Mechanisms of disease: lessons from ethnicity in the role of triglyceride metabolism in ischemic heart disease

ABSTRACT Mean risk factor levels in various ethnic groups illustrate the potential importance of triglyceride metabolism in the risk for ischemic heart disease (IHD). Serum triglyceride

concentrations are a surrogate for a range of potentially atherogenic disturbances in lipoprotein species, including increased concentrations of remnants of VLDL and chylomicron metabolism,

increased small, dense LDL concentrations and reduced HDL concentrations. Differences between at-risk groups in lipoprotein profiles reflect alterations in the metabolism of triglycerides

that might be greater than differences observed when only circulating triglyceride concentrations are measured. This atherogenic lipoprotein profile is typically found in association with

increased visceral fat, insulin resistance and type 2 diabetes and might be a characteristic of Asian Indian ethnicity. By contrast, despite being relatively insulin resistant,

Afro-Caribbean men in the UK have a low risk of IHD and lack the adverse lipoprotein profile. This could result from secretion of relatively large proportions of their VLDL as small,

triglyceride-poor particles, levels of which are not augmented in response to loss of insulin action. These considerations re-endorse the potential importance of triglyceride metabolism in

IHD and present opportunities for identifying useful areas in which drug targets for reducing IHD risk can be sought. KEY POINTS * Mean triglyceride concentrations are the strongest

covariate with variation in ischemic heart disease according to ethnicity, sex and diabetes * The importance of triglycerides is likely to have been underestimated in risk-factor studies *

Triglyceride levels provide an index of the atherogenic lipoprotein profile * Differences in features of the atherogenic lipoprotein profile according to ethnicity, sex and diabetes might be

greater than differences in triglycerides * The paradoxical association between insulin resistance, high risk of diabetes, low expression of the atherogenic lipoprotein profile and low risk

of ischemic heart disease in Afro-Caribbeans might be explained by their increased secretion of small, triglyceride-poor VLDL Access through your institution Buy or subscribe This is a

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PREVENTION Article 16 May 2023 REFERENCES * Wild S and Mckeigue P (1997) Cross sectional analysis of mortality by country of birth in England and Wales, 1970-92. _BMJ_ 314: 705–710 Article 

CAS  Google Scholar  * Chaturvedi N _ et al_. (1996) Differences in mortality and morbidity in African Caribbean and European people with non-insulin dependent diabetes mellitus: results of

20 year follow up of a London cohort of a multinational study. _BMJ_ 313: 848–852 Article  CAS  Google Scholar  * UK Prospective Diabetes Study Group (1998) Ethnicity and Cardiovascular

Disease. The incidence of myocardial infarction in white, South Asian, and Afro-Caribbean patients with type 2 diabetes (UK Prospective Diabetes Study 32). _Diabetes Care_ 21: 1271–1277 *

Mather HM _ et al_. (1998) Mortality and morbidity from diabetes in South Asians and Europeans: 11-year follow-up of the Southall Diabetes Survey, London, UK. _Diabet Med_ 15: 53–59 Article

  CAS  Google Scholar  * Chaturvedi N _ et al_. (1994) Racial differences in hypertension. _BMJ_ 308: 1634–1635 Article  CAS  Google Scholar  * Zoratti R _ et al_. (2000) Relation of plasma

lipids to insulin resistance, non-esterified fatty acid levels and body fat in men from three ethnic groups: relevance to variation in risk of diabetes and coronary disease. _Metabolism_ 49:

245–252 Article  CAS  Google Scholar  * McKeigue PM _ et al_. (1991) Relation of central obesity and insulin resistance with high diabetes prevalence and cardiovascular risk in South

Asians. _Lancet_ 337: 382–386 Article  CAS  Google Scholar  * Cooper RS _ et al_. (1997) Prevalence of NIDDM among populations of the African diaspora. _Diabetes Care_ 20: 343–348 Article 

CAS  Google Scholar  * Guyton JR _ et al_. (1985) Relationship of plasma lipoprotein Lp(a) levels to race and to apolipoprotein B. _Arteriosclerosis_ 5: 265–272 Article  CAS  Google Scholar

  * Seedat YK (1996) Ethnicity, hypertension, coronary heart disease and renal diseases in South Africa. _Ethn Health_ 1: 349–357 Article  CAS  Google Scholar  * Miller GJ _ et al_. (1988)

Adult male all-cause, cardiovascular and cerebrovascular mortality in relation to ethnic group, systolic blood pressure and blood glucose concentration in Trinidad, West Indies. _Int J

Epidemiol_ 17: 62–69 Article  CAS  Google Scholar  * Fang J _ et al_. (1996) The association between birthplace and mortality from cardiovascular causes among black and white residents of

New York City. _N Engl J Med_ 335: 1545–1551 Article  CAS  Google Scholar  * National Institutes of Health, National Heart, Lung and Blood Institute. Morbidity and Mortality: 2004 Chart Book

on Cardiovascular Lung and Blood Disease [http://www.nhlbi.nih.gov/resources/docs/04_chtbk.pdf] (accessed 20 December 2006) * Kooner JS _ et al_. (1998) Abdominal obesity, impaired

nonesterified fatty acid suppression, and insulin-mediated glucose disposal are early metabolic abnormalities in families with premature myocardial infarction. _Arterioscler Thromb Vasc

Biol_ 18: 1021–1026 Article  CAS  Google Scholar  * Laws A _ et al_. (1994) Resistance to insulin-stimulated glucose uptake and dyslipidemia in Asian Indians. _Arterioscler Thromb_ 14:

917–922 Article  CAS  Google Scholar  * Frost GS _ et al_. (1998) Reduced adipocyte insulin sensitivity in Caucasian and Asian subjects with coronary heart disease. _Diabet Med_ 15:

1003–1009 Article  CAS  Google Scholar  * Forouhi NG _ et al_. (1999) Relation of triglyceride stores in skeletal muscle cells to central obesity and insulin sensitivity in European and

South Asian men. _Diabetologia_ 42: 932–935 Article  CAS  Google Scholar  * Bhatnagar D _ et al_. (1995) Coronary risk factors in people from the Indian subcontinent living in west London

and their siblings in India. _Lancet_ 345: 405–409 Article  CAS  Google Scholar  * Chaturvedi N _ et al_. (1994) Relationship of glucose intolerance to coronary risk in Afro-Caribbeans

compared with Europeans. _Diabetologia_ 37: 765–772 Article  CAS  Google Scholar  * Pacy PJ _ et al_. (1987) Differences in lipid and lipoprotein levels in white, black and Asian non-insulin

dependent (type 2) diabetics with hypertension. _Diabetes Res_ 4: 187–193 CAS  PubMed  Google Scholar  * Goldberg AP _ et al_. (1983) Racial differences in plasma high-density lipoproteins

in patients receiving hemodialysis. _N Engl J Med_ 308: 1245–1252 Article  CAS  Google Scholar  * Zoratti R (1998) A review on ethnic differences in plasma triglycerides and

high-density-lipoprotein cholesterol: is the lipid pattern the key factor for the low coronary heart disease rate in people of African origin? _Eur J Epidemiol_ 14: 9–21 Article  CAS  Google

Scholar  * Bachorik PS _ et al_. (1997) Apolipoprotein B and AI distributions in the United States, 1988–1991: results of the National Health and Nutrition Examination Survey III (NHANES

III). _Clin Chem_ 43: 2364–2378 CAS  PubMed  Google Scholar  * Anderson KM _ et al_. (1991) An updated coronary risk profile: a statement for health professionals. _Circulation_ 83: 356–362

Article  CAS  Google Scholar  * Chaturvedi N _ et al_. (1993) Resting and ambulatory blood pressure differences in Afro-Caribbeans and Europeans. _Hypertension_ 22: 90–96 Article  CAS 

Google Scholar  * Miller GJ _ et al_. (1984) Serum lipoprotein concentrations in relation to ethnic composition and urbanization in men and women of Trinidad, West Indies. _Int J Epidemiol_

13: 413–421 Article  CAS  Google Scholar  * Thandroyen FT _ et al_. (1980) Comparative study of plasma lipids, carbohydrate tolerance and coronary angiography in three racial groups. _S Afr

Med J_ 57: 533–536 CAS  PubMed  Google Scholar  * Anand SS _ et al_. (2000) Differences in risk factors, atherosclerosis, and cardiovascular disease between ethnic groups in Canada: the

Study of Health Assessment and Risk in Ethnic groups (SHARE). _Lancet_ 356: 279–284 Article  CAS  Google Scholar  * Goff DCJ _ et al_. (2006) Dyslipidemia prevalence, treatment, and control

in the Multi-Ethnic Study of Atherosclerosis (MESA): gender, ethnicity, and coronary artery calcium. _Circulation_ 113: 647–656 Article  CAS  Google Scholar  * Bild DE _ et al_. (2005)

Ethnic differences in coronary calcification: the Multi-Ethnic Study of Atherosclerosis (MESA). _Circulation_ 111: 1313–1320 Article  Google Scholar  * Godsland IF _ et al_. (2004) Do ethnic

differences in ischaemic heart disease risk persist in diabetes? _Diabet Med_ 21 (Suppl 2): 13 Google Scholar  * Austin MA (1997) Triacylglycerol and coronary heart disease. _Proc Nutr Soc_

56: 667–670 Article  CAS  Google Scholar  * Cullen P (2000) Evidence that triglycerides are an independent coronary heart disease risk factor. _Am J Cardiol_ 86: 943–949 Article  CAS 

Google Scholar  * Tillin T _ et al_. (2006) The role of diabetes and components of the metabolic syndrome in stroke and coronary heart disease mortality in UK white and African-Caribbean

populations. _Diabetes Care_ 29: 2127–2129 Article  Google Scholar  * Forouhi NG _ et al_. (2006) 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_ 49: 2580–2588 Article  CAS  Google Scholar  * Austin MA _ et al_. (1990) Atherogenic

lipoprotein phenotype. A proposed genetic marker for coronary heart disease risk. _Circulation_ 82: 495–506 Article  CAS  Google Scholar  * Packard CJ (1999) Understanding coronary heart

disease as a consequence of defective regulation of apolipoprotein B metabolism. _Curr Opin Lipidol_ 10: 237–244 Article  CAS  Google Scholar  * Kugiyama K _ et al_. (1999) Remnant

lipoprotein levels in fasting serum predict coronary events in patients with coronary artery disease. _Circulation_ 99: 2858–2860 Article  CAS  Google Scholar  * Anber V _ et al_. (1996)

Influence of plasma lipid and LDL-subfraction profile on the interaction between low density lipoprotein with human arterial wall proteoglycans. _Atherosclerosis_ 124: 261–271 Article  CAS 

Google Scholar  * Austin MA _ et al_. (1988) Low-density lipoprotein subclass patterns and risk of myocardial infarction. _JAMA_ 260: 1917–1921 Article  CAS  Google Scholar  * de Graaf J _

et al_. (1991) Enhanced susceptibility to _in vitro_ oxidation of the dense low density lipoprotein subfraction in healthy subjects. _Arterioscler Thromb Vasc Biol_ 11: 298–306 Article  CAS

  Google Scholar  * Galeano NF _ et al_. (1994) Apoprotein B structure and receptor recognition of triglyceride-rich low density lipoprotein LDL is modified in small LDL but not in

triglyceride-rich LDL of normal size. _J Biol Chem_ 7: 511–519 Google Scholar  * Björnheden T _ et al_. (1996) Accumulation of lipoprotein fractions and subfractions in the arterial wall,

determined in an _in vitro_ perfusion system. _Atherosclerosis_ 123: 43–56 Article  Google Scholar  * Nofer JR _ et al_. (2002) HDL and arteriosclerosis: beyond reverse cholesterol

transport. _Atherosclerosis_ 161: 1–16 Article  CAS  Google Scholar  * Skoglund-Andersson C _ et al_. (2003) Influence of common variants in theCETP, LPL, HL and APO E genes on LDL

heterogeneity in healthy, middle-aged men. _Atherosclerosis_ 167: 311–317 Article  CAS  Google Scholar  * Coresh J _ et al_. (1993) Association of plasma triglyceride concentration and LDL

particle diameter, density, and chemical composition with premature coronary artery disease in men and women. _J Lipid Res_ 34: 1687–1697 CAS  PubMed  Google Scholar  * Johnson JL _ et al_.

(2004) Gender and racial differences in lipoprotein subclass distributions: the STRRIDE study. _Atherosclerosis_ 176: 371–377 Article  CAS  Google Scholar  * Miljkovic-Gacic I _ et al_.

(2006) Lipoprotein subclass and particle size differences in Afro-Caribbeans, African Americans, and white Americans: associations with hepatic lipase gene variation. _Metabolism_ 55: 96–102

Article  CAS  Google Scholar  * Miller GJ _ et al_. (1988) Dietary and other characteristics relevant for coronary heart disease in men of Indian, West Indian and European descent in

London. _Atherosclerosis_ 70: 63–72 Article  CAS  Google Scholar  * Borkman M _ et al_. (1993) The relation between insulin sensitivity and the fatty acid composition of skeletal-muscle

phospholipids. _N Engl J Med_ 328: 238–244 Article  CAS  Google Scholar  * Albu JB _ et al_. (1999) Systemic resistance to the antilipolytic effect of insulin in black and white women with

visceral obesity. _Am J Physiol_ 277: E551–E560 CAS  PubMed  Google Scholar  * Racette SB _ et al_. (2000) Racial differences in lipid metabolism in women with abdominal obesity. _Am J

Physiol_ 279: R944–R950 CAS  Google Scholar  * Després J-P _ et al_. (2000) Race, visceral adipose tissue, plasma lipids and lipoprotein lipase activity in men and women. The HERITAGE family

study. _Arterioscler Thromb Vasc Biol_ 20: 1932–1938 Article  Google Scholar  * Hill JO _ et al_. (1999) Racial differences in amounts of visceral adipose tissue in young adults: the CARDIA

(Coronary Artery Risk Development in Young Adults) Study. _Am J Clin Nutr_ 69: 381–387 Article  CAS  Google Scholar  * Friday KE _ et al_. (1999) Black-White differences in postprandial

triglyceride response and postheparin lipoprotein lipase and hepatic triglyceride lipase among young men. _Metabolism_ 48: 749–754 Article  CAS  Google Scholar  * Hall S _ et al_. (1997) A

common mutation in the lipoprotein lipase gene promoter, −93T/G, is associated with lower plasma triglyceride levels and increased promoter activity _in vitro_ . _Arterioscler Thromb Vasc

Biol_ 17: 1969–1976 Article  CAS  Google Scholar  * Talmud PJ _ et al_. (1998) LPL promoter -93T/G transition influences fasting and postprandial plasma triglycerides response in

African-Americans and Hispanics. _J Lipid Res_ 39: 1189–1196 CAS  PubMed  Google Scholar  * McConathy WJ _ et al_. (1990) Lp(a) and plasma triglyceride-rich lipoproteins. _Klin Wochenschr_

68 (Suppl 22): 117–119 PubMed  Google Scholar  * Herd SL _ et al_. (2001) Body fat, fat distribution and serum lipids, lipoproteins and apolipoproteins in African-American and

Caucasian-American prepubertal children. _Int J Obesity_ 25: 198–204 Article  CAS  Google Scholar  * Freedman DS _ et al_. (2002) Differences in the relation of obesity to serum

triacylglycerol and VLDL subclass concentrations between black and white children: the Bogalusa Heart Study. _Am J Clin Nutr_ 75: 827–833 Article  CAS  Google Scholar  * Hall S _ et al_.

(2000) Frequency and allelic association of common variants in the lipoprotein lipase gene in different ethnic groups: the Wandsworth Heart and Stroke Study. _Genetic Epidemiol_ 18: 203–216

Article  CAS  Google Scholar  * Vega GL _ et al_. (1998) Hepatic lipase activity is lower in African American men than in white American men: effects of 5′ flanking polymorphism in the

hepatic lipase gene (LIPC). _J Lipid Res_ 39: 228–232 CAS  PubMed  Google Scholar  * Aitman TJ _ et al_. (2000) Malaria susceptibility and CD36 mutation. _Nature_ 405: 1015–1016 Article  CAS

  Google Scholar  * Waterworth DM _ et al_. (2001) Variable effect of the APOC3 −482C>T variant on insulin, glucose and triglyceride concentrations in different ethnic groups.

_Diabetologia_ 44: 245–248 Article  CAS  Google Scholar  * Loktionov A _ et al_. (1999) Apolipoprotein E and methylenetetrahydrofolate reductase genetic polymorphisms in relation to other

risk factors for cardiovascular disease in UK Caucasians and Black South Africans. _Atherosclerosis_ 145: 125–135 Article  CAS  Google Scholar  * Walek T _ et al_. (1995) Effect of

hypertriglyceridaemia on lipoprotein (a) serum concentrations. _Eur J Clin Invest_ 25: 311–316 Article  CAS  Google Scholar  * Gaubatz JW _ et al_. (2001) Isolation, quantitation, and

characterization of a stable complex formed by Lp[a] binding to triglyceride-rich lipoproteins. _J Lipid Res_ 42: 2058–2068 CAS  PubMed  Google Scholar  * Bower JF _ et al_. (2001) Plasma

lipoprotein subpopulation distribution in Caucasian and African-American women with gestational diabetes. _Diabetes Care_ 24: 169–171 Article  CAS  Google Scholar  * Malmström R _ et al_.

(1997) Defective regulation of triglyceride metabolism by insulin in the liver in NIDDM. _Diabetologia_ 40: 454–462 Article  Google Scholar  * Sumner A _ et al_. (1999) A study of the

metabolism of apolipoprotein B100 in relation to insulin resistance in African American males. _Proc Soc Exp Biol Med_ 221: 352–360 CAS  PubMed  Google Scholar  * Packard CJ _ et al_. (2000)

Apolipoprotein B metabolism and the distribution of VLDL and LDL subfractions. _J Lipid Res_ 41: 305–317 CAS  PubMed  Google Scholar  * Miyazaki M _ et al_. (2001) A lipogenic diet in mice

with a disruption of the stearoyl-CoA desaturase 1 gene reveals a stringent requirement of endogenous monounsaturated fatty acids for triglyceride synthesis. _J Lipid Res_ 42: 1018–1024 CAS

  Google Scholar  * Attie AD _ et al_. (2002) Relationship between stearoyl-CoA desaturase activity and plasma triglycerides in human and mouse hypertriglyceridemia. _J Lipid Res_ 43:

1899–1907 Article  CAS  Google Scholar  * Ntambi JM (1999) Regulation of stearoyl-CoA desaturase by polyunsaturated fatty acids and cholesterol. _J Lipid Res_ 40: 1549–1558 CAS  PubMed 

Google Scholar  * Wetterau JR _ et al_. (1997) Microsomal triglyceride transfer protein. _Biochim Biophys Acta_ 1345: 136–150 Article  CAS  Google Scholar  * Malmström R _ et al_. (1997)

Metabolic basis of hypotriglyceridemic effects of insulin in normal men. _Arterioscler Thromb Vasc Biol_ 17: 1454–1464 Article  Google Scholar  * Shachter NS (2001) Apolipoproteins C-I and

C-III as important modulators of lipoprotein metabolism. _Curr Opin Lipidol_ 12: 297–304 Article  CAS  Google Scholar  * Murakami T _ et al_. (1995) Triglycerides are major determinants of

cholesterol esterification/transfer and HDL remodeling in human plasma. _Arterioscler Thromb Vasc Biol_ 15: 819–828 Google Scholar  * Brinton E _ et al_. (1991) Increased apo A-I and apo

A-II fractional catabolic rate in patients with low high density lipoprotein-cholesterol levels with or without hypertriglyceridaemia. _J Clin Invest_ 87: 536–544 Article  CAS  Google

Scholar  * Karpe F _ et al_. (1993) Metabolism of triglyceride-rich lipoproteins during alimentary lipemia. _J Clin Invest_ 91: 748–758 Article  CAS  Google Scholar  Download references

ACKNOWLEDGEMENTS IF Godsland is supported by the Heart Disease and Diabetes Research Trust. We thank N Forouhi, T Tillin and P McKeigue for their critical readings of the manuscript and

supporting data analysis. AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * in the Division of Medicine, IF Godsland is Wynn Reader in Human Metabolism, Endocrinology and Metabolic Medicine, and

DG Johnston is Professor of Endocrinology and Metabolic Medicine, Endocrinology and Metabolic Medicine, Imperial College London, London, UK., Ian F Godsland & Desmond G Johnston * N

Chaturvedi is Professor of Cardiovascular Epidemiology, in the National Heart and Lung Institute, Imperial College London., Nishi Chaturvedi Authors * Ian F Godsland View author publications

You can also search for this author inPubMed Google Scholar * Desmond G Johnston View author publications You can also search for this author inPubMed Google Scholar * Nishi Chaturvedi View

author publications You can also search for this author inPubMed Google Scholar CORRESPONDING AUTHOR Correspondence to Ian F Godsland. ETHICS DECLARATIONS COMPETING INTERESTS The authors

declare no competing financial interests. RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Godsland, I., Johnston, D. & Chaturvedi, N. Mechanisms of

Disease: lessons from ethnicity in the role of triglyceride metabolism in ischemic heart disease. _Nat Rev Endocrinol_ 3, 530–538 (2007). https://doi.org/10.1038/ncpendmet0530 Download

citation * Received: 10 October 2006 * Accepted: 29 December 2006 * Issue Date: July 2007 * DOI: https://doi.org/10.1038/ncpendmet0530 SHARE THIS ARTICLE Anyone you share the following link

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