Recommendations for lipid modification in patients with ischemic stroke or transient ischemic attack: A clinical guide by the Hellenic Stroke Organization and the Hellenic Atherosclerosis Society.

This document presents the consensus recommendations of the Hellenic Stroke Organization and the Hellenic Atherosclerosis Society for lipid modification in patients with ischemic stroke or transient ischemic attack. This clinical guide summarizes the current literature on lipid management and can be of assistance to the physicians treating stroke patients in clinical practice.

Postprandial Hypertriglyceridaemia Revisited in the Era of Non-Fasting Lipid Profile Testing: A 2019 Expert Panel Statement, Narrative Review.

Postprandial hypertriglyceridaemia, defined as an increase in plasma triglyceride-containing lipoproteins following a fat meal, is a potential risk predictor of atherosclerotic cardiovascular disease and other chronic diseases. Several non-modifiable factors (genetics, age, sex and menopausal status) and lifestyle factors (diet, physical activity, smoking status, obesity, alcohol and medication use) may influence postprandial hypertriglyceridaemia. This narrative review considers the studies published over the last decade that evaluated postprandial hypertriglyceridaemia. Additionally, the genetic determinants of postprandial plasma triglyceride levels, the types of meals for studying postprandial triglyceride response, and underlying conditions (e.g. familial dyslipidaemias, diabetes mellitus, metabolic syndrome, non-alcoholic fatty liver and chronic kidney disease) that are associated with postprandial hypertriglyceridaemia are reviewed; therapeutic aspects are also considered.

Hellenic Postprandial Lipemia Study (HPLS): Rationale and design of a prospective, open-label trial to determinate the prevalence of abnormal postprandial lipemia as well as its interaction with statins in patients at high- and very high-risk for cardiovascular disease.

Fasting and postprandial hypertriglyceridemia have been related to cardiovascular (CV) disease. We describe the design and methods of the Hellenic Postprandial Lipemia Study (HPLS, NCT02163044), a prospective, open-label, randomized, multicentre trial. The study will recruit 900 participants from 8 centers, and aims to determinate the prevalence of abnormal postprandial lipemia in patients at high- and very high-risk for CV disease, the efficacy of statin treatment and other medications on postprandial lipemia, and the interaction between postprandial lipemia and CV risk during a treatment period of 3 years. Participants will be screened in an outpatient lipid clinic setting. METHODS: High- and very high-risk individuals with fasting triglycerides (TGs) <220 mg/dL (2.5 mmol/L) will be included. At baseline visit demographic and clinical characteristics will be recorded. At the first follow-up visit (within 2-4 weeks from baseline), plasma TG concentrations will be measured, following an overnight 12 h fasting period, before and 4 h after ingestion of a commercially available oral fat tolerance test (OFTT) meal. Then a statin will be prescribed. At the second follow-up visit (within 3-5 month from baseline), plasma TG concentrations will be measured again following an overnight 12 h fasting period, before and 4 h after ingestion of OFTT and then patients will be followed annually for 3 years. CONCLUSION: HPLS is the largest trial assessing the effects of statin therapy on postprandial lipemia. Its results will provide useful insight on the prevalence of postprandial lipemia, the efficacy of statins regarding postprandial lipemia and the clinical significance of this effect. Clinical trial registration information The HPLS trial is registered with clinicaltrials.gov (NCT Identifier: NCT02163044).

Postprandial Hypertriglyceridaemia Revisited in the Era of Non-Fasting Lipid Profile Testing: A 2019 Expert Panel Statement, Main Text.

Residual vascular risk exists despite the aggressive lowering of Low-Density Lipoprotein Cholesterol (LDL-C). A contributor to this residual risk may be elevated fasting, or non-fasting, levels of Triglyceride (TG)-rich lipoproteins. Therefore, there is a need to establish whethe a standardised Oral Fat Tolerance Test (OFTT) can improve atherosclerotic Cardiovascular (CV) Disease (ASCVD) risk prediction in addition to a fasting or non-fasting lipid profile. An expert panel considered the role of postprandial hypertriglyceridaemia (as represented by an OFTT) in predicting ASCVD. The panel updated its 2011 statement by considering new studies and various patient categories. The recommendations are based on expert opinion since no strict endpoint trials have been performed. Individuals with fasting TG concentration <1 mmol/L (89 mg/dL) commonly do not have an abnormal response to an OFTT. In contrast, those with fasting TG concentration ≥2 mmol/L (175 mg/dL) or nonfasting ≥2.3 mmol/L (200 mg/dL) will usually have an abnormal response. We recommend considering postprandial hypertriglyceridaemia testing when fasting TG concentrations and non-fasting TG concentrations are 1-2 mmol/L (89-175 mg/dL) and 1.3-2.3 mmol/L (115-200 mg/dL), respectively as an additional investigation for metabolic risk prediction along with other risk factors (obesity, current tobacco abuse, metabolic syndrome, hypertension, and diabetes mellitus). The panel proposes that an abnormal TG response to an OFTT (consisting of 75 g fat, 25 g carbohydrate and 10 g proteins) is >2.5 mmol/L (220 mg/dL). Postprandial hypertriglyceridaemia is an emerging factor that may contribute to residual CV risk. This possibility requires further research. A standardised OFTT will allow comparisons between investigational studies. We acknowledge that the OFTT will be mainly used for research to further clarify the role of TG in relation to CV risk. For routine practice, there is a considerable support for the use of a single non-fasting sample.

Non-traumatic and non-drug-induced rhabdomyolysis.

Rhabdomyolysis (RM), a fortunately rare disease of the striated muscle cells, is a complication of non-traumatic (congenital (glycogen storage disease, discrete mitochondrial myopathies and various muscular dystrophies) or acquired (alcoholic myopathy, systemic diseases, arterial occlusion, viral illness or bacterial sepsis)) and traumatic conditions. Additionally, RM can occur in some individuals under specific circumstances such as toxic substance use and illicit drug abuse. Lipid-lowering drugs in particular are capable of causing RM. This comprehensive review will focus on non-traumatic and non-drug-induced RM. Moreover, the pathology of RM, its clinical manifestation and biochemical effects, and finally its management will be discussed.

Five gene variants in nonagenarians, centenarians and average individuals.

INTRODUCTION: Genetic factors contribute to the variation of human life span which is believed to be more profound after 85 years of age. The aim of the present study was to evaluate the frequency of 5 gene polymorphisms between nonagenarians, centenarians and average individuals. MATERIAL AND METHODS: Single nucleotide polymorphisms (SNPs) of telomerase reverse transcriptase (TERT; rs2736098), insulin-like growth factor-1 binding protein-3 (IGFBP3; A-202C, rs2857744), fork-head box O3A (FOXO3A; rs13217795 and rs2764264) factor and adiponectin (ADIPOQ; rs2241766) were evaluated in 405 individuals: n = 256 nonagenarians and centenarians (study group) and n = 149 average lifespan individuals (control group aged 18 - < 80 years). RESULTS: The frequency of women was significantly higher in the study group than the control group (64.5 vs. 49.7%, p = 0.004). Genotypic and allele frequencies did not differ between groups according to gender. However, in men, the frequency of TT genotype of FOXO3A; rs2764264 was higher in the study group than the control group (45.6 vs. 28.0%, p = 0.05). Overall, the frequency of the C allele of FOXO3A; rs2764264 was significantly lower in the study group than the control group (3.9 vs. 9.5%, respectively, p = 0.023). Furthermore, in the study group, the T allele was significantly more frequent in the nonagenarians (n = 239) than the centenarians (n = 17) in both FOXO3A; rs13217795 and rs2764264 (64.4 vs. 44.1%, p = 0.018 and 69.7 vs. 50.0%, p = 0.017, respectively). CONCLUSIONS: According to survival status, there is differentiation in the prevalence of both studied FOXO3A gene polymorphisms. The study group had half of the C alleles compared with the control group and centenarians less frequently had the T allele of both FOXO3A gene polymorphisms compared with nonagenarians. No difference was found between groups according to TERT, IGFBP3 and ADIPOQ gene polymorphisms. It seems that some polymorphisms may be significant in prolonging our lifespan. Nevertheless, confirmation in additional study populations is needed.

The use of statins alone, or in combination with pioglitazone and other drugs, for the treatment of non-alcoholic fatty liver disease/non-alcoholic steatohepatitis and related cardiovascular risk. An Expert Panel Statement.

Non-alcoholic fatty liver disease (NAFLD), the most common liver disease, is characterized by accumulation of fat (>5% of the liver tissue), in the absence of alcohol abuse or other chronic liver diseases. It is closely related to the epidemic of obesity, metabolic syndrome or type 2 diabetes mellitus (T2DM). NAFLD can cause liver inflammation and progress to non-alcoholic steatohepatitis (NASH), fibrosis, cirrhosis or hepatocellular cancer (HCC). Nevertheless, cardiovascular disease (CVD) is the most common cause of death in NAFLD/NASH patients. Current guidelines suggest the use of pioglitazone both in patients with T2DM and in those without. The use of statins, though considered safe by the guidelines, have very limited use; only 10% in high CVD risk patients are on statins by tertiary centers in the US. There are data from several animal studies, 5 post hoc analyses of prospective long-term survival studies, and 5 rather small biopsy proven NASH studies, one at baseline and on at the end of the study. All these studies provide data for biochemical and histological improvement of NAFLD/NASH with statins and in the clinical studies large reductions in CVD events in comparison with those also on statins and normal liver. Ezetimibe was also reported to improve NAFLD. Drugs currently in clinical trials seem to have potential for slowing down the evolution of NAFLD and for reducing liver- and CVD-related morbidity and mortality, but it will take time before they are ready to be used in everyday clinical practice. The suggestion of this Expert Panel is that, pending forthcoming randomized clinical trials, physicians should consider using a PPARgamma agonist, such as pioglitazone, or, statin use in those with NAFLD/NASH at high CVD or HCC risk, alone and/or preferably in combination with each other or with ezetimibe, for the primary or secondary prevention of CVD, and the avoidance of cirrhosis, liver transplantation or HCC, bearing in mind that CVD is the main cause of death in NAFLD/NASH patients.

Ageing, longevity, exceptional longevity and related genetic and non genetics markers: panel statement.

In May 2012, a group of scientists and clinicians met in Athens (Greece) to consider the relevance of ageing, longevity, exceptional longevity and related genetic and non genetic markers. During this meeting, we firstly reviewed recent epidemiological and clinical studies on ageing, longevity and exceptional longevity, briefly analyzed the ageing theories and discussed successful and unsuccessful ageing also taking into account the evolutionary perspective. Secondly, we considered the three phenotypes based on the definition of ageing, longevity and exceptional longevity and the associated biomarkers. Third, we discussed proposed treatments suitable to counteract or slow down ageing. Finally, this panel produced a consensus statement to highlight the importance of ageing, longevity and exceptional longevity, since this is a rapidly increasing phenotype worldwide. We acknowledge that not all experts in this field may completely agree with this statement.

The challenges in moving from ageing to successful longevity.

During the last decades survival has significantly improved and centenarians are becoming a fast-growing group of the population. Human life span is mainly dependent on environmental and genetic factors. Favourable modifications of lifestyle factors (e.g. physical activity, diet and not smoking) and healthcare (e.g. effective vascular disease prevention) have also increased human life span. Genetic factors contribute to the variation of human life span by around 25%, which is believed to be more profound after 85 years of age. It is likely that multiple factors influence life span and we need answers to questions such as: 1) What does it take to reach 100?, 2) Do centenarians have better health during their lifespan compared with contemporaries who died at a younger age?, 3) Do centenarians have protective modifications of body composition, fat distribution and energy expenditure, maintain high physical and cognitive function, and sustained engagement in social and productive activities?, 4) Do centenarians have genes which contribute to longevity?, 5) Do centenarians benefit from epigenetic phenomena?, 6) Is it possible to influence the transgenerational epigenetic inheritance (epigenetic memory) which leads to longevity?, 7) Is the influence of nutrigenomics important for longevity?, 8) Do centenarians benefit more from drug treatment, particularly in primary prevention?, and, 9) Are there any potential goals for drug research? Many definitions of successful ageing have been proposed, but at present there is no consensus definition. Such definitions may need to differentiate between "Longevity Syndrome" and "Exceptional Longevity".

Ageing mechanisms and associated lipid changes.

Ageing is related to slowdown/breakdown of the somatotropic axis (i.e. the somatopause) leading to many physiological changes. The somatopause is accompanied by DNA and other macromolecule damage, and is characterized by a progressive decline in vitality and tissue function. We still do not have a definitive understanding of the mechanism( s) of ageing. Several overlapping theories have been proposed such as: 1) The free radical theory, 2) Mitochondrial Ageing, 3) The Glycation Theory, 4) Protein Damage and Maintenance in Ageing, and, 5) DNA Damage and Repair. Furthermore, several models of ageing were introduced such as genetically programmed senescence, telomere shortening, genomic instability, heterochromatin loss, altered epigenetic patterns and long lived cells. There are certain lipid modifications associated with the somatopause, characterized mainly by an increase in total cholesterol and triglyceride levels in both genders. In this review we consider the mechanisms of ageing and the associated changes in lipid metabolism according to gender.

The frequency of 4 common gene polymorphisms in nonagenarians, centenarians, and average life span individuals.

Single nucleotide polymorphisms of angiotensin-converting enzyme (ACE) such as rs1799752, nuclear factor kappa B (NFkB) such as rs28362491 and cholesteryl ester transport protein (CETP) such as rs708272 (TaqB1) and rs5882 (I405V) were evaluated in nonagenarians, centenarians, and average life span individuals (controls). The study population (n = 307; 190 nonagenarians, 12 centenarians and 105 middle-aged controls) was genotyped for ACE, NFkB, and CETP genetic variants. The age of nonagenarian and centenarian group ranged between 90 and 111 years; centenarians and controls age ranged from 99 to 111, and from 18 to 80 years, respectively. The I carriers of ACE I/D gene were fewer in nonagenarians compared to centenarians (37.6% vs 62.5%, P = .016). The I carriers of ACE gene were more frequent in centenarians compared to controls (62% vs 41%, P = .045). No differences in frequency of common NFkB and CETP genotypes between patients with exceptional longevity and middle-aged patients were observed.

Changes in Lipids and Lipoproteins after Selective LDL Apheresis (7-Year Experience).

Background. The aim of the study was to investigate the changes in plasma lipids and lipoproteins and the cardiovascular events after selective LDL apheresis. Methods and Results. Two pediatric patients with familial hypercholesterolemia aged 11 and 13 years and 19 dyslipidemic adults aged 41 ± 14 years underwent direct adsorption of lipoproteins (DALI) sessions. The mean follow-up period was 47 ± 23 months. The total cholesterol (TC) values before and after treatment were 8.2 ± 2.2 and 3.1 ± 1.6 mmol/l (318 ± 86 and 122 ± 62 mg/dL), respectively. The interval mean of TC was 6.9 ± 1.9 mmol/l (268 ± 75 mg/dL). The LDL cholesterol concentrations before and after treatment were 6.6 ± 2.1 and 1.7 ± 1.1 mmol/l, (256 ± 82 mg/dL and 65 ± 41 mg/dL), respectively. The percentage of acute LDL cholesterol reduction was 75 ± 11%. Cardiovascular events were observed in seven patients. The average annual event rate was 5.51%. Conclusion. LDL apheresis is a very important therapeutic tool in managing patients at high risk for premature CAD or with aggressive CAD, despite adequate medical treatment.

The role of common variants of the cholesteryl ester transfer protein gene in left main coronary artery disease.

BACKGROUND: The cholesteryl ester transfer protein (CETP) has a central role in the lipid metabolism and therefore may alter the susceptibility to atherosclerosis. METHODS: The DNA of 471 subjects [133 subjects with angiographically documented left main coronary artery disease (LMCAD), 241 subjects with more peripheral coronary artery disease (MPCAD) and 97 subjects self reported healthy (Controls)] was analyzed for the frequency of TaqIB and I405V polymorphisms in the gene coding CETP. RESULTS: There is no significant difference in CETP allele frequency or genotype distribution among LMCAD and MPCAD patients although there is statistical difference between LMCAD and Controls (p = 0.001). Specifically, patients with LMCAD and B1B1 genotype of TaqIB polymorphism were more frequent present compared to Controls (33.8% vs 22.9%, respectively). The frequency of B2B2 genotype was 3 times lower in the LMCAD group compared to Controls (10.5% vs 30.2%, respectively). In the LMCAD group the frequency of B1 allele compared to Controls was higher (62% vs 46%, respectively, p = 0.001). The relationship between TaqIB gene polymorphism and the LMCAD was independent of lipid profile, with the exception of apolipoprotein A. CONCLUSIONS: These findings indicate that the TaqIB polymorphism may have potential importance in screening individuals at high risk for developing CAD. However, this polymorphism cannot distinguish between LMCAD and MPCAD. Further prospective investigations in larger populations are required to confirm these findings.

Postprandial lipemia in children and adolescents.

Atherosclerosis is a result of a lifelong process that has its origins in childhood. Data in adults suggest that impaired postprandial lipoprotein metabolism may contribute to, or be a marker of, the development and progression of atherosclerosis. After an 8-year follow up period, the Bogalusa Heart Study showed that children with low high density lipoprotein cholesterol, high triglyceride levels and high body mass index had a notably increased occurrence of dyslipidemia as adults. A significantly greater postprandial response of triglycerides in children with elevated fasting triglyceride levels was reported. It is well known that dietary fat is associated with higher plasma triglyceride levels. It is not clear if postprandial lipemia should be evaluated in children and adolescents. However, in special situations this may help determine the underlying lipid disorder. This review discusses the current status in this field.

Definition of postprandial lipaemia.

At the present time, there is no widely agreed definition of postprandial lipaemia (PPL). This lack of a shared definition limits the identification and treatment of patients with exaggerated PPL as well as the evaluation of potential therapeutic agents. PPL is a complex syndrome characterized by non-fasting hypertriglyceridaemia that is associated with an increased risk of vascular events. This review considers the definition of PPL and the methodology for assessing this process.