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• This is an analysis from HELLAS-FH registry. • 1655 adults with heterozygous FH (HeFH) were included. • Over half of HeFH adults have overweight or obesity. • Obesity was associated with increased prevalence of coronary artery disease. 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. To investigate the association of obesity with prevalent ASCVD in individuals with heterozygous FH (HeFH) enrolled in the Hellenic Familial Hypercholesterolemia Registry (HELLAS-FH). 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. 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. Over half of adults with HeFH have overweight or obesity. Obesity was independently associated with increased prevalence of CAD in this population. [Display omitted] [ABSTRACT FROM AUTHOR]

Non-alcoholic fatty liver disease (NAFLD) or, as recently renamed, metabolic dysfunction-associated steatotic liver disease (MASLD), has common metabolic pathways with diabetes and cardiovascular disease (CVD). Non-invasive tools (NITs) for liver steatosis and steatohepatitis (MASH) were studied as potential predictors of diabetes, cardiovascular disease (CVD) and mortality over a 20-year period. In 2001–02, 3042 individuals from the Attica region of Greece were recruited randomly, and were stratified by subgroups of sex, age and region to reflect the general urban population in Athens, Greece. Validated NITs for hepatic steatosis (Hepatic Steatosis Index (HIS), Fatty Liver Index (FLI), Lipid Accumulation Product (LAP), NAFLD liver fat score (NAFLD-LFS)) and steatohepatitis (Index of non-alcoholic steatohepatitis (ION), aminotransferase-creatinine-clearance non-alcoholic steatohepatitis (acNASH)) were calculated. Incidence of diabetes, CVD and mortality were recorded 5, 10 and 20 years later. Within a 20-year observation period, the diabetes and CVD incidence was 26.3% and 36.1%, respectively. All hepatic steatosis and steatohepatitis NITs were independently associated with diabetes incidence. ION and acNASH presented independent association with CVD incidence [(Hazard Ratio (HR) per 1 standard deviation (SD) = 1.33, 95% Confidence Interval (95% CI) (1.07, 1.99)) and (HR per 1 SD = 1.77, 95% CI (1.05, 2.59)), respectively]. NAFLD-LFS which is a steatosis NIT indicating features of steatohepatitis, was linked with increased CVD mortality (HR per 1 SD = 1.35, 95% CI (1.00, 2.30)) and all-cause mortality (HR per 1 SD = 1.43, 95% CI (1.08, 2.01)). Overall, steatohepatitis NITs (i.e., ION and acNASH) presented stronger associations with the outcomes of interest compared with steatosis NITs. Clinically important trends were observed in relation to diabetes and CVD incidence progressively over time, i.e. 5, 10 and 20 years after baseline. Easily applicable and low-cost NITs representing steatohepatitis may be early predictors of diabetes and CVD onset. More importantly, these NITs increased the attributable risk conveyed by conventional CVD risk factors by 10%. Thus, their potential inclusion in clinical practice and guidelines should be studied further. [Display omitted] [ABSTRACT FROM AUTHOR]

The recently launched Food Compass Score (FCS) is a novel nutrient profiling system (NPS), which evaluates food and diet quality to assist in food choices and policy design. The Food compass score (FCS) is a holistic food score assessing 54 parameters. The aim of this study was, firstly, to evaluate the relation of FCS with inflammatory markers and secondly, to prospectively assess the relationship of FCS with the 20-year incidence of cardiovascular disease (CVD). Adults free-of-CVD from the ATTICA cohort study, with complete data for the calculation of FCS and incident CVD were included (n=759). C-reactive protein and amyloid A were determined by immunonephelometry, fibrinogen by nephelometry, homocysteine by fluorometry, while tumor necrosis factor-a (TNF-a), interleukin-6 (IL-6), adiponectin and leptin were determined by ELISA in fasting blood samples. Development of CVD was determined at 20 years after baseline (in 2022). Dietary intake was evaluated through a validated food frequency questionnaire. FCS was calculated for each participant based on the published values. Mean FCS was 56 (Standard deviation: 5.7). In multiple linear regression models, after adjusting for confounders, FCS was inversely associated with CRP (-0.03, 0.01), TNF-a (-0.04, 0.01), amyloid A (-0.10, 0.04) and homocysteine (-0.09, 0.04) (b coefficients, standard errors, all p-values<0.05). FCS was not associated with IL-6, fibrinogen, adiponectin, leptin nor lipids (total cholesterol, high density lipoprotein, low density lipoprotein, triacyclglycerols) in multivariate models (all p-values>0.05). Moreover, FCS was inversely associated with the 20-year CVD incidence [Hazard Ratio-HR for 20-year follow-up: 0.97] in multi-adjusted models. A diet containing higher quality foods, as evaluated by FCS, was associated with lower levels of inflammatory indices, as well as CVD risk in a cohort of apparently healthy adults prospectively studied for 20-years. Thus, FCS was proved to be a useful tool not only to evaluate dietary habits, but also inflammation and CVD risk. [ABSTRACT FROM AUTHOR]

• This was a retrospective study including 1241 individuals with dyslipidemia. • We investigated which factors increase type 2 diabetes risk in those who were statin-treated. • Atherogenic dyslipidemia was an independent risk factor for new-onset diabetes. • Prediabetes, obesity, and family history of diabetes remained risk factors in this group. To investigate which metabolic factors increase the risk of incident diabetes (T2D) in statin-treated patients. A retrospective study conducted in Greece including 1241 consecutive individuals with dyslipidemia attending a lipid clinic for ≥3 years. After defining associations with incident T2D, we assessed the risk of new-onset T2D based on the presence of impaired fasting glucose (IFG), atherogenic dyslipidemia, and overweight/obesity. After excluding 166 patients with baseline T2D and 193 subjects taking lipid-lowering therapy at the baseline visit, 882 participants were included in the study. Eleven percent (n = 94) developed T2D during their follow-up (median 6 years; IQR: 4–10). Baseline patients' age (OR: 1.05; 95% CI: 1.02–1.08, p < 0.01), family history of diabetes (OR: 3.58; 95% CI: 1.86–6.91, p < 0.01), IFG (OR: 6.56; 95% CI: 3.53–12.12, p < 0.01), overweight/obesity (OR: 2.65; 95% CI: 1.39–5.05, p < 0.01), atherogenic dyslipidemia (OR: 3.27; 95% CI: 1.50–7.15, p < 0.01), and treatment with high-intensity statins (OR: 3.51; 95% CI: 1.89–6.51, p < 0.01) were independently associated with increased risk of T2D in statin-treated patients. Among the IFG subjects, atherogenic dyslipidemia (OR: 3.44; 95% CI: 1.31–9.04, p = 0.01) and overweight/obesity (OR: 2.54; 95% CI: 1.14–5.66, p < 0.05) independently increased the risk of T2D. Among the overweight/obese ones, atherogenic dyslipidemia independently increased the risk of T2D (adjusted OR: 5.60; 95% CI: 2.19–14.30, p < 0.01). Atherogenic dyslipidemia appears to be an independent risk factor for new-onset T2D in statin-treated patients, while IFG, overweight/obesity and family history of diabetes remain risk factors for new-onset T2D in this group. [ABSTRACT FROM AUTHOR]

Background/purpose A reduction of cardiovascular events has been reported in phase 2 and 3 trials of the proprotein convertase subtilisin kexin 9 (PCSK9) inhibitors alirocumab and evolocumab. We aimed to investigate the effect PCSK9 inhibition on stroke risk in a meta-analysis involving data from randomized studies with alirocumab and evolocumab. Methods Data from pre-specified combined analysis of 4465 patients who completed phase 2 or 3 studies of evolocumab over a period of 1 year and a randomized trial on alirocumab including 2341 patients with hyperlipidemia on maximally tolerated statin who were at high risk for coronary heart disease over a period of 1.5 years were used. Results The number of patients having an ischemic stroke was small in both trials. PCSK9 inhibition showed no significant effect on stroke rate (risk ratio 1.43; 95% CI, 0.45–4.57, p = 0.55). No significant differences in stroke risk were evident when transient ischemic attacks were included in the analysis (risk ratio 0.65; 95% CI, 0.25–1.68, p = 0.37). No hemorrhagic strokes were reported in either study. Conclusion Although a benefit towards reduction of cardiovascular events in the overall has been documented, longer exposure is warranted to be able to evaluate the effect on stroke risk. [ABSTRACT FROM AUTHOR]

Objective To assess the correlation of Apolipoprotein B (Apo-B) with low-density (LDL-C) and non-high-density lipoprotein cholesterol (non-HDL-C) in untreated individuals attending a lipid clinic. Methods This was a retrospective study conducted in Greece and including 1000 dyslipidemic subjects. We included individuals not taking lipid-lowering therapy at baseline visit and divided them in 2 groups: subjects diagnosed with diabetes or fulfilling the criteria of metabolic syndrome (MetS) and hyperlipidemic subjects without diabetes or MetS. The correlations (r 2 ) of Apo-B with LDL-C and non-HDL-C were assessed in these 2 groups. Further analyses were performed according to the baseline triglyceride (TG) levels (

Objective To assess the risk of progression from normoglycemia or prediabetes to overt diabetes among individuals treated with statins alone or in combination with ezetimibe. Methods This was a retrospective study conducted in Greece including 877 subjects treated for dyslipidemia. We included individuals without overt diabetes at baseline and divided them in 2 subgroups according to their baseline fasting glucose: <100 (normal glucose) and 100 to 125 mg/dL (prediabetes). High and moderate-intensity statin therapy was defined according to the expected low-density lipoprotein cholesterol reduction (≥50% and 30 to <50%, respectively). We identified the predictors of incident diabetes and assessed the risk of new-onset diabetes among subgroups on various intensity statin or no statin treatment at all. Similar analyses were performed across different potency of statin monotherapy or combination of statin plus ezetimibe treatment. Results A total of 877 subjects were eligible and followed-up for a median of 7 years. There were no differences between statins regarding diabetes development. However, a higher risk of incident diabetes was observed in prediabetic individuals receiving high-intensity statin therapy compared with those on moderate intensity (adjusted odds ratio [OR] = 2.12, 95% confidence interval [CI] = 1.06–4.24, P < .05) and those not taking a statin (adjusted OR = 4.90; 95% CI = 1.16–20.66, P < .05). The addition of ezetimibe to statin treatment did not increase the risk of incident diabetes in prediabetic individuals (adjusted OR = 0.89; 95% CI = 0.36–2.22, P > .05). Baseline fasting glucose, presence of metabolic syndrome, family history of diabetes, and follow-up duration were independent predictors of new-onset diabetes. Conclusion High-intensity statin treatment is associated with a higher risk of incident diabetes in prediabetic individuals, whereas the addition of ezetimibe to statin therapy has a neutral effect on glucose metabolism. [ABSTRACT FROM AUTHOR]

Background Familial hypercholesterolemia (FH) is undoubtedly associated with premature coronary heart disease, but it is debatable whether FH increases the risk for stroke. Objective To meta-analyze available evidence regarding the incidence of stroke in individuals with heterozygous (He) FH. Methods We conducted a systematic review and a meta-analysis of epidemiological studies, including English-language publications until June 2015; four observational studies, with 3374 participants with HeFH, were included in the analysis. Cerebrovascular disease comprised of ischemic stroke or transient ischemic attack. Since studies did not include any control subjects, the corresponding general population of the same reference area and period of time for each HeFH study served as control group. Analyses were performed according to the period of time during which the studies were conducted: prestatin and statin era (before and after 1987 when lovastatin was launched). Results In the prestatin era, individuals with HeFH exhibited a higher risk for stroke compared with the general population [odds ratio (OR) = 7.658, 95% confidence interval (CI): 6.059–9.678, p < 0.01]. In contrast, FH subjects had a lower odds for stroke following the generalization of statin therapy (OR = 0.251, 95% CI: 0.176–0.358, p < 0.01). Conclusions Taking into account the small number of studies and methodological issues, HeFH was associated with a higher risk of cerebrovascular disease compared with the general population in the prestatin era, which was significantly reduced after the introduction of statin therapy. [ABSTRACT FROM AUTHOR]

Background: Recent evidence indicates that treatment with sodium-glucose cotransporter-2 inhibitors (SGLT2i) may favorably affect the risk of stroke in patients with type 2 diabetes mellitus (T2DM) and chronic kidney disease.Objectives: This meta-analysis considered data from cardiovascular outcome trials (CVOTs) regarding the effect of SGLT2i treatment on stroke risk in T2DM patients with an emphasis on patients with impaired renal function.Selection Criteria: Double-blind randomized trials (RCTs) representing CVOTs were included if they compared SGLT2i add-on therapy with placebo, and reported stroke among primary or secondary endpoints.Results: Six eligible multicenter RCTs were included. The pooled analysis of 5 RCTs (n = 40,393) showed a neutral effect on the risk of total stroke from treatment with SGLT2i vs. placebo (hazard ratio, HR 0.90, 95% CI: 0.74-1.09, p = 0.29, I2 = 58%). Subgroup analysis (4 RCTs) involving patients with impaired renal function (n = 17,072) demonstrated a significant benefit in favor of SGLT2i (HR: 0.66, 95% CI: 0.54-0.82, p<0.0001, I2 = 8%). The pooled analysis of 2 RCTs (n = 14,543) showed a significant reduction in the risk of hemorrhagic stroke in T2DM patients (HR: 0.46, 95% CI: 0.25-0.83, p = 0.01; I2 = 0). No differences were noticed regarding the risk of ischemic stroke (HR: 0.97, 95% CI: 0.85-1.12, p = 0.69; I2 = 0), non-fatal stroke (HR: 0.98, 95% CI: 0.83-1.16, p = 0.79, I2 = 28%), and fatal stroke (HR: 0.77, 95% CI: 0.50-1.17, p = 0.22, I2 = 0).Conclusions: Available data suggest that SGLT2i reduce the risk of total stroke in patients with T2DM and impaired renal function. Based on the findings of two RCTs, these drugs may offer a protection against hemorrhagic stroke. [ABSTRACT FROM AUTHOR]

Statins and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors interfere with several pathophysiological pathways of coronavirus disease 2019 (COVID-19). Statins may have a direct antiviral effect on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by inhibiting its main protease. Statin-induced up-regulation of angiotensin-converting enzyme 2 (ACE2) may also be beneficial, whereas cholesterol reduction might significantly suppress SARS-CoV-2 by either blocking its host-cell entry through the disruption of lipid rafts or by inhibiting its replication. Available human studies have shown beneficial effects of statins and PCSK9 inhibitors on pneumonia and sepsis. These drugs may act as immunomodulators in COVID-19 and protect against major complications, such as acute respiratory distress syndrome and cytokine release syndrome. Considering their antioxidative, anti-arrhythmic, antithrombotic properties and their beneficial effect on endothelial dysfunction, along with the increased risk of mortality of patients at high cardiovascular risk infected by SARS-CoV-2, statins and PCSK9 inhibitors might prove effective against the cardiovascular and thromboembolic complications of COVID-19. On the whole, randomized clinical trials are needed to establish routine use of statins and PCSK9 inhibitors in the treatment of SARS-CoV-2 infection. In the meantime, it is recommended that lipid-lowering therapy should not be discontinued in COVID-19 patients unless otherwise indicated. [ABSTRACT FROM AUTHOR]

Increased adiposity predisposes to cardiovascular disease (CVD). We hypothesized that the presence of obesity would be positively associated with CVD risk, and that the co-presence of central obesity would modify/enhance this association. This was a prospective study (2002–2022) among 1845 Greek adults (mean age, 44.8 ± 13.5 years; men, 49.8%). At baseline, the presence of overweight/obesity was assessed via body mass index (BMI), whereas central obesity was defined as waist circumference ≥102/88 cm, waist-to-hip-ratio ≥0.95/0.80, or waist-to-height-ratio ≥0.50 in men/women. BMI was reevaluated at 10 years and longitudinal BMI trajectories (2002–2012) were identified. CVD incidence was recorded at 20 years (ratio of new cases to the number of participants assessed). Compared with participants with normal weight at baseline, those with obesity exhibited a 27% higher 20-year CVD risk after adjustment for age, sex, lifestyle habits, and medical status (hazard ratio, 1.271; 95% confidence interval, 1.012–1.597). In similar multiadjusted models, compared with participants who were always non-overweight/obese, those who were always overweight/obese exhibited a 40% higher 20-year CVD risk (hazard ratio, 1.403; 95% confidence interval, 1.018–1.936). Additional control for high-sensitivity C-reactive protein attenuated the associations. In the combined baseline body weight classification analysis, CVD incidence was the lowest in participants with normal weight without central obesity, moderate in those with overweight/obesity without central obesity, and highest in those with normal weight and central obesity and overweight/obesity and central obesity (P <.001). Obesity leads to increased CVD risk, partly mediated by inflammation. The combination of BMI with simple measures of abdominal adiposity is superior for CVD risk screening. In a sample of 1845 healthy Greek adults, compared with subjects with normal weight at baseline, those with obesity exhibited a ∼2 times higher 20-year CVD risk, partly mediated by inflammation. When baseline general and central adiposity measures were combined, CVD risk was significantly higher for subjects with central obesity, even those in the normal range of BMI, indicating the superiority of their combination for CVD risk screening. Abbreviations: BMI, body mass index; CVD, cardiovascular disease; WC, waist circumference; WHR, waist-to-hip ratio; WHtR, waist-to-height ratio. [Display omitted] [ABSTRACT FROM AUTHOR]

We aimed to predict lifetime risk for cardiovascular disease (CVD). The sample consisted of 1988 participants with complete CVD data during the 20-year follow-up (50% men, 45 ± 14 years) of the ATTICA study. Lifetime risk for CVD was predicted at specific index ages (40, 50, and 60 years), based on the life-table method, with death free-of-CVD treated as a competing event. 718 participants experienced a fatal or nonfatal CVD event, corresponding to a crude CVD incidence of 36.1% (men: 40.2%, women: 32.1%, P -value <.001). Overall, women and men had similar lifetime CVD risk (P -value =.245); at index age of 40, the lifetime risk for CVD was 68% for men and 63% for women, with a progressive decline to 56% and 50% at the index age of 50, and to 55% for both men and women, at the index age of 60 years, respectively. These results on lifetime risk for CVD can guide the allocation of resources to improve public health and preventive services, especially in ages below 50 years, in both men and women. [Display omitted] [ABSTRACT FROM AUTHOR]

Meat consumption has shown from detrimental to beneficial effects against cardiovascular disease (CVD) incidence, mainly depending on the type of meat studied (i.e., red/white, processed/unprocessed) and quantity consumed. To examine the associations between meat type consumption patterns and incident CVD among apparently healthy adults. ATTICA study was conducted in the greater metropolitan Athens area, Greece, during 2001–2002 studying adults free-of-CVD at baseline. Twenty-year follow-up was performed in n = 1988 participants (n = 718 incident cases). Meat consumption during the follow-up period was categorized as: never/rare meat consumption (i.e., <1 time/week), mostly red meat (i.e., compared to other types of meat or processed meat), mostly white meat, and mostly processed meat products (e.g., bacon, sausage). Approximately 38% of the participants reported rare or no consumption of any type of meat, 31% consumed mostly red meat, 19% mostly white meat and the remainder 12% mostly processed meat. In multivariate analysis, compared to never/rarely consuming any type of meat, consuming mostly processed meat [HR: 2.89, 95%CI: 1.05, 7.89], but not red meat [HR: 1.22, 95%CI: 0.81, 1.82], was positively associated with incident CVD during 20 years of follow-up, while consuming mostly white meat was inversely associated with incident CVD [HR: 0.35, 95%CI: 0.17, 0.71]. The findings of this study suggest that the type of meat, irrespective of the frequency of consumption, plays a role in the risk of developing CVD. In clinical practice, emphasis should be placed on avoiding processed meat and replacing it with white unprocessed meat. [ABSTRACT FROM AUTHOR]