SPECIAL ARTICLE

Year : 2016  |  Volume : 5  |  Issue : 2  |  Page : 51-61

Lipid Association of India Expert Consensus Statement on Management of Dyslipidemia in Indians 2016: Part 1 - Executive summary

Shamanna S Iyengar MD, DM ¹, Raman Puri MD, DM ², SN Narasingan MD ^3
1 Department of Cardiology, Manipal Hospital, Bengaluru, Karnataka, India
² Department of Cardiology, Indraprastha Apollo Hospitals, New Delhi, India
³ SNN Specialties Clinic, Chennai, Tamil Nadu, India

Correspondence Address:
Raman Puri
Lipid Association of India, A -26, 2nd Floor, South Extension Part-2, New Delhi - 110 049
India

Source of Support: None, Conflict of Interest: None

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DOI: 10.4103/2250-3528.186492

Methodology

• To ensure that the document remained simple yet scientifically robust
• To be more informative rather than prescriptive
• To maximally utilize the available Indian data
• To make all the efforts to ensure practical applicability of the recommendations to the Indian population.

Key Messages and Summary of Recommendations

• Although data are sparse, the available evidence suggests that the cholesterol levels are steadily rising among Indians, a trend which is opposite to what is observed in the Western populations
• Compared with the Western populations, Indians tend to have higher triglyceride (TG) levels and lower high-density lipoprotein cholesterol (HDL-C) levels but the total cholesterol and low-density lipoprotein cholesterol (LDL-C) levels are generally lower
• Among various lipid markers, the ratio of apolipoprotein B to apolipoprotein A-I appears to be the best indicator of ASCVD risk.

Figure 1: Recommended approach to atherosclerotic cardiovascular disease risk stratification in Indians. ASCVD: Atherosclerotic cardiovascular disease; CKD: Chronic kidney disease; HDL-C: High-density lipoprotein cholesterol; IMT: Intima-media thickness Click here to view

Table 1: Atherosclerotic cardiovascular disease risk categories Click here to view

• History of MI or documented coronary artery disease (CAD)
• History of ischemic stroke or transient ischemic attack or hemodynamically significant carotid plaque
• Atherosclerotic peripheral arterial disease (includes ankle-brachial index <0.9)
• Atherosclerotic aortic aneurysms
• Atherosclerotic renal artery stenosis.

• There is robust evidence to support prognostic value of coronary artery calcium (CAC) for ASCVD risk assessment. However, its cost, relatively limited availability, and radiation exposure are major limitations to its wider use. It is, therefore, recommended as an optional tool for ASCVD risk assessment in individuals at low- to moderate-risk. A CAC score >300 Agatston units indicates high ASCVD risk
• Compared with CAC, carotid intima media thickness is simpler to perform, more widely available, and completely safe, but its accuracy for ASCVD risk prediction is inferior to that of CAC
• Aortic pulse wave velocity (PWV) is a measure of arterial stiffness which is primarily a marker of arteriosclerosis. Measurement of aortic PWV is most useful in hypertensive subjects
• Although there is enough evidence to support value of high sensitivity C-reactive protein as an ASCVD risk marker, its routine use in Indians is not recommended due to issues related to standardization of assays and the high prevalence of infectious diseases in our country
• Lipoprotein (a) [Lp(a)] appears to be an important marker for ASCVD risk in Indians, particularly in those with family history of premature CAD. Lp(a) value of >20 mg/dL indicates increased ASCVD risk in Indians. Only those assays that are not influenced by Lp(a) isoform size should be used for its estimation
• Homocysteine estimation is not recommended in asymptomatic individuals
• Obesity and metabolic syndrome are associated with significantly increased risk of diabetes in the short-term and increased risk of ASCVD in the long-term.

Table 2: Treatment goals and statin initiation thresholds according to atherosclerotic cardiovascular disease risk categories Click here to view

• Given the epidemiological association of LDL-C levels with ASCVD risk and the evidence showing reduction in such risk with LDL-C lowering, LDL-C remains the primary target for lipid-lowering therapy
• LDL-C lowering to a low level is essential to achieve the desired reduction in the risk of vascular disease. In those with elevated levels of ASCVD risk, lower LDL-C levels are associated with better outcomes
• Various imaging trials and meta-analysis have shown that more aggressive lowering of LDL-C level to 50 mg/dL or less results in significant reduction in atheroma volume and ASCVD events
• The available evidence also shows that LDL-C level <50 mg/dL is safe.

• Non-HDL-C, which is equal to total cholesterol - HDL-C, includes all atherogenic lipoproteins in blood [Figure 2] and is, therefore, a more accurate predictor of ASCVD risk, particularly in patients who have elevated TG levels (e.g., diabetics, obese persons, those with metabolic syndrome) and those already on statin therapy

  Figure 2: Various plasma lipoproteins. Apo A: Apolipoprotein A; Apo B: Apolipoprotein B; HDL: High-density lipoprotein; HDL-C: High-density lipoprotein cholesterol; IDL: Intermediate-density lipoprotein; LDL: Low-density lipoprotein; LDL-C: Low-density lipoprotein cholesterol; Lp (a): Lipoprotein (a); TG: Triglyceride; VLDL: Very low-density lipoprotein Click here to view

• LAI recommends non-HDL-C as a co-primary target, as important as LDL-C, for lipid-lowering therapy
• Monitoring of non-HDL-C will provide a simple, practical tool for treatment decisions relating to lipid-lowering therapy since it does not require a fasting blood sample and takes care of both LDL-C and TG targets
• Non-HDL-C also covers, to some extent, the excess ASCVD risk imparted by the small, dense form of LDL, which is significantly more atherogenic than the normal large buoyant particles. Unfortunately, LDL-C levels do not provide any information about the LDL particle size but an elevated non-HDL-C, being a surrogate for elevated TG, indirectly suggests greater proportion of the small, dense variety of LDL particles
• In all individuals, the non-HDL-C level should be kept within 30 mg/dL of LDL-C levels
• Statins remain the first-line agent for lipid-lowering, regardless of whether LDL-C is the target for therapy or non-HDL-C
• Increasing the dosage of statin or switching to a more potent statin and intensifying lifestyle measures should be the first step to achieve further non-HDL-C lowering when LDL-C target has already been reached. Correction of secondary causes of hypertriglyceridemia and adding a nonstatin drug such as ezetimibe, fibrate, etc., should be considered when above measures prove inadequate.

• Elevated TG is associated with increased risk of ASCVD, independent of LDL-C levels. A combination of high TG and LDL-C imparts even greater risk
• High TG is often accompanied by low HDL-C levels and increased proportion of small, dense LDL-C, a pattern known as atherogenic dyslipidemia
• It is advisable to maintain TG level <150 mg/dL and preferably <100 mg/dL
• In all patients with hypertriglyceridemia, intensification of lifestyle modification should be the first step, which can reduce TG by as much as 50%
• It is also important to rule out secondary causes of hypertriglyceridemia and correct them. Common secondary causes of hypertriglyceridemia include:



• Diabetes
• Hypothyroidism
• Nephrotic syndrome
• Chronic renal failure
• Obstructive liver disease
• Drugs such as steroids, beta-blockers, protease inhibitors for treatment of human immune deficiency virus infections.
• Unless TG is very high (>500 mg/dL), statin should be the first drug to be prescribed in all patients requiring lipid-lowering therapy. Routine addition of a fibrate or another nonstatin drug must be avoided
• Only when TG is not sufficiently lowered with above measures, a nonstatin drug should be added
• Currently, fibrates are recommended for use in the treatment of severe hypertriglyceridemia (TG >500 mg/dL) and as an add-on to statin in combined dyslipidemia (when not corrected with statins alone)
• In diabetic subjects, saroglitazar, which is a dual peroxisome proliferator-activated receptor-α/g agonist, is another option. It has been approved by the Drug Controller General of India for the treatment of diabetic dyslipidemia, not corrected with statin therapy alone. However, large-scale CV outcomes studies are needed to clearly establish the role of saroglitazar in the management of dyslipidemia.

• Low HDL-C is an independent risk factor for ASCVD. It becomes even more relevant when LDL-C is not elevated
• Lifestyle modification plays an important role in raising HDL-C
• Among pharmacological agents, statins remain mainstay in the treatment of low HDL-C also. Although several other agents have been tried specifically for raising HDL-C, none of them has been shown to result in clinical benefit.

• Primary prevention of ASCVD should occupy the prime place in clinical practice
• Screen for ASCVD - all adults at 20 years of age/college entry
• Primary prevention should focus on controlling modifiable risk factors for ASCVD. While there are many conventional and nonconventional modifiable risk factors for ASCVD, the most robust are diabetes, tobacco use, high blood pressure (BP), lipid abnormalities, and obesity. Less often and in selected situations, one may look for the novel risk factors or markers of subclinical atherosclerosis for ASCVD risk assessment and management. In addition, one must also be aware of the disease conditions and drugs that may cause secondary dyslipidemia [Table 3]

  Table 3: Drugs and disease conditions that may cause secondary dyslipidemia Click here to view

• Assess ASCVD risk and discuss the health program with the individual
• Follow the "magnificent seven:"



• No tobacco
• Physical activity: ≥150 min moderate-intensity or equivalent exercise per week
• Body mass index <23 kg/m ²
• Healthy diet: Achieving at least four of the five important dietary components, focusing on fruits and vegetables, fish, fiber, and sodium intake and sweetened beverage intake
• LDL-C level should be below 100 mg/dL
• BP: <120/80 mmHg
• Fasting plasma glucose level: <100 mg/dL.
• Stains are safe and effective in both primary and secondary prevention of ASCVD. Their use for primary prevention of ASCVD should be guided by the estimated ASCVD risk in a given individual.

• All adults should avoid inactivity
• For substantial health benefits, adults should do at least 150 min (2 h and 30 min) a week of moderate-intensity, or 75 min (1 h and 15 min) a week of vigorous-intensity aerobic physical activity, or an equivalent combination of moderate- and vigorous-intensity aerobic activity. Aerobic activity should be performed in episodes of at least 10 min, and preferably, it should be spread throughout the week
• For additional and more extensive health benefits, adults should increase their aerobic physical activity to 300 min (5 h) a week of moderate-intensity, or 150 min (2 h 30 min) a week of vigorous-intensity aerobic physical activity, or an equivalent combination of moderate- and vigorous-intensity activity. Additional health benefits are gained by engaging in physical activity beyond this amount
• Adults should also do muscle-strengthening activities that are moderate- or high-intensity and involve all major muscle groups on 2 or more days a week. However, time spent in muscle-strengthening activities does not count toward the aerobic activity guidelines.

• Dietary patterns are more significant rather than individual dietary components. Thus, we recommend the adoption of a dietary pattern that emphasizes intake of vegetables, fruits, and whole grains, low-fat dairy products, poultry, fish, legumes, nontropical vegetable oils, nuts, etc.
• Limit intake of sweets, sugar-sweetened beverages, and red meat
• This above can be achieved by adopting a diet pattern such as Mediterranean or Indo-Mediterranean diet.

• Alcohol intake, even in moderation should preferably be avoided by Indians
• Patients with ASCVD who do not consume alcohol should not be encouraged to start regular drinking
• However, for patients who drink, alcohol should not exceed 1 drink per day for women or up to 2 drinks per day for men (1 drink = 12 oz beer, 5 oz wine, or 1.5 oz distilled spirits).

• Complete abstinence from tobacco products is recommended. Avoid passive smoking as well.

• Although no clear, large-scale studies are available with different forms of practice, we recommend that all Indians should be encouraged to incorporate yogasana and meditation in daily life.

• Its true frequency is unknown; however, reported incidence is around 10%
• Routine monitoring is not needed
• When patients present with symptoms, check serum creatine kinase level and rule out drug-drug interactions, Vitamin D deficiency, hypothyroidism, and other potential causes of statin-induced myopathy. Treatment options include using statin treatment in lower doses, reduced frequency or use of alternative statins.

• An asymptomatic rise in hepatic enzyme activity is one of the most common adverse effects of statin therapy but the incidence of elevated aminotransferase activity >3 times upper limit of normal is still no >3%. Hepatitis, cholestasis, and acute liver failure are extremely rare
• In patients with nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH), statin treatment is safe and substantially reduces ASCVD risk by a greater margin than in those with normal liver function. In fact, statins may even contribute to the resolution of NAFLD/NASH.

• Although statins are associated with an increase in the risk of new-onset diabetes, this risk is significantly outweighed by the benefits
• The risk is greater with intensive statin therapy and in patients already predisposed to develop diabetes
• Patients with risk factors for diabetes mellitus should be screened with fasting blood glucose or glycosylated hemoglobin, ideally before starting statin therapy. Thereafter, monitoring should be repeated within 1 year of initiation and at intervals no longer than 3 years
• Aggressive lifestyle management is very important in preventing development of diabetes in patients receiving statin therapy.

• A very small relationship exists between statin therapy and hemorrhagic stroke, mainly in patients who have had a previous hemorrhagic stroke and who have poorly controlled BP. However, this risk is generally outweighed by the reduction in ischemic stroke with statins
• There is no definitive evidence to suggest that statins lead to cognitive impairment or peripheral neuropathy
• If a patient presents with symptoms suggestive of cognitive impairment or peripheral neuropathy and no alternate etiology is found, statins may have to be withdrawn temporarily.

• Statin therapy had no effect on the incidence of, or mortality from, any type of cancer (or the aggregate of all cancers).

• As already emphasized, LDL-C remains the primary target for lipid-lowering therapy and statins remain the first choice for LDL-C lowering
• Nonstatin drugs may be used in the following settings:



• As alternative to statins when the patient is completely statin intolerant
• In combination with statins when the desired dose of statin cannot be used due to intolerance
• In combination with statins when serum TG levels remain persistently elevated despite optimum dose of statins, adequate lifestyle modifications, and correction of other treatable causes of hypertriglyceridemia (e.g., uncontrolled diabetes), and
• As first-line of treatment, before adding a statin, when serum TG levels are very high (>500 mg/dL)
• Fibrates are the most commonly used nonstatin lipid-lowering agents. Ezetimibe, omega-3 fatty acids, and bile acid sequestrants are other options. Saroglitazar is another new molecule, being used as an add-on to statin therapy for management of diabetic dyslipidemia. Alirocumab and evolocumab are monoclonal antibodies against the enzyme proprotein convertase subtilisin/kexin type 9 and result in profound LDL-C reduction. They are currently approved for the use in patients with heterozygous familial hypercholesterolemia and also in nonfamilial dyslipidemia when LDL-C goal is not achieved with statin alone or if the patient is intolerant to statin.

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