Executive summary of the Hellenic Atherosclerosis Society guidelines for the diagnosis and treatment of dyslipidemias - 2023.

Atherosclerotic cardiovascular disease (ASCVD) remains the main cause of death worldwide, and thus its prevention, early diagnosis and treatment is of paramount importance. Dyslipidemia represents a major ASCVD risk factor that should be adequately managed at different clinical settings. 2023 guidelines of the Hellenic Atherosclerosis Society focus on the assessment of ASCVD risk, laboratory evaluation of dyslipidemias, new and emerging lipid-lowering drugs, as well as diagnosis and treatment of lipid disorders in women, the elderly and in patients with familial hypercholesterolemia, acute coronary syndromes, heart failure, stroke, chronic kidney disease, diabetes, autoimmune diseases, and non-alcoholic fatty liver disease. Statin intolerance is also discussed.

Cardiovascular magnetic resonance detects silent heart disease missed by echocardiography in systemic lupus erythematosus.

Background Accurate diagnosis of cardiovascular involvement in systemic lupus erythematosus (SLE) remains challenging, due to limitations of echocardiography. We hypothesized that cardiovascular magnetic resonance can detect cardiac lesions missed by echocardiography in SLE patients with atypical symptoms. Aim To use cardiovascular magnetic resonance in SLE patients with atypical symptoms and investigate the possibility of silent heart disease, missed by echocardiography. Patients/methods From 2005 to 2015, 80 SLE patients with atypical cardiac symptoms/signs (fatigue, mild shortness of breath, early repolarization and sinus tachycardia) aged 37 ± 6 years (72 women/8 men), with normal echocardiography, were evaluated using a 1.5 T system. Left and right ventricular ejection fractions, T2 ratio (oedema imaging) and late gadolinium enhancement (fibrosis imaging) were assessed. Acute and chronic lesions were defined as late gadolinium enhancement-positive plus T2>2 and T2<2, respectively. Lesions were characterized according to late gadolinium enhancement patterns as: diffuse subendocardial, subepicardial and subendocardial/transmural, due to vasculitis, myocarditis and myocardial infarction, respectively. Results Abnormal cardiovascular magnetic resonance findings were identified in 22/80 (27.5%) of SLE patients with normal echocardiography, including 4/22 with recent silent myocarditis, 5/22 with past myocarditis (subepicardial scar in inferolateral wall), 9/22 with past myocardial infarction (six inferior and three anterior subendocardial infarction) and 4/22 with diffuse subendocardial fibrosis due to vasculitis. No correlation between cardiovascular magnetic resonance findings and inflammatory indices was identified. Conclusions Cardiovascular magnetic resonance in SLE patients with atypical cardiac symptoms/signs and normal echocardiography can assess occult cardiac lesions including myocarditis, myocardial infarction and vasculitis that may influence both rheumatic and cardiac treatment.

Complementary role of cardiovascular imaging and laboratory indices in early detection of cardiovascular disease in systemic lupus erythematosus.

Background Cardiovascular disease (CVD) has been documented in >50% of systemic lupus erythematosus (SLE) patients, due to a complex interplay between traditional risk factors and SLE-related factors. Various processes, such as coronary artery disease, myocarditis, dilated cardiomyopathy, vasculitis, valvular heart disease, pulmonary hypertension and heart failure, account for CVD complications in SLE. Methods Electrocardiogram (ECG), echocardiography (echo), nuclear techniques, cardiac computed tomography (CT), cardiovascular magnetic resonance (CMR) and cardiac catheterization (CCa) can detect CVD in SLE at an early stage. ECG and echo are the cornerstones of CVD evaluation in SLE. The routine use of cardiac CT and nuclear techniques is limited by radiation exposure and use of iodinated contrast agents. Additionally, nuclear techniques are also limited by low spatial resolution that does not allow detection of sub-endocardial and sub-epicardial lesions. CCa gives definitive information about coronary artery anatomy and pulmonary artery pressure and offers the possibility of interventional therapy. However, it carries the risk of invasive instrumentation. Recently, CMR was proved of great value in the evaluation of cardiac function and the detection of myocardial inflammation, stress-rest perfusion defects and fibrosis. Results An algorithm for CVD evaluation in SLE includes clinical, laboratory, ECG and echo assessment as well as CMR evaluation in patients with inconclusive findings, persistent cardiac symptoms despite normal standard evaluation, new onset of life-threatening arrhythmia/heart failure and/or as a tool to select SLE patients for CCa. Conclusions A non-invasive approach including clinical, laboratory and imaging evaluation is key for early CVD detection in SLE.

Lifestyle may modify the glucose-raising effect of genetic loci. A study in the Greek population.

BACKGROUND AND AIMS: Lifestyle habits including dietary intake and physical activity are closely associated with multiple body processes including glucose metabolism and are known to affect human health. Recent genome-wide association studies have identified several single nucleotide polymorphisms (SNPs) associated with glucose levels. The hypothesis tested here is whether a healthy lifestyle assessed via a score is associated with glycaemic traits and whether there is an interaction between the lifestyle and known glucose-raising genetic variants in association with glycaemic traits. METHODS AND RESULTS: Participants of Greek descent from the THISEAS study were included in this analysis. We developed a glucose preventive score (GPS) including dietary and physical activity characteristics. We also modelled a weighted genetic risk score (wGRS), based on 20 known glucose-raising loci, in order to investigate the impact of lifestyle-gene interaction on glucose levels. The GPS was observed to be significantly associated with lower glucose concentrations (ß ± SE: -0.083 ± 0.021 mmol/L, P = 1.6 × 10(-04)) and the wGRS, as expected, with increased glucose levels (ß ± SE: 0.020 ± 0.007 mmol/L, P = 8.4 × 10(-3)). The association of the wGRS with glucose levels was attenuated after interaction with the GPS. A higher GPS indicated decreasing glucose levels in the presence of an increasing wGRS (ß interaction ± SE: -0.019 ± 0.007 mmol/L, P = 0.014). CONCLUSION: Our results indicate that lower glucose levels underlie a healthier lifestyle and also support an interaction between the wGRS for known glycaemic loci and GPS associated with lower glucose levels. These scores could be useful tools for monitoring glucose metabolism.

Cardiovascular magnetic resonance evaluation of paediatric patients with systemic lupus erythematosus and cardiac symptoms.

OBJECTIVES: To evaluate the cardiovascular magnetic resonance (CMR) findings in a paediatric population with systemic lupus erythematosus (SLE) and cardiac symptoms. METHODS: Twenty-five SLE children, aged 10.2 ± 2.6 years, with cardiac symptoms and normal routine non-invasive evaluation were examined by CMR, using a 1.5 T system and compared with sex-matched SLE adults. Left ventricular (LV) volumes, ejection fraction, T2 ratio, early (EGE) and late (LGE) gadolinium enhancement were assessed. Acute and chronic lesions were characterised as LGE-positive plus T2 > 2, EGE > 4 or T2 < 2, EGE < 4, respectively. According to LGE, lesions were characterized as: (a) diffuse subendocardial, (b) subepicardial and (c) subendocardial/transmural, due to vasculitis, myocarditis and myocardial infarction, respectively. RESULTS: LV ejection fraction (LVEF) was normal in all SLEs. T2 > 2, EGE > 4 and positive epicardial LGE wall was identified in 5/25 children. Diffuse subendocardial fibrosis was documented in 1/25. No evidence of myocardial infarction was identified in any children. In contrast, in SLE adults, LGE indicative of myocardial infarction was identified in 6/25, myocarditis in 3/25, Libman-Sacks endocarditis in 1/25 and diffuse subendocardial fibrosis in 2/25. The incidence of heart disease in SLE children was lower compared to SLE adults (p < 0.05), with a predominance of myocarditis in children and myocardial infarction in adults. A significant correlation was documented between disease duration and CMR lesions (p < 0.05). CONCLUSION: CMR identifies a predominance of myocarditis in paediatric SLE with cardiac symptoms and normal routine non-invasive evaluation. However, the incidence of cardiac lesions is lower compared to SLE adults, probably due to shorter disease duration. SIGNIFICANCE AND INNOVATION: CMR identifies heart involvement in a significant percentage of SLE children with cardiac symptoms and normal routine noninvasive evaluation.The incidence of heart disease is lower in SLE children compared with SLE adults.Predominance of myocarditis and myocardial infarction is observed in SLE children and SLE adults, respectively.

The Emerging Role of Cardiovascular Magnetic Resonance Imaging in the Evaluation of Metabolic Cardiomyopathies.

The aim of this review is to discuss the role of Cardiovascular Magnetic Resonance (CMR) in the diagnosis, risk stratification, and follow-up of metabolic cardiomyopathies. The classification of myocardial diseases, proposed by WHO/ISFC task force, distinguished specific cardiomyopathies, caused by metabolic disorders, into 4 types: 1) endocrine disorders, 2) storage or infiltration disorders (amyloidosis, hemochromatosis and familial storage disorders), 3) nutritional disorders (Kwashiorkor, beri-beri, obesity, and alcohol), and 4) diabetic heart. Thyroid disease, pheochromocytoma, and growth hormone excess or deficiency may contribute to usually reversible dilated cardiomyopathy. Glucogen storage diseases can be presented with myopathy, liver, and heart failure. Lysosomal storage diseases can provoke cardiac hypertrophy, mimicking hypertrophic cardiomyopathy and arrhythmias. Hereditary hemochromatosis, an inherited disorder of iron metabolism, leads to tissue iron overload in different organs, including the heart. Cardiac amyloidosis is the result of amyloid deposition in the heart, formed from breakdown of normal or abnormal proteins that leads to increased heart stiffness, restrictive cardiomyopathy, and heart failure. Finally, nutritional disturbances and metabolic diseases, such as Kwashiorkor, beri-beri, obesity, alcohol consumption, and diabetes mellitus may also lead to severe cardiac dysfunction. CMR, through its capability to reliably assess anatomy, function, inflammation, rest-stress myocardial perfusion, myocardial fibrosis, aortic distensibility, iron and/or fat deposition can serve as an excellent tool for early diagnosis of heart involvement, risk stratification, treatment evaluation, and long term follow-up of patients with metabolic cardiomyopathies.

Body mass index, lipid metabolism and estrogens: their impact on coronary heart disease.

Estrogens influence lipid metabolism and body fat distribution in women. Premenopausal women have increased lipoprotein lipase action in abdominal and femoral subcutaneous fat compared with men of the same age. Estrogens may also affect adipose tissue either directly through specific estrogen receptors or indirectly via their effects on other tissues. As adipose tissue produces several cytokines including leptin, adiponectin and interleukin-6, estrogens may alter their levels, thus influencing various biological processes. Lack of estrogens such as in menopause, causes an increase in visceral adiposity, leading to changes in lipid and lipoprotein metabolism. Due to those alterations, postmenopausal women are more prone to coronary heart disease. In this review the influence of estrogens on body mass index, lipid metabolism and some of the therapeutic options will be analyzed.

No impact of SLCO1B1 521T>C, 388A>G and 411G>A polymorphisms on response to statin therapy in the Greek population.

Interindividual variability exists in statin lipid-lowering response, partially attributed to genetic factors. Organic anion-transporting polypeptide 1B1 (OATP1B1) encoded by SLCO1B1 gene (solute carrier organic anion transporter family member 1B1) facilitates hepatic uptake of simvastatin and atorvastatin. SLCO1B1 polymorphisms are strongly associated with statin-induced myopathy whereas few studies have assessed their effect on statin differential response. In the present study, we analyzed the association of SLCO1B1 521T>C, 388A>G and 411G>A polymorphisms with response to atorvastatin and simvastatin in 386 adults (201 atorvastatin-treated and 185 simvastatin-treated) with primary hypercholesterolemia, all of Greek origin. Total cholesterol and low-density lipoprotein cholesterol were measured at baseline and on 6 months of treatment. Genetic polymorphisms were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. A novel RFLP protocol was developed for the simultaneous identification of 388A>G and 411G>A polymorphisms. SLCO1B1 521T>C, 388A>G and 411G>A polymorphisms were not associated with lipid-lowering response to atorvastatin or simvastatin. No sex-gene or statin dose-gene interaction was observed on the effect of the analyzed SLCO1B1 polymorphisms in statin lipid lowering response in either statin-treated patient cohort. Further studies in different populations are required to draw firm conclusion on the potential association of SLCO1B1 polymorphisms with statin lipid-lowering response.

Sudden cardiac death and diabetes mellitus.

Sudden cardiac death (SCD) affects a significant percentage of diabetic patients. SCD in these patients can be due to several factors, such as diastolic dysfunction, heart failure, altered platelet function, inflammation, sympathetic nervous stimulation and other factors. In the present review, we discuss the association between diabetes mellitus and SCD.

Multivessel spontaneous dissection of the left coronary tree in the postpartum period: case report and review of the literature.

Spontaneous coronary artery dissection is a rare cause of myocardial infarction predominantly associated with young women during the third trimester of pregnancy or during the postpartum period. Multivessel spontaneous coronary artery dissection is an even less frequent condition with limited reports in medical literature. Hormonal changes as well as hemodymanic stress are some of the factors that have been implicated in the etiology of this condition. However, the exact pathophysiological process leading to spontaneous coronary artery dissection has not yet been elucidated. The spectrum of clinical presentation ranges from mild symptoms to cardiac arrest. Herein, we report the case of a 39-year-old woman with spontaneous two coronary vessel dissection during her postpartum period presented with ST elevation myocardial infarction on electrocardiogram complicated with pulmonary edema and cardiorespiratory arrest.

The diagnostic role of cardiac magnetic resonance imaging in detecting myocardial inflammation in systemic lupus erythematosus. Differentiation from viral myocarditis.

OBJECTIVE: The objective of this paper is to evaluate the diagnostic role of cardiac magnetic resonance imaging (CMR) in detecting myocardial inflammation in systemic lupus erythematosus (SLE) and its differentiation from viral myocarditis. PATIENTS AND METHODS: Fifty patients with suspected infective myocarditis (IM), with chest pain, dyspnoea or altered ECG, increase in troponin I and/or NT-pro BNP, with or without a history of flu-like syndrome or gastroenteritis and elevated C-reactive protein (CRP) within three to five (median four) weeks before admission, 25 active SLE patients, aged 38 ± 3 years, and 20 age-matched controls were prospectively evaluated by clinical assessment, ECG, echocardiogram and CMR. All patients underwent coronary angiography, and those with significant coronary artery disease (CAD) were excluded. CMR was performed using STIR T2-W (T2W), early T1-W (EGE) and late T1-W (LGE). Endomyocardial biopsies were performed when clinically indicated by current guidelines. Specimens were examined by immunohistological and polymerase chain reaction (PCR) analysis. RESULTS: Positive coronary angiography for CAD excluded 10/50 suspected IM and 5/25 active SLE. Positive clinical criteria for acute myocarditis were fulfilled by 28/40 suspected IM and only 5/20 active SLE. CMR was positive for myocarditis in 35/40 suspected IM and in 16/20 active SLE. Endomyocardial biopsy (EMB), performed in 25/35 suspected IM and 7/16 active SLE with positive CMR, showed positive immunohistology in 18/25 suspected IM and 3/7 active SLE. Infectious genomes were identified in 24/25 suspected IM and 1/7 active SLE. CONCLUSIONS: CMR-positive IM patients were more symptomatic than active SLE. More than half of CMR-positive patients also had positive EMB. PCR was positive in almost all IM, but unusual in SLE. Due to the subclinical presentation of SLE myocarditis and the limitations of EMB, CMR presents the best alternative for the diagnosis of SLE myocarditis.

Pathophysiology of Q waves in II, III, avF in systemic lupus erythematosus. Evaluation using cardiovascular magnetic resonance imaging.

OBJECTIVES: To investigate the pathophysiology of Q waves in II, III, avF in systemic lupus erythematosus (SLE) by cardiovascular magnetic resonance (CMR). METHODS: Inflammation evaluation by CMR using T2, early (EGE) and late gadolinium enhanced images (LGE) was performed in 20 SLE patients with mild cardiac symptoms and Q in leads II, III, avF of ECG. Their results were compared with 20 SLE patients with the same symptoms and normal ECG. RESULTS: In both groups, T2, EGE and left ventricular ejection fraction were normal. However, in 3/20 with Q in II, III, avF, CMR revealed lesions indicative of acute myocarditis. In the rest of them, CMR documented transmural LGE, due to past inferior myocardial infarction in 4/20 and epicardial LGE due to past myocarditis in 8/20 (4/8 in the inferior and 4/8 in the lateral wall of left ventricle). No LGE was found in 5/20 and the Q was attributed to the position of the heart. In 3/20 with normal ECG, CMR detected past myocarditis in 2/3 and myocardial infarction in 1/3. Coronary angiography assessed coronary artery disease in all SLE with evidence of myocardial infarction and normal coronaries in 9/10 patients with past myocarditis. CONCLUSION: Q in II, III, avF in SLE may indicate myocardial infarction, acute or past inflammation or be a positional finding. The lack of Q does not exclude the possibility of infarction or inflammation. CMR is the best tool to reveal the pathophysiology of Q waves in SLE and guide treatment of heart involvement in these patients.

Cholesterol ester transfer protein (CETP), postprandial lipemia and hypolipidemic drugs.

Cholesterol ester transfer protein (CETP) plays a significant role in high density lipoprotein (HDL) metabolism and reverse cholesterol transport (RCT). A reduction in CETP activity leads to an increase in HDL-cholesterol levels. However, the relationship between reduced CETP function and atherosclerosis is complex and confusing. In the hypertriglyceridemic state, CETP is highly expressed and RCT leads to the formation of small dense low density lipoprotein (LDL) and small dense HDL, both of which are involved in the progression of atherosclerosis. Significant associations of the B1B1 genotype with higher plasma CETP concentration and/or CETP activity and lower HDL cholesterol were reported in several, but not all, studies. The magnitude of postprandial lipemia is also associated with plasma CETP concentration and lipoprotein content and size. Several conditions such as metabolic syndrome, hypertension, insulin resistance, obesity and familial hypercholesterolaemia are characterized by a more pronounced postprandial hypertriglyceridemia and delayed TG clearance than normal states. Thus, CETP is considered as a candidate target for drug therapy. A number of synthetic CETP inhibitors (CGS25159 and JTT-705) were evaluated in animals with satisfactory results. In humans, two CETP inhibitors were evaluated, JTT-705 and torcetrapib, leading to HDL increase. However, torcetrapib administration was associated with an increase in blood pressure and other "off-target" effects. It is also not clear whether the HDL produced during treatment with torcetrapib is bioactive (i.e. an "on target" undesirable action). In the current review, CETP function regarding lipid metabolism (in fasting and fed states) from human and animal studies as well as the current knowledge on CETP inhibitors are discussed. We also discuss gender influence on the action of hypolipidemic drugs and their effect on CETP mass and activity, as well as on the lipid profile.

Tangier disease four decades of research: a reflection of the importance of HDL.

Reduced circulating levels of high density lipoprotein cholesterol (HDL-C) are a frequent lipoprotein disorder in coronary heart disease patients and can be caused by either genetic and/or environmental factors (sedentary lifestyle, diabetes mellitus, smoking, obesity or a diet enriched in carbohydrates). Extremely low serum HDL-C levels occur in patients with Tangier disease (TD), which is caused by mutations in the adenosine triphosphate (ATP)-binding cassette transporter A1 (ABCA1). Clinical manifestations are related to the storage of cholesteryl esters in reticuloendothelial tissues and to peripheral neuropathy. This review focuses on the genetic and lipid abnormalities of TD, the consequence of these on clinical outcome and the possible treatment options. These abnormalities reflect the importance of HDL in the pathogenesis of vascular disease.

Pathophysiology of dyslipidaemia in the metabolic syndrome.

The insulin resistance/metabolic syndrome is characterised by the variable coexistence of hyperinsulinaemia, obesity, dyslipidaemia, and hypertension. The pathogenesis of the syndrome has multiple origins, but obesity and sedentary lifestyle coupled with diet and still largely unknown genetic factors clearly interact to produce the syndrome. Dyslipidaemia, the hallmark of the metabolic syndrome, includes increased flux of free fatty acids, raised triglycerides, apolipoprotein B, and small dense low density lipoprotein, and decreased high density lipoprotein cholesterol. The widely prevalent nature of the metabolic syndrome emphasises the importance of its diagnosis and treatment. This review analyses the clinical and dynamic features of this syndrome in the aspect of dyslipidaemia and its management.

Heterozygote men with familial hypercholesterolaemia may have an abnormal triglyceride response post-prandially. Evidence for another predictor of vascular risk in familial hypercholesterolaemia.

Familial hypercholesterolaemia (FH) is associated with premature coronary heart disease (CHD). Post-prandial hypertriglyceridaemia has also been associated with cardiovascular disease. Thus, an abnormal post-prandial triglyceride (TG) clearance may contribute to the heterogeneity in the risk of CHD in heterozygous (h) FH. Therefore, we investigated the response of TG levels to a fatty meal in men with hFH. We studied 26 Greek men divided into two groups: the hFH group of 14 men, mean age 39 (SD = 11) years and the control group of 12 healthy men, mean age 43 (50:5) years. An increased TG response to the fatty meal was defined as a post-prandial TG concentration (at 4, 6 or 8 h) greater than the highest TG concentration in any hour in any control individual. All hFH patients had normal baseline fasting TG levels. However, seven hFH men showed an abnormal TG response after the fatty meal; these patients had higher baseline fasting TG levels than others [1.5 (0.2) vs. 1.0 (0.4) mmol/l, p = 0.005]. The hFH men constituted a heterogeneous group regarding their TG response to the fatty meal compared with healthy men because 50% with higher, but nevertheless 'normal' basal TG levels, had an abnormal post-prandial TG response. The reduced activity of low-density lipoprotein receptors in hFH together with other defects in TG handling may explain the abnormal rise of TG levels post-prandially.

The effect of nicotinic acid and alcohol co-administration in Wistar rats.

The effects of co-administration of nicotinic acid (NA) and alcohol (Alc) on liver function in male Wistar rats were evaluated. The rats were randomized into five groups: (i) Olive oil (Oil), (ii) Alc+Oil, (iii) NA+Oil, (iv) NA+Alc+Oil, and (v) Controls (fed only normal rat chow). Alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (AP), total cholesterol and triglycerides (TG) were measured. Liver histopathology was also assessed. The Alc+Oil group had higher TG levels compared with the NA+Alc+Oil group and all other groups, as well. NA+Oil group had higher levels of AP compared with Alc+Oil and Oil groups. The NA+Oil group had higher ALT levels compared with the Oil group. The Oil group had lower ALT levels compared with the control group. The Alc+Oil group had higher AST levels compared with the NA+Alc+Oil group, as well as with all other groups. Liver histopathology was within the normal range. A moderate amount of Alc daily together with NA is safe in rats. The NA and Alc co-administration reduces the TG and AST levels in rats, compared with the administration of Alc alone.