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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. © 2021, American Society of Nuclear Cardiology.

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 Hypercholes-terolemia 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%, respec-tively. 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. © 2021 Bentham Science Publishers.

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. © 2019 Hellenic Society of Cardiology

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. © 2020 The Author(s).

To test the hypothesis that virtual functional assessment index (vFAI) is related with regional flow parameters derived by quantitative positron emission tomography (PET) and can be used to assess abnormal vasodilating capability in coronary vessels with stenotic lesions at coronary computed tomography angiography (CCTA). Methods and results: vFAI, stress myocardial blood flow (MBF), and myocardial flow reserve (MFR) were assessed in 78 patients (mean age 62.2 ± 7.7 years) with intermediate pre-test likelihood of coronary artery disease (CAD). Coronary stenoses ≥50% were considered angiographically significant. PET was considered positive for significant CAD, when more than one contiguous segments showed stress MBF ≤2.3 mL/g/min for O-water or

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). © 2019, Springer Science+Business Media, LLC, part of Springer Nature.

Non-response cardiac resynchronization therapy (CRT) remains an issue, despite the refinement of selection criteria. The purpose of this study was to investigate the role of stress echocardiography along with dyssynchrony parameters for identification of CRT responders or late responders. 106 symptomatic heart failure patients were examined before, 6 months and 2–4 years after CRT implementation. Inotropic contractile reserve (ICR) and inferolateral (IL) wall viability were studied by stress echocardiography. Dyssynchrony was assessed by: (1) Septal to posterior wall motion delay (SPWMD) by m-mode. (2) Septal to lateral wall delay (SLD) by TDI. (3) Interventricular mechanical delay (IVMD) by pulsed wave Doppler for (4) difference in time to peak circumferential strain (TmaxCS) by speckle tracking. (5) Apical rocking (ApR) and septal flash (SF) by visual assessment. At 6 months there were 54 responders, with 12 additional late responders. TmaxCS had the greatest predictive value with an area under curve (AUC) of 0.835, followed by the presence of both ICR and viability of IL wall (AUC 0.799), m-mode (AUC = 0.775) and presence of either ApR or SF (AUC = 0.772). Predictive ability of ApR and of ICR is augmented if late responders are also included. Performance of dyssynchrony parameters is enhanced, in patients with both ICR and IL wall viability. Stress echocardiography and dyssynchrony parameters are simple and reliable predictors of 6-month and late CRT response. A stepwise approach with an initial assessment of ICR and viability and, if positive, further dyssynchrony analysis, could assist decision making. © 2019, Springer Nature B.V.

Importance: Aortic stiffness, as assessed by carotid-femoral pulse wave velocity, is an independent predictor of future events in individuals with hypertension. Recent data suggest a predictive role of estimated pulse wave velocity (ePWV) calculated by previously published equations using age and blood pressure in future events in individuals with hypertension. Objective: To investigate whether ePWV and its response to treatment predict survival in the Systolic Blood Pressure Intervention Trial (SPRINT). Design, Setting, and Participants: This exploratory, hypothesis-generating, post hoc secondary analysis conducted from October 1, 2018, to August 31, 2019, examined data from 9361 participants in SPRINT and calculated ePWV at baseline and at 12 months. Adjusted hazard ratios (HRs) with 95% CIs of ePWV per 1 SD were estimated using Cox proportional hazards regression models. A total of 8450 patients were assigned to 4 groups according to their treatment allocation and their response in ePWV after 12 months. Interventions: Participants were assigned a systolic blood pressure target of less than 120 mm Hg (intensive treatment) or less than 140 mm Hg (standard treatment). Main Outcomes and Measures: The primary composite cardiovascular outcome was myocardial infarction, other acute coronary syndromes, stroke, heart failure, or death from cardiovascular causes. Results: In the SPRINT population (3332 women and 6029 men; mean [SD] age, 67.9 [9.4] years), ePWV predicted the primary outcome (HR, 1.30 [95% CI, 1.17-1.43]; P

Background and aims: Although familial hypercholesterolemia (FH) is one of the most common genetic disorders, it remains largely underdiagnosed and undertreated. The Hellenic Atherosclerosis Society has established the Hellenic Familial Hypercholesterolemia (HELLAS-FH) Registry, part of the Familial Hypercholesterolemia Studies Collaboration (FHSC), to evaluate the characteristics and management of patients with FH in Greece. Methods: Patients with diagnosed FH were recruited by a network of sites throughout Greece. The prevalence of cardiovascular disease (CVD) risk factors, as well as management of FH, was recorded. Results: This interim analysis included 1093 patients (556 male; 950 adults). The median age of FH diagnosis was 42.2 years (interquartile range 27.2–53.0). A family history of CVD was present in 47.8%, while 21.1% of patients had a personal history of CVD. At diagnosis, low-density lipoprotein cholesterol (LDL-C) was 241 ± 76 mg/dL in adults and 229 ± 57 mg/dL in children. Overall, 63.1% of the patients were receiving hypolipidemic drug treatment, mainly statins, at inclusion in the registry. Mean LDL-C of patients receiving drug treatment was 154 ± 76 mg/dL in adults and 136 ± 47 mg/dL in children. The majority of treated patients (87.9%) did not achieve LDL-C targets. Conclusions: FH in Greece is characterized by a significant delay in diagnosis and a high prevalence of both family and personal history of established CVD. The vast majority of FH patients do not achieve LDL-C targets. Improved awareness and management of FH are definitely needed. © 2018 Elsevier B.V.

Background: Familial dyslipidemias of either heterozygous (heFH) or combined (FCH) type lead to accelerated atherogenesis and increased cardiovascular risk. Objective: The aim of this study was to investigate in statin-naïve adult patients with familial dyslipidemias whether inflammatory activation and liver, spleen and bone marrow metabolic activity differ compared with normolipidemic subjects and between dyslipidemic groups. Methods: Fourteen patients with FCH, 14 with heFH, and 14 normolipidemic individuals were enrolled. Serum lipids, high-sensitivity C-reactive protein, and fibrinogen levels were measured, followed by 18 F-fluorodeoxyglucose positron-emission tomography/computed tomography imaging. Radiotracer uptake in the aortic wall, spleen, bone marrow, and liver was quantified as tissue-to-background ratio (TBR). Results: Patients with heFH had significantly higher low-density lipoprotein levels compared with those with FCH and controls (P < .001). However, aortic TBRs were higher in FCH compared with heFH patients and controls (P = .02 and P < .001, respectively). FCH patients exhibited higher FDG uptake in the spleen compared with controls (P = .05). In addition, FCH exhibited higher bone marrow FDG uptake compared with heFH patients and controls (P = .03 and P = .02, respectively). FCH had higher liver uptake compared with heFH patients and controls (P < .001 for both). Significant correlations were observed between inflammatory biomarkers and imaging indices as well as between aortic TBR and FDG uptake of hematopoietic organs and liver. Conclusions: Systemic, as well as vascular inflammation and spleen, bone marrow, and hepatic metabolic activity are increased in patients with FCH despite lower levels of low-density lipoprotein. © 2017 National Lipid Association