Physical signs and atherosclerotic cardiovascular disease in familial hypercholesterolemia: the HELLAS-FH Registry.

AIMS: Three physical signs, namely tendon xanthomas, corneal arcus and xanthelasma, have been associated with heterozygous familial hypercholesterolemia (heFH). The prevalence and clinical significance of these signs are not well established among contemporary heFH individuals. This study explored the frequency as well as the association of these physical signs with prevalent atherosclerotic cardiovascular disease (ASCVD) in heFH individuals. METHODS: Data from the Hellenic Familial Hypercholesterolemia Registry were applied for this analysis. The diagnosis of heFH was based on the Dutch Lipid Clinic Network Score. Multivariate logistic regression analysis was conducted to examine the association of heFH-related physical signs with prevalent ASCVD. RESULTS: Adult patients ( n  = 2156, mean age 50 ±â€Š15 years, 47.7% women) were included in this analysis. Among them, 14.5% had at least one heFH-related physical sign present. The prevalence of corneal arcus before the age of 45 years was 6.6%, tendon xanthomas 5.3%, and xanthelasmas 5.8%. Among physical signs, only the presence of corneal arcus before the age of 45 years was independently associated with the presence of premature coronary artery disease (CAD). No association of any physical sign with total CAD, stroke or peripheral artery disease was found. Patients with physical signs were more likely to receive higher intensity statin therapy and dual lipid-lowering therapy, but only a minority reached optimal lipid targets. CONCLUSION: The prevalence of physical signs is relatively low in contemporary heFH patients. The presence of corneal arcus before the age of 45 years is independently associated with premature CAD.

Obesity and atherosclerotic cardiovascular disease in adults with heterozygous familial hypercholesterolemia: An analysis from HELLAS-FH registry.

BACKGROUND: Familial hypercholesterolemia (FH) and obesity are well-established risk factors of atherosclerotic cardiovascular disease (ASCVD). Despite high prevalence, their joint association with ASCVD remains largely unknown. OBJECTIVE: To investigate the association of obesity with prevalent ASCVD in individuals with heterozygous FH (HeFH) enrolled in the Hellenic Familial Hypercholesterolemia Registry (HELLAS-FH). METHODS: FH diagnosis was based on Dutch Lipid Clinic Network (DLCN) criteria. Adults with at least possible FH diagnosis (DLCN score ≥3) and available body mass index (BMI) values were included. Homozygous FH individuals were excluded. RESULTS: 1655 HeFH adults (mean age 51.0 ± 14.4 years, 48.6% female) were included; 378 (22.8%) and 430 (26.0%) were diagnosed with probable and definite FH, respectively. Furthermore, 371 participants (22.4%) had obesity and 761 (46.0%) were overweight. Prevalence of ASCVD risk factors increased progressively with BMI. Prevalence of coronary artery disease (CAD) was 23.4% (3.2% for stroke and 2.7% for peripheral artery disease, PAD), and increased progressively across BMI groups. After adjusting for traditional ASCVD risk factors and lipid-lowering medication, individuals with obesity had higher odds of established CAD (OR: 1.54, 95% CI: 1.04-2.27, p = 0.036) as well as premature CAD (OR: 1.74, 95% CI: 1.17-2.60, p = 0.009) compared with those with normal BMI. No association was found with stroke or PAD. CONCLUSIONS: Over half of adults with HeFH have overweight or obesity. Obesity was independently associated with increased prevalence of CAD in this population.

Familial Hypercholesterolemia in the Elderly: An Analysis of Clinical Profile and Atherosclerotic Cardiovascular Disease Burden from the Hellas-FH Registry.

BACKGROUND: Familial hypercholesterolemia (FH) carries a high risk of atherosclerotic cardiovascular disease (ASCVD). As the population ages, the age-related influence on clinical characteristics and outcomes becomes increasingly pertinent. This cross-sectional analysis from the HELLAS-FH registry aims to explore potential differences in clinical characteristics, treatment, ASCVD, and goal achievement between those younger and older than 65 years with FH. RESULTS: A total of 2273 adults with heterozygous FH (51.4% males) were studied. Elderly FH patients (n = 349) had a higher prevalence of ASCVD risk factors, such as hypertension (52.1% vs. 20.9%, p < 0.05) and type 2 diabetes (16.9% vs. 6.0%, p < 0.05), compared to younger patients (n = 1924). They also had a higher prevalence of established ASCVD (38.4% vs. 23.1%, p < 0.001), particularly CAD (33.0% vs. 20.2%, p < 0.001), even after adjusting for major ASCVD risk factors. Elderly patients were more frequently and intensively receiving lipid-lowering treatment than younger ones. Although post-treatment LDL-C levels were lower in elderly than younger patients (125 vs. 146 mg/dL, p < 0.05), both groups had similar attainment of the LDL-C target (3.7% vs. 3.0%). CONCLUSIONS: Elderly FH patients have a higher prevalence of ASCVD, particularly CAD. Despite more aggressive treatment, the achievement of LDL-C targets remains very poor. These results emphasize the importance of early FH diagnosis and treatment in reducing ASCVD.

Lipoprotein(a), metabolic profile and new-onset type 2 diabetes in patients with familial combined hyperlipidemia: A 9 year follow-up study.

BACKGROUND: Lipoprotein(a) [Lp(a)] appears to have an inverse association with the risk of type 2 diabetes mellitus in the general population. OBJECTIVE: This study aimed to investigate the prognostic role of Lp(a) regarding the development of type 2 diabetes in the special population of subjects with familial combined hyperlipidemia (FCH). METHODS: This cohort study included 474 patients (mean age 49.7±11.3 years, 64% males) with FCH, without diabetes at baseline who were followed for a mean period of 8.2±6.8 years. At baseline evaluation venous blood samples were obtained for the determination of lipid profile and Lp(a) levels. The endpoint of interest was the development of diabetes. RESULTS: Patients with increased Lp(a) levels ≥30 mg/dl compared to those with low Lp(a) levels <30 mg/dl had lower levels of triglycerides (238±113 vs 268±129 mg/dl, p = 0.01), greater levels of high-density lipoprotein (HDL) cholesterol (44±10 vs 41±10 mg/dl, p = 0.01) and hypertension in a greater percentage (42% vs 32%, p = 0.03). The incidence of new-onset diabetes during the follow-up period was 10.1% (n = 48). Multiple Cox regression analysis revealed that increased Lp(a) is an independent predictor of lower diabetes incidence (HR 0.39, 95% CI 0.17-0.90, p = 0.02) after adjustment for confounders. CONCLUSION: Among subjects with FCH those with higher Lp(a) levels have lower risk for the development of type 2 diabetes. Moreover, the presence of increased Lp(a) seems to differentiate the expression of metabolic syndrome characteristics in patients with FCH, as increased Lp(a) is related to lower levels of triglycerides, greater prevalence of hypertension and higher levels of HDL cholesterol.

Comparative performance of equations to estimate low-density lipoprotein cholesterol levels and cardiovascular disease incidence: The ATTICA study (2002-2022).

Accurate estimation of low-density lipoprotein cholesterol (LDL-C) is important for monitoring cardiovascular disease (CVD) risk and guiding lipid-lowering therapy. This study aimed to evaluate the magnitude of discordance of LDL-C levels calculated by different equations and its effect on CVD incidence. The study sample consisted of 2354 CVD-free individuals (49% males, mean age 45 ± 14 years); 1600 were re-evaluated at 10 years and 1570 at 20 years. LDL-C was estimated using the Friedewald, Martin/Hopkins, and Sampson equations. Participants were categorized as discordant if estimated LDL-C was below the CVD-risk specific cut-off for one equation and equal/above for its comparator. The Friedewald and Martin/Hopkins equations presented a similar performance in estimating LDL-C; however, both yielded lower values compared to the Sampson. In all pairwise comparisons, differences were more pronounced at lower LDL-C levels, while the Friedewald equation significantly underestimated LDL-C in hypertriglyceridemic participants. Discordance was evident in 11% of the study population, and more specifically 6%, 22%, and 20% for Friedewald versus Martin/Hopkins, Friedewald versus Sampson and Martin/Hopkins versus Sampson equations, respectively. Among discordant participants, median (1st, 3rd quartile) difference in LDL-C was -4.35 (-10.1, 1.95), -10.6 (-12.3, -9.53) and -11.3 (-11.9, -10.6) mg/dL for Friedewald versus Martin/Hopkins, Friedewald versus Sampson and Martin/Hopkins versus Sampson equations, respectively. The 10- and 20-year CVD survival model that included LDL-C values of the Martin-Hopkins equation outperformed the predictive ability of those based on the Friedewald or Sampson equations. Significant differences in estimated LDL-C exist among equations, which may result in LDL-C underestimation and undertreatment.

Long-term prognostic value of LDL-C, HDL-C, lp(a) and TG levels on cardiovascular disease incidence, by body weight status, dietary habits and lipid-lowering treatment: the ATTICA epidemiological cohort study (2002-2012).

BACKGROUND: The link between blood lipids and cardiovascular disease (CVD) is complex. Our aim was to assess the differential effect of blood lipids on CVD risk according to age, sex, body weight, diet quality, use of lipid-lowering drugs and presence of hypercholesterolemia. METHODS: In this secondary analysis of the ATTICA prospective cohort study, serum blood lipids, i.e., total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG) and liproprotein(a) [Lp(a)], and sociodemographic, anthropometric, lifestyle and clinical parameters were evaluated at baseline (2001/2002) in 2020 CVD-free men and women. CVD incidence was recorded at the 10-year follow-up (2011/2012). RESULTS: All blood lipids assessed were univariately related to CVD risk; however, associations remained significant only for HDL-C and TG in multivariate models adjusted for age, sex, body mass index, smoking, Mediterranean Diet Score, physical activity, presence of hypercholesterolemia, hypertension and diabetes mellitus, use of lipid-lowering drugs, and family history of CVD [RR per 1 mg/dL (95% CI): 0.983 (0.967, 1.000) and 1.002 (1.001, 1.003), respectively]. In stratified analyses, TC and LDL-C predicted CVD risk in younger subjects, normal-weight subjects, and those not on lipid-lowering drugs, while HDL-C and TG were significant predictors in older subjects, those with low adherence to the Mediterranean diet, and hypercholesterolemic subjects; a significant effect on CVD risk was also observed for TG in males, overweight participants and lipid-lowering medication users and for Lp(a) in older subjects and females (all p ≤ 0.050). CONCLUSIONS: The impact of blood lipids on CVD risk differs according to several biological, lifestyle and clinical parameters.

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.

Visceral adipose tissue phenotype and hypoadiponectinemia are associated with aortic Fluorine-18 fluorodeoxyglucose uptake in patients with familial dyslipidemias.

BACKGROUND: The role of adipose tissue (AT) in arterial inflammation in familial dyslipidaemias is poorly studied. We investigated the relationship between AT and arterial inflammation in patients with heterozygous familial hypercholesterolemia (heFH) and familial combined hyperlipidemia (FCH). METHODS AND RESULTS: A total of 40 patients (20 heFH/20 FCH) and a subgroup of 20 of non-heFH/FCH patients were enrolled. Participants underwent blood sampling for serum adipokine measurements and Fluorine-18 fluorodeoxyglucose (18F-FDG) PET/CT imaging. Abdominal visceral (VAT) and subcutaneous (SAT) AT volumes and AT and abdominal aorta 18F-FDG uptake were quantified. FCH patients had increased VAT (pANOVA = 0.004) and SAT volumes (pANOVA = 0.003), lower VAT metabolic activity (pANOVA = 0.0047), and lower adiponectin levels (pANOVA = 0.007) compared to heFH or the control group. Log(Serum adiponectin) levels were correlated with aortic TBR (b = - 0.118, P = 0.038). In mediation analysis, VAT volume was the major determinant of circulating adiponectin, an effect partly mediated via VAT TBR. Clustering of the population of heFH/FCH by VAT volume/TBR and serum adiponectin identified two distinct patient clusters with significant differences in aortic TBR levels (2.11 ± 0.06 vs 1.89 ± 0.05, P= 0.012). CONCLUSIONS: VAT phenotype (increased VAT volume and/or high VAT TBR) and hypoadiponectinemia may account for the observed differences in arterial inflammation levels between heFH and FCH patients.

Prevalence of Diabetes and Its Association with Atherosclerotic Cardiovascular Disease Risk in Patients with Familial Hypercholesterolemia: An Analysis from the Hellenic Familial Hypercholesterolemia Registry (HELLAS-FH).

Familial hypercholesterolemia (FH) and type 2 diabetes mellitus (T2DM) are both associated with a high risk of atherosclerotic cardiovascular disease (ASCVD). Little is known about the prevalence of T2DM and its association with ASCVD risk in FH patients. This was a cross-sectional analysis from the Hellenic Familial Hypercholesterolemia Registry (HELLAS-FH) including adults with FH (n = 1719, mean age 51.3 ± 14.6 years). Of FH patients, 7.2% had a diagnosis of T2DM. The prevalence of ASCVD, coronary artery disease (CAD), and stroke was higher among subjects with T2DM compared with those without (55.3% vs. 23.3%, 48.8% vs. 20.7%, 8.3% vs. 2.7%, respectively, p < 0.001). When adjusted for age, systolic blood pressure, smoking, body mass index, hypertension, waist circumference, triglyceride levels, high-density lipoprotein cholesterol levels, and gender, T2DM was significantly associated with prevalent ASCVD [OR 2.0 (95% CI 1.2−3.3), p = 0.004]. FH patients with T2DM were more likely to have undergone coronary revascularization than those without (14.2% vs. 4.5% for coronary artery bypass graft, and 23.9% vs. 11.5% for percutaneous coronary intervention, p < 0.001). T2DM is associated with an increased risk for prevalent ASCVD in subjects with FH. This may have implications for risk stratification and treatment intensity in these patients.

Carotid Artery Temperature Reduction with Statin Therapy in Patients with Familial Hyperlipidemia Syndromes.

BACKGROUND: Microwave radiometry (MWR) assesses non-invasive carotid artery temperatures reflecting inflammation. In the present study, we aimed to investigate the impact of hypolipidemic therapy either with simvastatin or with combination simvastatin plus ezetimibe on carotid artery temperatures of patients with familial hyperlipidemia syndromes (FHS). METHODS: Consecutive patients with diagnosis of either familial heterozygous hypercholesterolemia (heFH) or familial combined hyperlipidemia (FCH) were included in the study. Patients were assigned to either simvastatin 40 mg or simvastatin 40 mg plus ezetimibe 10 mg, according to the discretion of the physician. FHS patients who refused statin therapy were used as a control group. Common carotid intima-media thickness (ccIMT) was measured and ΔΤ (maximum-minimum) temperature measurements were performed across each carotid during MWR evaluation. RESULTS: In total, 115 patients were included in the study. Of them, 40 patients received simvastatin (19 heFH and 21 FCH), 41 simvastatin + ezetimibe (31 heFH and 10 FCH), and 34 (21 heFH and 13 FCH) no statin. Carotid artery temperatures were significantly reduced at 6 months in FH patients who received hypolipidemic treatment (0.83 ± 0.34 versus 0.63 ± 0.24 °C, p = 0.004 for simvastatin, 1.00 ± 0.38 versus 0.69 ± 0.23 °C, p < 0.001 for simvastatin + ezetimibe), but no change was recorded in controls (0.72 ± 0.26 versus 0.70 ± 0.26 °C, p = 0.86). CONCLUSIONS: Hypolipidemic therapy reduced carotid temperatures in FHS patients.

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.

Eligibility for PCSK-9 inhibitors treatment in acute coronary syndrome, chronic coronary artery disease and outpatient dyslipidemic patients.

BACKGROUND AND AIMS: We aimed to investigate potential eligibility for proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors in patients with coronary artery disease and dyslipidaemia according to patient characteristics and variable criteria. METHODS: We prospectively enrolled 2000 patients (acute coronary syndrome = 407, chronic coronary artery disease inpatients = 1087, outpatient Lipid's clinic = 506). To calculate PCSK-9 inhibitors real-world eligibility, a proprietary adjustable software was developed, which stores data and patient characteristics and can determine eligibility depending on different criteria. We tested four scenarios with different LDL thresholds according to ESC/EAS 2016 and 2019 Guidelines, 2017 American College of Cardiology Expert Consensus, and National criteria. RESULTS: The eligible percentage was 18.85%, 9.75%, 8.55% and 2.15%, in the total population for the four classifications, respectively, and it varied according to clinical status. The increase toward more recent guidelines was mostly attributed to the increasing number of coronary patients who become eligible as our criteria become stricter. CONCLUSIONS: For the first time, a realistic estimation of PCSK-9 eligibility is provided via an adjustable predictive model in a population of 2000 patients with acute coronary syndrome, chronic coronary artery disease and dyslipidaemia. This can be a valuable tool for the incorporation of PCSK-9 inhibitors in health care systems.

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.

PCSK9 inhibitors in clinical practice: Novel directions and new experiences.

BACKGROUND: In randomized clinical trials, proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) effectively reduce low-density lipoprotein-cholesterol (LDL-C) with a favorable tolerability and safety profile. Our purpose is to provide real-world data regarding the indications, efficacy and safety of PCSK9i. METHODS: The cohort comprised 141 patients who attended the lipid clinic of 3 hospitals in Greece and started using PCSK9i. Patients were requested to attend the lipid clinic at 3 months and at 1 year. RESULTS: Ninety percent of patients had heterozygous familial hypercholesterolaemia (heFH) and 75% had cardiovascular disease (CVD). A PCSK9i [evolocumab 140 mg/2 weeks (n = 82), alirocumab 75 mg/2 weeks (n = 46) and alirocumab 150 mg/2 weeks (n = 13)] was prescribed due to failure to achieve LDL-C targets despite maximum lipid-lowering therapy (LLT) in 75% of patients, while in the remaining cases, the indication was statin intolerance. The mean reduction of LDL-C at 3 months was 56.2% and remained constant at 12 months (55.8% reduction from baseline). LDL-C target was achieved by 68.1% of patients at 3 months. "Totally" intolerant to statins patients (unable to tolerate any statin dose, n = 23) showed the lowest LDL-C reduction (47.7%). Side effects attributed to treatment were reported by 14 patients (10%). The total number of patients who stopped PCSK9i at 1 year was 14 (10%) but only 2 (1.4%) discontinued treatment because of side effects (myalgias). CONCLUSIONS: Our real-world results of PCSK9i showed comparable efficacy and tolerability to those reported in clinical trials and highlighted the value of treatment with PCSK9i heFH patients not achieving LDL-C targets despite maximum LLT and high or very high risk statin intolerant patients.

PCSK9 and Lp(a) levels of children born after assisted reproduction technologies.

PURPOSE: Proprotein convertase subtilisin/kexin type 9 (PCSK9) and lipoprotein (a) (Lp[a]) levels are associated with cardiovascular risk. To investigate PCSK9 and Lp(a) levels of children born after assisted reproduction technologies (ART) compared with naturally conceived (NC) controls. METHODS: In this exposure-matched cohort study, 73 racial-, sex-, and age-matched children (mean age 98 ± 35 months) of ART (intracytoplasmic sperm injection [ICSI] n = 33, classic in vitro fertilization [IVF] n = 40) and 73 NC children were assessed. Blood lipid profile, including PCSK9 and Lp(a) levels, was measured. Children were grouped according to age (< 8 years, 8-10 years, ≥ 10 years). RESULTS: In the overall population, PCSK9 levels were related to total cholesterol, low-density lipoprotein, and systolic blood pressure, while Lp(a) levels were related to age, apolipoprotein-B, birth weight, height, waist-to-hip ratio, insulin resistance, insulin, and high-sensitivity C-reactive protein. No significant differences were observed regarding lipid biomarkers between ART and NC children. However, a significant interaction was found between age groups and conception method (p < 0.001) showing that PCSK9 levels increase with age in ART children, while they decline with age in NC offspring. IVF children showed higher levels of adjusted mean Lp(a) than ICSI (13.5 vs. 6.8 mg/dl, p = 0.010) and NC children (12.3 vs. 8.3 mg/dl, p = 0.048). CONCLUSIONS: We show that PCSK9 levels increase with age in ART children, indicating a gradual deterioration of lipidemic profile that could lead to increased cardiovascular risk. Moreover, our results indicate that ART method may be of importance given that classic IVF is associated with higher levels of Lp(a).

Visceral adiposity index outperforms common anthropometric indices in predicting 10-year diabetes risk: Results from the ATTICA study.

BACKGROUND: Visceral adiposity index (VAI) is a novel marker of visceral adipose tissue accumulation and dysfunction. The study aim was to explore the association of VAI with the 10-year type 2 diabetes mellitus (T2DM) incidence in apparently healthy individuals and compare its T2DM predictive ability against common anthropometric indices. METHODS: In 2001 to 2002, the ATTICA study (Greece) recruited a random sample of 1514 and 1528 CVD-free men (18-87 years old) and women (18-89 years old), respectively. Sociodemographic, lifestyle, clinical, and biochemical characteristics of participants were measured at baseline, and the 10-year follow-up was performed during 2011 to 2012. After excluding participants with diabetes at baseline and participants without complete follow-up information regarding diabetes status and/or baseline VAI values, the working sample consisted of 1049 participants. In this sample, the predictive value of baseline VAI value was studied in relation to 10-year diabetes incidence. RESULTS: One hundred thirty-three incident cases of diabetes were documented (10-year incidence: 12.7%). In the fully adjusted model, VAI significantly increased diabetes risk by 22% (OR per 1-unit increase =1.22; 95%CI, 1.09-1.37). Markers of oxidative stress and inflammation were found to, at least partly, mediate this relationship. Also, a moderating effect of menstruation status was revealed among women. VAI showed the highest predictive ability and contributed the most, along with waist-to-height ratio, to the correct classification of participants who developed diabetes. CONCLUSIONS: The present findings suggest that VAI may be a useful index for predicting long-term diabetes development and may exhibit better predictive ability to commonly used anthropometric indices.