Management of lipid variables in primary cardiovascular prevention: A position paper from the Heart, Vessels and Metabolism Group of the French Society of Cardiology.

Low-density lipoprotein cholesterol has been established as a powerful cardiovascular risk factor; its reduction provides a clinical benefit in primary cardiovascular prevention, irrespective of the characteristics of the patients treated. It is useful to tailor low-density lipoprotein cholesterol targets according to the magnitude of cardiovascular risk (low, high or very high) in order to reduce the cardiovascular risk as fully as possible. In order to provide a uniform approach, it is necessary to propose recommendations for good practice, defining strategies for reducing low-density lipoprotein cholesterol. It is also necessary to know their merits, to analyse their practical limits and to propose adaptations, taking into account limitations and national specifics. This position paper aims to analyse the contribution and limits, as well as the adaptation to French practice, of 2019 and 2021 European Society of Cardiology recommendations for the management of lipid variables and cardiovascular prevention.

Evinacumab and Cardiovascular Outcome in Patients With Homozygous Familial Hypercholesterolemia.

BACKGROUND: Patients with homozygous familial hypercholesterolemia (HoFH) remain at very high cardiovascular risk despite the best standard of care lipid-lowering treatment. The addition of evinacumab, an angiopoietin-like protein 3 monoclonal antibody, more than halves low-density lipoprotein cholesterol in short-term studies. This study evaluated whether the evinacumab response was durable in the long term and improved cardiovascular outcome. METHODS: The OLE ELIPSE HoFH (Open-Label Extension to Evinacumab Lipid Studies in Patients With HoFH) study included newly diagnosed patients and those completing the ELIPSE HoFH trial, on stable lipid-lowering therapy including lipoprotein apheresis but not lomitapide. All patients received evinacumab (15 mg/kg intravenously) every 4 weeks, with no change in concomitant lipid-lowering treatment during the first 6 months. The primary efficacy end points were the mean absolute and percentage changes in low-density lipoprotein cholesterol from baseline to 6 months. A key secondary end point was cardiovascular event-free survival, which was compared with a control HoFH cohort not treated with evinacumab or lomitapide and matched for age, sex, and lipoprotein apheresis, derived from French Registry of Familial hypercholesterolemia. RESULTS: Twelve patients, 5 women and 7 men (12-57 years), were enrolled in 3 centers in France. At 6 months, the mean low-density lipoprotein cholesterol reduction with evinacumab was 3.7 mmol/L or 56% (from 6.5 mmol/L at baseline to 2.8 mmol/L; P<0.0001) and was sustained over the median 3.5-year follow-up. No patients on evinacumab experienced cardiovascular events versus 13 events for 5/21 (24%) over 4 years in the control cohort (likelihood P=0.0267). CONCLUSIONS: Real-life, long-term evinacumab adjunctive to lipid-lowering therapy including lipoprotein apheresis led to sustained low-density lipoprotein cholesterol lowering and improved cardiovascular event-free survival of patients with HoFH.

Characteristics and prognosis of patients with elevated triglycerides in acute myocardial infarction: observational data from a large database over a 17-year period: High triglycerides in acute myocardial infarction.

From a large regional registry, we aimed to address the characteristics and prognosis of patients with elevated triglycerides (TG) among patients hospitalized for an acute myocardial infarction (MI). From the multicenter database of the RICO survey, all consecutive patients hospitalized for an acute MI (2001-2017) and alive at discharge were included. Among the 10,667 patients included, 17.7% had elevated TG. When compared with patients with TG ≤ 200 mg/dL, patients with high TG (>200 mg/dL) were 10 years younger, had a higher BMI, were more frequently men, diabetic, and smokers. At 1-year follow-up, recurrent ischemic events were more frequent in elevated TG patients. In multivariate logistic regression analysis, high TG (OR (95%CI): 1.356 (1.095-1.679)) remained an independent estimate for recurrent ischemic events, even after adjustment for confounding factors. In our large population-based cohort, elevated TG are common in acute MI, and associated with residual risk of recurrent ischemic events, beyond traditional prognostic markers.

Non-HDL-cholesterol in dyslipidemia: Review of the state-of-the-art literature and outlook.

Dyslipidemia refers to unhealthy changes in blood lipid composition and is a risk factor for atherosclerotic cardiovascular diseases (ASCVD). Usually, low-density lipoprotein-cholesterol (LDL-C) is the primary goal for dyslipidemia management. However, non-high-density lipoprotein cholesterol (non-HDL-C) has gained attention as an alternative, reliable goal. It encompasses all plasma lipoproteins like LDL, triglyceride-rich lipoproteins (TRL), TRL-remnants, and lipoprotein a [Lp(a)] except high-density lipoproteins (HDL). In addition to LDL-C, several other constituents of non-HDL-C have been reported to be atherogenic, aiding the pathophysiology of atherosclerosis. They are acknowledged as contributors to residual ASCVD risk that exists in patients on statin therapy with controlled LDL-C levels. Therefore, non-HDL-C is now considered an independent risk factor or predictor for CVD. The popularity of non-HDL-C is attributed to its ease of estimation and non-dependency on fasting status. It is also better at predicting ASCVD risk in patients on statin therapy, and/or in those with obesity, diabetes, and metabolic disorders. In addition, large follow-up studies have reported that individuals with higher baseline non-HDL-C at a younger age (<45 years) were more prone to adverse CVD events at an older age, suggesting a predictive ability of non-HDL-C over the long term. Consequently, non-HDL-C is recommended as a secondary goal for dyslipidemia management by most international guidelines. Intriguingly, geographical patterns in recent epidemiological studies showed remarkably high non-HDL-C attributable mortality in high-risk countries. This review highlights the independent role of non-HDL-C in ASCVD pathogenesis and prognosis. In addition, the need for a country-specific approach to dyslipidemia management at the community/population level is discussed. Overall, non-HDL-C can become a co-primary or primary goal in dyslipidemia management.

Evaluation of hypercholesterolemia management in at-risk patients by cardiologists in France: a case vignette-based study.

Aim: This online interactive survey investigated lipid-lowering approaches of French cardiologists in high- and very high-cardiovascular risk patients with hypercholesterolemia. Materials & methods: Physicians assessed three hypothetical patients at three clinic visits, and selected the patients' cardiovascular risk category, target low-density lipoprotein cholesterol (LDL-C) and treatment. Results: A total of 162 physicians completed 480 risk assessments; 58% of assessments correctly categorized the hypothetical patients. Most physicians chose the correct LDL-C target for one of the very high-risk patients, but higher-than-recommended targets were selected for the other very high-risk patient and the high-risk patient. Statins were the most commonly chosen treatment. Conclusion: French cardiologists often underestimate cardiovascular risk in patients with hypercholesterolemia, select a higher-than-recommended LDL-C target and prescribe less intensive treatment than that recommended by guidelines.

Bempedoic acid in the management of lipid disorders and cardiovascular risk. 2023 position paper of the International Lipid Expert Panel (ILEP).

Cardiovascular disease (CVD) is a chronic non-communicable disease (NCD) and the predominant cause of morbidity and mortality worldwide. Substantial reductions in the CVD prevalence have been achieved in recent years by the attenuation of risk factors (particularly hypertension and dyslipidaemias) in primary and secondary prevention. Despite the remarkable success of lipid lowering treatments, and of statins in particular, in reducing the risk of CVD, there is still an unmet clinical need for the attainment of guideline lipid-targets in even 2/3 of patients. Bempedoic acid, the first in-class inhibitor of ATP-citrate lyase presents a new approach to lipid-lowering therapy. By reducing the endogenous production of cholesterol, upstream of the rate-limiting enzyme HMG-CoA-reductase, i.e., the target of statins, bempedoic acid reduces circulating plasma concentrations of low-density lipoprotein cholesterol (LDL-C), and major adverse CVD events (MACE). Bempedoic acid has the potential to contribute to the reduction of CVD risk not only as monotherapy, but even further as part of a lipid-lowering combination therapy with ezetimibe, reducing LDL-C cholesterol up to 40%. This position paper of the International Lipid Expert Panel (ILEP) summarises the recent evidence around the efficacy and safety of bempedoic acid and presents practical recommendations for its use, which complement the 'lower-is-better-for-longer' approach to lipid management, which is applied across international guidelines for the management of CVD risk. Practical evidence-based guidance is provided relating to the use of bempedoic acid in atherosclerotic CVD, familial hypercholesterolaemia, and statin intolerance. Although there are still no sufficient data avilable for the role of bempedoic acid in the primary prevention of CVD, its favourable effects on plasma glucose and inflammatory markers makes this drug a rational choice in the patient-centred care of specific groups of primary prevention.

Lipid-lowering efficacy and safety of alirocumab in a real-life setting in France: Insights from the ODYSSEY APPRISE study.

BACKGROUND: Recently, a multicentre, prospective, single-arm, phase 3b, open-label trial was conducted to determine the safety and efficacy of alirocumab, a proprotein convertase subtilisin/kexin type 9 inhibitor, in a real-life setting. This study enrolled patients at high cardiovascular risk, with heterozygous familial hypercholesterolaemia (HeFH) or non-familial hypercholesterolaemia (non-FH). Results showed that alirocumab was well tolerated and resulted in a clinically significant reduction in low-density lipoprotein cholesterol (LDL-C). AIM: This ancillary analysis aimed to describe the characteristics of the French patients enrolled in the study, the main results observed in this population according to their familial hypercholesterolaemia status, and adherence to treatment. METHODS: French data were analysed separately from the original dataset of the study. RESULTS: Among 215 French patients in the ODYSSEY APPRISE trial, 63.7% had non-FH, with a mean LDL-C concentration of 5.0±1.8mmol/L at baseline. The mean duration of alirocumab exposure was 72.4±42.5 weeks, with only 48.4% of patients receiving statins concomitantly. At week 12, a mean reduction in LDL-C of 56.5±17.8% was observed: 51.2±22.8% in HeFH; 59.5±13.2% in non-FH. This improvement in LDL-C started from week 4 and remained stable and sustained until week 120 in both populations. The overall incidence of severe treatment-emergent adverse events (TEAEs) was 33.5%. The most frequent TEAEs were myalgia (15.8%) and asthenia (15.3%). No tolerance or efficacy differences were observed between patients with or without established coronary artery disease or other cardiovascular disease, whatever the age of these events or considering the concomitant use of other lipid-lowering therapies. CONCLUSIONS: In the French setting, alirocumab was well tolerated, safe and highly effective at reducing LDL-C. These findings support the use of alirocumab to manage hypercholesterolaemia in patients at high cardiovascular risk.

Factors Predicting Statin Initiation During Childhood in Familial Hypercholesterolemia: Importance of Genetic Diagnosis.

OBJECTIVE: To identify childhood and parental factors associated with initiation of statin therapy in children with heterozygous familial hypercholesterolemia (HeFH), including underlying genetic diagnosis or parental premature atherosclerotic cardiovascular disease (ASCVD). STUDY DESIGN: This multicenter cohort study included 245 HeFH child-parent pairs from the REFERCHOL national register (2014-2020). Demographic and clinical characteristics at the last visit were collected. Vascular disease in parents was defined as a history of ASCVD, and/or a coronary artery calcium score >100, and/or stenosis of >50% in at least carotid artery. Statistical analyses included descriptive analysis, logistic regression for univariate and multivariate effects of statins, and a sensitivity analysis combining the characteristics of children and parents. RESULTS: Among the 245 children in the study cohort, 135 (58%), with a mean age of 14 ± 3 years, were treated with a statin. In multivariable analysis, the predictive childhood factors associated with statin treatment were genetic diagnosis (OR, 2.5; 95% CI, 1.3 to 4.9; P = .01), older age (OR, 4.4; 95% CI, 1.8-10.6; P = .01), more than 2 visits (OR, 2.36; 95% CI, 1.18-4.73; P = .015), and longer duration of follow-up (OR, 1.3; 95% CI, 1.1-1.6; P < .001). The predictive parental factor associated with childhood treatment was the presence of vascular disease (OR, 2.4; 95% CI, 1.0-5.7; P = .04). CONCLUSIONS: HeFH confirmed by DNA testing during childhood and a history of vascular disease in parents were independently associated with statin treatment in children with HeFH. Genetic diagnosis may be useful for cardiovascular prevention in children.

Projected impact of treatment intensification with statin, ezetimibe, and statin plus ezetimibe fixed-dose combination on MACE across six countries.

AIMS: The 2019 European Society of Cardiology/European Atherosclerosis Society (ESC/EAS) dyslipidaemia guidelines recommend achievement of low-density lipoprotein cholestrol (LDL-C) goals based on an individual's risk. We aimed to evaluate the impact of guideline adoption with statin, ezetimibe, and statin plus ezetimibe fixed-dose combination (FDC) on LDL-C goal achievement and incidence of major adverse cardiovascular events (MACE) across six countries. METHODS AND RESULTS: A simulation model with a five-year horizon (2020-2024) was developed based on Institute for Health Metrics and Evaluation Global Burden of Disease Study database with a business-as-usual (BAU) scenario representing status quo, intervention scenario-1 representing treatment with statin and ezetimibe as separate agents, and intervention scenario-2 representing treatment with statin or statin plus ezetimibe FDC. MACE was defined as the composite of myocardial infarction, ischaemic stroke, and cardiovascular death. The mean population LDL-C was reduced from 4.25 mmol/L in the BAU scenario, to 3.65 mmol/L and 3.59 mmol/L in intervention scenarios-1 and -2, respectively. Compared with BAU, intervention scenarios-1 and-2 resulted in relative reduction of MACE by 5.4% and 6.4% representing ∼3.7 and 4.4 million MACE averted, respectively, across six countries over 5 years. The absolute benefit in terms of MACE averted was highest for China, whereas France had highest relative reduction in MACE with both intervention scenarios compared with BAU. CONCLUSION: The 2019 ESC/EAS guideline-based treatment intensification with strategies based on statin, ezetimibe, and statin plus ezetimibe FDC is estimated to result in a substantial population-level benefit in terms of MACE averted compared with BAU.

High lipoprotein(a) levels predict severity of coronary artery disease in patients hospitalized for acute myocardial infarction. Data from the French RICO survey.

BACKGROUND: Lipoprotein(a) (Lp(a)) is a well-recognized independent risk factor for atherosclerotic cardiovascular disease (ASCVD). However, limited data are available on the relationship between coronary artery disease (CAD) burden and Lp(a) levels in patients with acute myocardial infarction (MI). OBJECTIVE: The objective of this study was to assess the severity of CAD according to Lp(a) levels from a French regional registry of acute MI. METHODS: CAD burden was assessed in 1213 consecutive patients hospitalized for acute MI in 2019-2020 who underwent coronary angiography. Patients were compared according to their Lp(a) levels: <50 mg/dL (normal), ≥50 mg/dL and ≤100 mg/dL (high) and >100 mg/dL (very high). RESULTS: The prevalence of high and very high Lp(a) was 13% and 6%, respectively. Median age, and rates of diabetes and smoking were similar in all groups. Patients with high or very high Lp(a) were more often under statin therapy, their corrected LDL-cholesterol levels were lower and previous ASCVD rates higher. When compared with lower levels, patients with very high Lp(a) levels had more elevated SYNTAX scores and more frequent multivessel disease. By multivariate logistic regression analysis, the odd ratio for the estimate of multivessel disease was the highest for patients with Lp(a) >100 mg/dL. Moreover, there was a gradual increase in the number of in-hospital deaths across the three Lp(a) groups (p=0.028). CONCLUSIONS: In real-world patients hospitalized for acute MI in France, very high Lp(a) levels are independently associated with a severe CAD burden, supporting the need for systematic screening of Lp(a) in these patients.

Retinal Microvascular Changes in Familial Hypercholesterolemia: Analysis with Swept-Source Optical Coherence Tomography Angiography.

Familial hypercholesterolemia (FH) is a common but underdiagnosed genetic disorder affecting cholesterol metabolism, leading to atherosclerotic disease. The relationship between retinal microvascular changes and the presence of atheroma in patients with FH (FH group), and in comparison to volunteers without FH (CT group), needs further investigation. This cross-sectional study was conducted in a university hospital between October 1, 2020 and May 31, 2021. Cardiovascular data, including the Coronary Artery Calcium (CAC) score, were recorded for FH patients. Macula angiograms were acquired using swept-source optical coherence tomography angiography (SS OCT-A) to analyze both the superficial capillary plexus (SCP) and deep capillary plexus (DCP). A total of 162 eyes of 83 patients were enrolled in the FH group and 121 eyes of 78 volunteers in the CT group. A statistically significant association was found between the CAC score and both vessel density (ß = -0.002 [95% CI, -0.004; -0.0005], p = 0.010) and vessel length (ß = -0.00005 [95% CI, -0.00008; -0.00001], p = 0.010) in the DCP. The FH group had a significantly lower foveal avascular zone circularity index than the CT group in multivariate analysis (0.67 ± 0.16 in the FH group vs. 0.72 ± 0.10 in the CT group, ß = 0.04 [95% CI, 0.002; 0.07], p = 0.037). Retinal microvascularization is altered in FH and retinal vascular densities are modified according to the CAC score.

Whole Exome/Genome Sequencing Joint Analysis of a Family with Oligogenic Familial Hypercholesterolemia.

Autosomal Dominant Hypercholesterolemia (ADH) is a genetic disorder caused by pathogenic variants in LDLR, APOB, PCSK9 and APOE genes. We sought to identify new candidate genes responsible for the ADH phenotype in patients without pathogenic variants in the known ADH-causing genes by focusing on a French family with affected and non-affected members who presented a high ADH polygenic risk score (wPRS). Linkage analysis, whole exome and whole genome sequencing resulted in the identification of variants p.(Pro398Ala) in CYP7A1, p.(Val1382Phe) in LRP6 and p.(Ser202His) in LDLRAP1. A total of 6 other variants were identified in 6 of 160 unrelated ADH probands: p.(Ala13Val) and p.(Aps347Asn) in CYP7A1; p.(Tyr972Cys), p.(Thr1479Ile) and p.(Ser1612Phe) in LRP6; and p.(Ser202LeufsTer19) in LDLRAP1. All six probands presented a moderate wPRS. Serum analyses of carriers of the p.(Pro398Ala) variant in CYP7A1 showed no differences in the synthesis of bile acids compared to the serums of non-carriers. Functional studies of the four LRP6 mutants in HEK293T cells resulted in contradictory results excluding a major effect of each variant alone. Within the family, none of the heterozygous for only the LDLRAP1 p.(Ser202His) variant presented ADH. Altogether, each variant individually does not result in elevated LDL-C; however, the oligogenic combination of two or three variants reveals the ADH phenotype.

Burden of cardiovascular disease in a large contemporary cohort of patients with heterozygous familial hypercholesterolemia.

Background and aims: Heterozygous familial hypercholesterolemia (HeFH) is increasingly better diagnosed and treatments can improve the cardiovascular prognosis. We evaluated the long-term cardiovascular risk of HeFH using the French REgistry of Familial hypERCHOLesterolemia (REFERCHOL). Methods: We studied HeFH patients diagnosed genetically and clinically by the Dutch Lipid Clinic Network (DLCN) criteria in all lipid clinics across the country and their 5-year risk of cardiovascular events (all fatal and non-fatal acute coronary, cerebral and peripheral arterial disease events, aortic valve replacement surgery) using the French national health data system. Results: The database comprised 3202 individuals, 2010 (62.8%) with genetically verified HeFH and 1192 (37.2%) a DLCN score ≥6. Of these individuals, 2485 (77.6%) were in primary prevention and 717 (22.4%) in secondary prevention. The incidence of cardiovascular events was 24.58 per 1000 person-years for the overall sample, 19.15 in primary prevention and 43.40 in secondary prevention. The incidence of myocardial infarction, cerebral infarction and death was 16.32 per 1000 person-years for the overall sample, 12.93 in primary prevention and 28.08 in secondary prevention. The incidence of aortic valve replacement was 1.78 per 1000 person-years. In the overall sample, at inclusion, 41% were not treated for LDL cholesterol, 48% of these in primary prevention and 20% in secondary prevention and high-dose statins were used by only 24% of individuals, 15% of these in primary prevention and 45% in secondary prevention. Conclusions: The incidence of cardiovascular events in HeFH is high and lipid-lowering treatment is far from optimal. The cardiovascular risk of HeFH is underestimated and patients are inadequately treated.

Control of Low-Density Lipoprotein Cholesterol in Secondary Prevention of Coronary Artery Disease in Real-Life Practice: The DAUSSET Study in French Cardiologists.

INTRODUCTION: Patients with established coronary artery disease (CAD) are at very high risk for cardiovascular events. METHODS: The DAUSSET study is a national, multicenter, non-interventional study that included very high-risk CAD patients followed by French cardiologists. It aimed to describe real-life clinical practices for low-density lipoprotein (LDL) cholesterol control in the secondary prevention of CAD. RESULTS: A total of 912 patients (mean age, 65.4 years; men, 76.1%; myocardial infarction, 69.4%; first episode, 80.1%) were analyzed. The LDL cholesterol goal was 70 mg/dL in most cases (84.9%). The LDL cholesterol goal <70 mg/dL was achieved in 41.7% of patients. Of the 894 (98.0%) patients who received lipid-lowering therapy, 81.2% had been treated more intensively after the cardiac event, 27.0% had been treated less intensively and 13.1% had been maintained. Participating cardiologists were very satisfied or satisfied with treatment response in 72.6% of patients. Moderate satisfaction or dissatisfaction with lipid-lowering therapy was related to not achieving objectives (100%), treatment inefficacy (53.7%), treatment intolerance (23.4%) and poor adherence (12.3%). CONCLUSION: These real-world results show that lipid control in very high-risk patients remains insufficient. More than half of the patients did not achieve the LDL cholesterol goal. Prevention of cardiovascular events in these very high-risk patients could be further improved by better education and more intensive lipid-lowering therapy.

Lipoprotein(a): Pathophysiology, measurement, indication and treatment in cardiovascular disease. A consensus statement from the Nouvelle Société Francophone d'Athérosclérose (NSFA).

Lipoprotein(a) is an apolipoprotein B100-containing low-density lipoprotein-like particle that is rich in cholesterol, and is associated with a second major protein, apolipoprotein(a). Apolipoprotein(a) possesses structural similarity to plasminogen but lacks fibrinolytic activity. As a consequence of its composite structure, lipoprotein(a) may: (1) elicit a prothrombotic/antifibrinolytic action favouring clot stability; and (2) enhance atherosclerosis progression via its propensity for retention in the arterial intima, with deposition of its cholesterol load at sites of plaque formation. Equally, lipoprotein(a) may induce inflammation and calcification in the aortic leaflet valve interstitium, leading to calcific aortic valve stenosis. Experimental, epidemiological and genetic evidence support the contention that elevated concentrations of lipoprotein(a) are causally related to atherothrombotic risk and equally to calcific aortic valve stenosis. The plasma concentration of lipoprotein(a) is principally determined by genetic factors, is not influenced by dietary habits, remains essentially constant over the lifetime of a given individual and is the most powerful variable for prediction of lipoprotein(a)-associated cardiovascular risk. However, major interindividual variations (up to 1000-fold) are characteristic of lipoprotein(a) concentrations. In this context, lipoprotein(a) assays, although currently insufficiently standardized, are of considerable interest, not only in stratifying cardiovascular risk, but equally in the clinical follow-up of patients treated with novel lipid-lowering therapies targeted at lipoprotein(a) (e.g. antiapolipoprotein(a) antisense oligonucleotides and small interfering ribonucleic acids) that markedly reduce circulating lipoprotein(a) concentrations. We recommend that lipoprotein(a) be measured once in subjects at high cardiovascular risk with premature coronary heart disease, in familial hypercholesterolaemia, in those with a family history of coronary heart disease and in those with recurrent coronary heart disease despite lipid-lowering treatment. Because of its clinical relevance, the cost of lipoprotein(a) testing should be covered by social security and health authorities.

Intentionality in adherence to long-term therapies. Results from an online survey of 3,001 patients with cardio-metabolic pathologies in France.

PURPOSE: Some patients make a rational choice not to follow medical prescriptions; others fail to take their medications for reasons beyond their control, such as mere forgetfulness or a weak medication routine. The aim of this study was to elucidate the functioning of patient intentionality in medication adherence. PATIENTS AND METHODS: This online study was conducted in metropolitan France in 2019. A cross-sectional survey of 50 questions was conducted with 3001 respondents diagnosed with diabetes, hypertension, and/or hypercholesterolemia identified from a panel of 54,000 people. These questions included a validated six-item questionnaire to detect nonadherence, two questions to detect intentional nonadherence by patients, and three questions on the effects of habit. Our questionnaire also included questions on the feelings of respondents regarding their doctor's attitude to their problems and needs, their trust in general practitioners (GP) and specialists, their sense of being involved in treatment decisions, and the influence of side effects and habits on patients' adherence. This study used the strategy of focusing on strictly adherent patients in the hope of finding ways to improve adherence. For this reason, we defined adherence as the absence of a positive response to the 6-item nonadherence screening questionnaire. RESULTS: Of 3001 respondents, 1804 were diagnosed with hypertension, 1458 with hypercholesterolemia, and 774 with diabetes. Of the total number of patients, 72% were afflicted with one disease, 21% with two ailments, and 7% with three simultaneous illnesses. One-third (33%) of the patients did not tender a positive answer to the adherence questionnaire and were deemed adherent. 1) Thirty-two percent of the patients reported occasionally omitting their medication deliberately, and 84% said they had a reason for missing doses. These statements suggesting intentional nonadherence were negatively associated with adherence as identified via multivariate analysis (P = 0.0012 and P < 0.0001, for the first and second statement, respectively). 2) Univariate analyses revealed strong associations (P < 0.0001) between strict adherence on one hand and lack of intentional nonadherence, patient age, absence of drug side effects, taking drugs by habit, feeling involved in treatment decisions, getting information about treatment, and disease, and trust in doctors, on the other hand. 3) Specifically, univariate analysis of the absence of reported side effects revealed strong associations (P < 0.0001) with adequate information about medicines and diseases and trust in GP. These original data were consistent with the concept of the nocebo effect. 4) We observed a strong association between the absence of intentional nonadherence (statement of never deliberately missing medication) and respondent statements about generally sticking to the routine (P < 0.0001), ie, "I take my medication because I am used to taking it." This important result suggests that patients are strictly adherent in two ways: the absence of intentional nonadherence and reliance on habit, which we term as "unintentional adherence." 5) Finally, a multiple correspondence analysis illustrated all statistically significant relationships found in this study. CONCLUSION: We present a new global model of adherence in which patient adherence was improved both by reducing intentional nonadherence and by promoting the abovementioned unintentional adherence by habit. This model highlights the role of shared decision-making and the trust felt by patients in their doctors. These results could exert a major impact on medical practice and education by demonstrating the importance of physicians' attitudes, involving the patient in decisions (shared decision-making), offering information about medicines and diseases (patient education), understanding the problems of patients, and taking their needs into account (empathy). The development of these attitudes should be an important aspect of the medical curricula.

Coronary lesion complexity in patients with heterozygous familial hypercholesterolemia hospitalized for acute myocardial infarction: data from the RICO survey.

BACKGROUND: Although patients with familial heterozygous hypercholesterolemia (FH) have a high risk of early myocardial infarction (MI), the coronary artery disease (CAD) burden in FH patients with acute MI remains to be investigated. METHODS: The data for all consecutive patients hospitalized in 2012-2019 for an acute MI and who underwent coronary angiography were collected from a multicenter database (RICO database). FH (n = 120) was diagnosed using Dutch Lipid Clinic Network criteria (score ≥ 6). We compared the angiographic features of MI patients with and without FH (score 0-2) (n = 234) after matching for age, sex, and diabetes (1:2). RESULTS: Although LDL-cholesterol was high (208 [174-239] mg/dl), less than half of FH patients had chronic statin treatment. When compared with non-FH patients, FH increased the extent of CAD (as assessed by SYNTAX score; P = 0.005), and was associated with more frequent multivessel disease (P = 0.004), multiple complex lesions (P = 0.022) and significant stenosis location on left circumflex and right coronary arteries. Moreover, FH patients had more multiple lesions, with an increased rate of bifurcation lesions or calcifications (P = 0.021 and P = 0.036, respectively). In multivariate analysis, LDL-cholesterol levels (OR 1.948; 95% CI 1.090-3.480, P = 0.024) remained an independent estimator of anatomical complexity of coronary lesions, in addition to age (OR 1.035; 95% CI 1.014-1.057, P = 0.001). CONCLUSIONS: FH patients with acute MI had more severe CAD, characterized by complex anatomical features that are mainly dependent on the LDL-cholesterol burden. Our findings reinforce the need for more aggressive preventive strategies in these high-risk patients, and for intensive lipid-lowering therapy as secondary prevention.

Practical guidance for combination lipid-modifying therapy in high- and very-high-risk patients: A statement from a European Atherosclerosis Society Task Force.

BACKGROUND AND AIMS: This European Atherosclerosis Society (EAS) Task Force provides practical guidance for combination therapy for elevated low-density lipoprotein cholesterol (LDL-C) and/or triglycerides (TG) in high-risk and very-high-risk patients. METHODS: Evidence-based review. RESULTS: Statin-ezetimibe combination treatment is the first choice for managing elevated LDL-C and should be given upfront in very-high-risk patients with high LDL-C unlikely to reach goal with a statin, and in primary prevention familial hypercholesterolaemia patients. A proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor may be added if LDL-C levels remain high. In high and very-high-risk patients with mild to moderately elevated TG levels (>2.3 and < 5.6 mmol/L [>200 and < 500 mg/dL) on a statin, treatment with either a fibrate or high-dose omega-3 fatty acids (icosapent ethyl) may be considered, weighing the benefit versus risks. Combination with fenofibrate may be considered for both macro- and microvascular benefits in patients with type 2 diabetes mellitus. CONCLUSIONS: This guidance aims to improve real-world use of guideline-recommended combination lipid modifying treatment.