Implementation of a cardiogenic shock team in a tertiary academic center.

OBJECTIVE: Observational studies have shown that the management of patients with cardiogenic shock (CS) by dedicated multidisciplinary teams improves clinical outcomes. Nevertheless, these studies reflect a specific organizational setting with most patients being transferred from referring hospitals, hospitalized in cardiac intensive care units (ICU), or treated with mechanical circulatory support (MCS) devices. The purpose of this study was to document the organization and outcomes of a CS team offering acute care in an all-comer population. METHODS: A CS team was developed in a large academic tertiary institution. The team consisted of emergency care physicians, critical care cardiologists, interventional cardiologists, cardiac surgeons, ICU physicians, and heart failure specialists and was supported by a predefined operating protocol, a dedicated communication platform, and regular team meetings. RESULTS: Over 12 months, 70 CS patients (69 ± 13 years old, 67% males) were included. Acute myocardial infarction (AMI-CS) was the most common cause (64%); 31% of the patients presented post-resuscitated cardiac arrest and 56% needed invasive mechanical ventilation (IMV). Coronary angiography was performed in 70% and 53% had percutaneous coronary intervention. MCS was used in 10% and 6% were referred for urgent cardiac surgery. The in-hospital mortality in our center was 40% with 39% of the patients dying within 24 h from presentation. Overall, 76% of the live patients were discharged home. CONCLUSION: Across an all-comer population, AMI was the most common cause of CS. A significant number of patients presented post-cardiac arrest, and the majority required IMV. Mortality was high with a significant number dying within hours of presentation.

Transoesophageal echocardiography beyond the echo-laboratory. An expert consensus paper of the working group of echocardiography of the hellenic society of cardiology.

Transoesophageal echocardiography (TOE) is a well-established and valid imaging modality, providing more accurate and of higher quality information than transthoracic echocardiography (TTE) for several specific diagnoses and recently a useful guide of an increasing number of catheter-based and surgical interventions. The present paper represents an effort by the Echocardiography Working Group (WG) of the Hellenic Society of Cardiology to state the essential steps of the TOE exam performed beyond the echo lab: a) in the operating rooms intraoperatively during either transcatheter interventions, or cardiothoracic surgery and b) in the intensive care unit for critically ill patients' monitoring. This paper includes information and tips and tricks about the pre-procedural evaluation, the procedural echocardiographic guidance, and post-procedural evaluation of the result and potential complications.

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.

Gender Differences Among Very Young Patients With Acute Coronary Syndrome: Long-Term Follow-Up of the STAMINA Study.

The rate of hospitalization for acute coronary syndrome (ACS) among young patients is increasing. Healthcare disparities remain unsolved among female patients. We explored gender differences regarding risk factors, clinical presentation, in-hospital treatment, and long-term outcomes among ACS patients. A total of 445 patients with very early ACS (men ≤ 35 years and women ≤ 40 years of age) were followed for a median of 5 years. Primary clinical endpoint was the composite of cardiac death, non-fatal myocardial infarction, stroke, and coronary revascularization. Women accounted for 16% of cases. Smoking was the most prevalent risk factor, 56% and 60% of the females and males, respectively, continued to smoke after ACS. Chest pain was typical in 85% and 83% of the female and male patients, respectively. In-hospital treatment (pharmacological and reperfusion) as well as the composite clinical endpoint during follow-up did not differ between female and male patients. Lipid-lowering therapy was suboptimal in both genders, and persistence of smoking was the sole predictor for the composite clinical endpoint (hazard ratio: 2.30 [95% CI: 1.26-4.20]; P = .007). In conclusion, in-hospital treatment was similar between male and female patients. However, the majority of them continued smoking, and this was an independent predictor for future adverse outcomes.

Emergent Inflammatory Markers and Echocardiographic Indices in Patients with Bronchial Asthma.

Asthma is a heterogeneous disease, characterized by chronic inflammation and oxidative stress of the airways. Several inflammatory pathways including activation of the receptor for advanced glycation end products (RAGE) have been described in the course of the disease. DJ-1 is a redox-sensitive protein with multifaceted roles in mast cell homeostasis and an emerging role in the pathogenesis of asthma. Moreover, cardiac function abnormalities have been described via echocardiography in patients with asthma. The main aim of this study was to investigate the plasma levels of RAGE, its ligands and DJ-1 in asthmatic patients pre- and post-treatment along with echocardiographic indices of cardiovascular function. The study population was divided into two groups. Group A included 13 patients with newly diagnosed bronchial asthma who were free of treatment for at least two weeks and Group B included 12 patients without asthma. An echocardiography examination was performed on all patients. The plasma levels of RAGE, its ligands (AGEs, S100A12, S100B, S100A8/A9), the interleukins (IL-6, IL-1ß) and DJ-1 were measured. No differences were noted among the two groups for baseline characteristics and echocardiographic indices of cardiac function. In Group A, 31% suffered from mild asthma, 54% from moderate asthma and 15% from severe asthma. Plasma levels of IL-6, AGEs and AGE/RAGE ratio were increased and those of S100A12 and DJ-1 were decreased in asthmatics. Pharmacotherapy with corticosteroids/ß2-agonists decreased IL-6, and AGEs, and increased DJ-1. In search of novel approaches in diagnosing and treating patients with asthma, S100A12, ratio AGE/sRAGE, and DJ-1 in addition to IL-6 may prove to be useful tools.

Emerging markers of inflammation and oxidative stress as potential predictors of coronary artery disease.

BACKGROUND AND AIMS: The multi-ligand receptor for advanced glycation end products (RAGE) and its ligands AGEs and S100/calgranulin proteins are important mediators of inflammation and oxidative stress whereas the soluble form of RAGE (sRAGE) by acting as a decoy and the antioxidant PARK7/DJ-1 exert antiatherogenic effects. We examined whether sRAGE and its ligands AGEs, S100A8/A9, S100B, S100A12 and DJ-1 are associated with the presence of angiographic coronary artery disease (CAD) in asymptomatic patients with and without diabetes. METHODS AND RESULTS: Plasma levels of RAGE ligands, sRAGE and DJ-1 were determined in 50 patients with angiographically proven CAD and in 50 age-matched healthy controls. In the whole cohort, lower levels of sRAGE and higher levels of interleukin-6 (IL-6), the RAGE ligands S100B, S100A12 and the AGEs/sRAGE ratio were associated with CAD. In patients without diabetes (n = 72), lower levels of sRAGE and DJ-1 and higher levels of IL-6 and AGEs/sRAGE ratio were associated with CAD. In multivariable analysis, AGEs/sRAGE ratio was an independent predictor of CAD both in the whole cohort (p = 0.034, OR = 1.247, [95%CI: 1.024, 1.0519]) and in the subgroup of patients without diabetes (p = 0.021, OR = 1.363, 95%CI [1.048, 1.771]) on top of established cardiovascular risk factors. CONCLUSION: Alterations in plasma RAGE axis inflammatory mediators are associated with atherosclerosis, and higher levels of AGEs/sRAGE ratio are independently associated with CAD in asymptomatic patients and may act as a novel biomarker for predicting CAD. DJ-1 emerges as promising marker of oxidative stress in CAD patients without diabetes, a finding that deserves further study.

Risk for Arterial Thromboembolic Events (ATEs) in Patients with Advanced Urinary Tract Cancer (aUTC) Treated with First-Line Chemotherapy: Single-Center, Observational Study.

Arterial thromboembolism has been associated with cancer or its treatment. Unlike venous thromboembolism, the incidence and risk factors have not been extensively studied. Here, we investigated the incidence of arterial thromboembolic events (ATEs) in an institutional series of advanced urinary tract cancer (aUTC) treated with cytotoxic chemotherapy. The ATE definition included peripheral arterial embolism/thrombosis, ischemic stroke and coronary events. A total of 354 aUTC patients were analyzed. Most patients (95.2%) received platinum-based chemotherapy. A total of 12 patients (3.4%) suffered an ATE within a median time of 3.6 months from the start of chemotherapy. The most frequent ATE was ischemic stroke (n = 7). Two ATEs were fatal. The 6-month and 24-month incidence were 2.1% (95% confidence interval [CI]: 0.9-4.1) and 3.6% (95% CI: 1.9-6.2), respectively. Perioperative chemotherapy increased the risk for ATE by 5.55-fold. Tumors other than UTC and pure non-transitional cell carcinoma histology were also independent risk factors. No association with the type of chemotherapy was found. Overall, ATEs occur in 4.6% of aUTC patients treated with chemotherapy and represent a clinically relevant manifestation. Perioperative chemotherapy significantly increases the risk for ATE. The role of prophylaxis in high-risk groups should be prospectively studied.

Causes, Angiographic Characteristics, and Management of Premature Myocardial Infarction: JACC State-of-the-Art Review.

Among patients presenting with acute myocardial infarction (AMI), the proportion of young individuals has increased in recent years. Although coronary atherosclerosis is less extensive in young patients with AMI, with higher prevalence of single-vessel disease and rare left main involvement, the long-term prognosis is not benign. Young patients with AMI with obstructive coronary artery disease have similar risk factors as older patients except for higher prevalence of smoking, lipid disorders, and family history of premature coronary artery disease, and lower prevalence of diabetes mellitus and hypertension. Smoking cessation is by far the most effective secondary preventive measure. Myocardial infarction with nonobstructive coronary arteries is a relatively common clinical entity (10%-20%) among young patients with AMI, with intravascular and cardiac magnetic resonance imaging being key for diagnosis and potentially treatment. Spontaneous coronary artery dissection is a frequent pathogenetic mechanism of AMI among young women, requiring a high degree of suspicion, especially in the peripartum period.

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.

ST-elevation myocardial infarction in a 39-year-old patient with "normal" coronary arteries as a thrombotic complication of COVID-19.

We report the case of a 39-year-old male without traditional risk factors for coronary artery disease (CAD), i.e. smoking, hypercholesterolemia, hypertension, diabetes mellitus, familial history of premature CAD, admitted with anterior ST-segment elevation myocardial infarction and concurrent coronavirus disease-2019 infection. Coronary angiography showed high intracoronary thrombus burden and thrombotic occlusion of the proximal segment of left anterior descending artery, while optical coherence tomography revealed intact endothelium after thromboaspiration.

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.

Differential prognostic value of resistin for cardiac death in patients with coronary artery disease according to the presence of metabolic syndrome.

Resistin is associated with atherosclerosis progression by affecting inflammation and insulin resistance. There are controversial data regarding the prognostic value of resistin in stable coronary artery disease (CAD) patients. We prospectively investigated the long-term prognostic value of resistin in patients with stable CAD. A total 741 consecutive patients with stable CAD were followed for a median of 5.5 years. Serum resistin, lipids, high-sensitivity C-reactive protein (hsCRP) and interleukin-6 (IL-6) levels were measured at baseline. Primary endpoints were cardiac death and secondary hospitalizations for acute coronary syndrome, arrhythmic event or ischemic stroke. Follow-up data were obtained from 703 patients of whom 79 had a cardiac death (11.2%) and 205 (29.2%) met the secondary endpoints. Resistin was positively correlated with hsCRP (r = 0.159, p < 0.001) and IL-6 (r = 0.165, p = 0.002), and negatively with high-density lipoprotein-cholesterol (r = - 0.176, p < 0.001). Resistin levels could not predict cardiac death [HR 1.044; 95% CI 0.994-1.096; p = 0.087] neither secondary endpoints [HR 1.025; 95% CI 0.983-1.068; p = 0.250). Among 298 patients (42.4%) with metabolic syndrome (MS) resistin levels were independently associated with cardiac death after adjustment for conventional risk factors [HR 1.121; 95% CI 1.045-1.204; p = 0.002). Further adjustment for ejection fraction of left ventricle (LVEF) did not change the association (HR 1.145; 95% CI 1.057-1.240; p = 0.001). Patients with resistin values ≥ 7.6 ng/mL (median level) had 2.8 times higher risk of cardiac death compared to those with resistin levels < 7.6 ng/mL after adjustment for traditional risk factors and LVEF (HR 2.882; 95% CI 1.311-6.336; p = 0.008). Resistin is independently associated with cardiac death in patients with stable CAD and MS.

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.

Differential Regulation of Circulating Soluble Receptor for Advanced Glycation End Products (sRAGEs) and Its Ligands S100A8/A9 Four Weeks Post an Exercise Intervention in a Cohort of Young Army Recruits.

Apart from its beneficial effects on cardiovascular risk factors, an anti-inflammatory effect of exercise is strongly implicated. Yet, data regarding the effect of an exercise intervention on healthy individuals are limited and contradictory. The present study aimed to investigate the effects of a physical activity intervention on the soluble form of the receptor for advanced glycation end products (sRAGEs) and its ligands S100A8/A9. A total of 332 young army recruits volunteered and 169 completed the study. The participants underwent the standard basic training of Greek army recruits. IL-6, IL-1ß, S100A8/A9, and sRAGEs were measured at the beginning and at the end of the training period. Primary rodent adult aortic smooth muscle cells (ASMCs) were analyzed for responsiveness to direct stimulation with S100A8/A9 alone or in combination with sRAGEs. At the end of the training period, we observed a statistically significant reduction in S100A8/A9 (630.98 vs. 472.12 ng/mL, p = 0.001), IL-1ß (9.39 [3.8, 44.14] vs. 5.03 [2.44, 27.3] vs. pg/mL, p = 0.001), and sRAGEs (398.38 vs. 220.1 pg/mL, p = 0.001). IL-6 values did not change significantly after exercise. S100A8/A9 reduction was positively correlated with body weight (r = 0.236 [0.095, 0.370], p = 0.002) and BMI (r = 0.221 [0.092, 0.346], p = 0.004). Direct stimulation of ASMCs with S100A8/A9 increased the expression of IL-6, IL-1ß, and TNF-α and, in the presence of sRAGEs, demonstrated a dose-dependent inhibition. A 4-week military training resulted in significant reduction in the pro-inflammatory cytokines IL-1ß and S100A8/A9 complex. The observed reduction in sRAGEs may possibly reflect diminished RAGE axis activation. Altogether, our findings support the anti-inflammatory properties of physical activity.

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.

The value of physical signs in identifying patients with familial hypercholesterolemia in the era of genetic testing.

Familial hypercholesterolemia (FH) is a common, inherited disorder of cholesterol metabolism characterized by very high plasma concentrations of low-density lipoprotein cholesterol. It is crucial to diagnose and treat this disorder early since if left untreated it increases the risk for coronary artery disease (CAD) at least by 10-fold. Although genetic testing for FH, when available and affordable, should ideally be offered to most individuals with clinical phenotype suggestive of FH, it is underutilized in most countries. Therefore, FH diagnosis in the majority of cases is made by combining cholesterol levels and clinical characteristics of the patient leaving the need for genetic testing usually in equivocal cases. The presence of some cutaneous and ocular signs can raise the suspicion or even lead to the diagnosis of FH among usually "healthy" individuals. These physical signs comprise cutaneous lesions such as tendon xanthomas or the less specific xanthelasmata and ocular signs, such as corneal arcus in individuals under the age of 45 years. The presence of these signs should prompt the physician to request lipid tests and use clinical scores to diagnose FH. If the diagnosis of FH is likely, aggressive lipid-lowering therapy should be initiated to reduce the risk of CAD and a cascade screening of family members should also be requested.

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.