Association between lipoprotein(a) concentrations and atherosclerotic cardiovascular disease risk in patients with familial hypercholesterolemia: an analysis from the HELLAS-FH.

AIMS: Lipoprotein(a) [Lp(a)] is an independent risk factor for atherosclerotic cardiovascular disease (ASCVD) in the general population. However, such a role in patients with familial hypercholesterolemia (FH) is less documented. The purpose of this study was to evaluate the association between Lp(a) concentrations and ASCVD prevalence in adult patients with FH. METHODS: This was a cross-sectional study from the Hellenic Familial Hypercholesterolemia Registry (HELLAS-FH). Patients were categorized into 3 tertiles according to Lp(a) levels. RESULTS: A total of 541 adult patients (249 males) with possible/probable/definite FH heterozygous FH (HeFH) were included (mean age 48.5 ± 15.0 years at registration, 40.8 ± 15.9 years at diagnosis). Median (interquartile range) Lp(a) concentrations in the 1st, 2nd and 3rd Lp(a) tertile were 6.4 (3.0-9.7), 22.4 (16.0-29.1) and 77.0 (55.0-102.0) mg/dL, respectively. There was no difference in lipid profile across Lp(a) tertiles. The overall prevalence of ASCVD was 9.4% in the first, 16.1% in the second and 20.6% in the third tertile (p = 0.012 among tertiles). This was also the case for premature ASCVD, with prevalence rates of 8.5, 13.4 and 19.8%, respectively (p = 0.010 among tertiles). A trend for increasing prevalence of coronary artery disease (8.3, 12.2 and 16.1%, respectively; p = 0.076 among tertiles) was also observed. No difference in the prevalence of stroke and peripheral artery disease was found across tertiles. CONCLUSIONS: Elevated Lp(a) concentrations are significantly associated with increased prevalence of ASCVD in patients with possible/probable/definite HeFH.

LDL cholesterol target achievement in heterozygous familial hypercholesterolemia patients according to 2019 ESC/EAS lipid guidelines: Implications for newer lipid-lowering treatments.

BACKGROUND: The 2019 European guidelines (ESC/EAS) for the treatment of dyslipidaemias recommend more aggressive targets for low-density lipoprotein cholesterol (LDL-C) in patients with familial hypercholesterolemia (FH). Current lipid-lowering treatment is often inadequate to achieve these targets. METHODS: Data from the HELLAS-FH registry were analysed to assess achievement of LDL-C targets in adults with FH based on the 2019 ESC/EAS guidelines. In patients who had not achieved LDL-C target, the maximally reduced LDL-C value was calculated after theoretical switch to rosuvastatin/ezetimibe 40/10 mg/day. The percentage of patients who remained candidates for proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) was then calculated. RESULTS: Patients (n = 1694, mean age 50.8 ± 14.7 years) had LDL-C levels 242 ± 71 mg/dL (6.3 ± 1.8 mmol/L) at diagnosis. Most treated patients were receiving statins (97.5%) and about half were on additional ezetimibe (47.5%). Based on the 2019 ESC/EAS guidelines the percentage of patients achieving LDL-C goals was only 2.7%. Following theoretical up titration to rosuvastatin/ezetimibe 40/10 mg, LDL-C target achievement rate would increase to 5.9%. In this scenario, most patients (55.9%) would be eligible for PCSK9i treatment. Following theoretical administration of a PCSK9i, LDL-C target achievement rate would rise to 57.6%. However, 42.4% of patients would still be eligible for further LDL-C lowering treatment. CONCLUSIONS: Most FH patients do not reach new LDL-C targets even if on maximum intensity statin/ezetimibe treatment. In this case, more than half of FH patients are candidates for PCSK9i therapy and a considerable proportion may still require additional LDL-C lowering.

Prevalence of Non-coronary Heart Disease in Patients with Familial Hypercholesterolemia: An Analysis from the HELLAS-FH.

AIMS: Despite the established link between familial hypercholesterolemia (FH) and increased risk of coronary heart disease (CHD), its association with other common atherosclerotic and metabolic diseases has not been extensively studied. The aim of this study was to report the prevalence of peripheral arterial disease (PAD) [i.e., common carotid artery disease (CCAD) and lower extremity arterial disease (LEAD)], aortic valve stenosis, chronic kidney disease (CKD) and non-alcoholic fatty liver disease (NAFLD) in patients with FH. MATERIALS & METHODS: This was a cross-sectional study retrieving data from the Hellenic Familial Hypercholesterolemia Registry (HELLAS-FH). RESULTS: A total of 1,633 adult patients (850 males) with heterozygous FH (HeFH) were included (mean age 51.3±14.6 years at registration and 44.3±15.9 years at diagnosis). Any common carotid artery stenosis (CCAS) was diagnosed in 124 out of 569 patients with available related data (21.8%), while the prevalence of CCAD (defined as a CCAS ≥50%) was 4.2%. The median (interquartile range - IQR) CCAS was 30% (20-40), whereas the median (IQR) carotid intima-media thickness (CIMT) was 0.7 (0.1-1.4) mm. LEAD was reported in 44 patients (prevalence 2.7%). The prevalence of aortic valve stenosis and CKD was 2.0% and 6.4%, respectively. NAFLD was present in 24% of study participants. CONCLUSION: HeFH is associated with a relatively high prevalence of any CCAS and CCAD. The prevalence of LEAD, CKD and aortic valve stenosis was relatively low, whereas the prevalence of NAFLD was similar to that of the general population.

Achieving low-density lipoprotein cholesterol targets as assessed by different methods in patients with familial hypercholesterolemia: an analysis from the HELLAS-FH registry.

BACKGROUND: Familial hypercholesterolemia (FH) is characterized by elevated low-density lipoprotein cholesterol (LDL-C) levels and increased cardiovascular disease (CVD) risk. FH patients often have increased lipoprotein(a) [Lp(a)] levels, which further increase CVD risk. Novel methods for accurately calculating LDL-C have been proposed. METHODS: Patients with FH were recruited by a network of Greek sites participating in the HELLAS-FH registry. LDL-C levels were calculated using the Friedewald (LDL-CF) and the Martin/Hopkins (LDL-CM/H) equations as well as after correcting LDL-CM/H for Lp(a) levels [LDL-CLp(a)corM/H]. The objective was to compare LDL-C levels and target achievement as estimated by different methods in FH patients. RESULTS: This analysis included 1620 patients (1423 adults and 197 children). In adults at diagnosis, LDL-CF and LDL-CM/H levels were similar [235 ± 70 mg/dL (6.1 ± 1.8 mmol/L) vs 235 ± 69 mg/dL (6.1 ± 1.8 mmol/L), respectively; P = NS], while LDL-CLp(a)corM/H levels were non-significantly lower than LDL-CF [211 ± 61 mg/dL (5.5 ± 1.6 mmol/L); P = 0.432]. In treated adults (n = 966) both LDL-CF [150 ± 71 mg/dL (3.9 ± 1.8 mmol/L)] and LDL-CM/H levels [151 ± 70 mg/dL (6.1 ± 1.8 mmol/L); P = 0.746] were similar, whereas LDL-CLp(a)corM/H levels were significantly lower than LDL-CF [121 ± 62 mg/dL (3.1 ± 1.6 mmol/L); P < 0.001]. Target achievement as per latest guidelines in treated patients using the LDL-CM/H (2.5%) and especially LDL-CLp(a)corM/H methods (10.7%) were significantly different than LDL-CF (2.9%; P < 0.001). In children, all 3 formulas resulted in similar LDL-C levels, both at diagnosis and in treated patients. However, target achievement by LDL-CF was lower compared with LDL-CM/H and LDL-CLp(a)corM/H methods (22.1 vs 24.8 vs 33.3%; P < 0.001 for both comparisons). CONCLUSION: LDL-CLp(a)corM/H results in significantly lower values and higher target achievement rate in both treated adults and children. If validated in clinical trials, LDL-CLp(a)corM/H may become the method of choice to more accurately estimate 'true' LDL-C levels in FH patients.

Association of the Common Catalase Gene Polymorphism rs1001179 With Glycated Hemoglobin and Plasma Lipids in Hyperlipidemic Patients.

Catalase represents perhaps the most effective antioxidant defense in the body under conditions of increased oxidative stress, and rs1001179 (CAT-262C >T) is its most extensively studied gene polymorphism. Using an established PCR-RFLP method for genotyping, we examined the association of rs1001179 with glycated hemoglobin (HbA1c) and plasma lipids using univariate analyses with age, sex, body mass index (BMI), smoking, and alcohol abuse as covariates, in a group of dyslipidemic patients from northern Greece. Our results suggest that the TT genotype is a risk factor for increased HbA1c and plasma triglycerides, and that this association is modulated by the BMI and/or age of the patients.

Association of the CETP Taq1B and LIPG Thr111Ile Polymorphisms with Glycated Hemoglobin and Blood Lipids in Newly Diagnosed Hyperlipidemic Patients.

OBJECTIVE: To examine the association of 2 common polymorphisms in high-density lipoprotein (HDL)-related genes, namely, cholesterol ester transfer protein CETP Taq1B (rs708272) and endothelial lipase LIPG Thr111Ile (rs2000813), with glycated hemoglobin (A1C), blood lipid levels and the risk for type 2 diabetes in a group of hyperlipidemic patients from northern Greece. METHODS: We categorized 175 patients with hyperlipidemia into 2 subgroups according to the presence or absence of type 2 diabetes, defined as a recent diagnosis, A1C >6.5% and/or fasting glucose >126 mg/dL. Genotypes for the 2 polymorphisms studied were determined by polymerase chain reaction-restriction fragment length polymorphism. Both polymorphisms were analyzed by multivariate and univariate analyses of baseline A1C levels and plasma lipids. The genotype and allele frequencies of the 2 subgroups were compared. RESULTS: The CETP Taq1B polymorphism was associated with HDL-cholesterol (HDL-C) and A1C levels, but this association was affected by type 2 diabetes; the association with A1C levels was significant only in type 2 diabetes (p=0.005), whereas the association with HDL-C occurred only in the subgroup without type 2 diabetes (p<0.001). LIPG Thr111Ile did not affect plasma HDL-C or A1C levels independently but appeared to modulate their association with CETP Taq1B, and LIPG 111IleIle homozygotes tended to be present at a higher frequency in the hyperlipidemic patients with type 2 diabetes compared to the hyperlipidemic patients without type 2 diabetes (p=0.056). CONCLUSIONS: In hyperlipidemic patients, apart from its known association with HDL-C, CETP Taq1B is also associated with A1C levels, and both associations are modified by type 2 diabetes and LIPG Thr111Ile.

Prophylactic antibiotic treatment in severe acute ischemic stroke: the Antimicrobial chemopRrophylaxis for Ischemic STrokE In MaceDonIa-Thrace Study (ARISTEIDIS).

Infections represent a leading cause of mortality in patients with acute ischemic stroke, but it is unclear whether prophylactic antibiotic treatment improves the outcome. We aimed to evaluate the effects of this treatment on infection incidence and short-term mortality. This was a pragmatic, prospective multicenter real-world analysis of previously independent consecutive patients with acute ischemic stroke who were >18 years, and who had at admission National Institutes of Health Stroke Scale (NIHSS) >11. Patients with infection at admission or during the preceding month, with axillary temperature at admission >37 °C, with chronic inflammatory diseases or under treatment with corticosteroids were excluded from the study. Among 110 patients (44.5 % males, 80.2 ± 6.8 years), 31 (28.2 %) received prophylactic antibiotic treatment, mostly cefuroxime (n = 21). Prophylactic antibiotic treatment was administered to 51.4 % of patients who developed infection, and to 16.4 % of patients who did not (p < 0.001). Independent predictors of infection were NIHSS at admission [relative risk (RR) 1.16, 95 % confidence interval (CI) 1.08-1.26, p < 0.001] and prophylactic antibiotic treatment (RR 5.84, 95 % CI 2.03-16.79, p < 0.001). The proportion of patients who received prophylactic antibiotic treatment did not differ between patients who died during hospitalization and those discharged, or between patients who died during hospitalization or during follow-up and those who were alive 3 months after discharge. Prophylactic administration of antibiotics in patients with severe acute ischemic stroke is associated with an increased risk of infection during hospitalization, and does not affect short-term mortality risk.

Common ABCB1 polymorphisms in Greek patients with chronic hepatitis C infection: A comparison with hyperlipidemic patients and the general population.

BACKGROUND: Hepatitis C virus infectivity and replication efficiency appears to be dependent on the lipid content and organization of the plasma membrane of the host cell, as well as of the intracellular membranous web. As there is increasing awareness of a role played by the efflux pump ABCB1 (p-glycoprotein, P-gp) in lipid homeostasis, its function could be a determinant of chronic HCV infection. The aim of the present study was to examine and compare the distribution of common ABCB1 genotypes in patients with chronic HCV infection (n=168), hyperlipidemic patients (n=168) and a control group (n=173), all from Greece. METHODS: Participants were genotyped for the ABCB12677G>T/A and 3435C>T polymorphisms with previously reported PCR-RFLP methods. Genotype and allele frequency distributions were compared between the three groups with the χ(2) test of independence. RESULTS: The ABCB1 2677GG (ancestral) genotypes were significantly over-represented in patients with chronic hepatitis C compared to controls (39.3% vs. 26.6%, p=0.015 according to the dominant model). A similar result was obtained when hyperlipidemic patients were compared to controls (45.2% vs. 26.6%, p<0.001 according to the dominant model). Comparison of ABCB1 3435C>T genotype and allele distributions provided similar but not as significant differences. Genotype and allele distributions for both ABCB12677G>T/A and 3435C>T were very similar between HCV patients and hyperlipidemic patients. CONCLUSION: Our findings imply an influence of ABCB1 polymorphisms on HCV infectivity, possibly through an effect on lipid homeostasis.

Coagulation and inflammation biomarkers may help predict the severity of community-acquired pneumonia.

BACKGROUND AND OBJECTIVE: There are limited data on the relationship between the severity of community-acquired pneumonia (CAP) and biomarkers of inflammation and coagulation. The aim of this study was to evaluate the association between the severity of CAP and serum levels of antithrombin III (AT-III), protein C (P-C), D-dimers (D-D) and CRP, at hospital admission. METHODS: This was a prospective observational study in 77 adults (62.3% men), who were hospitalized for CAP. The severity of CAP was assessed using the confusion, uraemia, respiratory rate >or=30 breaths/min, low blood pressure, age >or=65 years (CURB-65) score. RESULTS: Forty patients (52%) had severe CAP (CURB-65 score 3-5). Serum levels of AT-III were lower and levels of D-D and CRP were higher in patients with severe CAP than in patients with mild CAP (CURB-65 score 0-2) (P < 0.001 for all comparisons). Levels of P-C were lower in patients with severe CAP compared with those with mild CAP, but the difference was not significant (P = 0.459). At a cut-off point of 85%, AT-III showed a sensitivity of 80% and a specificity of 75%, as a determinant of the need for hospitalization. At a cut-off point of 600 ng/mL, D-D showed a sensitivity of 90% and a specificity of 75% and at a cut-off point of 110 mg/L, CRP showed a sensitivity of 83% and a specificity of 79%, as determinants of the need for hospitalization. CONCLUSIONS: Serum levels of AT-III, D-D and CRP at admission appear to be useful biomarkers for assessing the severity of CAP.

Trend in incidence of cardiovascular risk factors in elderly and over-aged stroke patients between 2003 and 2007 in Greece.

The aim of this study is to identify the main cardiovascular risk factors (CRFs) in patients over 65 years with ischemic stroke. This is a retrospective study in 175 patients that were hospitalized in our department due to ischemic stroke in the period 2006-2007. The patients were divided in two groups: Group I--elderly (65-80 years) and Group II--over-aged (>or=81 years). The results were compared with a similar study performed in our department in the period 2002-2003 in 160 ischemic stroke patients. Statistical analysis was made by the chi2-test. Hypertension, either alone or in combination with other CRFs, constitutes the main CRF. Diabetes mellitus (DM) is not frequently the sole CRF but its coexistence with other CRFs ranks DM as the second most important CRF, with the largest percentage in the elderly. Dyslipipidemia is 4th CRF in order following the coronary heart disease (CHD). Taking into account that the provision of acute therapeutic intervention in elderly and over-aged ischemic stroke patients is in most cases difficult, because of their age and the high risk of thrombolysis in these patients, there is increased need to focus on primary prevention of ischemic stroke by treating associated CRF.

Hypokalemia induced myopathy as first manifestation of primary hyperaldosteronism - an elderly patient with unilateral adrenal hyperplasia: a case report.

INTRODUCTION: Primary hyperaldosteronism is only rarely caused by unilateral adrenal hyperplasia. CASE PRESENTATION: A 73-year-old hypertensive Greek man (on 10 mg amlodipine for the last ten years) presented in the emergency department with severe muscle weakness of all limbs. The initial physical and laboratory examination revealed normal blood pressure, muscle weakness, severe hypokalemia, sinus rhythm and U wave, rhabdomyolysis and metabolic alkalosis. The patient was immediately treated with intravenous administration of potassium-rich solutions, 25 mg spironolactone with progressive dose titration up to 100 mg. Because of high arterial blood pressure, irbesartan was added. On day 6, muscle weakness was completely restored with decrease of arterial blood pressure and further improvement of laboratory tests. The combination of hypokalemia with arterial hypertension raised the suspicion of primary hyperaldosteronism; therefore, we performed abdomen computed tomography scan, which revealed a nodular mass (15 mm in diameter) in the left adrenal gland. Plasma renin activity was in the lower normal range with a three-fold increase of plasma aldosterone concentration. We performed total resection of the left adrenal gland and the histopathological examination revealed hyperplasia of the left adrenal gland. CONCLUSION: This report presents a rare case of an elderly patient under antihypertensive treatment the last ten years for essential hypertension, who admitted to our emergency department with hypokalemia - induced myopathy as first manifestation of primary hyperaldosteronism due to unilateral adrenal hyperplasia.