Proportion Of Small LDL Particles Research Articles

Relationship between noninvasive scores of nonalcoholic fatty liver disease and nuclear magnetic resonance lipoprotein abnormalities: A focus on atherogenic dyslipidemia

Nonalcoholic fatty liver disease (NAFLD) is an emerging, highly prevalent, cardiovascular risk factor, and lipoprotein proatherogenic disturbances likely explain a large part of this risk. However, information regarding associations between detailed nuclear magnetic resonance (NMR) lipoprotein changes and noninvasive NAFLD scores is lacking. The objective of the study was to investigate the NMR-assessed atherogenic lipoprotein profile according to noninvasive NAFLD status. Lipoprotein profiles by NMR spectroscopy and NAFLD status by fatty liver index (FLI) and Gholam's models. We assessed 173 participants (55% males), mean age 60.8±7.8years, 87% overweight/obese, 53% with diabetes. An FLI <30, 30 to 60, and >60 was found in 32, 50, and 91 participants, respectively. Individuals with FLI >60 had lower high-density lipoprotein (HDL)-cholesterol (P<.001), higher triglyceride (P<.001), and similar non-HDL-cholesterol (P=.912) concentrations. In NMR analysis, FLI was related with very-low-density lipoprotein (VLDL) and HDL parameters in a dose-dependent manner. VLDL particle number (P<.001) and VLDL size (39.1±0.99, 39.7±0.96, 40.8±1.19nm, P<.001) increased with increased FLI (<30, 30-60, and >60, respectively). Conversely, although total HDL particle number did not differ by FLI (P=.377), larger HDL particles (P<.001), amount of cholesterol within HDL particles (P<.001), and HDL size (median [p25-p75]: 8.23 [8.08-8.41], 8.12 [8.03-8.29], 8.04 [7.93-8.16]nm, P<.001) decreased as FLI increased. FLI >60 (vs <60) was associated with a higher proportion of small LDL particles (P=.010) and lower LDL size (19.85±0.34 vs 19.98±0.25nm; P=.005). Similar findings were found for Gholam's model. Simple and noninvasive NAFLD scores are useful to detect many of the proatherogenic changes (especially in VLDL and HDL), beyond conventional lipids parameters that are common in individuals with this high-risk condition.

Alternate day fasting with a high fat diet: Impact on body weight, body composition, and coronary heart disease risk profile in obese adults

BackgroundAlternate day fasting (ADF) with a low‐fat (LF) diet is effective for weight loss and cardio‐protection. However, the applicability of these findings is questionable as most Americans consume a high‐fat (HF) diet. This study examined if these beneficial changes in weight and coronary heart disease (CHD) risk can be reproduced if a HF diet is used in place of a LF diet during ADF.MethodsThirty‐two obese subjects were randomized to an ADF‐HF (45% fat) or ADF‐LF diet (25% fat), which consisted of two phases: 1) a 2‐week baseline weight maintenance period, and 2) an 8‐week ADF weight loss period. All food was provided to subjects.ResultsBody weight was reduced (P &lt; 0.0001) by ADF‐HF (5 ± 1%) and by ADF‐LF (4 ± 1%). Fat mass decreased (P &lt; 0.0001) by ADF‐HF (5 ± 1 kg) and ADF‐LF (4 ± 1 kg). Fat free mass remained unchanged. Waist circumference decreased (P &lt; 0.001) by ADF‐HF (7 ( 1 cm) and ADF‐LF (7 ( 1 cm). LDL cholesterol and triacylglycerol concentrations were reduced (P &lt; 0.01) by both interventions (ADF‐HF: 18 ( 5%, 14 ( 5%; ADF‐LF: 24 ( 3%, 14 ( 4%). The proportion of small LDL particles decreased (P &lt; 0.05) in the ADF‐HF and ADF‐LF groups by 8 ( 3% and 10 ( 4%.ConclusionThus, an ADF‐HF diet produces similar reductions in weight and CHD risk as an ADF‐LF diet. These findings are important in terms of diet tolerability and long‐term adherence to ADF diets.

Improvement in coronary heart disease risk factors during an intermittent fasting/calorie restriction regimen: Relationship to adipokine modulations

BackgroundThe ability of an intermittent fasting (IF)‐calorie restriction (CR) regimen (with or without liquid meals) to modulate adipokines in a way that is protective against coronary heart disease (CHD) has yet to be tested.ObjectiveAccordingly, we examined the effects of an IFCR diet on adipokine profile, body composition, and markers of CHD risk in obese women.MethodsSubjects (n = 54) were randomized to either the IFCR‐liquid (IFCR‐L) or IFCR‐food based (IFCR‐F) diet for 10 weeks.ResultsGreater decreases in body weight and waist circumference were noted in the IFCR‐L group (4 ± 1 kg; 6 ± 1 cm) versus the IFCR‐F group (3 ± 1 kg; 4 ± 1 cm). Similar reductions (P &lt; 0.0001) in fat mass were demonstrated in the IFCR‐L (3 ± 1 kg) and IFCR‐F group (2 ± 1 kg). Reductions in total and LDL cholesterol levels were greater (P = 0.04) in the IFCR‐L (19 ± 10%; 20 ± 9%, respectively) versus the IFCR‐F group (8 ± 3%; 7 ± 4%, respectively). LDL peak particle size increased (P &lt; 0.01) in the IFCR‐L group only. The proportion of small LDL particles decreased (P &lt; 0.01) in both groups. Adipokines, such as leptin, interleukin‐6 (IL‐6), tumor necrosis factor‐alpha (TNF‐alpha), and insulin‐like growth factor‐1 (IGF‐1) decreased (P &lt; 0.05), in the IFCR‐L group only.ConclusionThese findings suggest that IFCR with a liquid diet favorably modulates visceral fat and adipokines in a way that may confer protection against CHD.

Abstract P410: Alternate Day Fasting with a High Fat Diet: Impact on Body Weight, Body Composition, and Coronary Heart Disease Risk Profile in Obese Adults

Background: Alternate day fasting (ADF) with a low-fat (LF) diet is effective for weight loss and cardio-protection. However, the applicability of these findings is questionable as most Americans consume a high-fat (HF) diet. This study examined if these beneficial changes in weight and coronary heart disease (CHD) risk can be reproduced if a HF diet is used in place of a LF diet during ADF. Methods: Thirty-two obese subjects were randomized to an ADF-HF (45% fat) or ADF-LF diet (25% fat), which consisted of two phases: 1) a 2-week baseline weight maintenance period, and 2) an 8-week ADF weight loss period. All food was provided to subjects. Results: Body weight was reduced (P &lt; 0.0001) by ADF-HF (5 ± 1%) and by ADF-LF (4 ± 1%). Fat mass decreased (P &lt; 0.0001) by ADF-HF (5 ± 1 kg) and ADF-LF (4 ± 1 kg). Fat free mass remained unchanged. Waist circumference decreased (P &lt; 0.001) by ADF-HF (7 ± 1 cm) and ADF-LF (7 ± 1 cm). LDL cholesterol and triacylglycerol concentrations were reduced (P &lt; 0.01) by both interventions (ADF-HF: 18 ± 5%, 14 ± 5%; ADF-LF: 24 ± 3%, 14 ± 4%). The proportion of small LDL particles decreased (P &lt; 0.05) in the ADF-HF and ADF-LF groups by 8 ± 3% and 10 ± 4%. Conclusion: Thus, an ADF-HF diet produces similar reductions in weight and CHD risk as an ADF-LF diet. These findings are important in terms of diet tolerability and long-term adherence to ADF diets.

Improvement in coronary heart disease risk factors during an intermittent fasting/calorie restriction regimen: Relationship to adipokine modulations

BackgroundThe ability of an intermittent fasting (IF)-calorie restriction (CR) regimen (with or without liquid meals) to modulate adipokines in a way that is protective against coronary heart disease (CHD) has yet to be tested.ObjectiveAccordingly, we examined the effects of an IFCR diet on adipokine profile, body composition, and markers of CHD risk in obese women.MethodsSubjects (n = 54) were randomized to either the IFCR-liquid (IFCR-L) or IFCR-food based (IFCR-F) diet for 10 weeks.ResultsGreater decreases in body weight and waist circumference were noted in the IFCR-L group (4 ± 1 kg; 6 ± 1 cm) versus the IFCR-F group (3 ± 1 kg; 4 ± 1 cm). Similar reductions (P < 0.0001) in fat mass were demonstrated in the IFCR-L (3 ± 1 kg) and IFCR-F group (2 ± 1 kg). Reductions in total and LDL cholesterol levels were greater (P = 0.04) in the IFCR-L (19 ± 10%; 20 ± 9%, respectively) versus the IFCR-F group (8 ± 3%; 7 ± 4%, respectively). LDL peak particle size increased (P < 0.01) in the IFCR-L group only. The proportion of small LDL particles decreased (P < 0.01) in both groups. Adipokines, such as leptin, interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), and insulin-like growth factor-1 (IGF-1) decreased (P < 0.05), in the IFCR-L group only.ConclusionThese findings suggest that IFCR with a liquid diet favorably modulates visceral fat and adipokines in a way that may confer protection against CHD.

Effects of alternate day modified fasting on LDL particle size and distribution in obese adults

Alternate day modified fasting (ADMF) beneficially modulates several indicators of coronary heart disease (CHD) risk, but its effects on LDL particle size have never been tested. Accordingly, we examined the effects of ADMF on LDL particle size and distribution in obese adults. Sixteen obese subjects participated in a 10‐week trial with three consecutive phases: 1) 2‐week control phase, 2) 4‐week ADMF controlled feeding phase, and 3) 4‐week ADMF self‐selected feeding phase. After 8 weeks of diet, body weight and waist circumference were reduced (P &lt; 0.05) by 5.6 ± 0.9 kg, and 4.0 ± 0.9 cm, respectively. LDL cholesterol and triacylglycerol concentrations decreased (P &lt; 0.05) by 25 ± 10%, and 32 ± 6%, respectively. Peak LDL particle size increased (P &lt; 0.05) from 266 ± 1 to 268 ± 1 Å. Additionally, the proportion of small LDL particles decreased (P &lt; 0.05) from 13 ± 2% to 9 ± 3%, while the proportion of large LDL particles increased (P &lt; 0.05) from 68 ± 4% to 76 ± 4% post‐treatment. These findings suggest that ADMF is an effective diet strategy for increasing LDL particle size and decreasing the proportion of small, dense LDL particles in obese adults.

Comparison of effects of diet versus exercise weight loss regimens on LDL and HDL particle size in obese adults

BackgroundObesity is associated with an atherogenic lipid profile characterized by a predominance of small LDL and HDL particles. Weight loss, by dietary restriction or exercise, increases LDL particle size. Whether these interventions can augment HDL size in conjunction with LDL size remains unknown.ObjectiveThis study compared the effects of alternate day fasting (ADF), calorie restriction (CR), and endurance exercise on LDL and HDL particle size in overweight and obese subjects.MethodsIn a 12-week parallel-arm trial, adult subjects (n = 60) were randomized to 1 of 4 groups: 1) ADF (75% energy restriction for 24-h alternated with ad libitum feeding for 24-h), 2) CR (25% energy restriction every day), 3) exercise (moderate intensity training 3 x/week), or 4) control.ResultsBody weight was reduced (P < 0.001) by ADF, CR, and exercise (5.2 ± 1.1%, 5.0 ± 1.4%, 5.1 ± 0.9%, respectively). Plasma LDL cholesterol decreased (P < 0.05) with ADF (10 ± 4%) and CR (8 ± 4%), whereas HDL cholesterol increased (P < 0.05) with exercise (16 ± 5%). Integrated LDL particle size was augmented (P = 0.01) by ADF and CR. The proportion of small LDL particles decreased (P = 0.04) with ADF only, and the proportion of large HDL particles increased (P = 0.03) with exercise only.ConclusionThese results indicate that dietary restriction increases LDL particle size, while endurance training augments HDL particle size, with minimal weight loss. None of these interventions concomitantly increased both LDL and HDL particle size, however.

Improvements in LDL particle size and distribution by short-term alternate day modified fasting in obese adults

Alternate day modified fasting (ADMF) beneficially modulates several indicators of CHD risk, but its effects on LDL particle size have never been tested. Accordingly, we examined the effects of ADMF on LDL particle size and distribution in obese adults. Sixteen obese subjects participated in a 10-week trial with three consecutive phases: (1) 2-week control phase; (2) 4-week ADMF controlled feeding phase; (3) 4-week ADMF self-selected feeding phase. After 8 weeks of diet, body weight and waist circumference were reduced (P<0·05) by 5·6 (sem 0·9)kg and 4·0 (sem 0·9)cm, respectively. LDL-cholesterol and TAG concentrations decreased (P<0·05) by 25 (sem 10)% and 32 (sem 6)%, respectively. Peak LDL particle size increased (P<0·05) from 266 (sem 1) to 268 (sem 1)Å. Additionally, the proportion of small LDL particles decreased (P<0·05) from 13 (sem 2)% to 9 (sem 3)%, while the proportion of large LDL particles increased (P<0·05) from 68 (sem 4)% to 76 (sem 4)% post-treatment. These findings suggest that ADMF is an effective diet strategy for increasing LDL particle size and decreasing the proportion of small, dense LDL particles in obese adults.

Are post-treatment low-density lipoprotein subclass pattern analyses potentially misleading?

BackgroundSome patients administered cholesterol-lowering therapies may experience an increase in the proportion of small LDL particles, which may be misinterpreted as a worsening of atherosclerotic coronary heart disease risk. This study assessed the lipid effects of adding ezetimibe to atorvastatin or doubling the atorvastatin dose on low-density lipoprotein cholesterol (LDL-C) levels (and the cholesterol content of LDL subclasses), LDL particle number (approximated by apolipoprotein B), and LDL particle size. This was a multicenter, double-blind, randomized, parallel-group study of hypercholesterolemic, high atherosclerotic coronary heart disease risk patients. After stabilization of atorvastatin 40 mg, 579 patients with LDL-C >70 mg/dL were randomized to 6 weeks of ezetimibe + atorvastatin 40 mg or atorvastatin 80 mg. Efficacy parameters included changes from baseline in LDL-C, apolipoprotein B, non-high-density lipoprotein cholesterol (non-HDL-C), and lipoprotein subclasses (Vertical Auto Profile II) and pattern for the overall population, as well as patient subgroups with baseline triglyceride levels <150 mg/dL or ≥150 mg/dL.ResultsBoth treatments significantly reduced LDL-C (and the cholesterol content of most LDL subfractions [LDL1-4]) apolipoprotein B, non-HDL-C levels, but did not reduce the proportion of smaller, more dense LDL particles; in fact, the proportion of Pattern B was numerically increased. Results were generally similar in patients with triglyceride levels <150 or ≥150 mg/dL.ConclusionsWhen assessing the effects of escalating cholesterol-lowering therapy, effects upon Pattern B alone to assess coronary heart disease risk may be misleading when interpreted without considerations of other lipid effects, such as reductions in LDL-C, atherogenic lipoprotein particle concentration, and non-HDL-C levels.Trial Registration(Registered at clinicaltrials.gov: Clinical trial # NCT00276484)

Effect of type 2 diabetes on various electrophoretic characteristics of low-density lipoprotein particles in women

Coronary heart disease represents the leading cause of death in type 2 diabetic patients. As the small, dense LDL phenotype is a typical feature of the dyslipidaemic state found in type 2 diabetes, this characteristic could be an important mediator of the elevated coronary heart disease risk in this condition. We have therefore studied the effect of type 2 diabetes on various electrophoretic characteristics of LDL particles. Potential differences in LDL peak particle size and in concentration of LDL cholesterol in small (<255 A) and large (>260 A) LDL particles were assessed by polyacrylamide gradient gel electrophoresis among 183 non-diabetic and 56 type 2 diabetic women. LDL peak particle size was significantly smaller in type 2 diabetic women than in non-diabetic women (p<0.0001). In addition, the proportion of small LDL particles (<255 A) was higher in type 2 diabetic women, whereas the proportion of large LDL particles (>260 A) was lower than in non-diabetic women (p<0.0002). Type 2 diabetic women also had the highest waist circumference and triglyceride levels (p<0.03). When subgroups of non-diabetic and type 2 diabetic women were individually matched (n=41) for similar waist circumference and triglyceride levels, the differences initially found in LDL peak particle size and in the proportion of small and large LDL particles remained significantly different between the two groups (p<0.01). These results provide evidence that type 2 diabetes may have an independent effect on LDL peak particle size and on the proportion of small and large LDL particles.

Adverse change in low-density lipoprotein subfractions profile with oestrogen-only hormone replacement therapy.

In a prospective longitudinal study in 17 women, we investigated the effects of surgical menopause and subsequent oestrogen-only hormone replacement therapy (HRT) on plasma concentrations of total cholesterol, HDL cholesterol, LDL cholesterol, triglyceride and LDL subfractions profile. Plasma LDL is a heterogeneous population of particles of varying size, density and chemical composition. The predominance of small LDL particles is a newly-recognized risk factor for coronary artery disease. The LDL score is used to describe LDL subfractions profile and the greater the score, the higher the proportion of small LDL particles. Six weeks after hysterectomy and bilateral oopherectomy, total cholesterol and triglyceride concentrations were significantly increased (p < 0.01) as well as the LDL score (p < 0.05). After 6 weeks of oestrogen-only HRT, total cholesterol concentration was significantly lower and HDL cholesterol concentration significantly higher than before the treatment (p < 0.05). At the same time, mean LDL score significantly increased and in none of the women did LDL subfractions profile change favourably.