| 1. |
- Bays, Harold E., et al.
(författare)
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Dapagliflozin in patients with type II diabetes mellitus, with and without elevated triglyceride and reduced high-density lipoprotein cholesterol levels
- 2017
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Ingår i: Journal of Clinical Lipidology. - : Elsevier. - 1933-2874 .- 1876-4789. ; 11:2, s. 450-458
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Dapagliflozin is a selective sodium-glucose cotransporter 2 inhibitor that improves glycemic control in patients with type II diabetes mellitus (T2DM) by reducing renal glucose reabsorption.OBJECTIVE: The aim was to evaluate the lipid effects of dapagliflozin 10 mg or placebo in patients with T2DM with/without baseline elevated triglyceride and reduced high-density lipoprotein (HDL) cholesterol levels.METHODS: This was a post hoc analysis of 10 phase 3, placebo-controlled studies of dapagliflozin 10 mg (N = 2237) or placebo (N = 2164) administered for 24 weeks in patients with T2DM. Patients with elevated triglyceride (>= 150 mg/dL [1.69 mmol/L]) and reduced HDL cholesterol levels (<40 mg/dL [1.04 mmol/L] in men; <50 mg/dL [1.29 mmol/L] in women) were included (group A). The reference group (group B) included patients who did not meet the defined lipid criteria.RESULTS: The effects of dapagliflozin on fasting lipid profiles were generally similar in the 2 lipid groups (ie, groups A and B) and, compared with placebo, were associated with minor increases in non-HDL cholesterol, low-density lipoprotein, and HDL cholesterol levels. The effects on triglyceride levels were inconsistent. The incidence of adverse events (AEs)/serious AEs, and AEs of genital infection, urinary tract infection, volume reduction, renal function, and hypoglycemia were similar in the 2 lipid groups.CONCLUSION: Patients with T2DM treated with dapagliflozin experienced minor changes in lipid levels; the changes were generally similar in the 2 lipid groups. The clinical significance of these changes in lipids is unclear, especially in view of the positive effects of dapagliflozin on other cardiovascular disease risk factors.
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| 2. |
- Iggman, David, et al.
(författare)
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Role of different dietary saturated fatty acids for cardiometabolic risk
- 2011
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Ingår i: Journal of Clinical Lipidology. - 1933-2874 .- 1876-4789. ; 6:2, s. 209-223
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Forskningsöversikt (refereegranskat)abstract
- There is clinical and observational evidence to suggest that saturated fatty acids (SFA) increase cardiovascular disease risk compared with polyunsaturated fatty acids from vegetable oils. Replacing SFA intake has thus been a public health target, but the role of individual SFA in metabolic disease is still incompletely understood. Observational data Indicate that all SFA may not necessarily be detrimental. The cholesterol-raising effect of SFA differs among individual SFA and possibly also with regard to cardiovascular and metabolic risk factors. The impact of dietary SFA on cardiovascular disease remains somewhat controversial, possibly due to such individual differences. In this article, we will also separately discuss the effects of dairy SFA, including biomarkers, as a means to elucidate these relationships between fatty acids, foodstuffs and cardiometabolic disease.
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| 3. |
- Jose Ariza, Maria, et al.
(författare)
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Novel mutations in the GPIHBP1 gene identified in 2 patients with recurrent acute pancreatitis
- 2016
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Ingår i: Journal of Clinical Lipidology. - : Elsevier BV. - 1933-2874 .- 1876-4789. ; 10:1, s. 92-100
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Tidskriftsartikel (refereegranskat)abstract
- Background: Glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1 (GPIHBP1) has been demonstrated to be essential for the in vivo function of lipoprotein lipase (LPL), the major triglyceride (TG)-hydrolyzing enzyme involved in the intravascular lipolysis of TG-rich lipoproteins. Recently, loss-of-function mutations ofGPIHBP1 have been reported as the cause of type I hyperlipoproteinemia in several patients.Methods: Two unrelated patients were referred to our Lipid Units because of a severe hypertriglyceridemia and recurrent pancreatitis. We measured LPL activity in postheparin plasma and serum ApoCII and sequenced LPL, APOC2, and GPIHBP1.Results: The 2 patients exhibited very low LPL activity not associated with mutations in LPL gene or with ApoCII deficiency. The sequence of GPIHBP1 revealed 2 novel point mutations. One patient (proband 1) was found to be homozygous for a C>A transversion in exon 3 resulting in the conversion of threonine to lysine at position 80 (p.Thr80Lys). The other patient (proband 2) was found to be homozygous for a G>T transversion in the third base of the ATG translation initiation codon in exon 1, resulting in the conversion of methionine to isoleucine (p.Met1Ile).Conclusion: In conclusion, we have identified 2 novel GPIHBP1 missense mutations in 2 unrelated patients as the cause of their severe hypertriglyceridemia.
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| 4. |
- Kjellmo, Christian Abendstein, et al.
(författare)
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Bariatric surgery improves lipoprotein profile in morbidly obese patients by reducing LDL cholesterol, apoB, and SAA/PON1 ratio, increasing HDL cholesterol, but has no effect on cholesterol efflux capacity
- 2018
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Ingår i: Journal of Clinical Lipidology. - : ELSEVIER SCIENCE INC. - 1933-2874 .- 1876-4789. ; 12:1, s. 193-202
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Bariatric surgery has been shown to reduce cardiovascular events and cause specific mortality for coronary artery disease in obese patients. Lipoprotein biomarkers relating to low-density lipoprotein (LDL), high-density lipoprotein (HDL), their subfractions, and macrophage cholesterol efflux have all been hypothesized to be of value in cardiovascular risk assessment. OBJECTIVES: The objective of this study was to examine the effect of a lifestyle intervention followed by bariatric surgery on the lipid profile of morbidly obese patients. METHODS: Thirty-four morbidly obese patients were evaluated before and after lifestyle changes and then 1 year after bariatric surgery. They were compared with 17 lean subjects. Several lipoprotein metrics, serum amyloid A (SAA), serum paraoxonase-1 (PON1), and macrophage cholesterol efflux capacity (CEC) were assessed. RESULTS: Average weight loss after the lifestyle intervention was 10.5% and 1 year after bariatric surgery was 33.9%. The lifestyle intervention significantly decreased triglycerides (TGs; 28.7 mg/dL, P amp;lt; .05), LDL cholesterol (LDL-C; 32.3 mg/dL, P amp;lt; .0001), and apolipoprotein B (apoB; 62.9 mu g/mL, P amp;lt; .001). Bariatric surgery further reduced TGs (-36.7 mg/dL, P amp;lt; .05), increased HDL cholesterol (+12 mg/dL, P amp;lt; .0001), and reductions in LDL-C and apoB were sustained. Bariatric surgery reduced large, buoyant LDL (P amp;lt; .0001), but had no effect on the small, dense LDL.The large HDL subfractions increased (P amp;lt; .0001), but there was no effect on the smaller HDL sub fractions. The ratio for SAA/PON1 was reduced after the lifestyle intervention (P amp;lt; .01) and further reduced after bariatric surgery (P amp;lt; .0001). Neither the lifestyle intervention nor bariatric surgery had any effect on CEC. CONCLUSIONS: Lifestyle intervention followed by bariatric surgery in 34 morbidly obese patients showed favorable effects on TGs, LDL-C, and apoB. HDL cholesterol and apoA1 was increased, apoB/apoA1 ratio as well as SAA/PON1 ratio reduced, but bariatric surgery did not influence CEC. (C) 2017 National Lipid Association. All rights reserved.
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| 5. |
- Oscarsson, Jan, et al.
(författare)
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Effects of free omega-3 carboxylic acids and fenofibrate on liver fat content in patients with hypertriglyceridemia and non-alcoholic fatty liver disease : A double-blind, randomized, placebo-controlled study
- 2018
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Ingår i: Journal of Clinical Lipidology. - : Elsevier BV. - 1933-2874 .- 1876-4789. ; 12:6, s. 1390-1403
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Treatment with omega-3 fatty acids and fenofibrates reduces serum triglyceride levels, but few studies have compared the effect of these agents on liver fat. OBJECTIVE: The aim of the EFFECT I trial (NCT02354976) was to determine the effects of free omega-3 carboxylic acids (OM-3CA) and fenofibrate on liver fat in overweight or obese individuals with non-alcoholic fatty liver disease and hypertriglyceridemia. METHODS: Seventy-eight patients were randomized to receive oral doses of 4 g OM-3CA (n = 25), 200 mg fenofibrate (n = 27), or placebo (n = 26) for 12 weeks in a double-blind, parallel-group study. Liver proton density fat fraction (PDFF) and volume, pancreas volume, and adipose tissue volumes were assessed by magnetic resonance imaging. RESULTS: Changes in liver PDFF at 12 weeks were not significantly different across treatment groups (relative changes from baseline: placebo, +4%; OM-3CA, -2%; and fenofibrate, +17%). The common PNPLA3 genetic polymorphism (I148M) did not significantly influence the effects of OM-3CA or fenofibrate on liver PDFF. Fenofibrate treatment significantly increased liver and pancreas volumes vs placebo treatment, and the changes in liver and pancreas volumes were positively correlated (rho 0.45, P = .02). Total liver fat volume increased significantly in patients using fenofibrate vs OM-3CA (+23% vs 3%, P = .04). Compared with OM-3CA, fenofibrate increased total liver fat and liver volume. Serum triglycerides decreased with OM-3CA (-26%, P = .02) and fenofibrate (-38%, P < .001) vs placebo. In contrast to OM-3CA, fenofibrate reduced plasma docosahexaenoic acid levels and increased plasma acetylcarnitine and butyrylcarnitine levels, estimated delta-9 desaturase activity and the concentration of urine F2-isoprostanes. CONCLUSIONS: OM-3CA and fenofibrate reduced serum triglycerides but did not reduce liver fat. Fenofibrate increased total liver volume and total liver fat volume vs OM-3CA, indicating a complex effect of fenofibrate on human hepatic lipid metabolism.
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| 6. |
- Rioja, José, et al.
(författare)
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Role of lipoprotein lipase activity measurement in the diagnosis of familial chylomicronemia syndrome : diagnosis of the Familial Chylomicronemia Syndrome
- 2023
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Ingår i: Journal of Clinical Lipidology. - : Elsevier. - 1933-2874 .- 1876-4789. ; 17:2, s. 272-280
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Tidskriftsartikel (refereegranskat)abstract
- Background: Activity assays for lipoprotein lipase (LPL) are not standardised for use in clinical settings. Objective: This study sought to define and validate a cut-off points based on a ROC curve for the diagnosis of patients with familial chylomicronemia syndrome (FCS). We also evaluated the role of LPL activity in a comprehensive FCS diagnostic workflow.Methods: A derivation cohort (including an FCS group (n = 9), a multifactorial chylomicronemia syndrome (MCS) group (n = 11)), and an external validation cohort (including an FCS group (n = 5), a MCS group (n = 23) and a normo-triglyceridemic (NTG) group (n = 14)), were studied. FCS patients were previously diagnosed by the presence of biallelic pathogenic genetic variants in the LPL and GPIHBP1 genes. LPL activity was also measured. Clinical and anthropometric data were recorded, and serum lipids and lipoproteins were measured. Sensitivity, specificity and cut-offs for LPL activity were obtained from a ROC curve and externally validated.Results: All post-heparin plasma LPL activity in the FCS patients were below 25.1 mU/mL, that was cut-off with best performance. There was no overlap in the LPL activity distributions between the FCS and MCS groups, conversely to the FCS and NTG groups.Conclusion: We conclude that, in addition to genetic testing, LPL activity in subjects with severe hypertriglyceridemia is a reliable criterium in the diagnosis of FCS when using a cut-off of 25.1 mU/mL (25% of the mean LPL activity in the validation MCS group). We do not recommend the NTG patient based cut-off values due to low sensitivity.
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| 7. |
- Salamone, Dominic, et al.
(författare)
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Fatty acid composition of cholesterol esters reflects dietary fat intake after dietary interventions in a multinational population
- 2023
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Ingår i: Journal of Clinical Lipidology. - : Elsevier. - 1933-2874 .- 1876-4789. ; 17:4, s. 466-474
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundThe effects of different dietary fatty acids (FA) on cardiovascular risk still needs clarification. Plasma lipids composition may be a biomarker of FA dietary intake.PurposeTo evaluate in a composite population the relationships between changes in dietary fat intake and changes in FA levels in serum cholesterol esters.MethodsIn a multinational, parallel-design, dietary intervention (KANWU study), dietary intakes (3-day food record) and FA composition of serum cholesterol esters (gas-liquid chromatography) were evaluated at baseline and after 3 months in 162 healthy individuals, randomly assigned to a diet containing a high proportion of saturated (SFA) or monounsaturated (MUFA) fat, with a second random assignment to fish oil or placebo supplements.ResultsMain differences in serum lipid composition after the two diets included saturated (especially myristic, C14:0, and pentadecanoic, C15:0) and monounsaturated (oleic acid, C18:1 n-9) FA. C14:0 and C15:0 were related to SFA intake, while C18:1 n-9 was associated with MUFA intake. Fish oil supplementation induced a marked increase in eicosapentaenoic (C20:5 n-3) and docosahexaenoic (C22:6 n-3) acids. After the 3-month intervention, Δ-9 desaturase activity, calculated as palmitoleic acid/palmitic acid (C16:1/C16:0) ratio, was more reduced after the MUFA (0.31±0.10 vs 0.25±0.09, p<0.0001) than SFA diet (0.31±0.09 vs 0.29±0.08, p=0.006), with a statistically significant difference between the two groups (p<0.0001).ConclusionsThis study shows that serum cholesterol ester FA composition can be used during randomized controlled trials as an objective indicator of adherence to experimental diets based on saturated and monounsaturated fat modifications, as well as fish oil supplementation.
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| 8. |
- Wang, Kate N., et al.
(författare)
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Statin use and fall-related hospitalizations among residents of long-term care facilities : A case-control study
- 2020
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Ingår i: Journal of Clinical Lipidology. - : Elsevier BV. - 1933-2874 .- 1876-4789. ; 14:4, s. 507-514
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Statins are associated with muscle-related adverse events, but few studies have investigated the association with fall-related hospitalizations among residents of long-term care facilities (LTCFs).OBJECTIVE: The objective of the study is to investigate whether statin use is associated with fall-related hospitalizations from LTCFs.METHODS: A case-control study was conducted among residents aged >= 65 years admitted to hospital from 2013 to 2015. Cases (n = 332) were residents admitted for falls and fall-related injuries. Controls (n = 332) were selected from patients admitted for reasons other than cardiovascular and diabetes. Cases and controls were matched 1:1 by age (+/- 2 years), index date of admission (+/- 6 months), and sex. Adjusted odds ratios (aORs) and 95% confidence intervals (CIs) were estimated using conditional logistic regression, after considering for history of falls, hypertension, dementia, functional comorbidity index, polypharmacy (>= 9 regular preadmission medications), and fall-risk medications. Subanalyses were performed for individual statins, dementia, and statin intensity.RESULTS: Overall, 43.1% of cases and 27.1% of controls used statins. Statins were associated with fall-related hospitalizations (aOR = 2.24, 95% CI 1.56-3.23), in particular simvastatin (aOR = 2.26, 95% CI 1.22-4.20) and atorvastatin (aOR = 2.08, 95% CI 1.33-3.24). Statins were associated with fall-related hospitalizations in residents with (aOR = 2.34, 95% CI 1.33-4.11) and without dementia (aOR = 2.30, 95% CI 1.46-3.63). There was no association between statin intensity and fall-related hospitalizations (aOR = 0.78, 95% CI 0.43-1.40).CONCLUSION: This study suggests a possible association between statin use and fall-related hospitalizations among residents living in LTCFs. However, there was minimal evidence for a relationship between statin intensity and fall-related hospitalizations. Further research is required to substantiate these hypothesis-generating findings.
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| 9. |
- Wang, Shaoying, et al.
(författare)
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Characterizing lipid profiles associated with asymptomatic intracranial arterial stenosis in rural-dwelling adults : A population-based study
- 2020
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Ingår i: Journal of Clinical Lipidology. - : Elsevier BV. - 1933-2874 .- 1876-4789. ; 14:3, s. 371-380
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Although individual lipid parameters have been frequently examined in association with asymptomatic intracranial arterial stenosis (aICAS), few population-based studies have investigated the lipid profiles associated with aICAS among Chinese adults. OBJECTIVE: This study aims to characterize the lipid profiles associated with aICAS in rural-dwelling adults in China. METHODS: This population-based study included 2027 persons who were aged >= 40 years and free of stroke. Data were collected via interviews, clinical examinations, and laboratory testing. We diagnosed aICAS by integrating transcranial color Doppler with magnetic resonance angiography. Data were analyzed using binary and multinomial logistic regression models. RESULTS: Of the 2027 participants, 154 were detected with aICAS. The multiadjusted odds ratio (95% confidence interval) of aICAS was 1.41 (0.997-2.00) for high small dense low-density lipoprotein cholesterol, 1.44 (1.02-2.04) for high lipoprotein(a), 1.71 (1.21-2.44) for low apolipoprotein A-1, 1.43 (1.00-2.04) for low high-density lipoprotein cholesterol (HDL-C), 1.61 (1.14-2.27) for high apolipoprotein B/apolipoprotein A-1 ratio, 1.95 (1.38-2.76) for high low-density lipoprotein cholesterol/HDL-C ratio, and 1.51 (1.06-2.14) for high total cholesterol/HDL-C ratio. When severity of aICAS was analyzed, high levels of lipoprotein(a), small dense low-density lipoprotein cholesterol, and lipid ratios were significantly associated with an increased likelihood of moderate-to-severe aICAS (P < .05). An increasing number of abnormal lipid measurements was associated with an increased likelihood of aICAS (P for trend <.001). CONCLUSION: These findings suggest that lipid profiles for aICAS among rural residents in China are characterized by high atherogenic cholesterol, low antiatherogenic cholesterol, and high ratios of atherogenic-to-antiatherogenic cholesterol or lipoproteins.
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| 10. |
- Adiels, Martin, 1976, et al.
(författare)
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Niacin action in the atherogenic mixed dyslipidemia of metabolic syndrome: Insights from metabolic biomarker profiling and network analysis
- 2018
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Ingår i: Journal of Clinical Lipidology. - : Elsevier BV. - 1933-2874. ; 12:3, s. 810-821
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Niacin as an adjunct to statin treatment to reduce cardiovascular risk is questioned. OBJECTIVE: To evaluate interrelationships between the effects of niacin on mixed dyslipidemia and a spectrum of metabolic and inflammatory biomarkers. METHODS: Obese, nondiabetic, hypertriglyceridemic males (n = 19) with low high-density lipoprotein cholesterol levels received extended-release nicotinic acid for 8 weeks. Multiple biomarkers were measured using enzyme-linked immunosorbent assay, enzymatic/absorptiometric, or multiplex biochip assays. Treatment effects were determined for each variable and a differential correlation network created on the basis of univariate correlations between baseline and response to niacin treatment for all pairs of variables. RESULTS: Extended-release niacin treatment favoured normalization of plasma lipid and apolipoprotein profile. Plasma markers of inflammation, hepatic function, cellular adhesion and proliferation, and macrophage phenotype were attenuated; however, insulin resistance increased. Differential network analysis revealed that changes in triglycerides and high-density lipoprotein cholesterol were closely linked; equally, niacin mediated reductions in total cholesterol, apolipoprotein B, low-density lipoprotein cholesterol and lipoprotein(a) clustered together, as did homeostatic model assessment of insulin resistance, insulin, and interleukin-6 levels. Two clusters of inflammatory markers were identified, involving (1) intercellular adhesion molecule 1 and high-sensitive C-reactive protein and (2) soluble tumor necrosis factor receptors; and novel clusters involving matrix metallopeptidase 9 and apolipoprotein E, and adiponectin and cystatin C, respectively, were equally revealed. At lower stringency, lipid and insulin resistance clusters were linked; a C-reactive protein-centered cluster linked reduction in apolipoprotein Cu to intercellular adhesion molecule 1, gamma-glutamyltransferase, soluble tumor necrosis factor receptors, and E-selectin. CONCLUSION: A niacin-mediated trend to normalize atherogenic mixed dyslipidemia was intimately linked to attenuation of biomarkers of inflammation, cell adhesion, hepatic dysfunction and cell proliferation, but to enhanced insulin resistance and plasma homocysteine elevation. (C) 2018 National Lipid Association. Published by Elsevier Inc.
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