Browsing by Subject "Cholesterol, LDL"
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- ItemOpen AccessA 52-Week Placebo-Controlled Trial of Evolocumab in Hyperlipidemia(2014) Blom, Dirk J; Hala, Tomas; Bolognese, Michael; Lillestol, Michael J; Toth, Phillip D; Burgess, Lesley; Ceska, Richard; Roth, Eli; Koren, Michael J; Ballantyne, Christie M; Monsalvo, Maria Laura; Tsirtsonis, Kate; Kim, Jae B; Scott, Rob; Wasserman, Scott M; Stein, Evan ABACKGROUND Evolocumab, a monoclonal antibody that inhibits proprotein convertase subtilisin/ kexin type 9 (PCSK9), significantly reduced low-density lipoprotein (LDL) cholesterol levels in phase 2 studies. We conducted a phase 3 trial to evaluate the safety and efficacy of 52 weeks of treatment with evolocumab. METHODS We stratified patients with hyperlipidemia according to the risk categories outlined by the Adult Treatment Panel III of the National Cholesterol Education Program. On the basis of this classification, patients were started on background lipid-lowering therapy with diet alone or diet plus atorvastatin at a dose of 10 mg daily, atorvastatin at a dose of 80 mg daily, or atorvastatin at a dose of 80 mg daily plus ezetimibe at a dose of 10 mg daily, for a run-in period of 4 to 12 weeks. Patients with an LDL cholesterol level of 75 mg per deciliter (1.9 mmol per liter) or higher were then randomly assigned in a 2:1 ratio to receive either evolocumab (420 mg) or placebo every 4 weeks. The primary end point was the percent change from baseline in LDL cholesterol, as measured by means of ultracentrifugation, at week 52. RESULTS Among the 901 patients included in the primary analysis, the overall least-squares mean (±SE) reduction in LDL cholesterol from baseline in the evolocumab group, taking into account the change in the placebo group, was 57.0±2.1% (P<0.001). The mean reduction was 55.7±4.2% among patients who underwent background therapy with diet alone, 61.6±2.6% among those who received 10 mg of atorvastatin, 56.8±5.3% among those who received 80 mg of atorvastatin, and 48.5±5.2% among those who received a combination of 80 mg of atorvastatin and 10 mg of ezetimibe (P<0.001 for all comparisons). Evolocumab treatment also significantly reduced levels of apolipoprotein B, non-high-density lipoprotein cholesterol, lipoprotein(a), and triglycerides. The most common adverse events were nasopharyngitis, upper respiratory tract infection, influenza, and back pain. CONCLUSIONS At 52 weeks, evolocumab added to diet alone, to low-dose atorvastatin, or to high-dose atorvastatin with or without ezetimibe significantly reduced LDL cholesterol levels in patients with a range of cardiovascular risks.
- ItemOpen AccessAssociation between ethnicity and obesity with high-density lipoprotein (HDL) function and subclass distribution(2016) Woudberg, Nicholas J; Goedecke, Julia H; Blackhurst, Dee; Frias, Miguel; James, Richard; Opie, Lionel H; Lecour, SandrineAbstract Background Obesity and low high-density lipoprotein-cholesterol (HDL-C) levels are associated with cardiovascular risk. Surprisingly, despite a greater prevalence of obesity and lower HDL concentrations than white women, black South African women are relatively protected against ischaemic heart disease. Methods We investigated whether this apparent discrepancy may be related to different HDL function and subclass distribution in black and white, normal-weight and obese South African women (n = 40). HDL functionality was assessed by measuring paraoxonase (PON) activity, platelet activating factor acetylhydrolase (PAF-AH) activity, Oxygen Radical Absorbance Capacity (ORAC) and quantification of the expression of vascular cell adhesion molecule in endothelial cells. PON-1 and PAF-AH expression was determined in isolated HDL and serum using Western blotting. Levels of large, intermediate and small HDL subclasses were measured using the Lipoprint® system. Results PON activity was lower in white compared to black women (0.49 ± 0.09 U/L vs 0.78 ± 0.10 U/L, p < 0.05), regardless of PON-1 protein levels. Obese black women had lower PAF-AH activity (9.34 ± 1.15 U/L vs 13.89 ± 1.21 U/L, p <0.05) and HDL-associated PAF-AH expression compared to obese white women. Compared to normal-weight women, obese women had lower large HDL, greater intermediate and small HDL; an effect that was more pronounced in white women than black women. There were no differences in antioxidant capacity or anti-inflammatory function across groups. Conclusions Our data show that both obesity and ethnicity are associated with differences in HDL functionality, while obesity was associated with decreases in large HDL subclass distribution. Measuring HDL functionality and subclass may, therefore, be important factors to consider when assessing cardiovascular risk.
- ItemOpen AccessAssociation of serum leptin and adiponectin with anthropomorphic indices of obesity, blood lipids and insulin resistance in a Sub-Saharan African population(2016) Ayina, Clarisse Noël A; Noubiap, Jean Jacques N; Etoundi Ngoa, Laurent Serge; Boudou, Philippe; Gautier, Jean François; Mengnjo, Michel Karngong; Mbanya, Jean Claude; Sobngwi, EugèneAbstract Background There is little data on the metabolic effects of adipokines in sub-Saharan African populations. This study aimed to explore the potential relationship of leptin and adiponectin, with obesity, plasma lipids and insulin resistance in a Cameroonian population. Methods We enrolled 167 men and 309 women aged ≥18 years from the general population in Cameroon. Data were collected on waist circumference (WC), body mass index (BMI), waist-to-hip ratio (WHR), body fat (BF%), fasting blood glucose, plasma lipids, adiponectin, leptin, insulin and homeostasis model for assessment of insulin resistance (HOMA-IR). Pearson’s correlation and multiple stepwise linear regression analyses were used to determine correlates of leptin and adiponectin serum levels. Results The prevalence of obesity was higher in women compared to men (p < 0.0001), and Central obesity which is more prevalent particularly in women (WC = 42.4 %, WHR = 42.3 %), is almost for 90 % comparable to %BF (42.7 %). Adiponectin negatively with BMI (r = −0.294, p < 0.0001), WC (r = −0.294, p < 0.0001), %BF (r = −0.122, p = 0.028), WHR (r = −0.143, p = 0.009), triglycerides (r = −0.141, p = 0.011), HOMA-IR (r = −0.145, p = 0.027) and insulin (r = −0.130, p = 0.048). Leptin positively correlated with BMI (r = 0.628), WC (r = 0.530), BF% (r = 0.720), (all p < 0.0001); with DBP (r = 0.112, p = 0.043), total cholesterol (r = 0.324, p < 0.0001), LDL-cholesterol (r = 0.298, p < 0.0001), insulin (r = 0.320, p < 0.001 and HOMA-IR (r = 0.272, p < 0.0001). In multiple stepwise regression analysis, adiponectin was negatively associated with WC (β = −0.38, p = 0.001) and BF% (β = 0.33, p < 0.0001), while leptin was positively associated with BF% (β = 0.60, p < 0.0001), total cholesterol (β = 0.11, p = 0.02) and HOMA-IR (β = 0.11, p = 0.02). When controlled for gender, HOMA-IR was found significantly associated to adiponectin (β = 0.13, p = 0.046), but not BF%, while the association previously found between leptin and HOMA-IR disappeared; BMI and WC were significantly associated with leptin (β = 0.18, p = 0.04 & β = 0.19, p = 0.02 respectively). Conclusion This study, which includes a population who was not receiving potentially confounding medications, confirms the associations previously observed of adiponectin with reduced adiposity especially central adiposity and improved insulin sensitivity. Confirmatory associations were also observed between leptin and obesity, blood lipids and insulin resistance for the first time in an African population. Gender was significant covariate interacting with insulin sensitivity/insulin resistance and obesity indexes associations in this population.
- ItemOpen AccessBlood-Pressure and Cholesterol Lowering in Persons without Cardiovascular Disease(2016) Yusuf, Salim; Lonn, Eva; Pais, Prem; Bosch, Jackie; López-Jaramillo, Patricio; Zhu, Jun; Xavier, Denis; Avezum, Álvaro; Leiter, Lawrence A; Piegas, Leopoldo S; Parkhomenko, Alexander; Keltai, Matyas; Keltai, Katalin; Sliwa, Karen; Chazova, Irina; Peters, Ron JG; Held, Claes; Yusoff, Khalid; Lewis, Basil S; Jansky, Petr; Khunti, Kamlesh; Toff, William D; Reid, Christopher M; Varigos, John; Accini, Jose L; McKelvie, Robert; Pogue, Janice; Jung, Hyejung; Liu, Lisheng; Diaz, Rafael; Dans, Antonio; Dagenais, GillesBACKGROUND Elevated blood pressure and elevated low-density lipoprotein (LDL) cholesterol increase the risk of cardiovascular disease. Lowering both should reduce the risk of cardiovascular events ...
- ItemOpen AccessDecreased production of low density lipoprotein by atorvastatin after apheresis in homozygous familial hypercholesterolemia(1997) Marais, A David; Naoumova, R P; Firth, J C; Penny, C; Neuwirth, C K Y; Thompson, G RApheresis only partially controls raised low density lipoprotein cholesterol levels in patients with homozygous familial hypercholesterolemia, who usually respond poorly to lipid-lowering drugs. The efficacy and mechanism of action of a new 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, atorvastatin, was therefore investigated in seven homozygotes undergoing apheresis. One receptor-negative and six receptor-defective homozygotes undergoing plasma exchange or LDL apheresis every 2 weeks were studied during 2 months each on placebo and on atorvastatin 80 mg daily. Changes in plasma lipids and mevalonic acid, an index of cholesterol synthesis, were measured and the kinetics of the rebound of low density lipoprotein cholesterol and apolipoprotein B after apheresis were analyzed. All subjects had significant improvements on atorvastatin. Mean decreases in low density lipoprotein cholesterol were 31% greater both pre- and post-apheresis on atorvastatin compared with placebo, accompanied by a 63% decrease in mevalonic acid. Percentage changes in low density lipoprotein cholesterol and mevalonic acid were closely correlated (r = 0.89, P = 0.007). The mean production rates of low density lipoprotein cholesterol and apolipoprotein B were 21% and 25% lower, respectively, on atorvastatin than on placebo (P < 0.005 and <0.02) but changes in mean fractional clearance rates were not statistically significant. We conclude that atorvastatin enhances the efficacy of plasma exchange and low density lipoprotein apheresis in patients who lack low density lipoprotein receptors. This effect appears to be due to marked inhibition of cholesterol synthesis which results in a decreased rate of production of low density lipoprotein.
- ItemOpen AccessDietary lipid modification for mild and severe dyslipidaemias(2013) Marais, A DavidThe aim of this review is to place a historical perspective on linking dyslipidaemia with atherosclerosis and emphasises previous knowledge about the impact on the lipoprotein profile and health in persons with mild dyslipidaemia and in those with defined genetic disorders. CVD is becoming the leading cause of death and disability in developed and developing countries and is strongly related to lifestyle factors that influence plasma lipoprotein concentrations. It is established that risk of complications from atherosclerosis increases with increasing LDL and decreasing HDL and that there is potentiation of risk when these and other risk factors co-exist. High-fat diets used for losing body mass may increase risk through dyslipidaemia. Pharmaceutical modulation of the lipoproteins has lowered risk powerfully but residual risk persists, possibly relating to existing disease as well as progression relating in many instances to dietary lipids. The impact of various dietary lipids is reviewed as they relate to the conventional lipoprotein profile in persons who do not have significant metabolic defects, as well as the impact on inherited metabolic disease such as familial hypercholesterolaemia, hypertriglyceridaemia and phytosterolaemia. For most persons with dyslipidaemias a significant benefit will be seen on the lipid profile by adopting a low saturated fat diet with less cholesterol intake.
- ItemOpen AccessEfficacy and Safety of Evolocumab in Reducing Lipids and Cardiovascular Events(2015) Sabatine, Marc S; Giugliano, Robert P; Wiviott, Stephen D; Raal, Frederick J; Blom, Dirk J; Robinson, Jennifer; Ballantyne, Christie M; Somaratne, Ransi; Legg, Jason; Wasserman, Scott M; Scott, Robert; Koren, Michael J; Stein, Evan ABACKGROUND: Evolocumab, a monoclonal antibody that inhibits proprotein convertase subtilisin-kexin type 9 (PCSK9), significantly reduced low-density lipoprotein (LDL) cholesterol levels in short-term studies. We conducted two extension studies to obtain longer-term data. METHODS: In two open-label, randomized trials, we enrolled 4465 patients who had completed 1 of 12 phase 2 or 3 studies ("parent trials") of evolocumab. Regardless of study-group assignments in the parent trials, eligible patients were randomly assigned in a 2:1 ratio to receive either evolocumab (140 mg every 2 weeks or 420 mg monthly) plus standard therapy or standard therapy alone. Patients were followed for a median of 11.1 months with assessment of lipid levels, safety, and (as a prespecified exploratory analysis) adjudicated cardiovascular events including death, myocardial infarction, unstable angina, coronary revascularization, stroke, transient ischemic attack, and heart failure. Data from the two trials were combined. RESULTS: As compared with standard therapy alone, evolocumab reduced the level of LDL cholesterol by 61%, from a median of 120 mg per deciliter to 48 mg per deciliter (P<0.001). Most adverse events occurred with similar frequency in the two groups, although neurocognitive events were reported more frequently in the evolocumab group. The risk of adverse events, including neurocognitive events, did not vary significantly according to the achieved level of LDL cholesterol. The rate of cardiovascular events at 1 year was reduced from 2.18% in the standard-therapy group to 0.95% in the evolocumab group (hazard ratio in the evolocumab group, 0.47; 95% confidence interval, 0.28 to 0.78; P=0.003). CONCLUSIONS: During approximately 1 year of therapy, the use of evolocumab plus standard therapy, as compared with standard therapy alone, significantly reduced LDL cholesterol levels and reduced the incidence of cardiovascular events in a prespecified but exploratory analysis. (Funded by Amgen; OSLER-1 and OSLER-2 ClinicalTrials.gov numbers, NCT01439880 and NCT01854918.).
- ItemOpen AccessInsulin resistance and associated factors among HIV-infected patients in sub-Saharan Africa: a cross sectional study from Cameroon(2017) Noumegni, Steve Raoul Ngongang; Nansseu, Jobert Richie; Ama, Vicky Jocelyne Moor; Bigna, Jean Joël; Assah, Felix Kembe; Guewo-Fokeng, Magellan; Leumi, Steve; Katte, Jean-Claude; Dehayem, Mesmin; Kengne, André Pascal; Sobngwi, EugèneBACKGROUND: Little is known on the magnitude and correlates of insulin resistance in HIV-infected people in Africa. We determined the prevalence of insulin resistance and investigated associated factors in HIV-infected adult Cameroonians. METHODS: We conducted a cross-sectional study at the Yaoundé Central Hospital, Cameroon; during which we enrolled HIV-infected people aged 30 to 74 years with no previous history of cardiovascular disease. An homeostatic model assessment of insulin resistance (HOMA-IR) like index served to assess insulin sensitivity with insulin resistance defined by values of 2.1 or higher. RESULTS: We included 452 patients (20% men). Their mean age was 44.4 ± 9.8 years and 88.5% of them were on antiretroviral therapy (93.3% on first line regimen including Zidovudine, lamivudine and Efavirenz/Nevirapine). Of all participants, 28.5% were overweight, 19.5% had obesity and 2.0% had diabetes. The prevalence of insulin resistance was 47.3% without any difference between patients on ART and those ART-naïve (48.5% vs. 38.5%; p = 0.480). Obesity was the only factor independently associated with insulin resistance (adjusted odds ratio: 2.28; 95% confidence interval: 1.10-4.72). CONCLUSION: Insulin resistance is present in nearly half of HIV-infected patients in Cameroon despite a low prevalence rate of diabetes, and is associated with obesity.
- ItemOpen AccessOsteoprotegerin in relation to insulin resistance and blood lipids in sub-Saharan African women with and without abdominal obesity(2015) Ayina Ayina, Clarisse Noël; Sobngwi, Eugène; Essouma, Mickael; Noubiap, Jean Jacques N; Boudou, Philippe; Etoundi Ngoa, Laurent Serge; Gautier, Jean FrançoisBackgroundOsteoprotegerin (OPG), a soluble member of the tumor necrosis factor receptor superfamily that inhibits bone resorption, has been suggested as a potential marker of cardiovascular risk. This study aimed to assess the relationship between insulin resistance, lipid profile and OPG levels in obese and non-obese sub-Saharan African women.MethodsSixty obese (44) and non-obese (16) volunteer women aged 18 to 40years were recruited in this cross-sectional study. Their clinical (age, height, weight, waist circumference, systolic and diastolic blood pressures) and biochemical parameters (fasting blood glucose, total cholesterol, high density lipoprotein-cholesterol (HDL-C)) were measured using standard methods. Insulin levels were measured using an electrochemiluminescence immunoassay, while OPG levels were measured using the ELISA technique. Low density lipoprotein-cholesterol (LDL-C), body mass index (BMI) and Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) were calculated using standard methods. Abdominal obesity was defined as a waist circumference ≥ 80cm.ResultsOPG levels were higher in obese than in normal subjects, though the difference was not significant (p = 0.9). BMI, waist circumference, percent body fat and systolic blood pressure were significantly higher in obese than in non-obese subjects (p < 0.05). In these subjects, only age significantly correlated with OPG levels (r = 0.831, p = 0.003), while none of the anthropometric nor metabolic parameter did, even after adjustment for age. In obese subjects, OPG levels fairly correlated with HDL-C (r = 0.298, p = 0.058), and significantly correlated with HOMA-IR (r = −0.438, p = 0.018). After adjustment for age, OPG levels remained negatively correlated to HOMA-IR (r = −0.516, p = 0.020) and LDL-C (r = −0.535, p = 0.015) and positively correlated to HDL-C (r = 0.615, p = 0.004). In multiple linear regression analysis, age was a main determinant of OPG levels in non-obese (β = 0.647, p = 0.006) and obese (β = 0.356, p = 0.044) women. HDL-C was also associated to OPG levels in obese women (β = 0.535, p = 0.009).ConclusionThe positive correlation of OPG with HDL-C and HOMA-IR, and its negative correlation with LDL-C suggest that it may be a marker of insulin sensitivity/resistance and atherogenic risk in obese African women.