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Background: Patients with coronary artery disease (CAD) are characterized by an impaired cardiometabolic risk profile including high levels of atherogenic apolipoprotein (apo) B-containing lipoprotein levels. Genetic studies have highlighted a critical role for proprotein convertase subtilisin/kexin type 9 (PCSK9) in lipoprotein metabolism and CAD risk., Objective: To determine whether improving dietary quality and increasing physical activity levels improve parameters of the cardiometabolic risk profile such as plasma apoB and PCSK9 levels in patients with CAD., Methods: We recruited 86 men aged between 39 and 80 years (82 of them on statins) undergoing coronary artery bypass graft (CABG) surgery. These patients participated in a 1-year lifestyle modification program aiming at achieving a minimum of 150 minutes/week of physical activity and improving diet quality by following dietary guidelines. We used magnetic resonance imaging to measure visceral adipose tissue and a modified Bruce protocol to measure fitness levels before and after the intervention., Results: Plasma apoB and low-density lipoprotein cholesterol levels were not modified by the intervention (-3.0%, P = .08 and 1.3%, P = .56, respectively), whereas non-HDL cholesterol decreased by 4.5% (P = .04) and triglycerides by 13% (P = .002). In contrast, PCSK9 levels increased by 5.2% after the intervention (P = .05). HDL cholesterol and apolipoprotein A-I levels also increased (+12%, P < .0001 and + 6%, P < .0001, respectively). PCSK9 levels increased with improvements in fitness (r = 0.23, P = .04) and visceral fat mobilization (r = -0.23, P = .04)., Conclusion: In post-CABG patients, a lifestyle modification program lead to significant improvements in some parameters of the lipoprotein profile but unexpectedly increased plasma PCSK9 levels., (Copyright © 2016 National Lipid Association. Published by Elsevier Inc. All rights reserved.)

Objective: The goal was to examine lipoprotein subclass responses to regular exercise as measured in 10 exercise interventions derived from six cohorts., Methods: Nuclear magnetic resonance spectroscopy was used to quantify average particle size, total and subclass concentrations of very low-density lipoprotein, low-density lipoprotein, and high-density lipoprotein particles (VLDL-P, LDL-P, and HDL-P, respectively) before and after an exercise intervention in 1555 adults from six studies, encompassing 10 distinct exercise programs: APOE (N = 106), DREW (N = 385), GERS (N = 79), HERITAGE (N = 715), STRRIDE I (N = 168) and II (N = 102). Random-effects meta-analyses were performed to evaluate the overall estimate of mean change across the unadjusted and adjusted mean change values from each exercise group., Results: Meta-analysis of unadjusted data showed that regular exercise induced significant decreases in the concentration of large VLDL-P, small LDL-P, and medium HDL-P and mean VLDL-P size, with significant increases in the concentration of large LDL-P and large HDL-P and mean LDL-P size. These changes remained significant in meta-analysis with adjustment for age, sex, race, baseline body mass index, and baseline trait value., Conclusions: Despite differences in exercise programs and study populations, regular exercise produced putatively beneficial changes in the lipoprotein subclass profile across 10 exercise interventions. Further research is needed to examine how exercise-induced changes in lipoprotein subclasses may be associated with (concomitant changes in) cardiovascular disease risk., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

We investigated the associations between the hepatic lipase gene (LIPC) -514C>T polymorphism and lipases, lipoproteins, and insulin sensitivity (Si) responses to exercise training. Hepatic lipase and lipoprotein lipase activities, plasma lipoprotein levels, and Si were measured in the sedentary state and post-exercise training in the Health, Risk Factors, Exercise Training, and Genetics (HERITAGE) Family Study (n=662). The LIPC -514C allele frequency was 0.516 (blacks) and 0.796 (whites). Baseline and post-exercise training hepatic lipase activities were 40% higher in CC homozygotes (P < 0.0001) in both races. Black CC homozygotes had lower baseline lipoprotein lipase activity, HDL cholesterol, HDL3, and apolipoprotein (apo)A-1 concentrations. White CC homozygotes had lower baseline HDL cholesterol, apoA-1, LDL cholesterol, and apoB levels that remained low post-exercise training. Baseline Si was not associated with the LIPC genotypes. However, training-induced improvements in Si both in blacks and whites were greater in CC homozygotes (+1.25 +/- 0.2 and +0.22 +/- 0.2 microU.min(-1).ml(-1)) than in the TT genotype (+0.27 +/- 0.3 and -0.97 +/- 0.3 microU.min(-1).ml(-1)) (P = 0.008 and P = 0.002, respectively). The LIPC -514C allele was associated with higher hepatic lipase activity in sedentary and physically active states and better Si responses to regular exercise both in black and white individuals. The benefits from an exercise program on Si are likely to be substantial in the general population given the high frequency of the LIPC -514C allele, particularly in whites.

The present study examined the associations between a major adipokine, adiponectin, and adiposity indices as well as metabolic risk variables in a sample of 190 untreated asymptomatic men. Anthropometric measurements and a complete fasting plasma lipoprotein and lipid profile were obtained, and subjects underwent an oral glucose tolerance test. Fasting plasma adiponectin concentrations were determined by an ELISA. Although all adiposity and adipose tissue (AT) distribution indices were negatively correlated with plasma adiponectin levels (-0.14 /=30 kg/m(2)) but who markedly differed in their level of visceral AT (< vs. >/=130 cm(2); n = 15) revealed significant differences in adiponectin levels (7.0 +/- 3.0 vs. 11.1 +/- 4.9 microg/ml; P < 0.02 for men with high vs. low visceral AT, respectively). Finally, when men were stratified into tertiles of visceral AT and further classified on the basis of the 50th percentile of adiponectin levels (8.8 microg/ml), a 3 x 2 ANOVA revealed an independent contribution of adiponectin on the variation of high-density lipoprotein cholesterol levels (P < 0.002) and of the glucose area (P < 0.02). These results support the notion that adiponectin concentration is influenced to a greater extent by visceral than sc obesity. Furthermore, adiponectin predicts glucose tolerance and plasma high-density lipoprotein cholesterol levels in a manner that is partly independent from the contribution of visceral adiposity.

The aim of this study was first to examine the relationships between adiponectin gene (Apm1) polymorphisms and anthropometric indices as well as plasma adiponectin and lipoprotein/lipid levels, and then to investigate whether the presence of visceral obesity or insulin resistance may modulate the impact of these polymorphisms on metabolic risk variables. Molecular screening of the Apm1 gene was achieved, and a sample of 270 unrelated men recruited from the greater Quebec City area and selected to cover a wide range of body fatness values was genotyped. Sequencing of the Apm1 gene revealed two previously reported polymorphisms (c.45T>G and c.276G>T) as well as two newly identified genetic variations (-13752delT and -13702G>C). Carriers of the c.276T allele had higher LDL-cholesterol and lower HDL-triglyceride concentrations than did 276G/G homozygotes (P=0.02 and P=0.01, respectively). Carriers of the c.45G allele exhibited higher plasma adiponectin concentrations than did 45T/T homozygotes (P=0.04). After dividing each genotype group into subgroups for visceral AT, homozygotes for the normal allele at position -13752delT, carriers of the c.45G allele, and carriers of the c.276T allele had similar total apolipoprotein B (apoB) concentrations, whether they were viscerally obese or not. These results suggest that some Apm1 gene polymorphisms influence plasma adiponectin concentrations and lipoprotein/lipid levels. In addition, the impact of these polymorphisms is modulated by the presence of visceral obesity.

Plasma lipid and lipoprotein concentrations were measured before and after a 58,000kcal (244MJ) negative energy balance protocol induced entirely by supervised endurance exercise over a 93-day period in seven pairs of young sedentary and healthy male monozygotic twins. The negative energy balance induced significant changes in all measures of body weight and composition except fat free mass. The mean weight loss was 5.0+/-0.6kg, and it was entirely accounted for by the loss of body fat. In response to the program, improvement in the plasma lipid profile was seen including decreases in plasma total (P=0.028) and low density lipoprotein (LDL) (P=0.004) cholesterol; total cholesterol/high density lipoprotein (HDL) cholesterol ratio (P=0.002); and HDL apolipoprotein A-I concentration (P=0.062). Statistically significant within-pair resemblance was found for the changes in total and very low density lipoprotein (VLDL) cholesterol; total, VLDL and LDL triglycerides, and total, VLDL and LDL apolipoprotein B. The findings suggest that favorable changes in the lipid profile can be obtained through chronic negative energy balance achieved by clamping daily energy intake and adding daily moderate intensity exercise even in persons with relatively normal lipid levels at baseline. Furthermore, within-pair resemblance among twin brothers strongly suggests that genetic differences partially account for the variation in the response of lipids and lipoproteins to the negative energy balance protocol.

Objective: Impaired glucose tolerance (IGT) has been associated with alterations in numerous coronary heart disease risk factors, including postprandial hyperlipidemia. An excess visceral adipose tissue accumulation is also predictive of IGT and of an exaggerated postprandial lipemia. The objective of the present study was therefore to compare the respective contributions of visceral adipose tissue accumulation versus IGT with the variation in postprandial lipemia., Research Design and Methods: Potential differences in postprandial triglyceride (TG)-rich lipoprotein (TRL) levels following a standardized breakfast with a high fat content were examined among men characterized by normal glucose tolerance (NGT) or IGT. Sixty-seven men were classified according to their glucose tolerance status (<7.8 mmol/l [NGT] or between 7.8 and 11.1 mmol/l [IGT] 2 h after a 75-g oral glucose test)., Results: Men with IGT showed the highest TRL-TG concentrations (P < 0.05) at the 4-, 6-, and 8-h time points compared with men with NGT. These higher postprandial TRL-TG levels among men with IGT were also accompanied by a greater postprandial TG total area under the incremental curve in all TRL fractions (large, medium, and small) (P < 0.05). Furthermore, subjects characterized by IGT had also the highest visceral adipose tissue accumulation (P < 0.009). When subgroups of IGT and NGT men were individually matched (n = 11) for similar visceral adipose tissue accumulation, no significant difference was found in postprandial responses of all TRL-TG fractions between the two groups., Conclusions: These results provide evidence that visceral adipose tissue accumulation is an important factor involved in the deterioration of postprandial lipemia noted among men with IGT.

Cholesterol efflux capacities (CECs) are negatively associated with cardiovascular disease risk, irrespective of plasma high-density lipoprotein (HDL) cholesterol levels. Whether interventions targeting lifestyle improve HDL-CECs is unknown. Our objective was to determine whether improving dietary quality and increasing physical activity levels improves HDL-CECs in men with abdominal obesity and dyslipidemia. Our study sample included men (48 ± 8.5 yr) with an elevated waist circumference (≥90 cm) associated with dyslipidemia (triglycerides ≥1.69 and/or HDL cholesterol <1.03 mmol/l); 113 men completed a 1-yr intervention, consisting of a healthy eating and physical activity/exercise program, and 32 were included in a control group. An oral lipid tolerance test (OLTT) was performed in a subsample of 28 men who completed the intervention, and blood was collected every 2 h for 8 h. HDL-CECs were measured using [3H]cholesterol-labeled J774 macrophages and HepG2 hepatocytes. The lifestyle modification program led to an overall improvement in the cardiometabolic risk profile, increases in J774-HDL-CEC by 14.1% (+0.88 ± 1.09%, P < 0.0001), HepG2-HDL-CEC by 3.4% (+0.17 ± 0.75%, P = 0.01), and HDL cholesterol and apolipoprotein A-1 levels (13.5%, P < 0.0001 and 14.9%, P < 0.0001, respectively). J774-HDL-CECs and HepG2-HDL-CECs did not change in the control group. The best predictor for changes in HDL-CEC was apolipoprotein A-1 level. The lifestyle modification program also improved HDL-CEC response in postprandial lipemia during an OLTT. HDL-CEC did not change during the OLTT. Our results suggest that increasing physical activity levels and improving diet quality can have a positive impact on both HDL quantity and quality in men with abdominal obesity and dyslipidemia. [ABSTRACT FROM AUTHOR]

Context: Glucose and lipids stimulate the gut-hormones glucagon-like peptide (GLP)-1, GLP-2 and glucose-dependent insulinotropic polypeptide (GIP) but the effect of these on human postprandial lipid metabolism is not fully clarified. Objective: To explore the responses of GLP-1, GLP-2 and GIP after a fat-rich meal compared to the same responses after an oral glucose tolerance test (OGTT) and to investigate possible relationships between incretin response and triglyceride-rich lipoprotein (TRL) response to a fat-rich meal. Design: Glucose, insulin, GLP-1, GLP-2 and GIP were measured after an OGTT and after a fat-rich meal in 65 healthy obese (BMI 26.5–40.2 kg/m2) male subjects. Triglycerides (TG), apoB48 and apoB100 in TG-rich lipoproteins (chylomicrons, VLDL1 and VLDL2) were measured after the fat-rich meal. Main Outcome Measures: Postprandial responses (area under the curve, AUC) for glucose, insulin, GLP-1, GLP-2, GIP in plasma, and TG, apoB48 and apoB100 in plasma and TG-rich lipoproteins. Results: The GLP-1, GLP-2 and GIP responses after the fat-rich meal and after the OGTT correlated strongly (r = 0.73, p<0.0001; r = 0.46, p<0.001 and r = 0.69, p<0.001, respectively). Glucose and insulin AUCs were lower, but the AUCs for GLP-1, GLP-2 and GIP were significantly higher after the fat-rich meal than after the OGTT. The peak value for all hormones appeared at 120 minutes after the fat-rich meal, compared to 30 minutes after the OGTT. After the fat-rich meal, the AUCs for GLP-1, GLP-2 and GIP correlated significantly with plasma TG- and apoB48 AUCs but the contribution was very modest. Conclusions: In obese males, GLP-1, GLP-2 and GIP responses to a fat-rich meal are greater than following an OGTT. However, the most important explanatory variable for postprandial TG excursion was fasting triglycerides. The contribution of endogenous GLP-1, GLP-2 and GIP to explaining the variance in postprandial TG excursion was minor. [ABSTRACT FROM AUTHOR]

Fibrinogen has been prospectively found to correlate with coronary heart disease (CHD) but a similar association has not been well established for lipoprotein (a) (Lp(a)). Plasma lipids, Lp(a), and fibrinogen levels were measured in 2,125 men (aged 47 to 76 years) who were free of clinical CHD. During a 5-year follow-up period, 116 first CHD events were documented. Men with CHD were older, smoked more, had a higher prevalence of diabetes, and higher levels of systolic blood pressure, cholesterol, low-density lipoprotein cholesterol, Lp(a), and fibrinogen, and lower plasma high-density lipoprotein cholesterol levels. Only fibrinogen levels in the upper tertile of the distribution compared with the lower tertiles were associated with a significant risk of CHD (adjusted risk ratio 2.5; 95% confidence interval [CI] 1.4 to 4.2; p = 0.0010). Such an association was not observed with Lp(a). To assess a possible relation between fibrinogen and Lp(a) to the risk of CHD events, men were assigned to 1 of 4 groups according to fibrinogen median levels and a Lp(a) cut-off level of 300 mg/L: group 1: fibrinogen <4.05 g/L and Lp(a) <300 mg/L; group 2: fibrinogen <4.05 g/L and Lp(a) ≥300 mg/L; group 3: fibrinogen ≥4.05 g/L and Lp(a) <300 mg/L; and group 4: fibrinogen ≥4.05 g/L and Lp(a) ≥300 mg/L. Using group 1 as a reference, a significant risk ratio was only documented in group 4 (2.5; 95% CI 1.2 to 5.1; p = 0.0132). In this population, high fibrinogen levels associated with high Lp(a) levels significantly increased the risk of CHD. [Copyright &y& Elsevier]

Objectives In this study, we sought to determine the metabolic markers associated with structural valve degeneration ( SVD). Background Structural valve degeneration ( SVD) is the major cause of bioprosthetic valve failure leading to bioprostheses ( BPs) stenosis or regurgitation. We hypothesized that lipoprotein-associated phospholipase A2 ( Lp- PLA2) is involved in the SVD of BPs. Methods We included 197 patients who underwent aortic valve replacement with a bioprosthetic valve and had echocardiographic follow-up to evaluate valve function. Moreover, explanted BPs ( n = 39) were analysed by immunohistochemistry for the expression of Lp- PLA2. Results After a mean follow-up of 7·9 ±0·2 years, forty-one patients (21%) were identified as developing SVD. Patients with SVD had significantly higher plasma level of Lp- PLA2 mass (151·8 ± 9·2 ng/mL vs. 133·2 ± 3·4 ng/mL, P = 0·03) and activity (27·6 ± 0·9 nmol/min/mL vs. 25·0 ± 0·4 nmol/min/mL, P = 0·005). Multivariate analysis revealed that Lp- PLA2 activity ( OR: 1·09, 95% CI: 1·01-1·18; P = 0·03) was the strongest independent predictor of SVD. Immunohistochemistry studies of explanted BP showed that 77% of explanted BPs had the expression of Lp- PLA2, which correlated with the density of macrophages ( CD68), and ox- LDL levels in bioprosthetic tissues. Conclusions Increased blood plasma activity of Lp- PLA2 is associated with higher prevalence of SVD. These findings open new avenues for the identification of patients at risk for SVD and for the development of pharmacotherapy aiming at the prevention of SVD. [ABSTRACT FROM AUTHOR]

Background Calcific aortic valve disease ( CAVD) is a chronic disorder characterized by a fibrocalcific remodelling. It is suspected that lipid retention within the aortic valve may be one important mechanism participating to aortic valve remodelling. Lipoprotein lipase ( LPL) is implicated in lipid metabolism and may play a role in lipid retention within the aortic valve. Methods In 57 patients, CAVD were analysed for the expression of LPL by q- PCR and immunohistochemistry. Expression of oxidized- LDL (ox- LDL) and decorin was also documented. In addition, a complete blood profile, including the size of LDL and high-density lipoprotein ( HDL) particles, were performed to find associations between the blood lipid profile and expression of ox- LDL and LPL within CAVD. Results Immunohistochemistry studies revealed that LPL was expressed in stenotic aortic valves as a diffuse staining and also in dense cellular areas where macrophages were abundant. Expression of LPL co-localized with decorin and ox- LDL. In turn, valves with higher amount of ox- LDL had elevated number of LPL transcripts. In addition, we documented that the small, dense HDL phenotype was associated with an elevated amount of ox- LDL and LPL transcripts within CAVD. Furthermore, expression of LPL was associated with several indices of fibrocalcific remodelling of the aortic valve. Conclusion Expression of LPL within CAVD is related to the amount of ox- LDL, which is, in turn, associated with the small, dense HDL phenotype. Lipid retention associated with smaller HDL particles may participate in the expression of LPL, whereby a fibrocalcific remodelling of the aortic valve is promoted. [ABSTRACT FROM AUTHOR]

Excess visceral adipose tissue (VAT) is associated with an increased cardiometabolic risk. The study examined whether changes in cardiometabolic risk markers after a 1-year lifestyle intervention in viscerally obese men were associated with changes in VAT or with changes in subcutaneous abdominal adipose tissue (SAT). The relative contributions of changes in global adiposity vs. changes in cardiorespiratory fitness to changes in VAT were also quantified. One hundred and forty four men were selected on the basis of an increased waist circumference (≥90 cm) associated with dyslipidemia (triglycerides ≥1.69 and/or high-density lipoprotein (HDL)-cholesterol <1.03 mmol/l); 117 men completed the 1-year intervention which consisted in a healthy eating, physical activity/exercise program. Body weight, body composition, and fat distribution were assessed by anthropometry and dual-energy X-ray absorptiometry (DEXA)/computed tomography. Cardiorespiratory fitness, plasma adipokine/inflammatory markers, fasting lipoprotein-lipid profile, and oral glucose tolerance test (OGTT) were assessed. VAT volume decreased by 26%, cardiorespiratory fitness improved by 20% (P < 0.0001) after 1 year. Plasma adipokine/inflammatory markers, lipids/lipoproteins, and glucose homeostasis were improved. One-year changes in triglyceride (r = 0.29), apolipoprotein B (r = 0.21), 120-min OGTT-glucose (r = 0.27), and fasting insulin (r = 0.27) levels correlated with changes in VAT (all P < 0.05) after adjustment for changes in SAT. Using a multilinear regression model, VAT reduction was independently associated with SAT reduction and with improvement in cardiorespiratory fitness (R2 = 0.58, P < 0.0001). Therefore, this healthy eating-physical activity/exercise program improved the cardiometabolic risk profile of viscerally obese men in relation to the reduction of VAT. Furthermore, the reduction in VAT was independently related to the reduction in global adiposity and to the improvement in cardiorespiratory fitness. [ABSTRACT FROM AUTHOR]

Objectives: Long-term durability of bioprosthetic heart valves (BPs) are limited by structural valve degeneration (SVD) leading to stenosis and/or regurgitation. In this study, we sought to determine the metabolic markers associated with SVD. Methods: In a cohort of 220 patients with an aortic BP (mean follow-up of 2.5 ± 1.2 years), we compared the metabolic and blood lipid profile including the levels of adiponectin and the proportion of small, dense low-density lipoprotein (LDL) particles (%LDL<255Å) in individuals developing echocardiographic evidence of early BP hemodynamic dysfunction with subjects having no features of BP dysfunction. Results: Patients developing BP dysfunction (n = 69; 31.3%) had a tendency of higher triglyceride levels. Moreover, patients with BP dysfunction had an increased proportion of %LDL<255Å. In multivariate linear regression analysis, after adjustment for age, gender, BP size and hypertension, the %LDL<255Å (p = 0.04) was significantly associated with BP dysfunction. In addition, patients with an elevated level of %LDL<255Å along with a decreased plasma adiponectin level were at a very high risk of developing early BP hemodynamic dysfunction (OR = 2.54, p = 0.04). Conclusion: BP dysfunction is significantly associated with an increased proportion of small, dense LDL. Copyright © 2012 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background Although the total to high-density lipoprotein cholesterol ratio (TC ⁄ HDL-C) has been used for decades to identify individuals at risk for coronary heart disease (CHD), apolipoprotein-based (apolipoprotein B⁄ apolipoprotein A-I [apoB ⁄ apoA-I]) and nuclear magnetic resonance spectroscopy (NMR)-based lipoprotein concentrations (low-density lipoproteinNMR ⁄ high-density lipoproteinNMR [LDLNMR ⁄HDLNMR]) may also be useful for CHD risk stratification. Materials and methods In a case–control study conducted within the European Prospective Investigation into Cancer and Nutrition (EPIC)-Norfolk study population, 870 individuals who developed CHD during a 6-year follow-up were matched to 1659 controls on the basis of gender, age and enrolment time. LDLNMR and HDLNMR were measured by proton NMR spectroscopy. Results After adjusting for traditional CHD risk factors, men in the top quintile of the various lipoprotein ratios proved to be at increased CHD risk (OR = 2Æ59 [95% IC, 1Æ76–3Æ83] for TC ⁄ HDL-C ratio, 2Æ59 [1Æ75–3Æ83] for apo- B⁄ apoA-I ratio and 2Æ78 [1Æ86–4Æ17] for LDLNMR ⁄HDLNMR ratio) compared with men in the bottom quintile. Similar associations were observed in women (OR = 2Æ86 [1Æ71–4Æ80] for TC ⁄ HDL-C ratio, 2Æ94 [1Æ74–4Æ97] for apoB ⁄ apoA-I ratio and 2Æ03 [1Æ21–3Æ43] for LDLNMR ⁄HDLNMR ratio). Compared with participants with only one component of the metabolic syndrome, those who had five had an increased TC ⁄ HDL-C ratio (73Æ0% and 80Æ4% in men and women respectively), apoB ⁄ apoA-I ratio (58Æ0% and 62Æ9% in men and women respectively) and for LDLNMR ⁄HDLNMR ratio (52Æ6% and 54Æ1% in men and women respectively). Conclusion In this European study population, the TC ⁄ HDL-C, apoB ⁄ apoA-I and LDLNMR ⁄HDLNMR ratios were similarly associated with components of the metabolic syndrome and CHD risk. [ABSTRACT FROM AUTHOR]

Global risk calculators such as the Framingham risk score generally take into account traditional risk factors such as age, sex, blood pressure, smoking status, total cholesterol and high-density lipoprotein cholesterol levels, and the presence of diabetes which are recommended to be used in clinical practice to estimate patients’ cardiovascular disease (CVD) risk. Over the last decades, the prevalence of obesity has dramatically increased all over the world. The deleterious form of obesity, visceral obesity, is the most prevalent form of the so-called metabolic syndrome, a constellation of risk factors associated with perturbations of the lipoprotein-lipid profile and of the plasma glucose-insulin homeostasis also likely to be associated with increased blood pressure and a proinflammatory and prothrombotic state. To this date, metabolic syndrome is still in need of a place in global CVD risk prediction. As the metabolic syndrome is not likely to replace currently used global risk scoring algorithms, both traditional risk factors and emerging metabolic markers associated with the metabolic syndrome should be incorporated in future risk scoring systems to be developed in order to adapt CVD risk prediction tools to the epidemic of obesity which has direct consequences on the daily life of health professionals. Copyright © 2008 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: High-density lipoprotein (HDL) cholesterol levels are inversely related to risk for coronary artery disease (CAD). Because HDL particles are heterogeneous in size and composition, they may be differentially associated with other cardiovascular risk factors and with cardiovascular risk. Objective: To study the independent relationships of HDL size and particle concentration to risk for future CAD. Design: Nested case-control study within the EPIC (European Prospective Investigation into Cancer and Nutrition)-Norfolk cohort; baseline survey between 1993 and 1997, follow-up until November 2003. Setting: Norfolk, United Kingdom. Participants: Case patients were 822 apparently healthy men and women who developed CAD during follow-up. Control participants were 1401 participants who remained without CAD and were matched to case patients by sex, age, and enrollment time. Measurements: First CAD event leading to either hospitalization or death. Results: Nuclear magnetic resonance spectroscopy-measured HDL particle concentration (mean, 33.9 μmol/L [SD, 5] vs. 32.9 μmol/L [SD, 6]; P = 0.001) and HDL size (mean, 8.9 nm [SD, 0.5] vs. 8.8 nm [SD, 0.5]; P < 0.001), as well as gradient gel electrophoresis- measured HDL size (mean, 8.9 nm [SD, 0.4] vs. 8.8 nm [SD, 0.4]; P < 0.005) were lower in case patients than in control participants. High-density lipoprotein size and HDL particle concentration were only weakly correlated (r = 0.08, for those measured with nuclear magnetic resonance spectroscopy; r = 0.10, for those measured with gradient gel electrophoresis). High-density lipoprotein size was strongly associated with risk factors characteristic of the metabolic syndrome, including waist-to-hip ratio, triglyceride level, and apolipoprotein B level, whereas HDL particle concentration was not. Both HDL size and HDL particle concentration were independently associated with CAD risk. The association between HDL size and CAD risk was abolished on adjustment for apolipoprotein B and triglyceride levels (adjusted odds ratio, 1.00 [95% CI, 0.71 to 1.39] for top vs. bottom quartile), whereas HDL particle concentration remained independently associated with CAD risk (adjusted odds ratio, 0.50 [CI, 0.37 to 0.66]). Limitation: Measurements were performed in nonfasting blood samples, and residual confounding cannot be excluded. Conclusion: Both HDL size and HDL particle concentration were independently associated with other cardiovascular risk factors and with the risk for CAD. The relationship between HDL size and CAD risk was explained by markers associated with the metabolic syndrome, indicating that part of the relationship between HDL cholesterol and CAD risk is merely a reflection of this metabolic risk. Funding: The Medical Research Council and Cancer Research UK, the European Union, Stroke Association, British Heart Foundation, United Kingdom Department of Health, Food Standards Agency, the Wellcome Trust, and the Future Forum. [ABSTRACT FROM AUTHOR]

We investigated the associations between the hepatic lipase gene (LIPC) -514C>T polymorphism and lipases, lipoproteins, and insulin sensitivity (Si) responses to exercise training. Hepatic lipase and lipoprotein lipase activities, plasma lipoprotein levels, and Si were measured in the sedentary state and post-exercise training in the Health, Risk Factors, Exercise Training, and Genetics (HERITAGE) Family Study (n = 662). The LIPC -514C allele frequency was 0.516 (blacks) and 0.796 (whites). Baseline and post-exercise training hepatic lipase activities were 40% higher in CC homozygotes (P < 0.0001) in both races. Black CC homozygotes had lower baseline lipoprotein lipase activity, HDL cholesterol, HDL3, and apolipoprotein (apo)A-1 concentrations. White CC homozygotes had lower baseline HDL cholesterol, apoA-1, LDL cholesterol, and apoB levels that remained low post-exercise training. Baseline Si was not associated with the LIPC genotypes. However, training-induced improvements in Si both in blacks and whites were greater in CC homozygotes (+1.25 ± 0.2 and +0.22 ± 0.2 µU ⋅ min-1 ⋅ ml-1) than in the TT genotype (+0.27 ± 0.3 and -0.97 ± 0.3 µU ⋅ min-1 ⋅ ml-1 (P = 0.008 and P = 0.002, respectively). The LIPC -514C allele was associated with higher hepatic lipase activity in sedentary and physically active states and better Si responses to regular exercise both in black and white individuals. The benefits from an exercise program on Si are likely to be substantial in the general population given the high frequency of the LIPC -514C allele, particularly in whites. [ABSTRACT FROM AUTHOR]

Microsomal triglyceride transfer protein (MTP) plays a critical role in the assembly of lipoproteins. The aim of this study was first to seek new MTP gene variants and then to verify whether MTP gene polymorphisms were associated with plasma lipoprotein/lipid levels in men with visceral obesity. Molecular screening of the MTP gene revealed 11 polymorphisms. The carriers of the c.933A allele and c.1151C allele or -400A/A homozygotes were characterized by increased levels of abdominal visceral adipose tissue (AT) measured by computed tomography (P=0.02,P=0.04,P=0.03, respectively). After dividing each genotype group into subgroups using 130 cm2 as a cutoff point for visceral AT, significantly higher low-density lipoprotein (LDL)-apolipoprotein B (apoB) concentrations were found in obese men bearing the c.891G allele, the -400 T allele, as well as for 282G/G homozygotes, 933C/C homozygotes, and 1151A/A homozygotes when compared to their lean counterparts. Haplotypes were not associated with phenotypes under study. In conclusion, some MTP gene polymorphisms in the French Canadian population are associated with the amount of abdominal visceral AT and plasma LDL-apoB concentrations. [ABSTRACT FROM AUTHOR]

Twelve pairs of male monozygotic (MZ) twins (mean age±S.D.: 21±2 years) were subjected to an overfeeding protocol of 4.2 MJ (1000 kcal) above their pre-established individual daily energy needs, 6 days a week, over a period of 100 days. Body weight increased significantly (gain of 8.1 kg, P<0.001), as did fat mass (5.4 kg, P<0.001) after overfeeding. Plasma triacylglycerol (TG) levels significantly increased (P<0.05) without change in plasma cholesterol (CHOL). Plasma very-low-density-lipoprotein (VLDL)–TG, VLDL–Apoprotein (Apo) B, low-density-lipoprotein cholesterol (LDL-C) and LDL–Apo B (P≤0.05) rose, whereas high-density-lipoprotein cholesterol (HDL-C) levels fell (P<0.05) raising the CHOL/HDL-C ratio (20%) (P<0.001). Considerable individual differences occurred in plasma lipoprotein responses to overfeeding. However, these changes were not random; significant within-pair resemblance registered for the response of plasma CHOL, TG, VLDL–TG, VLDL-C, LDL–TG, HDL-C, HDL–Apo A–I, HDL2-C, HDL3-C to overfeeding (0.48≤ri≤0.85). Furthermore, a high within-pair resemblance was found for changes in ratios of CHOL/HDL-C (ri=0.86, P<0.0001) and HDL2-C/HDL3-C (ri=0.69, P<0.01). These results strongly suggest that the response of plasma lipoproteins to chronic energy surplus has a significant genetic component as does the detrimental effect of chronic caloric affluence on CHD risk. [Copyright &y& Elsevier]

We compared the effects of ad libitum consumption of a defined high complex carbohydrate (CHO) diet (% of energy: CHO, 58.3; fat, 25.8) vs. a defined high monounsaturated fatty acid (MUFA) diet (% of energy: CHO, 44.7; fat, 40.1; MUFA, 22.5) on LDL electrophoretic characteristics. Healthy men [n = 65; age, 37.5 +/- 11.2 (mean +/- SD) y; BMI, 29.2 +/- 4.9 kg/m2] were randomly assigned to one of the two diets that they consumed for 6-7 wk. The high CHO diet significantly reduced body weight (-2%). The diet-induced reduction in plasma LDL cholesterol (C) levels in the high-CHO diet group was due mainly to concurrent reductions in the cholesterol content of small (<25.5 nm, P < 0.01) and medium-sized LDL (25.5-26.0 nm, P = 0.01). The high MUFA diet also reduced body weight, and LDL-C and LDL-apolipoprotein (apo)B levels, which were comparable to those in the high CHO group. The cholesterol levels of small LDL particles tended to be reduced (P = 0.24) in the high MUFA group (-12%), similar to changes in the high CHO group. These results suggest that, when associated with weight loss, ad libitum consumption of high CHO and high MUFA diets may be considered to be equally beneficial for the management of LDL-related atherogenic dyslipidemia. However, the high MUFA diet more favorably affected triglyceride levels, suggesting that it may be preferable to a high CHO diet in cardiovascular disease prevention. [ABSTRACT FROM AUTHOR]

The aim of the HERITAGE Family Study was to investigate individual differences in response to a standardized endurance exercise program, the role of familial aggregation, and the genetics of response levels of cardiorespiratory fitness and cardiovascular disease and diabetes risk factors. Here we summarize the findings and their potential implications for cardiometabolic health and cardiorespiratory fitness. It begins with overviews of background and planning, recruitment, testing and exercise program protocol, quality control measures, and other relevant organizational issues. A summary of findings is then provided on cardiorespiratory fitness, exercise hemodynamics, insulin and glucose metabolism, lipid and lipoprotein profiles, adiposity and abdominal visceral fat, blood levels of steroids and other hormones, markers of oxidative stress, skeletal muscle morphology and metabolic indicators, and resting metabolic rate. These summaries document the extent of the individual differences in response to a standardized and fully monitored endurance exercise program and document the importance of familial aggregation and heritability level for exercise response traits. Findings from genomic markers, muscle gene expression studies, and proteomic and metabolomics explorations are reviewed, along with lessons learned from a bioinformatics-driven analysis pipeline. The new opportunities being pursued in integrative -omics and physiology have extended considerably the expected life of HERITAGE and are being discussed in relation to the original conceptual model of the study. [ABSTRACT FROM AUTHOR]

Background and aims Elevated levels of lipoprotein(a) [Lp(a)] and oxidized phospholipids on apolipoprotein B-100 (OxPL-apoB) predict the progression of pre-existing mild-to-moderate calcific aortic valve stenosis (CAVS). Whether indirect markers of oxidation-specific epitopes (OSE) are also predictive is not known. The association between IgG and IgM autoantibodies and malondialdehyde-modified low density lipoprotein (MDA-LDL) and IgG and IgM apolipoprotein B immune complexes (apoB-IC), and the hemodynamic progression rate of CAVS was determined in the ASTRONOMER (Aortic Stenosis Progression Observation: Measuring Effects of Rosuvastatin, NCT00800800) trial. Methods Plasma levels of IgG and IgM MDA-LDL and apoB-IC were measured in 220 patients with mild-to-moderate CAVS from the ASTRONOMER trial. The endpoint of this study was the progression rate of CAVS, measured by the annualized increase in peak aortic jet velocity (V peak ) over a median follow-up of 3.5 [2.9–4.5] years. Results There was no difference in the progression rate of CAVS across tertiles of IgG and IgM MDA-LDL and apoB-IC levels (all p > 0.05). After multivariable analysis, no marker reached significance level to predict faster CAVS progression or need for aortic valve replacement (all p > 0.05). There was no interaction between the OSE antibody titers and plasma levels of Lp(a) or OxPL-apoB, as well as age, with regards to the progression rate of CAVS. Conclusions Autoantibody titers to MDA-LDL and apoB-IC, which are an indirect measurement of OSE, unlike direct measurements of OxPL-apoB or their major lipoprotein carrier Lp(a), do not predict the progression of CAVS or need for AVR. [ABSTRACT FROM AUTHOR]

Background: Elevated lipoprotein(a) (Lp[a]) is associated with aortic stenosis (AS). Oxidized phospholipids (OxPL) are key mediators of calcification in valvular cells and are carried by Lp(a). Objectives: This study sought to determine whether Lp(a) and OxPL are associated with hemodynamic progression of AS and AS-related events. Methods: OxPL on apolipoprotein B-100 (OxPL-apoB), which reflects the biological activity of Lp(a), and Lp(a) levels were measured in 220 patients with mild-to-moderate AS. The primary endpoint was the progression rate of AS, measured by the annualized increase in peak aortic jet velocity in m/s/year by Doppler echocardiography; the secondary endpoint was need for aortic valve replacement and cardiac death during 3.5 ± 1.2 years of follow-up. Results: AS progression was faster in patients in the top tertiles of Lp(a) (peak aortic jet velocity: +0.26 ± 0.26 vs. +0.17 ± 0.21 m/s/year; p = 0.005) and OxPL-apoB (+0.26 ± 0.26 m/s/year vs. +0.17 ± 0.21 m/s/year; p = 0.01). After multivariable adjustment, elevated Lp(a) or OxPL-apoB levels remained independent predictors of faster AS progression. After adjustment for age, sex, and baseline AS severity, patients in the top tertile of Lp(a) or OxPL-apoB had increased risk of aortic valve replacement and cardiac death. Conclusions: Elevated Lp(a) and OxPL-apoB levels are associated with faster AS progression and need for aortic valve replacement. These findings support the hypothesis that Lp(a) mediates AS progression through its associated OxPL and provide a rationale for randomized trials of Lp(a)-lowering and OxPL-apoB-lowering therapies in AS. (Aortic Stenosis Progression Observation: Measuring Effects of Rosuvastatin [ASTRONOMER]; NCT00800800). [ABSTRACT FROM AUTHOR]

Objectives: This study sought to document the presence and role of lipoprotein-associated phospholipase A2 (Lp-PLA2) in calcific aortic valve disease (CAVD). Background: CAVD is a chronic disorder characterized by pathological mineralization and remodeling. Studies have indicated that human CAVD tissues are infiltrated by lipids and that inflammation may play a role in the pathobiology. We hypothesized that Lp-PLA2 (encoded by the PLA2G7 gene) is expressed in CAVD and may play a role in the mineralization of valve interstitial cells. Methods: We have documented the expression of the phospholipase A2 family of genes in aortic valves by using a transcriptomic assay. Messenger ribonucleic acid and protein expression were confirmed in aortic valves explanted from 60 patients by quantitative polymerase chain reaction and immunohistochemistry, respectively. The effect of lysophosphatidylcholine, the product of Lp-PLA2 activity, was documented on the mineralization of valve interstitial cell cultures. Results: Transcriptomic analyses of CAVD and control nonmineralized aortic valves revealed that Lp-PLA2 was increased by 4.2-fold in mineralized aortic valves. Higher expression of Lp-PLA2 in stenotic aortic valves was confirmed by quantitative polymerase chain reaction, immunohistochemistry, and enzymatic Lp-PLA2 activity. The number of Lp-PLA2 transcripts correlated with several indexes of tissue remodeling. In vitro, lysophosphatidylcholine increased the expression of alkaline phosphatase, the ectonucleotide pyrophosphatase/phosphodiesterase 1 enzyme, sodium-dependent phosphate cotransporter 1 (encoded by the SLC20A1 gene), and osteopontin. We then showed that lysophosphatidylcholine-induced mineralization involved ectonucleotidase enzyme as well as apoptosis through a protein-kinase-A-dependent pathway. Conclusions: Together, these results demonstrated that Lp-PLA2 is highly expressed in CAVD, and it plays a role in the mineralization of valve interstitial cells. Further work is necessary to document whether Lp-PLA2 could be considered as a novel target in CAVD. [ABSTRACT FROM AUTHOR]

Background. Cardiovascular disease is a major cause of morbidity and mortality after renal transplantation. Prednisone (Pred) maintenance therapy is associated with risk factors for atherosclerosis. Therefore, we were interested in quantifying the effects of Pred withdrawal on body weight and waist circumference as well as on metabolic markers of coronary heart disease risk. Methods. Twenty-six cyclosporine-treated renal transplant patients (13 men and 13 women) were evaluated before and after at least 11 months (16 ± 2.9 months) of Pred withdrawal. A complete fasting lipoprotein-lipid profile as well as anthropometric measurements were obtained from each patient. Results. Pred withdrawal was associated with a 6.0% reduction of body weight (-4.34 ± 5.40 kg; P < 0.05) and with a 7.7% decrease in waist girth (-7.13 ± 5.75 cm; P < 0.005) in women, whereas no change in these variables were observed in men. In both genders, plasma low-density lipoprotein (LDL) cholesterol and triglyceride concentrations were unaffected by Pred withdrawal, whereas plasma high-density lipoprotein (HDL) cholesterol levels decreased by 14.0% in women (-0.22 ± 0.22 mmol/L; P < 0.005) and 22.0% in men (-0.36 ± 0.28 mmol/L; P < 0.005). Pred withdrawal was associated with a significant reduction in plasma apolipoprotein B concentrations in both women (-0.28 ± 0.15 g/L; -24.6%; P < 0.0001) and men (-0.22 ± 0.19 g/L; -20.5%; P < 0.005). A significant reduction in fasting insulin was observed in both women (-27.8 ± 27.9 pmol/L; -25.3%; P < 0.005) and men (-25.0 ± 32.8 pmol/L; -21.4%; P < 0.05), whereas the LDL peak particle size was unaffected by Pred withdrawal. Conclusions. Pred withdrawal modifies several anthropometric and metabolic cardiovascular risk factors in renal transplant patients. Furthermore, female patients may derive further benefits of Pred withdrawal resulting from the concomitant loss of body weight and abdominal... [ABSTRACT FROM AUTHOR]

The aim of the present study was to examine the impact of the defective D9N and the null P207L mutations in the lipoprotein lipase (LPL) gene on high density lipoprotein (HDL) particle size in relation to specific environmental factors such as obesity, gender and menopausal status. Analyses were carried out in 118 heterozygous carriers of the D9N mutation and 88 heterozygous for the P207L mutation. HDL particle size was measured on whole plasma by non-denaturing 4–30% polyacrylamide gradient gel electrophoresis. Although carriers of the P207L mutation presented a more deteriorated lipoprotein–lipid profile compared with carriers of the D9N mutation, there was no difference in HDL particle size between the P207L and D9N carriers (81.9±4.5 vs. 82.7±4.4 A˚, respectively, P=0.2). Multivariate analyses indicated that waist circumference (P=0.001) and HDL cholesterol levels (P<0.001) were independent predictors of HDL particle size among carriers of the defective D9N mutation. On the other hand, gender (P=0.03), plasma cholesterol (P=0.01) and TG (P=0.04) levels were significant predictors of HDL particle size among carriers of the null P207L mutation in multivariate analyses. These results suggest that the nature of the mutation in the LPL gene modifies the relationship of HDL particle size to other metabolic variables and secondary factors such as abdominal obesity and gender. [Copyright &y& Elsevier]

The dyslipidemic state of visceral obesity is characterized by increased plasma triglyceride levels, low high-density lipoprotein-cholesterol concentration and alterations in low-density lipoprotein (LDL) composition and concentration. A functional, non-coding microsomal triglyceride transfer protein (MTP) −493G/T polymorphism of the microsomal triglyceride transfer protein gene has been related to variations in LDL-cholesterol levels. To study the effect of the MTP −493G/T polymorphism on lipoprotein levels in visceral obesity and hyperinsulinemia, a total of 227 men were assigned into two groups on the basis of their MTP −493G/T polymorphism, including 121 GG homozygotes and 105 carriers of the T allele (92 GT and 13 TT). The two genotypic groups did not differ for their physiological characteristics nor for lipoprotein–lipid profiles, before and after adjustment for age. However, GG homozygotes were characterized by higher fasting insulin levels than carriers of the T allele (P<0.05). When the two genotypic groups were further divided on the basis of their visceral adipose tissue (AT) accumulation, assessed by computed tomography, we observed that T allele carriers with low levels of visceral AT (<130 cm2) had decreased plasma total cholesterol and LDL-apolipoprotein B (LDL-apoB) levels compared to viscerally obese men (P=0.035 and P=0.0001, respectively). Among GG homozygotes, no significant difference were observed. Although not significant, T allele carriers characterized by visceral obesity tended to have smaller, denser LDL particles than T allele carriers characterized by a low accumulation of visceral AT. When subjects were divided on the basis of their fasting insulin levels, it appears that hyperinsulinemic men were characterized by a deteriorated lipoprotein–lipid profile when they were carriers of the T allele compared to normoinsulinemic men. In summary, visceral obesity and hyperinsulinemia modulate the impact of the MTP −493G/T polymorphism on plasma total cholesterol and LDL-apoB levels, as well as on LDL peak particle diameter. [Copyright &y& Elsevier]

Introduction: Visceral adiposity increases the level of atherogenic lipoproteins and is linked to sex-related differences in cardiovascular risk. Hypothesis. Atherogenic lipoproteins could mediate the relationship between visceral fat and sex-related differences in atherosclerosis burden and composition, including the lipid-rich necrotic core (LRNC). Methods: This study included 294 women (39.4 ± 15.0 years) and 324 men (39.5 ± 13.8 years), matched for age and risk factors (hypertension, dyslipidemia, obesity, diabetes, smoking). Carotid atherosclerosis, visceral abdominal fat (VAT) and cardiac fat (CAT) were studied by magnetic resonance imaging. Results: For similar age and risk profile, women had less VAT (p <0.001) and CAT (p <0.001) than men. Carotid atherosclerosis prevalence (p <0.001) and carotid wall volume (p <0.001) were higher in men. Although LRNC prevalence was similar in women and men (p =0.23), men had a greater LRNC volume (p <0.001). An interaction was observed between waist-to-hip ratio (WHR) and sex on LRNC volume (p =0.025). There was also an interaction between sex, VAT, and total cholesterol/high-density lipoprotein cholesterol ratio (TC/HDL-C) on LRNC volume (p =0.012), beyond age and risk factors (p =0.011). Only 8.6% of men and none of the women were classified at high risk (presence of LRNC) by the Framingham Risk Score while 35.4% of men and 14.0% of women were classified at high risk by the Pathobiological Determinants of Atherosclerosis in Youth (PDAY) risk score (risk of advanced atherosclerosis). Elevated TC/HDL-C (≥3) and/or WHR (≥0.8 in women, ≥0.9 in men) were superior to the PDAY risk score, identifying 62.2% of women (Net Reclassification Improvement [NRI]=1.85, p <0.001) and 79.3% of men (NRI=0.26, p <0.001) with LRNC. Conclusions: Women had less visceral adiposity, carotid atherosclerosis burden and LRNC volume, independently of age and risk profile. Carotid LRNC volume varied with sex, VAT, and atherogenic lipoproteins. WHR and TC/HDL-C improved the identification of high-risk carotid atherosclerosis features in women as well as men. This evidence supports the clinical potential of the atherogenic lipoprotein profile and of adiposity distribution in atherosclerosis risk evaluation of both women and men. [ABSTRACT FROM AUTHOR]

Introduction: Elevated levels of apolipoprotein CIII (ApoCIII) are associated with elevated triglycerides, metabolic syndrome and cardiovascular disease. Objectives: To assess whether apoC-III, complexes of apoCIII-Lp(a), autotaxin mass on apolipoprotein B-100 (ATX-apoB) and Lp(a) (ATX-Lp(a)) associate with progression of calcific aortic valve stenosis (AS), need for aortic valve replacement (AVR) and if they associate with Lp(a) and oxidized phospholipids (OxPL) on apoB (OxPL-apoB) and Lp(a) (OxPL-apo(a)). Methods: A proteomic analysis of purified Lp(a) was performed. Immunostaining for ApoC-III was performed in aortic valve leaflets in 68 patients. The above biomarkers were measured in 218 patients with mild-moderate AS from the ASTRONOMER trial. The progression rate of AS, measured as annualized changes in peak aortic jet velocity (Vpeak), and combined rates of AVR and cardiac death were determined. Results: Proteomic analysis of Lp(a) showed that apoC-III was the 3rd most prominent protein after apoB-100 and apolipoprotein(a). Immunocytochemically-detected ApoC-III was prominent in all grades of leaflet lesion severity, co-localized with but present more broadly than Lp(a) and OxPL. Total ApoC-III, ApoCIII-Lp(a), ATX-apoB and ATX-Lp(a) showed no differences in annualized Vpeak. Significant interactions were present between ApoCIII-Lp(a) and Lp(a), OxPL-apoB and OxPL-apo(a) with annualized Vpeak (all p<0.05). After multivariable adjustment, patients in the top tertile of both apoCIII-Lp(a) and Lp(a) had significantly higher annualized Vpeak (0.37±0.08 vs. 0.18±0.02 m/s/year, p<0.001) and risk of AVR/cardiac death (HR=2.56, 95% CI 1.12-5.86, p=0.03) compared to middle and bottom tertiles. Similar results were noted with OxPL-apoB and OxPL-apo(a). Conclusions: ApoC-III is a prominent apolipoprotein on Lp(a) and in aortic valve leaflets. Elevated levels of ApoCIII-Lp(a) complexes in conjunction with Lp(a), OxPL-apoB or OxPL-apo(a) identify patients with pre-existing mild-moderate CAVS who display rapid progression of AS and higher rates of AVR/cardiac death [ABSTRACT FROM AUTHOR]

Given the controversy around HDL-C as a therapeutic target, there is a need to investigate other features of HDL and how they respond to various preventive interventions. We tested the hypothesis that regular exercise would have beneficial effects on HDL particle (HDL-P) traits in sedentary adults. Methods: The following HDL-P traits were measured via NMR (Liposcience Inc.) before and after completion of a 20-week exercise program in the HERITAGE Family Study (N=715): concentration of total, large, medium, and small HDL-P and mean HDL-P size. ANCOVA was used to test for aggregation of HDL-P trait responses in families controlling for age, sex, and baseline BMI and trait value. Results: The concentration of large HDL-P significantly increased in response to regular exercise in both Black and White participants, while the increase was significantly larger in females compared to males (Table 1). In general, regular exercise decreased the concentration of medium and small HDL-P. Together, these responses contributed to a significant increase in the average cholesterol content of HDL particles. Exercise-induced changes in large HDL-P were inversely correlated with changes in fat mass and systolic blood pressure. Moreover, changes in BMI were significantly associated with changes in all of the HDL-P traits, but not with HDL-C. We found significant evidence of familial aggregation for the exerciseinduced changes in HDL-P traits in both races, as there was 1.4 to 1.6 times more variance between than within families for the changes in total (p=0.02 in Whites) and large HDL-P (p=0.004 in Whites, p=0.02 in Blacks) and HDL-P size (p=0.0009 in Whites, p=0.009 in Blacks). Conclusion: The HDL-P subclass profile favorably responded to regular exercise in sedentary Black and White adults, highlighted by increases in the concentration of large HDL-P, and may be influenced by a significant genetic component. We provide evidence that regular exercise could potentially be used as an HDL-based therapy designed to target beneficial subfractions. [ABSTRACT FROM AUTHOR]