Triglycerides

• Triglycerides (or blood fats) are an important barometer of metabolic health; high levels may be associated with CAD (coronary artery disease), diabetes, and fatty liver.¹ New optimal  fasting triglyceride levels are less than 100 mg/dL.¹

• According to NHANES data, the mean triglycerides are 144 mg/dl and 13% of US population has high triglycerides. ^{2, 3} Mexican-Americans have the highest rates of triglycerides (35.5%), followed by non-Hispanic whites (33.2%), and African-Americans (15.9%).

• Blacks have lower triglycerides than whites, in both men (127 vs 158) and women (102 vs 135 mg/dl), despite higher rates of obesity.

• Non-fasting blood can now be used to screen for high triglyceride levels. A non-fasting level of <200 mg/dL is commensurate with a normal (<150 mg/dL) or optimal (<100 mg/dL) fasting triglyceride level and requires no further testing.¹ In fact non-fasting triglycerides predict CAD more strongly than fasting triglycerides.^4,6

• Non-fasting triglyceride levels are not used in the definition of MetS and should not be used in the calculation of LDL-C by the Friedewald formula. In fact non-fasting triglycerides predict CAD more strongly than fasting triglycerides.^4,6

• Familial combined hyperlipidemia is defined as hypertriglyceremic hyperbetalipoproteinemia  with triglycerides exceeding 177 mg/dl and apo B exceeding 125 mg/dl.⁷

Causes of High Triglycerides 

• Simple sugars (high fructose syrup), saturated fats, and trans-fats raise triglyceride levels, whereas weight loss or use of unsaturated fats, especially those containing marine omega-3 fatty acids, lower triglyceride levels.¹

• Consuming too many simple sugars, refined grains, and alcohol will increase triglyceride levels for those who have not been diagnosed with triglycerides outside normal range.¹

• Alcohol intake has a major effect on triglycerides, especially when consumption is in excessive ( 1-2 drinks or 10-30 g/day.⁸

• A consumption of 15-20% of energy from fructose, especially soft drinks or table sugar, results in 30-40% increase in triglycerides. Conversely regular exercise and weight reduction can cause a 20-30% decrease.⁴

• People with high triglycerides (≥ 150 mg/dL) should limit their intake of fructose that is mainly found in soda and fruits, and instead emphasize a healthy diet including an increase in consumption of vegetables and low fructose fruits.¹

• The American Heart Association recommends limiting added sugars to fewer than 100 calories daily (ie, 6 tsp) for women and 150 calories daily (9 tsp) for men (≈5% of total energy). The lowest triglyceride levels were observed when added sugar represented <10% of total energy. Conversely, higher triglyceride levels (5% to 10%) were observed when added sugar represented a greater proportion of energy intake.

• In general, most refined starchy foods in the diet have a high glycemic index, whereas nonstarchy vegetables, fruits, and legumes typically have a low glycemic index.

•  The glycemic index is defined as the ratio of the blood glucose response to a specific food and the glucose response to a standard food (ie, white bread). By comparison, the glycemic load of a food is calculated by multiplying the glycemic index by carbohydrate in grams and dividing by 100. High glycemic load is an important contributor of high triglycerides.^{1, 9, 10} See Figure 071.

• Americans consume fructose in large quantities (up to 150 g/d) but a dose >50 g increases triglycerides. The major sources of fructose include cola and other soft drinks with high fructose syrup (14-23 g per oz), honey (17 g per 2 tbsp). Fruits like apple and pear are low in fructose (4-10 g).¹

• Diet that produce significant and sustained weight loss offer the most favorable reduction in triglyceride levels, regardless of the carbohydrate, protein or fat intake.¹ For everyone, adopting and maintaining healthy lifestyle (i.e. diet and physical activity) is very effective and can lower triglyceride levels by up to 50%.¹ 

Importance of TG/HDL-C Ratio 

• Elevated triglyceride/HDL-cholesterol ratio is associated with insulin resistance,¹¹ chronic kidney disease,¹² small dense LDL,¹³ small dense HDL,¹⁴ metabolic syndrome,¹⁵ heart attack,¹⁶ stroke and all-cause mortality.¹⁷  A ratio >2.2 in boys and girls is a strong predictor of insulin resistance─a predictor, precursor and mediator of future risk of diabetes.¹⁸

• A triglyceride/HDL ratio of 3.0 and 3.8 has been found to be very useful in detecting small dense LDL which in turn is associated with metabolic syndrome, diabetes and CAD in south Asians and other populations.^{19, 20}

• Favorable effects of pioglitazone on the triglyceride/HDL-C ratio correlated with delayed atheroma progression in diabetic patients. This finding highlights the potential importance of targeting atherogenic dyslipidemia in diabetic patients with CAD.²¹ 

Prevention and Control of High Triglycerides

• Overall, the treatment of elevated triglyceride levels focuses on intensive therapeutic lifestyle change that can bring about a total reduction of 50%. Triglyceride levels can be reduced by weight reduction (5% to 10% reduction in body weight anticipates a triglyceride-lowering response of 20%).Reducing carbohydrates particularly added sugars and fructose while increasing unsaturated fat intake may contribute an additional 10% to 20% reduction in triglyceride levels. Elimination of trans fats, restriction of saturated fats, and increasing consumption of marine-based omega-3 products, coupled with aerobic activity, will further optimize triglyceride-lowering efforts. Meta-analyses have reported that for every kilogram of weight loss, triglyceride levels decrease 2%.¹

• Although up-to 60% of the calories from carbohydrates is permitted in the general population the upper limit should be 40-50% in those with high TG’s with or without MetS and/or diabetes. For each 1% isoenergetic replacement of carbohydrates with fat decreases triglyceride levels by 1-2%. The recommended substitution is poly or mono unsaturated fat since saturated fat can substantially increase the LDL.

• In patients with high triglycerides, potent statins such as rosuvastatin 20 mg/d or atorvastatin 40-80 mg/d can lower triglycerides 40-50% (similar magnitude as LDL-C reduction).²²

• It has not been determined whether lowering triglyceride levels beyond LDL-C and non-HDL-C  reduces the risk of heart disease and more research is needed to validate triglycerides as an independent risk factor for cardiovascular disease.¹

• Although epidemiologic data suggest that high triglycerides may be a more important risk factor in women than in men, clinical trials have not shown any benefit in specifically lowering triglycerides.  Besides ACCORD trial showed more harm in women from fenofibrate than in men.²³ Therefore, most physicians tend not to focus purely on triglyceride and instead focus on the ‘‘non-HDL cholesterol.’’ One exception is people with triglycerides >500 mg/dl which account for less than 2% of the US population.

• Triglycerides >500-1000 mg/dl is associated with acute pancreatitis─ the former accounting for 10% of the latter.⁴ Such patients require restriction of fats to 10-15% of energy, abstinence from alcohol, along with fibrates, omega-3 fatty acids 3-4g/day, and prescription niacin. Insulin therapy may be required in those with high blood sugar.⁴

• Very high triglycerides (levels above 1,000 mg/dL) are associated with acquired causes such as poorly controlled diabetes; medications such as steroids or estrogens, and/or poor diet with excess alcohol, and especially if there is an underlying genetic disorder of triglyceride metabolism.¹

•  The most selective of the triglyceride-reducing drugs are the fibrates. It is worth noting that, four clinical trials have shown reduction in CVD events with fibrates in people with high triglyceride and low HDL.²²

• Higher doses of omega-3 ethyl esters (EEC) (2.0 to 4.5 g of eicosapentaenoic acid [EPA] docosahexaenoic acid) lower plasma triglycerides with very little effect on plasma levels of LDL or HDL cholesterol; high doses of omega-3 EEC lower triglycerides by 30% to 35% by a number of mechanisms.²⁴ (See Table 034)

Unresolved issues

• Although hypertriglyceridemia is a common biochemical abnormality in humans, except for pancreatitis risk, its relationship to heart disease is far from certain. Is hypertriglyceridemia merely a marker of other metabolic abnormalities, or does it initiate or accelerate progression of vascular disease? Does this only occur in specific genetic or environmental settings? ²⁴

• Perhaps it is not the triglycerides themselves but VLDL particle number or changes in HDL or LDL that are most important for vascular biology. Importantly, the development of specific drugs to lower triglycerides would allow one to directly test in humans whether triglyceride reduction reduces CAD events.²⁴

• The correct trial in patients with hypertriglyceridemia needs to be performed. At this point, such drugs and clinical trials are but a dream. Thus, the hypothesis that triglycerides are an independent risk for human vascular disease will be around to challenge the next generation of basic and clinical scientists.²⁴

Sources 

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2. Ghandehari H, Kamal-Bahl S, Wong ND. Prevalence and extent of dyslipidemia and recommended lipid levels in US adults with and without cardiovascular comorbidities: the National Health and Nutrition Examination Survey 2003-2004. Am Heart J. Jul 2008;156(1):112-119.

3. Ghandehari H, Kamal-Bahl S, Wong ND. Prevalence and extent of dyslipidemia and recommended lipid levels in US adults with and without cardiovascular comorbidities: the National Health and Nutrition Examination Survey 2003-2004. Am Heart J. Jul 2008;156(1):112-119.

4. Catapano AL, Reiner Z, De Backer G, et al. ESC/EAS Guidelines for the management of dyslipidaemias The Task Force for the management of dyslipidaemias of the European Society of Cardiology (ESC) and the European Atherosclerosis Society (EAS). Atherosclerosis. Jul 2011;217 Suppl 1:1-44.

5. Bansal S, Buring JE, Rifai N, Mora S, Sacks FM, Ridker PM. Fasting compared with nonfasting triglycerides and risk of cardiovascular events in women. Jama. Jul 18 2007;298(3):309-316.

6. Nordestgaard BG, Benn M, Schnohr P, Tybjaerg-Hansen A. Nonfasting triglycerides and risk of myocardial infarction, ischemic heart disease, and death in men and women. Jama. Jul 18 2007;298(3):299-308.

7. Sniderman AD, Castro Cabezas M, Ribalta J, et al. A proposal to redefine familial combined hyperlipidaemia — third workshop on FCHL held in Barcelona from 3 to 5 May 2001, during the scientific sessions of the European Society for Clinical Investigation. Eur J Clin Invest. Feb 2002;32(2):71-73.

8. Rimm EB, Williams P, Fosher K, Criqui M, Stampfer MJ. Moderate alcohol intake and lower risk of coronary heart disease: meta- analysis of effects on lipids and haemostatic factors. BMJ. 1999;319(7224):1523-1528.

9. Liu S, Manson JE, Stampfer MJ, et al. Dietary glycemic load assessed by food-frequency questionnaire in relation to plasma high-density-lipoprotein cholesterol and fasting plasma triacylglycerols in postmenopausal women. Am J Clin Nutr. 2001;73(3):560-566.

10. Levitan EB, Cook NR, Stampfer MJ, et al. Dietary glycemic index, dietary glycemic load, blood lipids, and C-reactive protein. Metabolism. Mar 2008;57(3):437-443.

11. Gonzalez-Chavez A, Simental-Mendia LE, Elizondo-Argueta S. [Elevated triglycerides/HDL-cholesterol ratio associated with insulin resistance.]. Cir Cir. March-April 2011;79(2):126-131.

12. Kang HT, Shim JY, Lee YJ, et al. Association between the Ratio of Triglycerides to High-Density Lipoprotein Cholesterol and Chronic Kidney Disease in Korean Adults: The 2005 Korean National Health and Nutrition Examination Survey. Kidney Blood Press Res. 2011;34(3):173-179.

13. Boizel R, Benhamou PY, Lardy B, Laporte F, Foulon T, Halimi S. Ratio of triglycerides to HDL cholesterol is an indicator of LDL particle size in patients with type 2 diabetes and normal HDL cholesterol levels. Diabetes Care. Nov 2000;23(11):1679-1685.

14. Bhalodkar NC, Blum S, Enas EA. Accuracy of the ratio of triglycerides to high-density lipoprotein cholesterol for predicting low-density lipoprotein cholesterol particle sizes, phenotype B, and particle concentrations among Asian Indians. Am J Cardiol. Apr 1 2006;97(7):1007-1009.

15. Marotta T, Russo BF, Ferrara LA. Triglyceride-to-HDL-cholesterol ratio and metabolic syndrome as contributors to cardiovascular risk in overweight patients. Obesity (Silver Spring). Aug 2010;18(8):1608-1613.

16. Cordero A, Andres E, Ordonez B, et al. Usefulness of triglycerides-to-high-density lipoprotein cholesterol ratio for predicting the first coronary event in men. Am J Cardiol. Nov 15 2009;104(10):1393-1397.

17. Bittner V, Johnson BD, Zineh I, et al. The triglyceride/high-density lipoprotein cholesterol ratio predicts all-cause mortality in women with suspected myocardial ischemia: a report from the Women’s Ischemia Syndrome Evaluation (WISE). Am Heart J. Mar 2009;157(3):548-555.

18. Giannini C, Santoro N, Caprio S, et al. The triglyceride-to-HDL cholesterol ratio: association with insulin resistance in obese youths of different ethnic backgrounds. Diabetes Care. Aug 2011;34(8):1869-1874.

19. Mohan V, Deepa R, Velmurugan K, Gokulakrishnan K. Association of small dense LDL with coronary artery disease and diabetes in urban Asian Indians – the Chennai Urban Rural Epidemiology Study (CURES-8). J Assoc Physicians India. Feb 2005;53:95-100.

20. Bhalodkar NC, Blum S, Enas EA. Accuracy of the ratio of triglycerides to high-density lipoprotein cholesterol for predicting low-density lipoprotein cholesterol particle sizes, phenotype B, and particle concentrations among asian indians. Am J Cardiol. Apr 1 2006;97(7):1007-1009.

21. Nickenig G, Harrison DG. The AT(1)-type angiotensin receptor in oxidative stress and atherogenesis: part I: oxidative stress and atherogenesis. Circulation. 2002;105(3):393-396.

22. Enas E.A., Hancy Chennikkara Pazhoor MD, Arun Kuruvila MBBS, Krishnaswami Vijayaraghavan MD F. Intensive Statin Therapy for Indians:Part I Benefits. Indian Heart J 2011; 63: 211-227.

23. Ginsberg HN, Elam MB, Lovato LC, et al. Effects of combination lipid therapy in type 2 diabetes mellitus. N Engl J Med. Apr 29 2010;362(17):1563-1574.

24. Goldberg I.J, Eckel RH, McPherson R. Triglycerides and heart disease: still a hypothesis? Arterioscler Thromb Vasc Biol. Aug 2011;31(8):1716-1725.