223: Effect of Weight Loss on Cardiometabolic Risk Using a Structured Dietary Program

Abstracts plus either double-blind P-OM3 (4 g/d, Lovaza, GlaxoSmithKline, Middlesex, UK) or placebo in subjects with elevated levels of TG and non-high-density lipoprotein (non-HDL)-cholesterol (C). Methods: Men and women (N ⫽ 39) with TG 200 to 600 mg/dL and non-HDL-C greater than their National Cholesterol Education Program treatment goals after a 5-week diet lead-in and washout of lipid-lowering therapies were randomized to one of two treatment sequences. Subjects received 6 weeks of combination therapy with S⫹P-OM3 or S⫹placebo, then crossed over to receive the opposite treatment for an additional 6 weeks. Serum lipids and lipoprotein particle concentrations and sizes were measured at baseline and at the end of each treatment period. Results: Baseline levels of total-C, TG, low-density lipoprotein (LDL)-C, HDL-C, very low-density lipoprotein (VLDL)-C, and non-HDL-C were 259, 304, 163, 38, 56, and 209 mg/dL, respectively. Treatment with S⫹P-OM3 resulted in significant changes vs. S⫹placebo (p ⬍ 0.01 for all) in total-C (⫺31.0 vs. ⫺26.4%), TG (⫺43.6 vs. ⫺28.7%), HDL-C (⫹16.4 vs. ⫹10.6%), VLDL-C (⫺41.5 vs. ⫺22.4%), and non-HDL-C (⫺40.0 vs. ⫺34.3%). LDL-C responses were not significantly different between treatments (S⫹P-OM3, ⫺37.2% vs. S⫹placebo, ⫺38.4%). Baseline concentrations of VLDL, intermediate-density lipoprotein (IDL), LDL, and HDL particles were 152 nmol/L, 96 nmol/L, 1896 nmol/L, and 31 ␮mol/L, respectively. VLDL particle concentration decreased more with S⫹P-OM3 compared with S⫹placebo (⫺35.2 vs. ⫺28.0%, p ⫽ 0.036). Changes from baseline in IDL (⫺67.6 vs. ⫺50.3%), LDL (⫺32.9 vs. ⫺32.5%), and HDL (⫹4.0 vs. ⫹6.3%) particle concentrations were not significantly different between treatments. VLDL, LDL, and HDL particle sizes at baseline were 52.4, 19.9, and 8.5 nm respectively. S⫹P-OM3 was associated with a larger reduction in VLDL particle size vs. S⫹placebo (⫺17.0 vs. ⫺4.5%, p ⬍ 0.001) and a larger increase in LDL particle size (⫹3.2 vs. ⫹2.3%, p ⫽ 0.024). HDL particle size responses were not significantly different between treatments. Conclusions: Compared to S⫹placebo, S⫹P-OM3 lowered the circulating concentrations of VLDL-C and VLDL particles, while raising HDL-C and increasing LDL particle size. These findings suggest that P-OM3 improves the atherogenic lipoprotein profile of individuals with mixed dyslipidemia receiving simvastatin. 222 Lipoproteins in the Prediction of Coronary Artery Calcium (CAC) as Modified by Age in the Multi-Ethnic Study of Atherosclerosis (MESA) Pathmaja Paramsothy, MD, MSc, Gregory L. Burke, Ronit Katz, Kevin D. O’Brien (Senior Author), David S. Owens, Jeffrey L. Probstfield, (Seattle, WA) Synopsis: Abnormal lipoproteins and lipoprotein ratios are powerful risk factors for CVD events, but may be more

223 potent risk factors at younger age compared to older age. The attenuated association between lipoproteins and CVD in older adults may be due to the high prevalence of existing atherosclerosis in the oldest age diminishing any potential atherosclerosis-promoting effects of lipoproteins. Purpose: To determine whether associations of specific lipoproteins and lipoprotein ratios with the presence of CAC are attenuated with age in a multi-ethnic cohort of people free of cardiovascular disease (CVD) at baseline. Methods: MESA participants were White, Chinese, African-American, or Hispanic community-dwelling adults without clinical CVD. Baseline exams were performed between 2000 –2002. Those on lipid lowering therapy at baseline (16% of the cohort) were excluded. Multivariate relative risk regression was conducted to determine the crosssectional associations for each lipoprotein and lipoprotein ratio with the presence of CAC (presence or absence) as stratified by age categories. Interaction with age was determined a priori and deemed significant at p⬍0.05. Results: 4,959 subjects were included in the primary analysis. Interactions were significant for all lipoproteins and lipoprotein ratios with age in unadjusted models and for models adjusted for demographics and CVD risk factors for all except LDL-C. Table 1 reports relative risk (RR) for CAC per age category for selected lipoprotein/ratios. Conclusions: Baseline RR for sub-clinical CAC was increased for lipoproteins and lipoprotein ratios across all age categories in this multi-ethnic cohort. However, our findings demonstrate an attenuation of lipid effects on atherosclerosis in older adults. These findings mirror those reported previously for clinical CVD events. The underlying mechanisms accounting for the age-related attenuation are not well understood and require further investigation. Table 1. RR for having coronary artery calcium by lipoproteins and lipoprotein ratiosⴱ by Age Categoryⴱⴱ Total n ⫽4,959

Age 45-54 (n⫽1,609)

Age 55-64 (n⫽1,402)

Age 65-74 (n⫽1,319)

Age 75-84 (n⫽629)

LDL-C (mg/ dL)

1.19 (1.08, 1.30) p⬍0.001 1.07 (0.96, 1.18) p⫽0.22 1.17 (1.09, 1.26) p⬍0.001

1.08 (1.03, 1.14) p⫽0.003 0.98 (0.92, 1.04) p⫽0.49 1.07 (1.01, 1.13) p⫽0.02

1.07 (1.03, 1.11) p⬍0.001 1.02 (0.99, 1.07) p⫽0.15 1.07 (1.03, 1.12) p⬍0.001

1.05 (1.01, 1.09) p⫽0.013 1.02 (0.97, 1.06) p⫽0.47 1.04 (0.99, 1.08) p⫽0.07

Triglycerides ⫹ Total/HDL

ⴱ

Per SD, ⴱⴱadjusted for gender, race, education, site of enrollment, hypertension, glucose, log insulin, diabetes, current smoking, family history of MI, waist circumference, creatinine, and log IL6, ⫹ log transformed, p⬍0.05 for interaction with age.

223 Effect of Weight Loss on Cardiometabolic Risk Using a Structured Dietary Program Melissa J. Robledo, MD, Michael P. Flynn, (Skokie, IL)

224 Synopsis: Obesity has become a global epidemic. The treatment for reducing cardiovascular (CV) events focuses on major risk-factor and LDL reduction; however, other metabolic abnormalities may remain even if a patient’s LDL has been treated to NCEP/ATP III goal levels. Though not considered a major risk factor, abdominal obesity is likely a common underlying factor in the initiation of atherosclerosis. At the vascular level, adipocytes secrete highly inflammatory cytokines, such as PAI-1, TNF-1, and IL-6 that incite a cascade of deleterious events leading to accelerated plaque formation. The metabolic syndrome (atherogenic dyslipidemia, elevated blood pressure and insulin resistance) is recognized by ATP III as a secondary goal. There are excellent studies which show the effectiveness of therapeutic lifestyle changes (TLC) in the treatment of metabolic syndrome, however implementing TLC has been challenging for clinicians. Factors such as time, readiness-forchange, reimbursement, and follow-up are major obstacles. Purpose: To effectively implement TLC in obese individuals using a lifestyle educator and a structured nutrition program in an Internal Medicine/Clinical Lipidology practice. Methods: Individuals were enrolled in FirstLine Therapy (FLT); a program created by Metagenics, Inc. FLT consists of a Mediterranean-style, low glycemic load diet, a oncedaily soy protein- and phytosterol-based meal replacement, Omega-3-fatty acids and exercise. Patients were counseled by a lifestyle educator every two weeks. Markers such as weight, BMI, body fat, lean body mass (measured with the Biomarkers2000, a bioimpedance analyzer by Biodynamics), lipid profiles and blood pressure were followed. The study is ongoing. Results: In 22 consecutive men and women ages 17–75 with at least 2 components of the metabolic syndrome, we observed improvements in weight (-9.4 ⫾ 1.3 lb), BMI (-1.6 ⫾ 0.3 kg/m2), percent body fat (⫺3.4 ⫾ 0.5%), systolic blood pressure (⫺8 ⫾ 4 mmHg), HDL (2.9 ⫾ 2.4 mg/dL) and triglycerides (⫺34.4 ⫾ 23.0 mg/dL). Lean body mass was preserved or increased in all patients. Conclusions: Changing lipid parameters with medications does not stop the cascade of inflammation related to the interaction of the adipose tissue with the vasculature. Weight loss has been shown to alter multiple cardiometabolic risk factors. By implementing this highly structured lifestyle program, we observed a reduction in body fat, a reduction in blood pressure and positive changes in the lipid profile. The program was easy to integrate into our practice and continues to attract new patients at risk for cardiovascular disease. 224 Effects of Colesevelam HCL on Lipoprotein Subclasses in Subjects with Type 2 Diabetes Robert S. Rosenson, MD, Stacy L. Abby, Michael R. Jones, (Ann Arbor, MI)

Journal of Clinical Lipidology, Vol 2, No 3, June 2008 Synopsis: Colesevelam HCL, a bile acid sequestrant with established LDL-cholesterol (LDL-C) lowering efficacy, was recently approved for glycemic control in patients with Type 2 diabetes. A previous study demonstrated that colesevelam reduces LDL particle number and increases LDL size in patients with hypercholesterolemia. The effects on lipoprotein subclass changes have not previously been reported in patients with Type 2 diabetes. Purpose: To determine the effects of Colesevelam HCL on lipoprotein subclasses in subjects with Type 2 diabetes. Methods: This was a randomized, double-blind, placebo-controlled trial to examine the effects of colesevelam on glycemic and lipid control in type 2 diabetes patients with HbA1c (A1C) between 7.0% to 10.0%. After a 4-week placebo lead-in period, 65 subjects (31 colesevelam, 34 placebo) were randomized to receive colesevelam 3.75 g/d or matching placebo for 12 weeks in addition to maintaining their previous oral antihyperglycemic regimen. Primary endpoints of the GlucoseLowering Effect of Welchol Study (GLOWS) were previously published. Lipoprotein subclasses measured by NMR were secondary efficacy variables (26, colesevelam, 30 placebo) at baseline and week 12. Results: Relative to placebo, colesevelam treatment was associated with mean reductions in A1C of ⫺0.3% compared with ⫹0.2% in the placebo group (treatment difference, ⫺0.5%, p ⫽ 0.007). The mean percentage change in LDL-C was ⫺9.6% in the colesevelam group compared with ⫹2.1% in the placebo group (treatment difference, ⫺11.7%, p ⫽ 0.007). There was no significant effect on either total VLDL particle or total HDL particle concentration. Total LDL particle concentration (LDL-P) was reduced by 15.5% (⫺242 nmol/L [⫺412, ⫺72], p ⫽ 0.0063) primarily due to lowering in small LDL-P (⫺207.3 [⫺418, 3.5], p ⫽ 0.054) and a lesser reductions in large LDL-P [⫺30 nmol/L [⫺118, 53], p ⫽ 0.50) and IDL (⫺21 nmol/L [⫺182, 140], p ⫽ 0.79). The reduction in LDL-C did not correlate with improvement in glycemic measures, whereas LDL-P correlated with the improvement in A1C (r ⫽ 0.30, p ⫽ 0.025). Conclusions: In Type 2 diabetes patients, colesevelam improves glycemic status and reduces the concentration of LDL-C and LDL-P with little change in concentrations of other lipoprotein particles. 225 Implementation of a Coronary Artery Calcium ScoringBased Lipid Management Program in a University Medical Center: The EDUCATE Program Carl E. Orringer, MD, (Pepper Pike, OH) Synopsis: The guiding principle of The National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) is that the intensity of LDL-cholesterol-lowering therapy should be adjusted to the individual’s absolute risk for coronary heart disease (CHD). While Framingham risk scoring (FRS) was recommended by NCEP ATP III to assess CHD risk in asymptomatic individuals with two or more risk factors,