|Year : 2016 | Volume
| Issue : 2 | Page : 62-66
The Lipid Association of India Expert Consensus Statement 2016: A sea change for management of dyslipidemia in Indians
Enas A Enas MD, FACC 1, TS Dharmarajan MD, MACP, AGSF 2
1 Coronary Artery Disease among Asian Indians Research Foundation, Lisle, IL, USA
2 Department of Clinical Medicine, Albert Einstein College of Medicine; Department of Medicine, Montefiore Medical Center (Wakefield Campus), Bronx, NY, USA
|Date of Web Publication||18-Jul-2016|
Enas A Enas
Executive Director, Coronary Artery Disease among Asian Indians Research Foundation, Lisle, IL
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Enas EA, Dharmarajan T S. The Lipid Association of India Expert Consensus Statement 2016: A sea change for management of dyslipidemia in Indians. J Clin Prev Cardiol 2016;5:62-6
|How to cite this URL:|
Enas EA, Dharmarajan T S. The Lipid Association of India Expert Consensus Statement 2016: A sea change for management of dyslipidemia in Indians. J Clin Prev Cardiol [serial online] 2016 [cited 2019 Aug 18];5:62-6. Available from: http://www.jcpconline.org/text.asp?2016/5/2/62/186499
Elevated levels of atherogenic cholesterol (AC), generally measured as nonhigh-density lipoprotein cholesterol (NHDL-C), plays a central role in cardiovascular disease (CVD), especially among Asian Indians (hereafter termed "Indians").  For any given level of total cholesterol, Indians tend to have a greater elevation in NHDL-C by virtue of high triglycerides and low-HDL-C, common to this population.  Among the agents that lower AC, overwhelming clinical trial data support the use of statins - A class of extremely effective medications that lower risk for CVD in people with widely different low-density lipoprotein cholesterol (LDL-C levels).  Consequentially, statin therapy has become the bedrock of prevention and treatment for CVD with its use no longer limited to those with high-cholesterol levels. ,
Statin therapy is highly effective in lowering NHDL-C, LDL-C, apolipoprotein B, and remnant cholesterol, besides being remarkably safe. ,,, Yet, many health-care providers and patients underestimate the absolute benefits and overestimate the absolute risks of statin therapy, resulting in its underuse, especially in India.  Whereas the benefits of statin therapy relate to the magnitude of LDL-C reduction, the risks of muscle injury and liver toxicity are not. , Life-threatening adverse effects of statins are 100 times fewer than the CVD events prevented from statin therapy.  A meta-analysis of randomized clinical trials has demonstrated that across a broad range of LDL-C levels, there is a 20% relative risk reduction in adverse CVD events for each 39 mg/dL decrease in LDL-C with statin therapy. , In primary prevention, in every 1 million persons with 10-year CVD risk <10% high-intensity statin therapy can prevent 600 deaths and 1200-2400 CVD events. , Most importantly, the benefit of statin therapy in primary prevention far outweighs the risk even in those with 5% CVD risk within 10 years. , A 10-year CVD risk threshold of 5% for statin therapy seems appropriate among Indians. 
Recent cholesterol guidelines have significantly reduced the threshold of CVD risk to initiate statin therapy with some variations among American, European, and Indian guidelines. The 10-year risk threshold for statin therapy varies from 20% in India to 10% in the United Kingdom to 5 to 7.5% in the USA. ,, More recent scientific evidence shows that the benefits of statin therapy outweigh the risks in adults with 10-year CVD risk as low as 3% and lifetime risk as low as 30%.  Lowering the stain eligibility threshold from 10-year CVD risk ≥7.5% to ≥3.0% is estimated to expand the statin eligibility to 61% to 67% of the USA adults and avert an additional 161,560 CVD events.  Therapy would also be cost-effective using less expensive generic statins. 
| Not All 10-year Risk Estimation Tools Are Created Equal|| |
Several risk estimation equations/tools have been developed for assessing the 10-year CVD risk for initiating statin therapy in primary prevention. These include the American College of Cardiology/American Heart Association (ACC/AHA) Pooled Cohort Equation (PCE) in the USA, QRISK2 in the United Kingdom, and Systemic Coronary Risk Evaluation (SCORE) in other European countries. , All these equations incorporate age, gender, smoking, blood pressure, total cholesterol, and HDL-C levels.  However, they differ in the inclusion of other risk factors and ethnicities. The PCE incorporates White and Black ethnicities but not Hispanics, Indian Americans or Native Americans.  The QRISK 2 algorithm incorporates broader ethnicities (Whites, Chinese, Indian, Pakistani, Bangladeshi Caribbean Blacks, and African Blacks) as well as broader CVD risk indicators (socioeconomic status, microalbuminuria, chronic kidney disease, diabetes, obesity, atrial fibrillation, and rheumatoid arthritis).  Besides there are differences in CVD outcomes: SCORE incorporates only fatal CVD, PCE incorporates fatal and nonfatal CVD; QRISK incorporates fatal and nonfatal CVD plus soft end points such as unstable angina and transient ischemic attack. On reconciling these differences in CVD risk factors and CVD outcomes, the 10-year risk thresholds for statin eligibility - 5% by SCORE, 7.5% by PCE, and 10% by QRISK2 become comparable. ,,
All CVD risk scores have different accuracy in different populations, tending to over predict CVD risk in low-risk populations (such as Chinese, Japanese, and Southern Europeans) and under predict the risk in high-risk populations (such as Indians and Russians). ,, A multitude of protective and harmful factors contribute to these differences in absolute coronary artery disease (CAD) risk.  Despite equal access to free and comprehensive health care, several studies in the United Kingdom have shown a 150-220% higher CVD mortality among South Asians compared to Whites, after adjustment for all major CVD risk factors including diabetes. ,,, This has led the QRISK 2 risk estimator to incorporate a calibration factor of 1.5 for Indian men and 1.4 for Indian women (and even higher calibration factors for Pakistanis and Bangladeshis).  Nonetheless, a long-term follow-up of 1866 whites and 1377 South Asians, aged 40-69 years at baseline (1998-1991) in the United Kingdom reported that the observed CVD events were 50% higher than predicted from QRISK 2 among South Asian men and 100% higher among South Asian women compared with their white counterparts.  This contemporary data suggest the need to lower the threshold of intervention for statin therapy to compensate for the underestimation of CVD risk in Indians when QRISK2 is used. 
| Differences in Lipid Treatment Targets|| |
All but the ACC/AHA Guidelines recommend a target NHDL-C <130 mg/dL, LDL-C <100 mg/dL (total cholesterol <170 mg/dL) for the general population without CVD or high risk of CVD. ,, In people with very high risk, such as established CVD, diabetes, or lifetime risk >45%, the NHDL-C goal is <100 mg/dL and the LDL-C goal is <70 mg/dL. ,, The ACC/AHA guidelines recommend high-intensity statin therapy for high-risk subjects with baseline LDL-C >70 mg/dl. Such aggressive therapy could result in NHDL-C <80 mg/dL and LDL-C <50 mg/dL levels and would save thousands of additional lives. , Based on the guidelines, high-intensity statin therapy lowers LDL-C by >50%, moderate-intensity statin therapy lowers LDL-C by 30-<50%, and low-intensity statin therapy lowers LDL-C by <30%. 
| Malignant Coronary Artery Disease among Young Indians - A Rationale for Early, Aggressive Intervention|| |
The growth and the pace of preventive cardiology have had a dramatic impact - an almost 70% decline in CAD mortality rates in the USA, Finland, and elsewhere over the past three decades. , Data review confirms control of AC was the preeminent factor for the decline of CAD in comparison to all other factors. , Both reductions saturated fat intake in the entire population and statin therapy in high-risk population played a major role in the control of AC. During this period, the CAD rates increased steadily in India, with an estimated 3 million CAD deaths in 2015.  The escalating epidemic of CAD can be attributed to poor control of the major modifiable risk factors, superimposed on a genetic predisposition to CAD (possibly mediated by lipoprotein [a]). ,, Several studies show that Indians - both resident and diaspora - have a 2-fold risk of CAD and 3-fold risk of diabetes when adjusted for risk factors for these conditions. ,,, These data further underscore the need for interventions in Indians at a younger age and a lower threshold in contrast to those recommended for Western populations. 
| Highlights of the Lipid Association of India Consensus Statement on the Management of Dyslipidemia in Indians|| |
The LAI Consensus Statement  should be evaluated against the background of the brief literature review noted above. We commend Iyengar et al.  for publishing this elegant document that provides a framework for the aggressive management of dyslipidemia among Indians - a population with the highest risk of premature CAD.  The recommendations are scientifically consistent with the current lipid literature and incorporate key elements from the most recent guidelines issued by ACC/AHA, National Lipid Association (USA), and the Joint British Societies (United Kingdom).
We also commend the authors and contributors of this statement for lowering the bar for statin therapy in Indians while simplifying the risk assessment by risk factor counting; this would make it easy for busy practitioners who see 200-300 patients per day.  A major problem with the 10-year CVD risk calculation is that it is disproportionately influenced by age. Most young individuals with multiple major risk factors would have low 10-year CVD and would not qualify for statin therapy; however, most of them would have high-lifetime risk, which render them eligible for statin therapy.  The LAI guidelines have overcome this problem by estimating lifetime risk in those with low 10-year risk.  The major strengths of the LAI statement are listed in [Table 1].
|Table 1: Major strengths of the Lipid Association of India Expert Consensus Statement |
Click here to view
The LAI consensus statement did not recommend measurement of ankle brachial index (ABI), although data supporting its role in risk stratification is robust. , Instead, it recommends carotid intimal medial thickness and aortic pulse wave velocity. Again, the data supporting these tests are not as robust as ABI. In general, ultrasound screening is not recommended in asymptomatic people.  Caution is advised in adding fibrates to high-intensity statin therapy as this combination has never been tested in clinical trials for safety or efficacy; further, the combination is associated with significantly more adverse effects.  Recent studies suggest that in patients receiving high-intensity statin therapy and achieving on-treatment NHDL-C <100 mg/dl, on-treatment triglyceride levels are not related to CVD events.  This is attributable to a several-fold more efficacious lowering of remnant cholesterol with statin therapy than previously appreciated (from the modest lowering of triglycerides).  In patients having less than the expected therapeutic response, practitioners should ensure that their patients are actually adhering to the prescribed dosage of statins, before considering the addition of another medication, given the adherence to statin monotherapy at 1 year is only 54%.  Besides the data supporting the use of nonstatin medications is weak, although a single large clinical trial has demonstrated additional CVD risk reduction with ezetimibe when added to statin therapy. 
| When to Start and How Long to Continue Statin Therapy|| |
Indians are known to develop risk factors for malignant CAD at a younger age, possibly due to poor awareness, and adherence to primordial prevention.  It is estimated that in India, more people <30 years of age die from CAD annually (420,000) than people of all ages in the USA (375,000). , The absolute CVD benefits of statin therapy are proportional to the intensity of therapy, the baseline risk of the individual (but not necessarily the baseline cholesterol level,) and the age of initiation of such therapy.  Several recent studies have shown that CVD risk reduction with lifelong low LDL-C levels is 3-5 times greater than decreasing LDL-C in middle age. ,,, These facts provide a strong rationale for early initiation of maximal lifestyle therapy, beginning at age 1 or 2 years, when the children transition to adult food habits, and continuing through the remaining lifespan. The Integrated Guidelines for Cardiovascular Health and Risk Reduction in Children and Adolescents in the USA recommend universal screening of children for dyslipidemia between the ages 9 and 11 and then again between ages 15 and 17.  In addition to screening all adults for CVD risk factors (especially lipid panel) at 20 years of age or college entry, it would be reasonable to perform initial lipid screening of Indian children 10 years of age (similar to that in the USA), especially if they have a family history of premature CAD, dyslipidemia, obesity, or other risk factors. , Many statins are approved for the use in high-risk children as young as 10 years of age.  The duration of statin therapy remains lifelong in the absence of competing or comorbid illness (that reduces the quality or quantity of the life), frailty, or specific patient preferences dictating otherwise. In the future, statin therapy should made affordable to the vast majority of Indians, through government subsidy, the development of low-cost generic statins or other means.
| A Giant Leap Forward|| |
It is worth reemphasizing that over the past three decades, diabetes and obesity doubled in both India and the USA. During the same period, the CAD mortality at least doubled in India but decreased by 68% in the USA.  This spectacular decline in CAD mortality in the USA is attributed to reduction in smoking rates and effective control of elevated blood pressure and cholesterol.  While the efforts to control obesity and diabetes should continue in India, there is an urgent need to apply the lessons learnt from the USA. The consensus statement provides a roadmap for addressing co-existing risk factors such as smoking, hypertension and diabetes, and in particular high cholesterol in India. Lowering the bar for statin therapy threshold to <5% risk is a Giant Leap Forward, significantly expanding the number of statin eligible Indians, and reducing the CVD burden in India. It is worth emphasizing that a 10-year risk of 5% risk using QRISK 2 calculator is comparable 10-year risk of 3% using the ACC/AHA PCE (because of inclusion of additional risk factors and CVD outcomes in the former).  The next challenge is to offer education to health-care providers regarding the remarkable safety and benefits of statin therapy so that they embrace and implement these recommendations. Applied nationwide, the recommendations have the potential to achieve the 20% reduction in the prevalence in elevated cholesterol - a key component of United Nation's Goal "25 × 25" - 25% reduction in premature mortality by the year 2025.
| References|| |
Joshi P, Islam S, Pais P, Reddy S, Dorairaj P, Kazmi K, et al.
Risk factors for early myocardial infarction in South Asians compared with individuals in other countries. JAMA 2007;297:286-94.
Enas EA, Chacko V, Pazhoor SG, Chennikkara H, Devarapalli HP. Dyslipidemia in South Asian patients. Curr Atheroscler Rep 2007;9:367-74.
Taylor F, Huffman MD, Macedo AF, Moore TH, Burke M, Smith GD, et al.
Statins for the primary prevention of cardiovascular disease. Cochrane Database Syst Rev 2013;1:1-97.
Stone NJ, Robinson JG, Lichtenstein AH, Bairey Merz CN, Blum CB, Eckel RH, et al.
2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2014;63:2889-934.
Cholesterol Treatment Trialists′ (CTT) Collaboration, Baigent C, Blackwell L, Emberson J, Holland LE, Reith C, et al.
Efficacy and safety of more intensive lowering of LDL cholesterol: A meta-analysis of data from 170,000 participants in 26 randomised trials. Lancet 2010;376:1670-81.
Cholesterol Treatment Trialists′ (CTT) Collaborators, Mihaylova B, Emberson J, Blackwell L, Keech A, Simes J, et al.
The effects of lowering LDL cholesterol with statin therapy in people at low risk of vascular disease: Meta-analysis of individual data from 27 randomised trials. Lancet 2012;380:581-90.
Enas EA, Kuruvila A, Khanna P, Pitchumoni CS, Mohan V. Benefits and risks of statin therapy for primary prevention of cardiovascular disease in Asian Indians - A population with the highest risk of premature coronary artery disease & diabetes. Indian J Med Res 2013;138:461-91.
Baigent C, Keech A, Kearney PM, Blackwell L, Buck G, Pollicino C, et al.
Efficacy and safety of cholesterol-lowering treatment: Prospective meta-analysis of data from 90,056 participants in 14 randomised trials of statins. Lancet 2005;366:1267-78.
Enas EA, Dharmarajan TS, Varkey B. Consensus statement on the management of dyslipidemia in Indian subjects: A different perspective. Indian Heart J 2015;67:95-102.
National Institute for Health and Clinical Excellence (NICE) Guidelines. Lipid Modification. Cardiovadcular Risk Assessment and of Blood Lipids for the Primary and Secondary Prevention of Cardiovadculr Disease. [CG181] Published Date: July, 2014. Available from: https://www.nice.org.uk/guidance/cg181/chapter/key-priorities-for-implementation. [Last accessed on 2016 Mar 15].
Chandra KS, Bansal M, Nair T, Iyengar SS, Gupta R, Manchanda SC, et al.
Consensus statement on management of dyslipidemia in Indian subjects. Indian Heart J 2014;66 Suppl 3:S1-51.
Pandya A, Sy S, Cho S, Weinstein MC, Gaziano TA. Cost-effectiveness of 10-year risk thresholds for initiation of statin therapy for primary prevention of cardiovascular disease. JAMA 2015;314:142-50.
Goff DC Jr., Lloyd-Jones DM, Bennett G, Coady S, D′Agostino RB Sr., Gibbons R, et al.
2013 ACC/AHA guideline on the assessment of cardiovascular risk: A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2014;63:2935-59.
QRISK2. Welcome to the QRISK®
2-2014 Cardiovascular Disease Risk Calculator. Available from: http://www.qrisk.org/
. [Last accessed on 2016 Mar 15].
Menotti A, Lanti M, Puddu PE, Kromhout D. Coronary heart disease incidence in northern and southern European populations: A reanalysis of the seven countries study for a European coronary risk chart. Heart 2000;84:238-44.
Forouhi NG, Sattar N, Tillin T, McKeigue PM, Chaturvedi N. Do known risk factors explain the higher coronary heart disease mortality in South Asian compared with European men? Prospective follow-up of the Southall and Brent studies, UK. Diabetologia 2006;49:2580-8.
Tillin T, Hughes AD, Whincup P, Mayet J, Sattar N, McKeigue PM, et al.
Ethnicity and prediction of cardiovascular disease: Performance of QRISK2 and Framingham scores in a U.K. tri-ethnic prospective cohort study (SABRE - Southall And Brent REvisited). Heart 2014;100:60-7.
Tillin T, Sattar N, Godsland IF, Hughes AD, Chaturvedi N, Forouhi NG. Ethnicity-specific obesity cut-points in the development of Type 2 diabetes-a prospective study including three ethnic groups in the United Kingdom. Diabet Med 2015;32:226-34.
Tillin T, Hughes AD, Mayet J, Whincup P, Sattar N, Forouhi NG, et al.
The relationship between metabolic risk factors and incident cardiovascular disease in Europeans, South Asians, and African Caribbeans: SABRE (Southall and Brent Revisited) - A prospective population-based study. J Am Coll Cardiol 2013;61:1777-86.
Jacobson TA, Ito MK, Maki KC, Orringer CE, Bays HE, Jones PH, et al.
National Lipid Association recommendations for patient-centered management of dyslipidemia: Part 1-executive summary. J Clin Lipidol 2014;8:473-88.
Enas EA, Singh V, Munjal YP, Gupta R, Patel KC, Bhandari S, et al.
Recommendations of the second Indo-U.S. health summit on prevention and control of cardiovascular disease among Asian Indians. Indian Heart J 2009;61:265-74.
Mozaffarian D, Benjamin EJ, Go AS, Arnett DK, Blaha MJ, Cushman M, et al.
Heart disease and stroke statistics-2015 update: A report from the American Heart Association. Circulation 2015;131:e29-322.
Vartiainen E, Laatikainen T, Peltonen M, Juolevi A, Männistö S, Sundvall J, et al.
Thirty-five-year trends in cardiovascular risk factors in Finland. Int J Epidemiol 2010;39:504-18.
Ford ES, Ajani UA, Croft JB, Critchley JA, Labarthe DR, Kottke TE, et al.
Explaining the decrease in U.S. deaths from coronary disease, 1980-2000. N Engl J Med 2007;356:2388-98.
Capewell S, O′Flaherty M. What explains declining coronary mortality? Lessons and warnings. Heart 2008;94:1105-8.
Enas EA, Chacko V, Senthilkumar A, Puthumana N, Mohan V. Elevated lipoprotein(a) - A genetic risk factor for premature vascular disease in people with and without standard risk factors: A review. Dis Mon 2006;52:5-50.
Menke A, Casagrande S, Geiss L, Cowie CC. Prevalence of and trends in diabetes among adults in the United States, 1988-2012. JAMA 2015;314:1021-9.
Shrivastava U, Misra A. Need for ethnic-specific guidelines for prevention, diagnosis, and management of type 2 diabetes in South Asians. Diabetes Technol Ther 2015;17:435-9.
Enas EA, Singh V, Munjal YP, Bhandari S, Yadave RD, Manchanda SC. Reducing the burden of coronary artery disease in India: Challenges and opportunities. Indian Heart J 2008;60:161-75.
Shah AD, Vittinghoff E, Kandula NR, Srivastava S, Kanaya AM. Correlates of prediabetes and type II diabetes in US South Asians: Findings from the Mediators of Atherosclerosis in South Asians Living in America (MASALA) study. Ann Epidemiol 2015;25:77-83.
Iyengar SS, Puri R, Narasingan SN, Wangnoo SK, Mohan V, Mohan JC, et al
. Lipid Association of India expert consensus statement on management of dyslipidemia in Indians. Part 1. J Assoc Physicians India 2016;64:S7-52.
Enas EA, Mehta J. Malignant coronary artery disease in young Asian Indians: Thoughts on pathogenesis, prevention, and therapy. Coronary Artery Disease in Asian Indians (CADI) Study. Clin Cardiol 1995;18:131-5.
DeMaria AN. Cardiology in India. J Am Coll Cardiol 2010;56:678-9.
Mora S, Glynn RJ, Boekholdt SM, Nordestgaard BG, Kastelein JJ, Ridker PM. On-treatment non-high-density lipoprotein cholesterol, apolipoprotein B, triglycerides, and lipid ratios in relation to residual vascular risk after treatment with potent statin therapy: JUPITER (justification for the use of statins in prevention: An intervention trial evaluating rosuvastatin). J Am Coll Cardiol 2012;59:1521-8.
Würtz P, Wang Q, Soininen P, Kangas AJ, Fatemifar G, Tynkkynen T, et al.
Metabolomic profiling of statin use and genetic inhibition of HMG-CoA reductase. J Am Coll Cardiol 2016;67:1200-10.
Choudhry NK, Avorn J, Glynn RJ, Antman EM, Schneeweiss S, Toscano M, et al.
Full coverage for preventive medications after myocardial infarction. N Engl J Med 2011;365:2088-97.
Blazing MA, Giugliano RP, Cannon CP, Musliner TA, Tershakovec AM, White JA, et al.
Evaluating cardiovascular event reduction with ezetimibe as an adjunct to simvastatin in 18,144 patients after acute coronary syndromes: Final baseline characteristics of the IMPROVE-IT study population. Am Heart J 2014;168:205-12.e1.
Cohen JC, Boerwinkle E, Mosley TH Jr., Hobbs HH. Sequence variations in PCSK9, low LDL, and protection against coronary heart disease. N Engl J Med 2006;354:1264-72.
Myocardial Infarction Genetics Consortium Investigators. Inactivating mutations in NPC1L1 and protection from coronary heart disease. N Engl J Med 2014;371:2072-82.
Ference BA, Yoo W, Alesh I, Mahajan N, Mirowska KK, Mewada A, et al.
Effect of long-term exposure to lower low-density lipoprotein cholesterol beginning early in life on the risk of coronary heart disease: A Mendelian randomization analysis. J Am Coll Cardiol 2012;60:2631-9.
Ference BA, Majeed F, Penumetcha R, Flack JM, Brook RD. Effect of naturally random allocation to lower low-density lipoprotein cholesterol on the risk of coronary heart disease mediated by polymorphisms in NPC1L1, HMGCR, or both: A 2 × 2 factorial Mendelian randomization study. J Am Coll Cardiol 2015;65:1552-61.
Ma J, Ward EM, Siegel RL, Jemal A. Temporal trends in mortality in the United States, 1969-2013. JAMA 2015;314:1731-9.
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