Joy Pape, RN, BSN, CDE, WOCN, CFCN, FAADE
Dr. Ronald Krauss, MD, Senior Scientist and Director of Atherosclerosis Research at Children’s Hospital Oakland Research Institute, Adjunct Professor in the Department of Medicine at UCSF and in the Department of Nutritional Sciences at UC Berkeley, and Guest Senior Scientist in the Department of Genome Sciences of Lawrence Berkeley National Laboratory, provided a thought-provoking presentation for many at the American Diabetes Association’s 60th Annual Advanced Postgraduate Course in New York City, last February. He reported it is not just the typical lipid panel we need to be aware of for assessing the risk of coronary artery disease (CAD), but we should also consider the importance of lipoprotein particles, and how diet affects these.
Dr. Krauss reviewed the atherogenic dyslipidemia that is associated with obesity, insulin resistance, and diabetes. The characteristics are:
- High triglyceride level
- Low HDL-C level
- Absolute levels of LDL-C are not commonly elevated but there is an increased number of LDL particles — predominately small, dense LDL (defined as LDL phenotype B), and increased plasma apoB levels (These measures are not provided by a standard lipid profile.)
He discussed glycated apoB, that it is enriched in small, dense LDL particles, which increases atherogenicity.
He then discussed ApoC-III:
- A small exchangeable apolipoprotein, found in all lipoprotein classes
- ApoC-III in apoB-containing lipoproteins is associated with CHD risk
- Reduces lipolysis and plasma clearance of apoB-containing lipoproteins
- Increases proteoglycan binding of apoB containing lipoproteins
- Has direct pro-inflammatory properties
- Increases risk for developing CAD
- Is enriched in small dense LDL
He posed the question, “What is the effect of dietary composition on LDL phenotypes and atherogenic dyslipidemia?” He reported the evidence (see references):
- Low-fat, high-carbohydrate diet can induce expression of LDL phenotype B
- Prevalence of LDL subclass phenotype B is related to dietary carbohydrate, demonstrated by data from five studies in healthy men and women.
- ApoB-bound to apoCIII is increased with increase in dietary carbohydrate
- Carbohydrate limitation results in reduced expression of phenotype B in overweight men.
- Reduced carbohydrate intake and weight loss (7%) both reverse phenotype B
- Fructose increases the atherogenic particles more than glucose.
- Effects of reducing carbohydrate intake (26% vs. 54%) and high vs. low saturated fat (15% vs. 8%) on lipoprotein fractions. The lower the carb, higher saturated fat showed a more favorable profile.
- Meta–analysis of 21 prospective cohort trials show no significant association of saturated fat.
- Analysis of CAD risk with substitution of polyunsaturated fatty acids (PUFA), carbohydrate, or monounsaturated fatty acids (MUFA) in place of saturated fatty acids (SFA) showed an apparent benefit with PUFA, a trend toward higher risk with carbohydrate (especially white starches), and variable effects of MUFA. Thus the type of nutrient substituted for SFA is a major determinant of CHD risk.
He then asked, “So, does this mean eat a large cheeseburger on a white bun? No! This is a recipe for disaster.
A recent study by Dr. Krauss’ group showed that the combination of beef and saturated fat may have a worse effect on cardiometabolic risk than diets with similar fat but other sources of protein.
Dr. Krauss concluded his talk by saying:
- In atherogenic dyslipidemia, CAD risk is attributed to LDL, and perhaps to low HDL. This may be primarily due to a pathway resulting in increased levels of small LDL particles that are enriched in apoCIII, which has specific pathologic properties.
- In diabetics, these LDL particles may also increase CAD risk by virtue of their greater content of glycated apoB.
- The small LDL particle pathway is modulated both by adiposity and dietary carbohydrate intake.
- If sustained weight loss is not achieved, moderate carbohydrate limitation may provide comparable lipoprotein benefits that could reduce CAD risk.
- I too used to be against Dr. Atkins’ work, but now, with more evidence, I say “Perhaps he had something.”
- Austin MA, King MC, Vranizan KM, Krauss RM. Atherogenic lipoprotein phenotype. A proposed genetic marker for coronary heart disease risk. Circulation 1990; 82:495-506.
- Musunuru K, Orho-Melander M, Caulfield MP et al. Ion mobility analysis of lipoprotein subfractions identifies three independent axes of cardiovascular risk. Arterioscler Thromb Vasc Biol 2009; 29:1975-1980.
- Krauss RM. Lipoprotein subfractions and cardiovascular disease risk. Curr Op Lipidol 2010; 21:305-311.
- Berneis KK, Krauss RM. Metabolic origins and clinical significance of LDL heterogeneity. J Lipid Res 2002; 43:1363-1379.
- Younis N, Charlton-Menys V, Sharma R et al. Glycation of LDL in non-diabetic people: Small dense LDL is preferentially glycated both in vivo and in vitro. Atherosclerosis 2009; 202:162-168.
- Shin MJ, Krauss RM. Apolipoprotein CIII bound to apoB-containing lipoproteins is associated with small, dense LDL independent of plasma triglyceride levels in healthy men. Atherosclerosis 2010; 211:337-341.
- Deloukas P, Kanoni S, Willenborg C et al. Large-scale association analysis identifies new risk loci for coronary artery disease. Nat Genet 2012.
- Musunuru K, Strong A, Frank-Kamenetsky M et al. From noncoding variant to phenotype via SORT1 at the 1p13 cholesterol locus. Nature 2010; 466:714-719.
- Strong A, Ding Q, Edmondson AC et al. Hepatic sortilin regulates both apolipoprotein B secretion and LDL catabolism. J Clin Invest 2012; 122:2807-2816.
- Benn M, Nordestgaard BG, Grande P et al. PCSK9 R46L, low-density lipoprotein cholesterol levels, and risk of ischemic heart disease: 3 independent studies and meta- analyses. Journal of the American College of Cardiology 2010; 55:2833-2842.
- Voight BF, Peloso GM, Orho-Melander M et al. Plasma HDL cholesterol and risk of myocardial infarction: a mendelian randomisation study. Lancet 2012; 380:572-580.
- Krauss RM, Dreon DM. Low-density-lipoprotein subclasses and response to a low-fat diet in healthy men. Am J Clin Nutr 1995; 62:478S-487S.
- Stanhope KL, Schwarz JM, Keim NL et al. Consuming fructose-sweetened, not glucose- sweetened, beverages increases visceral adiposity and lipids and decreases insulin sensitivity in overweight/obese humans. J Clin Invest 2009; 119:1322-1334.
- Krauss RM, Blanche PJ, Rawlings RS et al. Separate effects of reduced carbohydrate intake and weight loss on atherogenic dyslipidemia. Am J Clin Nutr 2006; 83:1025-1031
- Siri-Tarino PW, Williams PT, Fernstrom HS et al. Reversal of small, dense LDL subclass phenotype by normalization of adiposity. Obesity 2009; 17:1768-1775.
- Mangravite LM, Chiu S, Wojnoonski K et al. Changes in atherogenic dyslipidemia induced by carbohydrate restriction in men are dependent on dietary protein source. J Nutr 2011; 141:2180-2185.