Effects of cardiovascular lifestyle change on lipoprotein subclass profiles defined by nuclear magnetic resonance spectroscopy

David J Decewicz, David M Neatrour, Amy Burke, Mary Jane Haberkorn, Heather L Patney, Marina N Vernalis, Darrell L Ellsworth, David J Decewicz, David M Neatrour, Amy Burke, Mary Jane Haberkorn, Heather L Patney, Marina N Vernalis, Darrell L Ellsworth

Abstract

Background: Low-density lipoprotein (LDL) cholesterol lowering is a primary goal in clinical management of patients with cardiovascular disease, but traditional cholesterol levels may not accurately reflect the true atherogenicity of plasma lipid profiles. The size and concentration of lipoprotein particles, which transport cholesterol and triglycerides, may provide additional information for accurately assessing cardiovascular risk. This study evaluated changes in plasma lipoprotein profiles determined by nuclear magnetic resonance (NMR) spectroscopy in patients participating in a prospective, nonrandomized lifestyle modification program designed to reverse or stabilize progression of coronary artery disease (CAD) to improve our understanding of lipoprotein management in cardiac patients.

Results: The lifestyle intervention was effective in producing significant changes in lipoprotein subclasses that contribute to CAD risk. There was a clear beneficial effect on the total number of LDL particles (-8.3%, p < 0.05 compared to matched controls), small dense LDL particles (-9.5%, p < 0.05), and LDL particle size (+0.8%; p < 0.05). Likewise, participants showed significant improvement in traditional CAD risk factors such as body mass index (-9.9%, p < 0.01 compared to controls), total cholesterol (-5.5%, p < 0.05), physical fitness (+37.2%, p < 0.01), and future risk for CAD (-7.9%, p < 0.01). Men and women responded differently to the program for all clinically-relevant variables, with men deriving greater benefit in terms of lipoprotein atherogenicity. Plasma lipid and lipoprotein responses to the lifestyle change program were not confounded by lipid-lowering medications.

Conclusion: In at risk patients motivated to participate, an intensive lifestyle change program can effectively alter traditional CAD risk factors and plasma lipoprotein subclasses and may reduce risk for cardiovascular events. Improvements in lipoprotein subclasses are more evident in men compared to women.

Figures

Figure 1
Figure 1
Changes in LDL particle concentrations during the lifestyle change program. All participants were included in the initial analyses (left panels), then stratified by gender (right panels). Improvement: decrease in total and small LDL particles; increase in LDL size.

References

    1. The Long-Term Intervention with Pravastatin in Ischaemic Disease (LIPID) Study Group Prevention of cardiovascular events and death with pravastatin in patients with coronary heart disease and a broad range of initial cholesterol levels. N Engl J Med. 1998;339:1349–1357. doi: 10.1056/NEJM199811053391902.
    1. Shepherd J, Barter P, Carmena R, Deedwania P, Fruchart J-C, Haffner S, Hsia J, Breazna A, LaRosa J, Grundy S, Waters D. Effect of lowering LDL cholesterol substantially below currently recommended levels in patients with coronary heart disease and diabetes: the Treating to New Targets (TNT) study. Diabetes Care. 2006;29:1220–1226. doi: 10.2337/dc05-2465.
    1. Cromwell WC, Otvos JD. Low-density lipoprotein particle number and risk for cardiovascular disease. Curr Atheroscler Rep. 2004;6:381–387. doi: 10.1007/s11883-004-0050-5.
    1. Austin MA, Breslow JL, Hennekens CH, Buring JE, Willett WC, Krauss RM. Low-density lipoprotein subclass patterns and risk of myocardial infarction. JAMA. 1988;260:1917–1921. doi: 10.1001/jama.260.13.1917.
    1. Gardner CD, Fortmann SP, Krauss RM. Association of small low-density lipoprotein particles with the incidence of coronary artery disease in men and women. JAMA. 1996;276:875–881. doi: 10.1001/jama.276.11.875.
    1. Lamarche B, Tchernof A, Moorjani S, Cantin B, Dagenais GR, Lupien PJ, Després JP. Small, dense low-density lipoprotein particles as a predictor of the risk of ischemic heart disease in men. Prospective results from the Québec Cardiovascular Study. Circulation. 1997;95:69–75.
    1. Blake GJ, Otvos JD, Rifai N, Ridker PM. Low-density lipoprotein particle concentration and size as determined by nuclear magnetic resonance spectroscopy as predictors of cardiovascular disease in women. Circulation. 2002;106:1930–1937. doi: 10.1161/01.CIR.0000033222.75187.B9.
    1. Kuller L, Arnold A, Tracy R, Otvos J, Burke G, Psaty B, Siscovick D, Freedman DS, Kronmal R. Nuclear magnetic resonance spectroscopy of lipoproteins and risk of coronary heart disease in the cardiovascular health study. Arterioscler Thromb Vasc Biol. 2002;22:1175–1180. doi: 10.1161/01.ATV.0000022015.97341.3A.
    1. Rosenson RS, Otvos JD, Freedman DS. Relations of lipoprotein subclass levels and low-density lipoprotein size to progression of coronary artery disease in the Pravastatin Limitation of Atherosclerosis in the Coronary Arteries (PLAC-I) trial. Am J Cardiol. 2002;90:89–94. doi: 10.1016/S0002-9149(02)02427-X.
    1. El Harchaoui K, van der Steeg WA, Stroes ES, Kuivenhoven JA, Otvos JD, Wareham NJ, Hutten BA, Kastelein JJP, Khaw K-T, Boekholdt SM. Value of low-density lipoprotein particle number and size as predictors of coronary artery disease in apparently healthy men and women: the EPIC-Norfolk Prospective Population Study. J Am Coll Cardiol. 2007;49:547–553. doi: 10.1016/j.jacc.2006.09.043.
    1. Otvos JD, Jeyarajah EJ, Cromwell WC. Measurement issues related to lipoprotein heterogeneity. Am J Cardiol . 2002;90:22i–29i. doi: 10.1016/S0002-9149(02)02632-2.
    1. Carels RA, Darby LA, Cacciapaglia HM, Douglass OM. Reducing cardiovascular risk factors in postmenopausal women through a lifestyle change intervention. J Womens Health. 2004;13:412–426. doi: 10.1089/154099904323087105.
    1. Roberts CK, Barnard RJ. Effects of exercise and diet on chronic disease. J Appl Physiol. 2005;98:3–30. doi: 10.1152/japplphysiol.00852.2004.
    1. Gould KL, Ornish D, Kirkeeide R, Brown S, Stuart Y, Buchi M, Billings J, Armstrong W, Ports T, Scherwitz L. Improved stenosis geometry by quantitative coronary arteriography after vigorous risk factor modification. Am J Cardiol. 1992;69:845–853. doi: 10.1016/0002-9149(92)90781-S.
    1. Haskell WL, Alderman EL, Fair JM, Maron DJ, Mackey SF, Superko HR, Williams PT, Johnstone IM, Champagne MA, Krauss RM, Farquhar JW. Effects of intensive multiple risk factor reduction on coronary atherosclerosis and clinical cardiac events in men and women with coronary artery disease. The Stanford Coronary Risk Intervention Project (SCRIP) Circulation. 1994;89:975–990.
    1. Aldana SG, Whitmer WR, Greenlaw R, Avins AL, Salberg A, Barnhurst M, Fellingham G, Lipsenthal L. Cardiovascular risk reductions associated with aggressive lifestyle modification and cardiac rehabilitation. Heart Lung. 2003;32:374–382. doi: 10.1016/S0147-9563(03)00106-7.
    1. Ellsworth DL, O'Dowd SC, Salami B, Hochberg A, Vernalis MN, Marshall D, Morris JA, Somiari RI. Intensive lifestyle modification: impact on cardiovascular disease risk factors in subjects with and without clinical cardiovascular disease. Prev Cardiol. 2004;7:168–175. doi: 10.1111/j.1520-037X.2004.3332.x.
    1. Gordon NF, Salmon RD, Franklin BA, Sperling LS, Hall L, Leighton RF, Haskell WL. Effectiveness of therapeutic lifestyle changes in patients with hypertension, hyperlipidemia, and/or hyperglycemia. Am J Cardiol. 2004;94:1558–1561. doi: 10.1016/j.amjcard.2004.08.039.
    1. Wister A, Loewen N, Kennedy-Symonds H, McGowan B, McCoy B, Singer J. One-year follow-up of a therapeutic lifestyle intervention targeting cardiovascular disease risk. CMAJ. 2007;177:859–865.
    1. Otvos JD, Shalaurova I, Freedman DS, Rosenson RS. Effects of pravastatin treatment on lipoprotein subclass profiles and particle size in the PLAC-I trial. Atherosclerosis. 2002;160:41–48. doi: 10.1016/S0021-9150(01)00544-5.
    1. Otvos JD, Collins D, Freedman DS, Shalaurova I, Schaefer EJ, McNamara JR, Bloomfield HE, Robins SJ. Low-density lipoprotein and high-density lipoprotein particle subclasses predict coronary events and are favorably changed by gemfibrozil therapy in the Veterans Affairs High-Density Lipoprotein Intervention Trial. Circulation. 2006;113:1556–1563. doi: 10.1161/CIRCULATIONAHA.105.565135.
    1. Des Jarlais DC, Lyles C, Crepaz N, TREND Group Improving the reporting quality of nonrandomized evaluations of behavioral and public health interventions: the TREND statement. Am J Public Health. 2004;94:361–366. doi: 10.2105/AJPH.94.3.361.
    1. Charpentier PA, Bogardus ST, Inouye SK. An algorithm for prospective individual matching in a non-randomized clinical trial. J Clin Epidemiol. 2001;54:1166–1173. doi: 10.1016/S0895-4356(01)00399-7.
    1. Koertge J, Weidner G, Elliott-Eller M, Scherwitz L, Merritt-Worden TA, Marlin R, Lipsenthal L, Guarneri M, Finkel R, Saunders DE, Jr, McCormac P, Scheer JM, Collins RE, Ornish D. Improvement in medical risk factors and quality of life in women and men with coronary artery disease in the Multicenter Lifestyle Demonstration Project. Am J Cardiol. 2003;91:1316–1322. doi: 10.1016/S0002-9149(03)00320-5.
    1. Vizza J, Neatrour DM, Felton PM, Ellsworth DL. Improvement in psychosocial functioning during an intensive cardiovascular lifestyle modification program. J Cardiopulm Rehabil Prev. 2007;27:376–383.
    1. Jeyarajah EJ, Cromwell WC, Otvos JD. Lipoprotein particle analysis by nuclear magnetic resonance spectroscopy. Clin Lab Med. 2006;26:847–870. doi: 10.1016/j.cll.2006.07.006.
    1. Bruce RA. Exercise Testing and Training of Apparently Healthy Individuals: A Handbook for Physicians. New York: American Heart Association; 1972. Multi-stage treadmill test of submaximal and maximal exercise; pp. 32–34.
    1. D'Agostino RB, Russell MW, Huse DM, Ellison RC, Silbershatz H, Wilson PWF, Hartz SC. Primary and subsequent coronary risk appraisal: new results from the Framingham study. Am Heart J. 2000;139:272–281.
    1. Leon AS, Sanchez OA. Response of blood lipids to exercise training alone or combined with dietary intervention. Med Sci Sports Exerc. 2001;33:S502–S515.
    1. Kelley GA, Kelley KS, Franklin B. Aerobic exercise and lipids and lipoproteins in patients with cardiovascular disease: a meta-analysis of randomized controlled trials. J Cardiopulm Rehabil. 2006;26:131–139. doi: 10.1097/00008483-200605000-00002.
    1. Kraus WE, Houmard JA, Duscha BD, Knetzger KJ, Wharton MB, McCartney JS, Bales CW, Henes S, Samsa GP, Otvos JD, Kulkarni KR, Slentz CA. Effects of the amount and intensity of exercise on plasma lipoproteins. N Engl J Med. 2002;347:1483–1492. doi: 10.1056/NEJMoa020194.
    1. Halverstadt A, Phares DA, Wilund KR, Goldberg AP, Hagberg JM. Endurance exercise training raises high-density lipoprotein cholesterol and lowers small low-density lipoprotein and very low-density lipoprotein independent of body fat phenotypes in older men and women. Metabolism. 2007;56:444–450. doi: 10.1016/j.metabol.2006.10.019.
    1. Archer WR, Lamarche B, St-Pierre AC, Mauger J-F, Dériaz O, Landry N, Corneau L, Després J-P, Bergeron J, Couture P, Bergeron N. High carbohydrate and high monounsaturated fatty acid diets similarly affect LDL electrophoretic characteristics in men who are losing weight. J Nutr. 2003;133:3124–3129.
    1. Westman EC, Yancy WS, Jr, Olsen MK, Dudley T, Guyton JR. Effect of a low-carbohydrate, ketogenic diet program compared to a low-fat diet on fasting lipoprotein subclasses. Int J Cardiol. 2006;110:212–216. doi: 10.1016/j.ijcard.2005.08.034.
    1. Shadid S, LaForge R, Otvos JD, Jensen MD. Treatment of obesity with diet/exercise versus pioglitazone has distinct effects on lipoprotein particle size. Atherosclerosis. 2006;188:370–376. doi: 10.1016/j.atherosclerosis.2005.10.038.
    1. Sacks FM, Campos H. Clinical review 163: Cardiovascular endocrinology 4: Low-density lipoprotein size and cardiovascular disease: a reappraisal. J Clin Endocrinol Metab. 2003;88:4525–4532. doi: 10.1210/jc.2003-030636.
    1. Berliner JA, Navab M, Fogelman AM, Frank JS, Demer LL, Edwards PA, Watson AD, Lusis AJ. Atherosclerosis: basic mechanisms. Oxidation, inflammation, and genetics. Circulation. 1995;91:2488–2496.
    1. Björnheden T, Babyi A, Bondjers G, Wiklund O. Accumulation of lipoprotein fractions and subfractions in the arterial wall, determined in an in vitro perfusion system. Atherosclerosis. 1996;123:43–56. doi: 10.1016/0021-9150(95)05770-6.
    1. de Graaf J, Hak-Lemmers HL, Hectors MP, Demacker PN, Hendriks JC, Stalenhoef AF. Enhanced susceptibility to in vitro oxidation of the dense low density lipoprotein subfraction in healthy subjects. Arterioscler Thromb. 1991;11:298–306.
    1. Anber V, Griffin BA, McConnell M, Packard CJ, Shepherd J. Influence of plasma lipid and LDL-subfraction profile on the interaction between low density lipoprotein with human arterial wall proteoglycans. Atherosclerosis. 1996;124:261–271. doi: 10.1016/0021-9150(96)05842-X.
    1. Dreon DM, Fernstrom HA, Williams PT, Krauss RM. A very low-fat diet is not associated with improved lipoprotein profiles in men with a predominance of large, low-density lipoproteins. Am J Clin Nutr. 1999;69:411–418.
    1. Varady KA, Lamarche B, Santosa S, Demonty I, Charest A, Jones PJH. Effect of weight loss resulting from a combined low-fat diet/exercise regimen on low-density lipoprotein particle size and distribution in obese women. Metabolism. 2006;55:1302–1307. doi: 10.1016/j.metabol.2006.05.014.
    1. Perreault L, Ma Y, Dagogo-Jack S, Horton E, Marrero D, Crandall J, Barrett-Connor E, The Diabetes Prevention Program Sex differences in diabetes risk and the effect of intensive lifestyle modification in the Diabetes Prevention Program. Diabetes Care. 2008;31:1416–1421. doi: 10.2337/dc07-2390.
    1. Schaefer EJ, Lamon-Fava S, Ausman LM, Ordovas JM, Clevidence BA, Judd JT, Goldin BR, Woods M, Gorbach S, Lichtenstein AH. Individual variability in lipoprotein cholesterol response to National Cholesterol Education Program Step 2 diets. Am J Clin Nutr. 1997;65:823–830.
    1. Knopp RH, Paramsothy P, Retzlaff BM, Fish B, Walden C, Dowdy A, Tsunehara C, Aikawa K, Cheung MC. Gender differences in lipoprotein metabolism and dietary response: basis in hormonal differences and implications for cardiovascular disease. Curr Atheroscler Rep. 2005;7:472–479. doi: 10.1007/s11883-005-0065-6.
    1. Williams KJ, Feig JE, Fisher EA. Rapid regression of atherosclerosis: insights from the clinical and experimental literature. Nat Clin Pract Cardiovasc Med. 2008;5:91–102. doi: 10.1038/ncpcardio1086.
    1. Rizzo M, Berneis K. The clinical relevance of low-density-lipoproteins size modulation by statins. Cardiovasc Drugs Ther. 2006;20:205–217. doi: 10.1007/s10557-006-8283-x.
    1. Deeg MA, Buse JB, Goldberg RB, Kendall DM, Zagar AJ, Jacober SJ, Khan MA, Perez AT, Tan MH, GLAI Study Investigators Pioglitazone and rosiglitazone have different effects on serum lipoprotein particle concentrations and sizes in patients with type 2 diabetes and dyslipidemia. Diabetes Care. 2007;30:2458–2464. doi: 10.2337/dc06-1903.
    1. Ikewaki K, Noma K, Tohyama J, Kido T, Mochizuki S. Effects of bezafibrate on lipoprotein subclasses and inflammatory markers in patients with hypertriglyceridemia – a nuclear magnetic resonance study. Int J Cardiol. 2005;101:441–447. doi: 10.1016/j.ijcard.2004.03.071.
    1. Ikewaki K, Tohyama J, Nakata Y, Wakikawa T, Kido T, Mochizuki S. Fenofibrate effectively reduces remnants, and small dense LDL, and increases HDL particle number in hypertriglyceridemic men – a nuclear magnetic resonance study. J Atheroscler Thromb. 2004;11:278–285.
    1. Berhanu P, Kipnes MS, Khan MA, Perez AT, Kupfer SF, Spanheimer RC, Demissie S, Fleck PR. Effects of pioglitazone on lipid and lipoprotein profiles in patients with type 2 diabetes and dyslipidaemia after treatment conversion from rosiglitazone while continuing stable statin therapy. Diab Vasc Dis Res. 2006;3:39–44. doi: 10.3132/dvdr.2006.005.
    1. McKenney JM, McCormick LS, Schaefer EJ, Black DM, Watkins ML. Effect of niacin and atorvastatin on lipoprotein subclasses in patients with atherogenic dyslipidemia. Am J Cardiol. 2001;88:270–274. doi: 10.1016/S0002-9149(01)01639-3.
    1. Morgan JM, Capuzzi DM, Baksh RI, Intenzo C, Carey CM, Reese D, Walker K. Effects of extended-release niacin on lipoprotein subclass distribution. Am J Cardiol. 2003;91:1432–1436. doi: 10.1016/S0002-9149(03)00394-1.
    1. Blake GJ, Albert MA, Rifai N, Ridker PM. Effect of pravastatin on LDL particle concentration as determined by NMR spectroscopy: a substudy of a randomized placebo controlled trial. Eur Heart J. 2003;24:1843–1847. doi: 10.1016/j.ehj.2003.07.008.
    1. Soedamah-Muthu SS, Colhoun HM, Thomason MJ, Betteridge DJ, Durrington PN, Hitman GA, Fuller JH, Julier K, Mackness MI, Neil HA, CARDS Investigators The effect of atorvastatin on serum lipids, lipoproteins and NMR spectroscopy defined lipoprotein subclasses in type 2 diabetic patients with ischaemic heart disease. Atherosclerosis. 2003;167:243–255. doi: 10.1016/S0021-9150(02)00428-8.
    1. Brousseau ME, Schaefer EJ, Wolfe ML, Bloedon LT, Digenio AG, Clark RW, Mancuso JP, Rader DJ. Effects of an inhibitor of cholesteryl ester transfer protein on HDL cholesterol. N Engl J Med. 2004;350:1505–1515. doi: 10.1056/NEJMoa031766.
    1. Barter PJ, Rye K-A. Cardioprotective properties of fibrates: which fibrate, which patients, what mechanism? Circulation. 2006;113:1553–1555. doi: 10.1161/CIRCULATIONAHA.105.620450.
    1. Cho N, Momose Y. Peroxisome proliferator-activated receptor gamma agonists as insulin sensitizers: from the discovery to recent progress. Curr Top Med Chem. 2008;8:1483–1507. doi: 10.2174/156802608786413474.
    1. Jasiñska M, Owczarek J, Orszulak-Michalak D. Statins: a new insight into their mechanisms of action and consequent pleiotropic effects. Pharmacol Rep. 2007;59:483–499.
    1. Brunzell JD, Davidson M, Furberg CD, Goldberg RB, Howard BV, Stein JH, Witztum JL. Lipoprotein management in patients with cardiometabolic risk: consensus conference report from the American Diabetes Association and the American College of Cardiology Foundation. J Am Coll Cardiol. 2008;51:1512–1524. doi: 10.1016/j.jacc.2008.02.034.

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