors such as elevated blood lipids. Based on clinical and observational clinical trials, it is well established that increased physical activity and regular exercise has a favourable impact on blood lipids and lipoprotein profiles. Exercise training significantly decreases blood triglycerides concen- tration and increases high density lipoprotein cholesterol levels. Though the Indian data depicting the effect of exercise on lipids is scarce, exercise directly improves atherogenic dyslipidaemia which is frequently present among Indians i.e. HDL-C is increased, TG is reduced and LDL-C particle size is improved. While drug therapy is key to the treatment of dyslipidaemia, lifestyle alterations such as exercise should continue to be actively pro- moted and encouraged by clinicians. Exercise is a low cost, non pharmacological therapeutic lifestyle change that is of value to lipid metabolism and cardiovascular fitness.Item Traditional and novel non-statin lipid-lowering drugs(Elsevier, 2024-03) Jain, PeeyushNon-statin drugs find utility in the management of dyslipidaemia in mixed dyslipidaemia, patients with statin intolerance, and when guidelines directed low-density lipoprotein cholesterol (LDL-C) target cannot be achieved despite maximally tolerated statin. The most definite indication of fenofibrate monotherapy is fasting serum triglyceride >500 mg/dl to reduce the risk of acute pancreatitis It offers a modest reduction in cardiovascular events. The statin-ezetimibe combination is commonly used for lipid lowering particularly after ACS. Fish oils reduce serum triglycerides by about 25 %. EPA (and not DHA) seems to have cardioprotective effects. Despite cardiovascular outcome benefits, bile-exchange resins have limited use due to poor tolerance. Bempedoic acid added to maximally tolerated statin therapy is approved to lower LDL-C in adults with primary hypercholes- terolemia or mixed dyslipidaemias, HeFH, in patients with ASCVD who require additional lowering of LDL-C, and in patients who are statin-intolerant. Inclisiran is a long-acting double-stranded small interfering RNA (siRNA) that inhibits the transcription of PCSK-9 leading to a decrease in PCSK9 generation in hepatocytes and an in- crease in LDL receptor expression in the liver cell membrane leading to about 50 % reduction in serum LDL-C levels. Lomitapide lowers plasma levels of all ApoB-containing lipoproteins, including VLDL, LDL, and chylo- microns by inhibiting the enzyme microsomal triglyceride transfer protein (MTP) and approved for the treatment of adult patients with homozygous familial hypercholesterolemia (HoFH). Close monitoring for hepatotoxicity is required. Mipomersen is a single-stranded synthetic antisense oligonucleotide (ASO) that affects the production and secretion of apoB-containing lipoproteins with demonstrated efficacy in both homozygous and heterozygous FH patients. It is approved for restricted use due to risk of hepatotoxicity. Pelacarsen is an antisense oligonu- cleotide that reduces the production of apo(a) in the liver.Item Role of PCSK9 inhibitors in the management of dyslipidaemia(Elsevier, 2024-03) Nair, TinyProprotein convertase subtilisin kexin9 (PCSK9) inhibitors are novel agents that lower LDL cholesterol and reduce cardio-vascular event rate. Being expensive, these agents are reserved for those with high risk or very high risk of CV events and with suboptimal response to statins and ezetimibe, with or without bempedoic acid or those intolerant to statins.Item Management of triglycerides, non-high density lipoprotein cholesterol and high density lipoprotein cholesterol(Elsevier, 2024-03) Zachariah, GeevarDyslipidaemia 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 car- diovascular events and reduce the risk of pancreatitis. Lifestyle modification is important. In severe hyper- triglyceridemia, 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 guide- lines, 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