Mean Low-density Lipoprotein Cholesterol Concentration Research Articles

Lipid-lowering efficacy and safety of alirocumab in a real-life setting in France: Insights from the ODYSSEY APPRISE study

BackgroundRecently, a multicentre, prospective, single-arm, phase 3b, open-label trial was conducted to determine the safety and efficacy of alirocumab, a proprotein convertase subtilisin/kexin type 9 inhibitor, in a real-life setting. This study enrolled patients at high cardiovascular risk, with heterozygous familial hypercholesterolaemia (HeFH) or non-familial hypercholesterolaemia (non-FH). Results showed that alirocumab was well tolerated and resulted in a clinically significant reduction in low-density lipoprotein cholesterol (LDL-C). AimThis ancillary analysis aimed to describe the characteristics of the French patients enrolled in the study, the main results observed in this population according to their familial hypercholesterolaemia status, and adherence to treatment. MethodsFrench data were analysed separately from the original dataset of the study. ResultsAmong 215 French patients in the ODYSSEY APPRISE trial, 63.7% had non-FH, with a mean LDL-C concentration of 5.0±1.8mmol/L at baseline. The mean duration of alirocumab exposure was 72.4±42.5 weeks, with only 48.4% of patients receiving statins concomitantly. At week 12, a mean reduction in LDL-C of 56.5±17.8% was observed: 51.2±22.8% in HeFH; 59.5±13.2% in non-FH. This improvement in LDL-C started from week 4 and remained stable and sustained until week 120 in both populations. The overall incidence of severe treatment-emergent adverse events (TEAEs) was 33.5%. The most frequent TEAEs were myalgia (15.8%) and asthenia (15.3%). No tolerance or efficacy differences were observed between patients with or without established coronary artery disease or other cardiovascular disease, whatever the age of these events or considering the concomitant use of other lipid-lowering therapies. ConclusionsIn the French setting, alirocumab was well tolerated, safe and highly effective at reducing LDL-C. These findings support the use of alirocumab to manage hypercholesterolaemia in patients at high cardiovascular risk.

Prevalence and Treatment of Familial Hypercholesterolemia and Severe Hypercholesterolemia in Older Adults in Ontario, Canada

BackgroundA simplified Canadian definition was recently developed to enable identification of individuals with familial hypercholesterolemia (FH) and severe hypercholesterolemia in the general population. Our objective was to use a modified version of this new definition to assess contemporary disease prevalence, treatment patterns, and low-density lipoprotein cholesterol (LDL-C) control in Ontario, Canada. MethodsWe identified individuals aged 66 to 105 years who were alive as of January 1, 2011, using the Cardiovascular Health in Ambulatory Care Research Team (CANHEART) database, which was created by linking 19 population-based health databases in Ontario. Hypercholesterolemia was identified using LDL-C values. Cholesterol reduction and lipid-lowering treatment were assessed at time of diagnosis and after at least 2 and 5 years’ follow-up. ResultsAmong 922,464 individuals, 2440 (0.26%) met criteria for definite or probable FH, and 72,893 (7.90%) for severe hypercholesterolemia. At diagnosis, mean LDL-C concentration was 9.52 mmol/L for those with definite FH, 5.83 mmol/L for those with probable FH, 5.73 mmol/L for those with severe hypercholesterolemia, and 3.33 mmol/L for all other individuals. After > 5 years, LDL-C concentration remained elevated at 3.58 mmol/L for those with definite FH, 2.72 mmol/L for those with probable FH, and 2.93 mmol/L for those with severe hypercholesteremia. Use of statin therapy was initially high (83% of those with definite FH, 78% of those with probable FH, 62% of those with severe hypercholesterolemia); however, fewer patients remained on statins at follow-up at > 5 years (62% of those with definite FH, 67% of those with probable FH, 58% of those with severe hypercholesterolemia). ConclusionsAmong older Ontarians, we estimated that 1 in 378 individuals had FH, and 1 in 13 had severe hypercholesterolemia. Despite being at substantially increased cardiovascular risk, these patients acheived suboptimal LDL-C level control and fewer were on medical therapy at follow-up.

Real-World Insights Into Evolocumab Use in Patients With Hyperlipidemia: Canadian Analysis From the ZERBINI Study

BackgroundThe 2021 Canadian Cardiovascular Society guidelines recommend proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitor therapy in patients with atherosclerotic cardiovascular disease whose low-density lipoprotein cholesterol (LDL-C) concentration remains ≥ 1.8 mmol/L despite maximally tolerated statin therapy. This retrospective and prospective observational study characterizes Canadian patients treated with evolocumab and describes its effectiveness and safety. MethodsBetween August 2017 and July 2019, a total of 131 patients initiated on evolocumab therapy were enrolled at 15 sites in Canada. Data were extracted from medical records every 3 months between 6 months prior to, and for 12 months following evolocumab therapy initiation, until July 6, 2020. Baseline and prospectively collected data are reported as available. ResultsA total of 131 patients were enrolled (59.5% male; mean age [standard deviation (SD)] 64.7 ± 10.6 years), most with a diagnosis of atherosclerotic cardiovascular disease and/or familial hypercholesterolemia (93.4%). Mean (± SD) LDL-C concentration at baseline was 3.7 (± 1.7) mmol/L (n = 119), with 58.0% of patients receiving a statin (36.6% high intensity). Mean (± SD) LDL-C concentration after evolocumab treatment was 1.6 (± 1.0) mmol/L (n = 120), representing a 58.7% decrease from baseline (n = 109). This level remained stable over 12 months. An LDL-C concentration < 1.8 mmol/L was achieved by 77.5% of patients. Persistence was 92%, and no serious treatment-emergent adverse events were reported. ConclusionsThese findings provide real-world evidence of guideline-recommended initiation of evolocumab therapy, as well as confirmation of its effectiveness and safety in a Canadian population. Evolocumab therapy can address a healthcare gap in the management of dyslipidemia, by increasing the proportion of patients achieving LDL-C goals recommended to lower cardiovascular risk.

Lipid control in adult Chinese patients with type 2 diabetes: a retrospective analysis of time trends and geographic regional differences.

Lipid control in adult Chinese patients with type 2 diabetes: a retrospective analysis of time trends and geographic regional differences.

Efficacy and safety of inclisiran in patients with polyvascular disease: pooled, post hoc analysis of the ORION-9, ORION-10 and ORION-11, phase 3 randomised controlled trials

Abstract Background Approximately 25% of patients (pts) with atherosclerotic cardiovascular disease (ASCVD) have polyvascular disease (PVD), which involves ≥2 coronary, cerebrovascular, and peripheral artery beds. PVD is an independent predictor of major adverse cardiovascular (CV) events (MACE) and death.[1,2] Agents that inhibit proprotein convertase subtilisin-kexin type 9 (PCSK9) resulted in reduced low-density lipoprotein cholesterol (LDL-C) concentration and MACE incidence in pts with PVD.[3,4] Inclisiran is a small interfering RNA (siRNA) agent targeting PCSK9 messenger RNA that provided effective and sustained reduction in LDL-C concentration and was well tolerated.[5] Purpose To describe the effect inclisiran versus placebo (pbo) in pts with and without PVD. Methods This was a post hoc analysis from the ORION-9 (NCT03397121), ORION-10 (NCT03399370) and ORION-11 (NCT03400800) trials. Pts with heterozygous familial hypercholesterolaemia, ASCVD or risk equivalents were randomised 1:1 to receive 300 mg inclisiran sodium (equivalent to 284 mg inclisiran) or pbo at baseline, Day 90, and 6-monthly thereafter. LDL-C percentage change from baseline to Day 510 and corresponding time-averaged change from Day 90 and to Day 540 were evaluated by presence or absence of PVD (intention-to-treat population). Safety was assessed over 540 days (safety population). Results Of 3454 pts, 470 (13.6%) had PVD and 2984 (86.4%) did not. Baseline characteristics were generally balanced between treatment arms in both groups (Table 1). A greater proportion of pts with vs without PVD had CV risk factors at baseline. Mean LDL-C concentration at baseline was lower in pts with vs without PVD (Table 1). Mean (95% CI) pbo-corrected LDL-C percentage change from baseline to Day 510 with inclisiran was −48.9 (−55.6 to −42.2) in pts with PVD and −51.5 (−53.9 to −49.1) in pts without PVD (Table 2). Proportions of pts with treatment-emergent adverse events (TEAE) and treatment-emergent serious adverse events (TESAE) were similar between treatment arms irrespective of PVD status although reported TESAEs were numerically greater in both treatment arms for pts with PVD (Table 2). Clinically relevant TEAEs at the injection site were reported more frequently with inclisiran vs pbo in both groups but all were mild or moderate (Table 2). Proportions of pts with clinically relevant laboratory measurements were low and similar between treatment arms for both groups (Table 2). Conclusions Twice-yearly dosing with inclisiran (after the initial and 3-month doses) provided effective and sustained LDL-C lowering in pts, irrespective of their PVD status, with a safety profile similar to pbo, except for a modest excess of mainly mild TEAEs at the injection site. Notably, TESAEs were reported more frequently in pts with PVD, which was likely due to their more advanced disease. Since pts with PVD are at high risk of CV events, intensive LDL-C lowering may be beneficial to reduce this risk. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Novartis Pharma AG, Basel, Switzerland

Trends in low-density lipoprotein cholesterol level among Chinese young adults hospitalized with first acute myocardial infarction.

BackgroundRepresentative data has shown a linear increase in mean low-density lipoprotein cholesterol (LDL-C) levels among Chinese adults, contributing to the burden of atherosclerotic cardiovascular disease (ASCVD). This study aimed to assess the trends in LDL-C levels and their association with coronary artery stenosis during the first acute myocardial infarction (AMI) in young Chinese adults.MethodsA retrospective study including 2,781 adults, aged 18–44 years, hospitalized for their first AMI in Beijing Anzhen hospital between 2007 and 2017 was performed.ResultsMean LDL-C level was 2.82±0.97 mmol/L with the prevalence of elevated LDL-C being 21.6% (601/2,781). Of the study, only 4.2% were aware of their elevated LDL-C status. Neither mean LDL-C concentration nor prevalence of elevated LDL-C showed a downward trend between 2007 and 2017 (P>0.05). Patients aged <35 years had the highest LDL-C level and frequency of elevated LDL-C among the three age groups (aged <35, 35–39, and 40–44 years; P<0.01). Patients with LDL-C ≥3.4 mmol/L evinced a more than 50% increased risk of coronary artery stenosis compared with those with LDL-C <1.4 mmol/L [adjusted odds ratio (OR) 3.19; 95% confidence interval (CI): 1.62 to 6.29]. Of the study, 62.0% had at least two conventional risk factors (RFs), and smoking, accompanied by hypertension, obesity, or elevated LDL-C were the most common combinations.ConclusionsThe current study provides an overview of trends in LDL-C level and elevated LDL-C among young adults at the time of first AMI. Patients had a high prevalence of elevated LDL-C but low awareness of this status. Coronary artery stenosis was positively correlated with LDL-C level. Preventive strategies, including public education regarding cholesterol levels and benefits of maintaining LDL-C below 3.4 mmol/L should be considered for young adults as a primary preventive strategy.

Sudanese diabetics with hypertension are at high risk for cardiovascular disease

Objectives: To measure blood glucose, lipid profile levels, and blood pressure in diabetic hypertensive patients in order to identify the association between the parameters measured and an increased risk of cardiovascular risk in the Sudanese diabetic hypertensive patients. Material and methods: During the months of April 2012 and March 2013, a case-control study was employed in Gezira State, Sudan. The study enrolled 200 patient who met the participation criteria, with respondents divided into diabetic hypertensive and non-diabetic categories to estimate fasting blood glucose levels (FBG), Glycosylated hemoglobin (HbA1C) and lipid profile which include; total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C) and triglycerides (TG). The random access auto-analyzer bio system, A15 was used to test samples for various biochemical parameters. Individual information, as well as anthropometric and biochemical measurements were collected on a questionnaire. After each participant gave verbal consent, venous blood samples were drawn after an overnight fast. The statistical evaluation was achieved with the aid of a statistical package for social sciences (SPSS version 16, Chicago, IL, USA). Result: The WC and BMI both increased significantly by (p=&lt;0.0001), according to the analysis of variance (ANOVA). FBG and HbA1C levels were significantly elevated by (p=&lt;0.0001). The increase in systolic blood pressure (SBP) was significant by (p=&lt;0.0001). The mean HDL-C level was at high risk (49.73) with a significant increase by (p=0.009). The mean LDL-C concentration was above the optimum level (109.03) with a non-significant increase (p=0.697). Conclusion: WC, BMI, DBP, FBG, and HDL-C all increased significantly. Diabetic- hypertensive participants were at a high risk of develops dyslipidemia and cardiovascular disease.

PCSK9 Antibody-based Treatment Strategies for Patients With Statin Intolerance.

Statin intolerance refers to the inability of a patient to tolerate statin therapy, presenting muscle aches, pains, weakness and muscle inflammation. Thus, numerous patients are not treated with suitable statin-based therapy or take only very low doses. As a result, the desired decrease in low-density lipoprotein cholesterol (LDL-C) is not achieved, resulting in patients at a high risk for cardiovascular events, requiring an alternative lipid-lowering treatment. Common treatments manage to reduce the LDL-C level by up to 20%. Recently, new alternative treatment options have been proved to lower the LDL-C level by up to 70%. These treatment strategies are based on human monoclonal antibodies against protein convertase subtilisin/kexin 9 (PCSK9). Herein, we review the efficiency of anti-PCSK9 in treatment of hypercholesterolemic patients with statin intolerance. We focused on the use of PCSK9 inhibitors in statin-intolerant patients and we estimated the clinical results concerning the reduction of the mean LDL-C concentration and the side effects that were observed. In the majority of cases, treatment strategy based on PCSK9 was successful and achieved the end-points. PCSK9 inhibition can be considered as a treatment of option for lipid-lowering in statin-intolerant patients.

Statins for children with familial hypercholesterolemia.

Familial hypercholesterolemia is one of the most common inherited metabolic diseases and is an autosomal dominant disorder meaning heterozygotes, or carriers, are affected. Those who are homozygous have severe disease. The average worldwide prevalence of heterozygous familial hypercholesterolemia is at least 1 in 500, although recent genetic epidemiological data from Denmark and next generation sequencing data suggest the frequency may be closer to 1 in 250. Diagnosis of familial hypercholesterolemia in children is based on elevated total cholesterol and low-density lipoprotein cholesterol levels or DNA-based analysis, or both. Coronary atherosclerosis has been detected in men with heterozygous familial hypercholesterolemia as young as 17 years old and in women with heterozygous familial hypercholesterolemia at 25 years old. Since the clinical complications of atherosclerosis occur prematurely, especially in men, lifelong treatment, started in childhood, is needed to reduce the risk of cardiovascular disease. In children with the disease, diet was the cornerstone of treatment but the addition of lipid-lowering medications has resulted in a significant improvement in treatment. Anion exchange resins, such as cholestyramine and colestipol, were found to be effective, but they are poorly tolerated. Since the 1990s studies carried out on children aged 6 to 17 years with heterozygous familial hypercholesterolemia have demonstrated significant reductions in their serum total and low-density lipoprotein cholesterol levels. While statins seem to be safe and well-tolerated in children, their long-term safety in this age group is not firmly established. This is an update of a previously published version of this Cochane Review. To assess the effectiveness and safety of statins in children with heterozygous familial hypercholesterolemia. Relevant studies were identified from the Group's Inborn Errors and Metabolism Trials Register and Medline. Date of most recent search: 04 November 2019. Randomized and controlled clinical studies including participants up to 18 years old, comparing a statin to placebo or to diet alone. Two authors independently assessed studies for inclusion and extracted data. We found 26 potentially eligible studies, of which we included nine randomized placebo-controlled studies (1177 participants). In general, the intervention and follow-up time was short (median 24 weeks; range from six weeks to two years). Statins reduced the mean low-density lipoprotein cholesterol concentration at all time points (high-quality evidence). There may be little or no difference in liver function (serum aspartate and alanine aminotransferase, as well as creatinine kinase concentrations) between treated and placebo groups at any time point (low-quality evidence). There may be little or no difference in myopathy (as measured in change in creatinine levels) (low-quality evidence) or clinical adverse events (moderate-quality evidence) with statins compared to placebo. One study on simvastatin showed that this may slightly improve flow-mediated dilatation of the brachial artery (low-quality evidence), and on pravastatin for two years may have induced a regression in carotid intima media thickness (low-quality evidence). No studies reported rhabdomyolysis (degeneration of skeletal muscle tissue) or death due to rhabdomyolysis, quality of life or compliance to study medication. Statin treatment is an effective lipid-lowering therapy in children with familial hypercholesterolemia. Few or no safety issues were identified. Statin treatment seems to be safe in the short term, but long-term safety remains unknown. Children treated with statins should be carefully monitored and followed up by their pediatricians and their care transferred to an adult lipidologist once they reach 18 years of age. Large long-term randomized controlled trials are needed to establish the long-term safety issues of statins.

Multimodal lipid-lowering treatment in pediatric patients with homozygous familial hypercholesterolemia-target attainment requires further increase of intensity.

Familial hypercholesterolemia (FH) causes premature cardiovascular disease (CVD). Lipoprotein apheresis (LA) is recommended as first-line lipid-lowering treatment (LLT) for homozygous (ho) FH. Efficacy of multimodal LLT including lifestyle counseling, drug treatment, and LA was analyzed in 17 pediatric hoFH or compound heterozygous (c-het) FH patients, who commenced chronic LA in Germany before the age of 18. At time of diagnosis, mean low-density lipoprotein cholesterol (LDL-C) concentration was 19.6mmol/l (756mg/dl). Multimodal LLT resulted in 73% reduction of mean LDL-C concentration including a 62% contribution of LA. Only three children (18%) achieved mean LDL-C concentrations below the recommended pediatric target of 3.5mmol/l (135mg/dl). In 13 patients (76%) during chronic LA, neither cardiovascular events occurred nor was CVD progression detected clinically or by routine imaging techniques. In four patients (24%), cardiovascular events documented progression of CVD despite weekly LA, including one death due to coronary and cerebrovascular CVD which was not stabilized after commencing LA. Based on the mutational status, only 6 out of the 17 children were candidates for proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibition. Two already responded with further LDL-C decrease by 40%. Next to drug therapy, regular LA is an essential component of LLT for approaching LDL-C targets in children with hoFH or c-hetFH, which was successful only in a minority of children. Progression of CVD morbidity and resulting mortality remain unresolved issues. Early and intensified multimodal LLT guided by risk factors beyond LDL-C concentration is needed to improve outcome.

Statins for children with familial hypercholesterolemia.

Familial hypercholesterolemia is one of the most common inherited metabolic diseases and is an autosomal dominant disorder meaning heterozygotes, or carriers, are affected. Those who are homozygous have severe disease. The average worldwide prevalence of heterozygous familial hypercholesterolemia is at least 1 in 500, although recent genetic epidemiological data from Denmark and next generation sequencing data suggest the frequency may be closer to 1 in 250. Diagnosis of familial hypercholesterolemia in children is based on elevated total cholesterol and low-density lipoprotein cholesterol levels or DNA-based analysis, or both. Coronary atherosclerosis has been detected in men with heterozygous familial hypercholesterolemia as young as 17 years old and in women with heterozygous familial hypercholesterolemia at 25 years old. Since the clinical complications of atherosclerosis occur prematurely, especially in men, lifelong treatment, started in childhood, is needed to reduce the risk of cardiovascular disease. In children with the disease, diet was the cornerstone of treatment but the addition of lipid-lowering medications has resulted in a significant improvement in treatment. Anion exchange resins, such as cholestyramine and colestipol, were found to be effective, but they are poorly tolerated. Since the 1990s studies carried out on children aged 6 to 17 years with heterozygous familial hypercholesterolemia have demonstrated significant reductions in their serum total and low-density lipoprotein cholesterol levels. While statins seem to be safe and well-tolerated in children, their long-term safety in this age group is not firmly established. This is an update of a previously published version of this Cochane Review. To assess the effectiveness and safety of statins in children with heterozygous familial hypercholesterolemia. Relevant studies were identified from the Group's Inborn Errors and Metabolism Trials Register and Medline.Date of most recent search: 20 February 2017. Randomized and controlled clinical studies including participants up to 18 years old, comparing a statin to placebo or to diet alone. Two authors independently assessed studies for inclusion and extracted data. We found 26 potentially eligible studies, of which we included nine randomized placebo-controlled studies (1177 participants). In general, the intervention and follow-up time was short (median 24 weeks; range from six weeks to two years). Statins reduced the mean low-density lipoprotein cholesterol concentration at all time points (moderate quality evidence). Serum aspartate and alanine aminotransferase, as well as creatinine kinase concentrations, did not differ between treated and placebo groups at any time point (low quality evidence). The risks of myopathy (low quality evidence) and clinical adverse events (moderate quality evidence) were very low and also similar in both groups. In one study simvastatin was shown to improve flow-mediated dilatation of the brachial artery (low quality evidence), and in another study treatment with pravastatin for two years induced a significant regression in carotid intima media thickness (low quality evidence). Statin treatment is an effective lipid-lowering therapy in children with familial hypercholesterolemia. No significant safety issues were identified. Statin treatment seems to be safe in the short term, but long-term safety remains unknown. Children treated with statins should be carefully monitored and followed up by their pediatricians and their care transferred to an adult lipidologist once they reach 18 years of age. Large long-term randomized controlled trials are needed to establish the long-term safety issues of statins.

Low-Density Lipoprotein Cholesterol Concentrations and Association of High-Sensitivity C-Reactive Protein Concentrations With Incident Coronary Heart Disease in the Multi-Ethnic Study of Atherosclerosis.

High-sensitivity C-reactive protein (hs-CRP) has been associated with coronary heart disease (CHD) in numerous but not all observational studies, and whether low levels of low-density lipoprotein cholesterol (LDL-C) alter this association is unknown. In the Multi-Ethnic Study of Atherosclerosis (2000-2012), we prospectively assessed the association of hs-CRP concentrations with incident CHD in participants who did not receive lipid-lowering therapy, as well as in those with LDL-C concentrations less than 130 mg/dL (n = 3,106) and those with LDL-C concentrations of 130 mg/dL or greater (n = 1,716) at baseline (2000-2002). Cox proportional hazard analyses were used to assess the associations after adjustment for socioeconomic status, traditional risk factors, body mass index, diabetes, aspirin use, kidney function, and coronary artery calcium score. Loge hs-CRP was associated with incident CHD in participants with LDL-C concentrations of 130 mg/dL or higher (hazard ratio (HR) = 1.29, 95% confidence interval (CI): 1.05, 1.60) but not in those with LDL-C concentrations less than 130 mg/dL (HR = 0.88, 95% CI: 0.74, 1.05; P for interaction = 0.003). As a whole, loge hs-CRP was not associated with incident CHD in participants who had not received lipid-lowering therapy at baseline (HR = 1.05, 95% CI: 0.92, 1.20) and who had mean LDL-C concentrations less than 130 mg/dL. These findings suggest that LDL-C concentrations might be a moderator of the contribution of hs-CRP to CHD.

Statins for children with familial hypercholesterolemia.

Familial hypercholesterolemia is one of the most common inherited metabolic diseases; the average worldwide prevalence of heterozygous familial hypercholesterolemia is at least 1 in 500. Diagnosis of familial hypercholesterolemia in children is based on highly elevated low-density lipoprotein (LDL) cholesterol level or DNA-based analysis, or both. Coronary atherosclerosis has been detected in men with heterozygous familial hypercholesterolemia as young as 17 years old and in women with heterozygous familial hypercholesterolemia at 25 years old. Since the clinical complications of atherosclerosis occur prematurely, especially in men, lifelong hypolipidemic measures, started in childhood, are needed to reduce the risk of cardiovascular disease. In children with familial hypercholesterolemia, diet is as yet the cornerstone of treatment. Anion exchange resins, such as cholestyramine and colestipol, have also been found to be effective, but are poorly tolerated. Since the 1990s statin studies have been carried out among children with familial hypercholesterolemia (aged 7 to 17 years). Statins greatly reduced their serum LDL cholesterol levels. Even though statins seem to be safe and well-tolerated in children, their long-term safety in this age group is not firmly established. To assess the effectiveness and safety of statins in children with familial hypercholesterolemia. Relevant studies were identified from the Group's Inborn Errors and Metabolism Trials Register and Medline.Date of most recent search: 14 October 2013. Randomized and controlled clinical studies including participants up to 18 years old, comparing a statin to placebo or to diet alone. Two authors independently assessed studies for inclusion and extracted data. We found 21 potentially eligible studies, of which we included eight randomized placebo-controlled studies (1074 participants). In general, the intervention and follow-up time was short (median 24 weeks; range from six weeks to two years). Statins reduced the mean LDL cholesterol concentration at all time points. Serum aspartate and alanine aminotransferase, as well as creatinine kinase concentrations, did not differ between treated and placebo groups at any time point. The risks of myopathy and clinical adverse events were very low and also similar in both groups. In one study simvastatin was shown to improve flow-mediated dilatation of the brachial artery, and in another study treatment with pravastatin for two years induced a significant regression in carotid intima media thickness. Statin treatment is an efficient lipid-lowering therapy in children with familial hypercholesterolemia. No significant safety issues were identified. Statin treatment seems to be safe in the short term, but long-term safety is unknown. Children treated with statins should be carefully monitored and followed up by their pediatricians or physicians into adulthood. Large long-term randomized controlled trials are needed to establish the long-term safety issues of statins.

Association Between Plasma Triglycerides and High-Density Lipoprotein Cholesterol and Microvascular Kidney Disease and Retinopathy in Type 2 Diabetes Mellitus

Background— Microvascular renal and retinal diseases are common major complications of type 2 diabetes mellitus. The relation between plasma lipids and microvascular disease is not well established. Methods and Results— The case subjects were 2535 patients with type 2 diabetes mellitus with an average duration of 14 years, 1891 of whom had kidney disease and 1218 with retinopathy. The case subjects were matched for diabetes mellitus duration, age, sex, and low-density lipoprotein cholesterol to 3683 control subjects with type 2 diabetes mellitus who did not have kidney disease or retinopathy. The study was conducted in 24 sites in 13 countries. The primary analysis included kidney disease and retinopathy cases. Matched analysis was performed by use of site-specific conditional logistic regression in multivariable models that adjusted for hemoglobin A 1c , hypertension, and statin treatment. Mean low-density lipoprotein cholesterol concentration was 2.3 mmol/L. The microvascular disease odds ratio increased by a factor of 1.16 (95% confidence interval, 1.11–1.22) for every 0.5 mmol/L (≈1 quintile) increase in triglycerides or decreased by a factor of 0.92 (0.88–0.96) for every 0.2 mmol/L (≈1 quintile) increase in high-density lipoprotein cholesterol. For kidney disease, the odds ratio increased by 1.23 (1.16–1.31) with triglycerides and decreased by 0.86 (0.82–0.91) with high-density lipoprotein cholesterol. Retinopathy was associated with triglycerides and high-density lipoprotein cholesterol in matched analysis but not significantly after additional adjustment. Conclusions— Diabetic kidney disease is associated worldwide with higher levels of plasma triglycerides and lower levels of high-density lipoprotein cholesterol among patients with good control of low-density lipoprotein cholesterol. Retinopathy was less robustly associated with these lipids. These results strengthen the rationale for studying dyslipidemia treatment to prevent diabetic microvascular disease.

Cochrane Review: Statins for children with familial hypercholesterolemia

AbstractBackgroundFamilial hypercholesterolemia is one of the most common inherited metabolic diseases; the average worldwide prevalence of heterozygous familial hypercholesterolemia is about 1 in 500. Diagnosis of familial hypercholesterolemia in children is based on two measurements of low‐density lipoprotein cholesterol level above 4.0 mmol/L or a DNA‐based analysis. Coronary stenosis has been detected in men with familial hypercholesterolemia as young as 17 years old and in women with familial hypercholesterolemia at 25 years old. Atherosclerosis and its clinical complications occur prematurely, especially in men, thus lifelong hypolipidemic measures, started in childhood, are needed to reduce the risk of cardiovascular diseases. In children with familial hypercholesterolemia children, so far diet has been the main mode of treatment. Anion exchange resins, such as cholestyramine and colestipol, have also been found to be effective but are generally considered unpalatable and therefore poorly tolerated. Since the 1990s statin trials have been carried out among children with familial hypercholesterolemia (aged 7 to 17 years), and statins reduced their serum low‐density lipoprotein cholesterol levels by 23% to 40%. The safety of statins among children is not well known even though statins seem to be safe and well‐tolerated in adults.ObjectivesTo assess the effectiveness and safety of statins in children with familial hypercholesterolemia.Search strategyRelevant trials were identified from the Group's Inborn Errors and Metabolism Trials Register and Medline.Date of most recent search: 11 March 2010.Selection criteriaRandomized and controlled clinical trials including participants up to 18 years old comparing a statin to placebo or to diet alone.Data collection and analysisTwo authors independently assessed studies for inclusion and extracted data.Main resultsWe found 19 potentially eligible studies of which we included eight randomized placebo‐controlled trials (897 participants). Statins reduced the mean low‐density lipoprotein cholesterol concentration at all time points. There was no difference between serum aspartate and alanine aminotransferase as well as creatine kinase concentrations at any time‐point. The risks of myopathy and clinical adverse events were also similar in both groups. In one study simvastatin was shown to improve flow‐mediated dilation of the brachial artery.Authors' conclusionsStatin treatment is an efficient lipid‐lowering therapy in children with familial hypercholesterolemia. It seems to be safe in the short term but long‐term safety is unknown. Children treated with statins should be carefully followed up by their pediatricians. Large long‐term randomized controlled trials are needed to establish the long‐term safety of statins.Plain Language SummaryStatins for children with inherited high blood cholesterolFamilial hypercholesterolemia is an inherited disease in which blood cholesterol level is high. Vascular diseases often occur prematurely, especially amongst men. Thus lifelong therapies to reduce blood cholesterol started in childhood are needed. In children with familial hypercholesterolemia, diet has been the main mode of treatment. Resins, such as cholestyramine and colestipol, have also been effective but usually taste unpleasant and are poorly tolerated. Since the 1990s statin trials have been carried out among children and adolescents with familial hypercholesterolemia. Statins have decreased their serum low‐density lipoprotein cholesterol levels by about one third. The safety of statins among children is poorly known, even though statins have seemed to be safe and well‐tolerated in adults.In this review we included randomized and controlled clinical trials with participants up to 18 years old. We found 19 potentially eligible studies, and included eight.Statins reduced the mean low‐density lipoprotein cholesterol concentration on average. The risk of a high increase in liver and muscle enzymes was similar in both the statin and the control groups. Neither was there any clinically important difference in the risk of myopathy nor clinical adverse events between the groups. The follow‐up time on average was only six months, and at longest lasted two years which occurred in one trial only.Statin treatment is an efficient lipid‐lowering therapy in children with familial hypercholesterolemia. It seems to be safe in the short term but long‐term safety is unknown.

Lipid profiles and trans fatty acids in serum phospholipids of semi-nomadic Fulani in northern Nigeria.

The Fulani are semi-nomadic pastoralists of West Africa whose diet, culture, and economy are centred on cattle. Previous studies have shown that the Fulani of northern Nigeria derive 50% of their total calories from fat and 30% of their calories from milk, cheese, yogurt, and butter oil that contain significant amounts of trans fatty acids (TFAs), primarily vaccenic acid, which raise total serum cholesterol and low-density lipoproteincholesterol (LDL-C), and lower high-density lipoprotein-cholesterol (HDL-C). The study was conducted to know how the consumption of relatively large amounts of dairy products by adult Fulani affected the TFA content of their serum phospholipids. Blood samples were collected from 22 male and 29 female Fulani, aged 35-60 years, who were living in rural areas of Gombe state in northeastern Nigeria. The total serum phospholipid fraction was isolated, and its fatty acid composition was determined. Surprisingly, vaccenic acid was not detected, and three other TFAs--18:1-t6, 18:1-t9, and 18:2-t9,t12--together accounted for only 0.16% of the total fatty acid. The mean serum total cholesterol, LDL-C, and triglyceride concentrations of the subjects were within the normal range for populations in developed countries; however, at 32 mg/dL, the mean serum HDL-C concentration of the Fulani males was slightly below the lower limit of the reference range. No correlations were observed between the total TFA percentage or that of the three individual TFAs and any of the parameters of the serum lipid profile. These findings indicate that, with respect to TFAs at least, the fatty acid pattern of the serum phospholipids of Fulani pastoralists does not reflect the high TFA content of their traditional diet. Despite the consumption of rumenic acid-rich dairy products, for unknown reasons, the semi-nomadic Fulani manage to maintain a low level of TFAs in their blood and a relatively healthful serum lipid profile. While the mechanism that accounts for this disconnect between the consumption of TFAs by Fulani pastoralists and the proportion of TFAs in their serum phospholipids is obscure, possibilities include discrimination against rumenic acid during the process of triglyceride synthesis and chylomicron synthesis in the intestine and the preferential oxidation of TFAs by Fulani the people compared to other ethnic groups.

Lipid Profile of Type 2 Diabetic and Hypertensive Patients in the Jamaican Population

Aims:Previous studies have shown that diabetes mellitus (DM) increases the risk of cardiovascular diseases in females to a greater extent than in males. In this cross-sectional study, we evaluated the lipid profiles of type 2 diabetic males and females.Materials and Methods:The study included 107 type 2 diabetic patients (41 males and 66 females), and 122 hypertensive type 2 diabetic patients (39 males and 83 females), aged 15 years and older. Total cholesterol (TC), triglycerides (TG), low density lipoprotein-cholesterol (LDL-C), very low density lipoprotein-cholesterol (VLDL-C) and high density lipoprotein-cholesterol (HDL-C) concentrations were assayed for each group using standard biochemical methods.Results:The mean TC, TG, VLDL-C, HDL-C and LDL-C concentrations, TG/HDL and LDL/HDL ratios were higher in type 2 diabetic and hypertensive type 2 diabetic patients compared with non-diabetic, and hypertensive non-diabetic control subjects, although these were not significant (P > 0.05). Hypertensive type 2 diabetic females had significantly higher serum TC (7.42 ± 1.63 mmol/L) than hypertensive non-diabetic males (5.76±1.57 mmol/L; P < 0.05). All the other lipid and lipoprotein parameters except HDL-C were non-significantly higher in females with type 2 DM and those with hypertension and type 2 DM, compared with type 2 diabetic and hypertensive type 2 diabetic males, respectively (P > 0.05).Conclusion:This study demonstrated that dyslipidemia exists in our type 2 diabetic population with greater TC in hypertensive type 2 diabetic females compared with hypertensive type 2 diabetic males. This suggests that hypertensive type 2 diabetic females are exposed more profoundly to risk factors including atherogenic dyslipidemia compared with males.

Switching Statin Therapy Using a Pharmacist‐Managed Therapeutic Conversion Program versus Usual Care Conversion Among Indigent Patients

STUDY OBJECTIVE. To evaluate the effectiveness of switching statin therapy using a therapeutic conversion program versus usual care conversion among patients enrolled in the Colorado Indigent Care Program when atorvastatin was removed from the formulary. Prospective cohort study. Family medicine center and other ambulatory care clinics of a university-based health care system. One hundred seventeen ambulatory care patients with dyslipidemia who were treated with atorvastatin. Clinical pharmacists in the family medicine center implemented a therapeutic conversion program (30 patients), switching atorvastatin to a new formulary regimen of simvastatin, rosuvastatin, or ezetimibe-simvastatin, using an algorithm designed to achieve patient-specific goals for low-density lipoprotein cholesterol (LDL). Usual care occurred in the other ambulatory care clinics without clinical pharmacists (87 patients), where medical providers switched atorvastatin to a formulary regimen based on a suggested (but optional) equipotency conversion algorithm. Primary end points were LDL concentration and LDL goal attainment before and after conversion. Before and after conversion, respectively, mean LDL concentrations were 86.7 and 82.3 mg/dl in the therapeutic conversion group (p=0.44) versus 78.3 and 85.2 mg/dl in the usual care group (p=0.01). Percentages of patients attaining LDL goal were 80% before and 97% after conversion in the therapeutic conversion group (p=0.04) compared with 90% before and 75% after conversion in the usual care group (p=0.01). Use of a prospective, therapeutic statin conversion program was associated with increased control of dyslipidemia, whereas usual care statin conversion was associated with decreased control. These data suggest that proactive involvement of clinical pharmacists in converting lipid-lowering drugs results in superior patient care outcomes compared with a less aggressive approach.

Development and clinical outcomes of pharmacist-managed diabetes care clinics

The development and outcomes of two pharmacist-managed diabetes care clinics (DCCs) are described. Retrospective data analysis was performed to determine the outcomes for patients with type 2 diabetes mellitus who were treated in two pharmacist-managed DCCs. Primary outcome measures included changes in glycosylated hemoglobin (HbA(1c)), fasting plasma glucose, body mass index, low-density-lipoprotein (LDL) cholesterol, high-density-lipoprotein cholesterol, triglycerides, and blood pressure and documented annual retinal and micro-albumin screening. Secondary outcome measures included the use of aspirin and kidney-sparing agents and annual screening for thyroid-stimulating hormone. Data from 113 patients in the DCCs were analyzed. After one year, the mean reduction in HbA(1c) levels was 1.3%, with a mean HbA(1c) of 7.8%. HbA(1c) goals were based on the institution's HbA(1c) normal range of 4.1-6.5%. Compared with baseline, over one third of patients met the HbA(1c) and blood pressure goals of <7.5% and <130/80 mm Hg, respectively. Mean LDL cholesterol concentration decreased from 110 to 94 mg/dL. The mean concentration of triglycerides decreased from 243 to 178 mg/dL. Mean systolic blood pressure decreased from 136 to 132 mm Hg. Whereas the national average for uncontrolled diabetes (HbA(1c) > 9.5%) was 36.9%, only 3.5% of patients at the pharmacist-managed DCCs had uncontrolled diabetes. Attainment rates of LDL cholesterol goals and annual retinal and microalbumin screenings were significantly higher in clinic patients compared with national averages. Three-year postclinic inception data revealed similar favorable outcomes, most notably an average HbA(1c) of 7.6% and 55% of patients meeting their target HbA(1c) goal of <7.5%. Compared with national averages, DCCs managed by clinical pharmacists achieved higher screening rates and attained treatment goals more often.

Effect of Low-Density Lipoprotein Cholesterol on Angiotensin II Sensitivity

Increased angiotensin II (Ang II) sensitivity predisposes to hypertension and plaque instability. Raised low-density lipoprotein cholesterol (LDL-c) may increase Ang II sensitivity, but evidence in humans for this effect of LDL-c is limited. In 28, healthy, nonsmoking subjects, aged 30+/-8 years, with familial hypercholesterolemia, we determined the difference in infusion rate of Ang II and norepinephrine required to increase systolic blood pressure by 20 mm Hg (Pd-20) after 4 weeks of placebo and fluvastatin 80 mg daily in a randomized, double-blind, placebo-controlled, crossover study. Before infusions were started, fasting blood samples were taken to measure lipids. After 4 weeks of placebo, the mean LDL-c concentration was 6.3+/-1.4 mmol/L. The average decrease of LDL-c was 1.7+/-0.7 mmol/L after 4 weeks of fluvastatin (P<0.001). The mean Pd-20 for Ang II increased by 1.28 ng/kg per minute (95% CI, 2.05 to 0.50; P=0.002) on fluvastatin, corresponding with a 26% decrease in Ang II sensitivity. Ang II sensitivity, however, remained increased compared with normocholesterolemic controls. The Pd-20 values for norepinephrine were unaffected by fluvastatin. The present study in healthy, young subjects with isolated hypercholesterolemia shows an increased sensitivity to Ang II that partly can be restored by LDL-c-lowering therapy. These findings indicate that LDL-c levels directly influence Ang II sensitivity.