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High-Density Lipoprotein cholesterol (HDL-C) levels do not correlate well with Coronary Artery Disease (CAD) risk, while HDL functionality affects atherogenesis and is a better prognostic marker for CAD. Often, the extreme HDL-C levels have a multigenic origin. Here, we searched for single-nucleotide polymorphisms (SNPs) in ten genes of HDL metabolism in a Greek cohort with very low (<10th percentile, n = 13) or very high (>90th percentile, n = 21) HDL-C. We also evaluated the association between HDL-C levels, HDL functionality (anti-oxidant capacity) and CAD in the subjects of this cohort. Individuals with low HDL-C levels had higher triglyceride levels, lower apoA-I levels, decreased HDL anti-oxidant capacity and higher incidence of CAD compared with individuals with control or high HDL-C levels. With next generation sequencing we identified 18 exonic SNPs in 6 genes of HDL metabolism and for selected amino acid changes we performed computer-aided structural analysis and modeling. A previously uncharacterized rare apolipoprotein A-IV variant, apoA-IV [V336M], present in a subject with low HDL-C (14 mg/dL) and CAD, was expressed in recombinant form and structurally and functionally characterized. ApoA-IV [V336M] had similar α-helical content to WT apoA-IV but displayed a small thermodynamic stabilization by chemical unfolding analysis. ApoA-IV [V336M] was able to associate with phospholipids but presented reduced kinetics compared to WT apoA-IV. Overall, we identified a rare apoA-IV variant in a subject with low HDL levels and CAD with altered biophysical and phospholipid binding properties and showed that subjects with very low HDL-C presented with HDL dysfunction and higher incidence of CAD in a Greek cohort.
Assuntos
Apolipoproteínas A/genética , HDL-Colesterol/metabolismo , Doença da Artéria Coronariana/genética , Doença da Artéria Coronariana/metabolismo , Lipoproteínas HDL/metabolismo , Adulto , Apolipoproteínas A/química , Arildialquilfosfatase/metabolismo , Estudos de Coortes , Feminino , Grécia , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Moleculares , Polimorfismo de Nucleotídeo ÚnicoRESUMO
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.
Assuntos
Anticolesterolemiantes/uso terapêutico , Técnicas de Química Analítica/métodos , LDL-Colesterol/sangue , Hiperlipoproteinemia Tipo II/sangue , Lipoproteína(a)/sangue , Sistema de Registros , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Feminino , Grécia , Humanos , Hiperlipoproteinemia Tipo II/tratamento farmacológico , Hipolipemiantes/uso terapêutico , Masculino , Pessoa de Meia-IdadeRESUMO
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.
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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.
Assuntos
Aterosclerose , Heterozigoto , Hiperlipoproteinemia Tipo II , Obesidade , Sistema de Registros , Humanos , Feminino , Masculino , Hiperlipoproteinemia Tipo II/complicações , Hiperlipoproteinemia Tipo II/epidemiologia , Hiperlipoproteinemia Tipo II/genética , Pessoa de Meia-Idade , Obesidade/complicações , Obesidade/epidemiologia , Aterosclerose/epidemiologia , Aterosclerose/complicações , Adulto , Índice de Massa Corporal , Fatores de Risco , Prevalência , IdosoRESUMO
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 â=â2156, mean age 50â±â15âyears, 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 45âyears was 6.6%, tendon xanthomas 5.3%, and xanthelasmas 5.8%. Among physical signs, only the presence of corneal arcus before the age of 45âyears 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 45âyears is independently associated with premature CAD.
Assuntos
Arco Senil , Aterosclerose , Doenças Cardiovasculares , Doença da Artéria Coronariana , Hipercolesterolemia , Hiperlipoproteinemia Tipo II , Xantomatose , Adulto , Humanos , Feminino , Pessoa de Meia-Idade , Idoso , Masculino , Doenças Cardiovasculares/epidemiologia , Arco Senil/diagnóstico , Arco Senil/epidemiologia , Arco Senil/etiologia , Heterozigoto , Hiperlipoproteinemia Tipo II/complicações , Hiperlipoproteinemia Tipo II/diagnóstico , Hiperlipoproteinemia Tipo II/tratamento farmacológico , Aterosclerose/epidemiologia , Hipercolesterolemia/complicações , Doença da Artéria Coronariana/etiologia , Doença da Artéria Coronariana/complicações , Lipídeos , Sistema de Registros , Xantomatose/etiologia , Xantomatose/complicaçõesRESUMO
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.
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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.
Assuntos
Aterosclerose , Doenças Cardiovasculares , Hiperlipoproteinemia Tipo II , Adulto , Aterosclerose/epidemiologia , Aterosclerose/etiologia , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Estudos Transversais , Feminino , Humanos , Hiperlipoproteinemia Tipo II/complicações , Hiperlipoproteinemia Tipo II/epidemiologia , Lipoproteína(a) , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Adulto JovemRESUMO
Hyperhomocysteinemia has been established as a risk factor for cardiovascular events. This case of a 23-year-old male, presenting with acute coronary thrombosis and unremarkable past medical history, highlights the importance of measuring homocysteine levels in young individuals with acute coronary syndromes, especially those without conventional risk factors.
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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.
Assuntos
Anticolesterolemiantes , Inibidores de Hidroximetilglutaril-CoA Redutases , Hiperlipoproteinemia Tipo II , Adulto , Idoso , Anticolesterolemiantes/uso terapêutico , LDL-Colesterol , Ezetimiba/uso terapêutico , Humanos , Hiperlipoproteinemia Tipo II/diagnóstico , Hiperlipoproteinemia Tipo II/tratamento farmacológico , Lipídeos , Pessoa de Meia-Idade , Pró-Proteína Convertase 9RESUMO
BACKGROUND: Homocysteine (Hcy) is considered a risk factor for cardiovascular disease. OBJECTIVE: To explore the long-term prognostic value of Hcy in patients with stable coronary artery disease (CAD) in the era of statins. METHODS: A total of 876 consecutive patients with stable CAD were recruited and followed up for a median of 6.1 years. Lipids and Hcy levels were measured at baseline. Primary endpoints were cardiac death and secondary endpoints were hospitalizations for acute coronary syndrome, myocardial revascularization, arrhythmic event or ischemic stroke. RESULTS: Follow-up data were obtained from 842 patients of whom 70 had a cardiac death (8.3%), while 258 (30.6%) met the secondary endpoints. Seven hundred four patients (83.6%) were on statins. In univariate Cox regression analysis Hcy predicted the occurrence of cardiac death [hazard ratio: 1.030; 95% confidence interval (CI): 1.018-1.042, P < 0.001] but not the occurrence of secondary endpoints (hazard ratio: 1.010; 95% CI: 0.999-1.020, P = 0.081). Hcy remained an independent predictor of cardiac death after adjustment for conventional risk factors, ejection fraction and statin use (hazard ratio: 1.030; 95% CI: 1.017-1.044, P < 0.001). Patients in the highest tertile of Hcy levels (>14.1 µmol/L) had three times higher risk of cardiac death compared with patients in the lowest tertile (<10.3 µmol/L) (hazard ratio = 3.036, CI: 1.983-4.649, P < 0.001). CONCLUSION: Hcy is an independent predictor of cardiac death in patients with stable CAD in the era of statins.
Assuntos
Doenças Cardiovasculares/mortalidade , Doença da Artéria Coronariana/sangue , Estenose Coronária/sangue , Homocisteína/sangue , Hiper-Homocisteinemia/epidemiologia , Síndrome Coronariana Aguda/epidemiologia , Idoso , Arritmias Cardíacas/epidemiologia , LDL-Colesterol/sangue , Feminino , Grécia/epidemiologia , Hospitalização/estatística & dados numéricos , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hiper-Homocisteinemia/sangue , AVC Isquêmico/epidemiologia , Masculino , Pessoa de Meia-Idade , Revascularização Miocárdica/estatística & dados numéricos , Prognóstico , Modelos de Riscos Proporcionais , Sistema de RegistrosRESUMO
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.
Assuntos
Inibidores de Hidroximetilglutaril-CoA Redutases , Hipercolesterolemia , Hiperlipoproteinemia Tipo II , LDL-Colesterol , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hipercolesterolemia/tratamento farmacológico , Pró-Proteína Convertase 9RESUMO
BACKGROUND: Heterozygous familial hypercholesterolemia (HeFH) and combined hyperlipidemia (CHL) phenotype are associated with premature myocardial infarction (MI). OBJECTIVE: To assess the prevalence of HeFH and CHL phenotype among young survivors of MI and compare patients' characteristics with these 2 lipid disorders. METHODS: We recruited 382 young survivors of MI (≤40 years). Fasting lipids, lipoprotein(a) [Lp(a)], apolipoprotein A-1, and apolipoprotein B (apoB) levels were determined. Using the Dutch Lipid Clinic Network (DLCN) algorithm, patients having definite or probable HeFH were identified. Patients with apoB levels >120 mg/dL and triglyceride levels >170 mg/dL (1.92 mmol/L) [>90th percentile of 326 age and sex-matched healthy controls] were classified as having CHL phenotype. Common carotid artery intima-media thickness (CCA-IMT) was measured by B-mode ultrasonography. RESULTS: Eighty-one patients (21.2%) had definite/probable HeFH and 62 (16.2%) had CHL phenotype. Twenty-three patients fulfilled the criteria for both HeFH and CHL phenotype and were removed from further comparisons. Patients with HeFH (n = 58) had higher levels of total cholesterol, low-density lipoprotein (LDL)-cholesterol, Lp(a), and apoB, whereas patients with CHL phenotype (n = 39) had higher levels of triglycerides and lower high-density lipoprotein (HDL)-cholesterol levels. The prevalence of metabolic syndrome was higher in patients with CHL phenotype compared to those with HeFH (67.0% vs 16.4%, P < .001). Patients with HeFH had more extensive coronary artery disease (3-vessel disease: 36.2% vs 12.8%, P = .011) and greater right CCA-IMT (0.67 ± 0.11 mm vs 0.56 ± 0.09 mm, P < .001) and left CCA-IMT (0.68 ± 0.10 mm vs 0.56 ± 0.08 mm, P < .001) compared to CHL phenotype patients. CONCLUSIONS: Both HeFH and CHL phenotype are common among patients with premature MI. CHL phenotype compared to HeFH is associated with less atheromatous burden in coronary and carotid arteries at the time of first MI.
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Doenças das Artérias Carótidas/complicações , Heterozigoto , Hiperlipoproteinemia Tipo II/complicações , Hiperlipoproteinemia Tipo II/epidemiologia , Infarto do Miocárdio/complicações , Fenótipo , Adulto , Feminino , Humanos , Hiperlipoproteinemia Tipo II/sangue , Hiperlipoproteinemia Tipo II/genética , Lipídeos/sangue , Masculino , PrevalênciaRESUMO
BACKGROUND AND AIMS: The latest guidelines from the American Association of Clinical Endocrinologists (AACE) and the American College of Endocrinology (ACE) proposed a new "extreme-risk" category of patients, for whom a low-density lipoprotein cholesterol (LDL-C) level <55â¯mg/dL (1.4â¯mmol/L) is advised. We aimed to identify the proportion of patients with stable coronary artery disease (CAD), who are at extreme cardiovascular (CV) risk, and explore how achievable is the new LDL-C goal. METHODS: We enrolled 1629 consecutive patients ≤80 years with stable CAD. Fasting lipids were determined and patients having probable or definite heterozygous familial hypercholesterolaemia (HeFH) were identified using the Dutch Lipid Clinic Network algorithm. RESULTS: The prevalence of risk factors/characteristics suggesting an extreme CV risk were as follows: 32% diabetes mellitus, 33% premature CAD and 9.2% HeFH. In total, 895 (55%) patients had at least one of those risk factors/characteristics and formed the extreme CV risk category. Among patients at extreme risk, 87% were on lipid-lowering therapy, of whom 20.3% had LDL-C <70â¯mg/dL (1.8â¯mmol/L) and only 5.3% had LDL-C <55â¯mg/dL. CONCLUSIONS: More than half of all patients with stable CAD are at extreme CV risk and very few (â¼5%) achieve LDL-C levels <55â¯mg/dL. Using maximally-tolerated high-intensity statin combined with ezetimibe, if necessary, is imperative to bridge the treatment gap, while in selected cases the addition of PCSK9 inhibitors will be required.