Severe Lipid Abnormalities Research Articles

Predictive value of plasma lipid levels for coronary artery disease (CAD)

Coronary artery disease (CAD) is a major cause of mortality and morbidity all over the world including Pakistan. CAD events are caused by the interplay of genetic and environmental factors, the effects of which are mainly mediated through cardiovascular risk factors. The major risk factors for CAD include hypertension, dyslipidemia, family history of premature atheroscleclerotic disease, obesity and sedentary lifestyle. However, it is clear from the existing literature that dyslipidemia plays a central role. This study was designed to examine the plasma lipid profile in coronary artery disease patients of both sexes receiving clinical care at various government hospitals in Lahore. Blood samples were collected from a total of 500 CAD patients and 250 healthy (control) subjects and subsequently analyzed for total cholesterol (TC), triglyceride (TG) and very low-density lipoprotein (VLDL), low-density lipoprotein (LDL) and high-density lipoprotein cholesterol (HDL) levels. These measurements showed that TC, LDL, TG and VLDL levels were significantly elevated, whereas HDL levels were significantly reduced in CAD patients as compared to ethnically matched controls (p < 0.0001). However, lipid levels did not differ significantly between the male and female patients. Furthermore, the lipid profile parameters were strongly associated with CAD status and association of LDL/HDL remained significant even after making an adjustment for confounders. In addition, patients with comorbidities exhibited severe lipid abnormalities. In conclusion, this study revealed elevated plasma TG, TC, VLDL and LDL levels and attenuated plasma HDL levels in the Pakistani patients with coronary artery disease. Also, plasma lipid levels have the potential to serve as biomarkers for CAD in Pakistani population.

Atypical familial dysbetalipoproteinemia associated with high polygenic cholesterol and triglyceride scores treated with ezetimibe and evolocumab

We present a 37-year-old man diagnosed with familial dysbetalipoproteinemia who presented with the severe hyperlipidemic phenotype. None of the usual metabolic triggers were found to explain his severe lipid abnormalities. Genetic analysis revealed the expected APOE E2/E2 genotype, but no other mutations were found to explain any monogenic dyslipidemia or syndrome. Polygenic risk scores for quantitative lipid traits did reveal scores placing the patient in the >99th percentile for the general population concerning polygenic susceptibility for both high cholesterol and triglycerides. Owing to his gastrointestinal intolerance to two high-intensity statins, he was treated with both ezetimibe 10 mg a day and evolocumab 140 mg subcutaneously every 2 weeks. All measures of potentially atherogenic lipids were markedly improved and remained so for more than 10 months of follow-up. This case report shows an unusual trigger for severe hyperlipidemia with familial dysbetalipoproteinemia and a favorable therapeutic response to the combination of ezetimibe and evolocumab.

A snapshot of lipid levels in the Republic of Ireland in 2017.

Abnormalities in blood lipid levels are causally linked with cardiovascular disease and pancreatitis. Data is limited regarding lipid abnormalities in Ireland. As part of a cholesterol awareness campaign, we performed a pilot study of current lipid levels to preliminarily assess the extent and pattern of lipid abnormalities in Ireland. Non-fasting, full lipid profiles and glucose measurements were performed in 259 people (32 on lipid-lowering medication and 225 untreated) using a validated Cholestech LDX machine. Untreated participants included 95 men and 130 women, aged 51 ± 16years. The mean ± SD, total, low-density lipoprotein (LDL), high-density lipoprotein cholesterol (HDL) and median(IQR) non-HDL cholesterol and triglyceride levels in untreated individuals were 5.0 ± 1.1, 2.8 ± 1.0, 1.5 ± 0.5 and 3.4 (2.8-4.3), 1.6 (1.0-2.3) mmol/l respectively. Glucose was 5.3 (4.8-5.8) mmol/l. Glucose > 7.8mmol/l occurred in 10 individuals (4%). Using defined criteria for non-fasting lipid levels, 60% of participants had some form of lipid abnormality with a frequency of 47% having a total cholesterol > 5, 35% with LDL > 3.0, 26% with HDL < 1.0/1.2, 33% with triglycerides > 2.0 and 32% with non-HDL cholesterol > 3.9mmol/l. Three individuals had untreated LDL > 5mmol/l (i.e. a ratio of 1:75 of those tested) and eight people had HDLc < 0.7 (1:28) and four had triglyceride above 7.3mmol/l (1:56). This pilot study reveals significant lipid abnormalities which require further larger more detailed lipid studies to assess the true burden of lipid abnormalities in Ireland. Cascade screening and genetic testing of relatives of those with severe lipid abnormalities should be considered.

A Pediatric Opportunity in Adolescents to Prevent Adult Heart Attacks

Importance: Cardiovascular disease is the number one cause of death in the adult population, greater than all cancers combined. When a heart attack or stroke occurs, many individuals have no advance warning, thus making prevention difficult. Cardiovascular disease begins early, i.e., in the developing fetus, and progresses throughout childhood and adolescence, such that it is identifiable both radiographically and ultrasonographically in the adolescent. Observations: There are multiple lines of evidence that atherosclerosis is present in the pediatric population. This evidence is based on autopsy studies in accident victims, coronary artery calcium scoring and carotid intermedia thickness measurements, intravascular ultrasound studies of hearts transplanted from teenage accident victims, and wartime casualties in young males. Multiple studies of cardiovascular risk factors (e.g., hypertension, obesity, insulin resistance, glucose intolerance and hyperlipidemia) have emphasized their importance in contributing to the pathogenesis of atherosclerosis. With the recent increase of obesity in the pediatric population, these risk factors will assume increasing importance in the development of clinical cardiovascular disease in the adult population. Prevention of atherosclerosis will require measuring a lipid profile in adolescents and initiating intervention to reduce the triglyceride and LDLc concentration. Education of both the adolescent at risk and his/her family will be necessary. Lifestyle changes are paramount. Hyperlipidemic medication should be reserved for individuals with severe lipid abnormalities. Conclusion and Relevance:Atherosclerotic changes of arteries begin during gestation and progress throughout the pediatric years into adulthood. Pediatricians’ contribution to reducing the progression of atherosclerosis in their patients can have major effects in controlling this epidemic in adults. Education of adolescents and their parents concerning a healthy lifestyle is paramount to a successful cardiovascular disease prevention program.

Anti-Retroviral Therapy Increases the Prevalence of Dyslipidemia in South African HIV-Infected Patients.

PurposeData on the prevalence of dyslipidaemia and associated risk factors in HIV-infected patients from sub-Saharan Africa is sparse. We performed a cross-sectional analysis in a cohort of HIV-infected South African adults.MethodsWe studied HIV-infected patients who were either antiretroviral therapy (ART)-naive or receiving non-nucleoside reverse transcriptase inhibitor (NNRTI)-based or protease inhibitor (PI)-based ART. Evaluation included fasting lipograms, oral glucose tolerance tests and clinical anthropometry. Dyslipidemia was defined using the NCEP ATPIII guidelines.ResultsThe median age of the participants was 34 years (range 19–68 years) and 78% were women. The prevalence of dyslipidemia in 406 ART-naive and 551 participants on ART was 90.0% and 85%, respectively. Low HDL-cholesterol (HDLC) was the most common abnormality [290/406 (71%) ART-naïve and 237/551 (43%) ART- participants]. Participants on ART had higher triglycerides (TG), total cholesterol (TC), LDL-cholesterol (LDLC) and HDLC than the ART-naïve group. Severe dyslipidaemia, (LDLC> 4.9 mmol/L or TG >5.0 mmol/L) was present in <5% of participants. In multivariate analyses there were complex associations between age, gender, type and duration of ART and body composition and LDLC, HDLC and TG, which differed between ART-naïve and ART-participants.ConclusionParticipants on ART had higher TG, TC, LDLC and HDLC than those who were ART-naïve but severe lipid abnormalities requiring evaluation and treatment were uncommon.

Lipids Apheresis: To Whom? When? And How?

Synopsis: Extracorporeal elimination of ApoB-100−containing atherogenic lipoproteins—low-density lipoprotein (LDL) apheresis or lipoprotein(a), ie, Lp(a), apheresis—is currently the most effective therapeutic approach for the following patients: those with familial hypercholesterolemia (FH); those with elevated LDL to whom target levels could not be achieved by lipid-lowering drugs therapy; those with normal TC and LDL but solo elevated Lp(a); and those with severe lipid abnormalities after coronary artery bypass grafting.

Novel Genetic Mutation in Apolipoprotein E2 Homozygosis and Its Implication in Organ Donation: A Case Report

Disorders in lipoprotein metabolism do not contraindicate liver procurement and transplantation (LT). In this circumstance, LT provides an intriguing opportunity to assess the in vivo contribution of the liver to the synthesis and degradation of genetically polymorphic plasma proteins. Apolipoprotein (APO) E exists with several common phenotypic differences due to gene polymorphism. Some authors have shown that the APOE phenotype of the recipient was virtually completely converted to that of the donor, providing evidence that >90% of plasma APOE arises from the liver. Homozygosis for APOE2 (E2-E2) is related to an increased incidence of type III hyperlipoproteinemia (HLP). Recently, some authors have identified 4 new APOE mutations that are strongly linked to a unique entity of renal lipidosis called lipoprotein glomerulopathy (LPG). At present, 65 cases of LPG have been reported worldwide, although most patients have been discovered in Japan and other East Asian countries. We have herein reported a case of LT in a patient with advanced hepatocarcinoma who received a liver from a caucasian donor affected by type III HLP due to homozygous E2-E2. The LPG was due to a novel genetic mutation in APOE. After the LT, the recipient, developed de novo severe lipid abnormalities despite good graft function. To our knowledge this is the first report of an LT using a graft from a non Asian donor with homozygous E2-E2 with the presence of a novel APOE mutation.

Vorinostat in Combination with Other Agents for Therapy of Cutaneous T-Cell Lymphomas: A Case Series.

Background: Mycosis fungoides (MF) and Sezary Syndrome (SS) are types of cutaneous T-cell lymphoma (CTCL), a non-Hodgkin's lymphoma that mainly affects the skin but can progress to involve lymph nodes, blood, and visceral organs. Cure is rarely achieved in patients with advanced (≥Stage IIB) CTCL and patients progress after becoming intolerant of, or refractory to multiple treatment modalities. Treatment decisions for advanced CTCL are based on small prospective studies, retrospective observations, small case-series, and physician preference. Vorinostat (suberoylanilide hydroxamic acid, SAHA), the first histone deacetylase (HDAC) inhibitor, was approved by the FDA in October 2006 for CTCL patients with progressive, persistent, or recurrent disease on or following two systemic therapies based on the results of a Phase IIB trial which demonstrated an objective response in 30% of patients with ≥Stage IIB disease. It has been recently incorporated into the NCCN Clinical Practice Guidelines in Oncology™ for NHL. However, there are no reports available on use of vorinostat in combination regimens in CTCL. Here we present a case series of patients with advanced CTCL treated with vorinostat in combination with other therapies.Case series: Patient A, a 77-year-old female with Stage IVA SS, failed prior bexarotene and ECP and was initiated on vorinostat (400mg/day). Clinical improvement of erythroderma and pruritus symptoms was noted within 5 weeks and clinical response was maintained for 26 months. Grade 3 thrombocytopenia precipitated a dose reduction to 300mg/day and resulted in relapse. IFN-γ (100μg sc 3 x weekly) was added; improvement in symptoms was noted within 4 weeks with ongoing response (>5 months). Patient B was a 64-year-old male with progressive Stage III disease on bexarotene (150mg/day), ECP (monthly), and SDTs. He had failed three other systemic treatment modalities including IFN-α and was unable to tolerate higher doses of bexarotene due to severe lipid abnormalities. Vorinostat (200mg/day) was added and a clinical response (resolution of pruritus and improvement of erythroderma) was apparent within 4 weeks and is ongoing (>4 months). Patient C, a 47-year-old male with Stage IIA disease (folliculotropic MF), had failed prior SDTs but had shown significant clinical response to combined narrow-band (NB) UVB therapy and bexarotene (675mg/day). Bexarotene was discontinued due to elevated CPKs, with disease relapse. Vorinostat (400mg/day) was added to ongoing NB-UVB therapy (3 x weekly) and a clinical response (resolution of pruritis and all skin lesions) was achieved within 12 weeks and is ongoing (>4 months). Vorinostat was generally well tolerated; most adverse events were transient and Grade 1 or 2 in intensity. Consistent with previous reports all three patients experienced mild-to-moderate anemia and thrombocytopenia; patient A experienced Grade 3 thrombocytopenia that was effectively managed via a dose reduction; patient B experienced Grade 1 fatigue.Conclusions: This case series documents the clinical application of vorinostat in combination with multiple other agents. No unexpected side effects or toxicity were observed. Clinical responses were noted in patients with progressive disease on their current therapies. This report supports the efficacy of vorinostat in inducing relatively quick, meaningful and prolonged responses and is suggestive of synergistic effects of this drug when used with other agents. These combinations should be further evaluated systemically in order to establish the most effective place of vorinostat in treatment algorithms for CTCL.

Il pericolo ancora sottovalutato delle interazioni tra farmaci. Un caso clinico esemplificativo

Treatment of hypercholesterolemia has been shown to reduce mortality in patients with coronary artery disease. Patients with severe lipid abnormalities may require high-dose statin therapy, at times used in combination with additional agents. The occurrence of rhabdomyolysis is one of the rare side-effects of the cholesterol-lowering agents. During the use of simvastatin, the risk of this side-effect might be increased when macrolides are used concomitantly. The interacting mechanism likely was inhibited cytochrome P450 (CYP) 3A4 metabolism and possibly P-glycoprotein transport of simvastatin as well. We present a patient who developed rhabdomyolysis during the concomitant use of simvastatin and erythromycin. Coprescribing of medications not compatible with statins occurs frequently: to prevent future events, it is crucial that clinicians recognize the interaction risk associated with coprescribing, to assure that the risk of untoward effects is mitigated.

Severe acute hypertriglyceridemia during acute lymphoblastic leukemia induction successfully treated with plasmapheresis

Children suffering from Acute Lymphoblastic Leukaemia (ALL) treated with asparaginase and corticosteroids are at risk of developing severe lipid abnormalities. The authors report the case of a 10-year-old male with extremely high plasma triglyceride concentrations (4,000 mg/dl) during the induction phase of ALL associated with mild pancreatitis. Hypertriglyceridemia was successfully managed with plasmapheresis with a decrease in triglyceride levels to 590 mg/dl. Apheresis appears to be safe and effective in reducing hypertriglyceridemia and preventing related complications.

Fatal Rhabdomyolysis Caused by Lipid-Lowering Therapy

Treatment of hypercholesterolemia has been shown to reduce mortality in patients with coronary artery disease. Patients with severe lipid abnormalities may require high-dose statin therapy, at times used in combination with additional agents. We report a case of fatal rhabdomyolysis caused by the combination of simvastatin and gemfibrozil. Clinicians should be aware of risk factors for rhabdomyolysis, which include underlying renal insufficiency, high-dose statin therapy, and combination therapy with a fibrate.

Fatal Rhabdomyolysis Caused by Lipid-Lowering Therapy

Treatment of hypercholesterolemia has been shown to reduce mortality in patients with coronary artery disease. Patients with severe lipid abnormalities may require high-dose statin therapy, at times used in combination with additional agents. We report a case of fatal rhabdomyolysis caused by the combination of simvastatin and gemfibrozil. Clinicians should be aware of risk factors for rhabdomyolysis, which include underlying renal insufficiency, high-dose statin therapy, and combination therapy with a fibrate.

ARE LIPID-LOWERING DRUGS CARCINOGENS?

Cholesterol-reducing agents have now convincingly been shown to reduce mortality from coronary heart disease, but should a large number of patients with moderate or severe lipid abnormalities use them? This summary of experimental rodent data raises the question …