Population health management in Belgium: a call-to-action and case study.

BACKGROUND: Although there are already success stories, population health management in Belgium is still in its infancy. A health system transformation approach such as population health management may be suited to address the public health issue of atherosclerotic cardiovascular disease, as this is one of the main causes of mortality in Belgium. This article aims to raise awareness about population health management in Belgium by: (a) eliciting barriers and recommendations for its implementation as perceived by local stakeholders; (b) developing a population health management approach to secondary prevention of atherosclerotic cardiovascular disease; and (c) providing a roadmap to introduce population health management in Belgium. METHODS: Two virtual focus group discussions were organized with 11 high-level decision makers in medicine, policy and science between October and December 2021. A semi-structured guide based on a literature review was used to anchor discussions. These qualitative data were studied by means of an inductive thematic analysis. RESULTS: Seven inter-related barriers and recommendations towards the development of population health management in Belgium were identified. These related to responsibilities of different layers of government, shared responsibility for the health of the population, a learning health system, payment models, data and knowledge infrastructure, collaborative relationships and community involvement. The introduction of a population health management approach to secondary prevention of atherosclerotic cardiovascular disease may act as a proof-of-concept with a view to roll out population health management in Belgium. CONCLUSIONS: There is a need to instill a sense of urgency among all stakeholders to develop a joint population-oriented vision in Belgium. This call-to-action requires the support and active involvement of all Belgian stakeholders, both at the national and regional level.

How to Measure Arterial Stiffness in Humans.

Despite the wide recognition of larger artery stiffness as a highly clinically relevant and independent prognostic biomarker, it has yet be incorporated into routine clinical practice and to take a more prominent position in clinical guidelines. An important reason may be the plethora of methods and devices claiming to measure arterial stiffness in humans. This brief review provides a concise overview of methods in use, indicating strengths and weaknesses. We classified and graded methods, highly weighing their scrutiny and purity in quantifying arterial stiffness, rather than focusing on their ease of application or the level at which methods have demonstrated their prognostic and diagnostic potential.

Effects of Gender-Affirming Hormones on Lipid, Metabolic, and Cardiac Surrogate Blood Markers in Transgender Persons.

BACKGROUND: Gender-affirming hormonal therapy consists of testosterone in transgender men and estrogens and antiandrogens in transgender women. Research has concluded that gender-affirming therapy generally leads to high satisfaction rates, increased quality of life, and higher psychological well-being. However, given the higher incidence of cardiometabolic morbidity and mortality in cisgender men compared with cisgender women, concerns about the cardiometabolic risk of androgen therapy have been raised. CONTENT: A literature research was conducted on PubMed, Embase, and Scopus, searching for relevant articles on the effects of gender-affirming hormone therapy on cardiometabolic risk and thrombosis. After screening 734 abstracts, 77 full text articles were retained, of which 11 were review articles. SUMMARY: Studies describing a higher risk for cardiometabolic and thromboembolic morbidity and/or mortality in transgender women (but not transgender men) mainly covered data on transgender women using the now obsolete ethinyl estradiol and, therefore, are no longer valid. Currently, most of the available literature on transgender people adhering to standard treatment regimens consists of retrospective cohort studies of insufficient follow-up duration. When assessing markers of cardiometabolic disease, the available literature is inconclusive, which may be ascribed to relatively short follow-up duration and small sample size. The importance of ongoing large-scale prospective studies/registries and of optimal management of conventional risk factors cannot be overemphasized.

Proximal aortic stiffening in Turner patients may be present before dilation can be detected: a segmental functional MRI study.

BACKGROUND: To study segmental structural and functional aortic properties in Turner syndrome (TS) patients. Aortic abnormalities contribute to increased morbidity and mortality of women with Turner syndrome. Cardiovascular magnetic resonance (CMR) allows segmental study of aortic elastic properties. METHOD: We performed Pulse Wave Velocity (PWV) and distensibility measurements using CMR of the thoracic and abdominal aorta in 55 TS-patients, aged 13-59y, and in a control population (n = 38;12-58y). We investigated the contribution of TS on aortic stiffness in our entire cohort, in bicuspid (BAV) versus tricuspid (TAV) aortic valve-morphology subgroups, and in the younger and older subgroups. RESULTS: Differences in aortic properties were only seen at the most proximal aortic level. BAV Turner patients had significantly higher PWV, compared to TAV Turner (p = 0.014), who in turn had significantly higher PWV compared to controls (p = 0.010). BAV Turner patients had significantly larger ascending aortic (AA) luminal area and lower AA distensibility compared to both controls (all p < 0.01) and TAV Turner patients. TAV Turner had similar AA luminal areas and AA distensibility compared to Controls. Functional changes are present in younger and older Turner subjects, whereas ascending aortic dilation is prominent in older Turner patients. Clinically relevant dilatation (TAV and BAV) was associated with reduced distensibility. CONCLUSION: Aortic stiffening and dilation in TS affects the proximal aorta, and is more pronounced, although not exclusively, in BAV TS patients. Functional abnormalities are present at an early age, suggesting an aortic wall disease inherent to the TS. Whether this increased stiffness at young age can predict later dilatation needs to be studied longitudinally.

The Link Between Obstructive Sleep Apnea and Cardiovascular Disease.

Obstructive sleep apnea (OSA) is common in the general population and highly prevalent in patients with cardiovascular disease. In this paper, we review (1) the pathophysiological mechanisms of OSA that may causally contribute to cardiovascular disease; (2) current evidence regarding the association between OSA and hypertension, stroke, ischemic heart disease, heart failure, atrial fibrillation, and cardiovascular mortality; and (3) the impact of continuous positive airway pressure (CPAP) treatment on cardiovascular risk factors and outcomes. We emphasize the importance of obesity as a comorbidity of OSA and a confounder in the association between OSA and cardiovascular disease. We also discuss the importance of addressing obesity in patients with OSA, as a strategy to reduce the burden of cardiovascular risk factors in this population. Implications for the approach of patients' OSA in clinical practice and future research directions are discussed.

MR pulse wave velocity increases with age faster in the thoracic aorta than in the abdominal aorta.

PURPOSE: To assess the difference between thoracic and abdominal aortic pulse wave velocity (PWV) in apparently healthy subjects including young adults to elderly subjects. MATERIALS AND METHODS: We performed PWV and distensibility measurements and analysis of thoracic and abdominal aortic segments in 96 apparently normal subjects aged 20-80 years with magnetic resonance (MR). Both unadjusted correlation and General Linear Model (GLM) analysis of log-transformed PWV (thoracic and abdominal aorta) and distensibility (four aortic cross-sections) were performed. RESULTS: Both thoracic and abdominal PWV values and distensibility values increased with age. In unadjusted analyses the correlation between the ln(thoracic PWV) and age (r = 0.71; P < 0.001) was stronger than between ln(abdominal PWV) and age (r = 0.50; P < 0.001). In GLM analysis, the only determinant of thoracic and abdominal PWV was age (F = 42.5 and F = 14.8, respectively; both P < 0.001). Similarly, correlation between ln(distensibility) and age was strong (r = -0.79, r = -0.67, r = -0.71, and r = -0.65 for ascending, descending, diaphragmatic, and low abdominal aorta, respectively; all P < 0.001). In GLM analysis, age was the major determinant for distensibility of the ascending aorta (F = 81.7; P < 0.001), descending aorta (F = 42.2; P < 0.001), diaphragmatic aorta (F = 39.2; P < 0.001), and low abdominal aorta (F = 32.8; P < 0.001). CONCLUSION: The thoracic aorta is less stiff than the abdominal aorta in young and middle-aged subjects, and stiffens more rapidly with age than the abdominal aorta, resulting in a stiffer thoracic than abdominal aorta at older age.

Associations between dietary inflammatory index and inflammatory markers in the Asklepios Study.

Previous research has shown that nutrients and certain food items influence inflammation. However, little is known about the associations between diet, as a whole, and inflammatory markers. In the present study, we examined the ability of a FFQ-derived dietary inflammatory index (DII) to predict inflammation. Data from a Belgian cross-sectional study of 2524 generally healthy subjects (age 35-55 years) were used. The DII is a population-based, literature-derived dietary index that was developed to predict inflammation and inflammation-related chronic diseases. The DII was calculated from FFQ-derived dietary information and tested against inflammatory markers, namely C-reactive protein (CRP), IL-6, homocysteine and fibrinogen. Analyses were performed using multivariable logistic regression, adjusting for energy, age, sex, BMI, smoking status, education level, use of non-steroidal anti-inflammatory drugs, blood pressure, use of oral contraceptives, anti-hypertensive therapy, lipid-lowering drugs and physical activity. Multivariable analyses showed significant positive associations between the DII and the inflammatory markers IL-6 (>1·6 pg/ml) (OR 1·19, 95 % CI 1·04, 1·36) and homocysteine (>15 µmol/l) (OR 1·56, 95 % CI 1·25, 1·94). No significant associations were observed between the DII and the inflammatory markers CRP and fibrinogen. These results reinforce the fact that diet, as a whole, plays an important role in modifying inflammation.

Clinical inertia in general practice, a matter of debate: a qualitative study with 114 general practitioners in Belgium.

BACKGROUND: Prescribing that is not concordant with guidelines is increasingly referred to as clinical inertia (CI). However, CI may be only apparent, and the absence of decision may actually reflect appropriate inaction as a result of good clinical reasoning. Our study aimed to: (i) elucidate GPs' beliefs regarding CI and the risk of CI in their own practice, (ii) identify modifiable provider-related factors associated with CI. METHODS: We conducted 8 group interviews with 114 general practitioners (GP) in Belgium, and used an integrated approach of thematic analysis. RESULTS: Our results call for a redefinition of CI, in order to take into account the GPs' extended health-promoting role, and acknowledge that inaction or delayed action follows a process of clinical reasoning that takes into account the patients' preferences, and that is appropriate most of the time. However, the participants in our study did acknowledge that the risk of CI exists in practice. The main factor of such a risk is when GPs feel overwhelmed and disempowered, due to characteristics of either the patients or the health care system, including contradictions between guidelines and reimbursement policies. CONCLUSIONS: Although situations of clinical inertia exist in practice and need to be prevented or corrected, the term clinical inertia could potentially increase the already existing gap between general practice and specialised care, whereas sustained efforts toward more collaborative work and integrated care are called for.

Use of combination therapy is associated with improved LDL-cholesterol management: 1-year follow-up results from the European observational SANTORINI study.

AIM: To assess whether implementation of the 2019 ESC/EAS dyslipidaemia guidelines observed between 2020-2021 improved between 2021-2022 in the SANTORINI study. METHODS: High- or very-high cardiovascular (CV) risk patients were recruited across 14 European countries from March 2020-February 2021, with 1-year prospective follow-up until May 2022. Lipid-lowering therapy (LLT) and 2019 ESC/EAS risk-based low-density lipoprotein cholesterol (LDL-C) goal attainment (defined as <1.4 mmol/L for patients at very high CV risk and <1.8 mmol/L for patients at high CV risk) at 1-year follow-up were compared with baseline. . RESULTS: Of 9559 patients enrolled, 9136 (2626 high risk, 6504 very high risk) had any follow-up data, and 7210 (2033 high risk, 5173 very high risk) had baseline and follow-up LDL-C data. LLT was escalated in one-third of patients and unchanged in two-thirds. Monotherapy and combination therapy usage rose from 53.6% and 25.6% to 57.1% and 37.9%, respectively. Mean LDL-C levels decreased from 2.4 mmol/L to 2.0 mmol/L. Goal attainment improved from 21.2% to 30.9%, largely driven by LLT use among those not on LLT at baseline. Goal attainment was greater with combination therapy compared with monotherapy at follow-up (39.4 vs 25.5%). CONCLUSIONS: LLT use and achievement of risk-based lipid goals increased over 1-year follow-up particularly when combination LLT was used. Nonetheless, most patients remained above goal, hence strategies are needed to improve implementation of combination LLT.

Cardiovascular diseases, a group of disorders of the heart and blood vessels, are the most common cause of death worldwide. Lowering low-density lipoprotein (LDL) cholesterol in the bloodstream reduces the risk of developing cardiovascular diseases, such as heart attacks and strokes. Guidelines recommend that those at highest risk of cardiovascular disease should achieve the lowest levels of LDL cholesterol. Several medications are available that help lower LDL cholesterol levels and prevent cardiovascular events, however, recent studies have shown that the majority of patients continue to have LDL cholesterol levels above optimal value in part due to suboptimal use of these medications. Here we report the results after 1 year of follow-up of the SANTORINI study (started in 2020) which aimed to document the management of LDL cholesterol in clinical practice across 14 countries in Europe. We found that better control of LDL cholesterol occurred when more than one drug was used (combination therapy). Use of combination therapy was low at the start of the study 25.6% but increased over 1 year to 37.9%, resulting in better control of LDL cholesterol at 1 year than observed at the start of the study. Nonetheless, only 31% of patients achieved their LDL cholesterol target levels based on the European guidelines. Greater use of combination therapies is needed in order to improve the overall population level control of LDL cholesterol.

Proteomic Associations of NT-proBNP (N-Terminal Pro-B-Type Natriuretic Peptide) in Heart Failure With Preserved Ejection Fraction.

BACKGROUND: NT-proBNP (N-terminal pro-B-type natriuretic peptide) levels are variably elevated in heart failure with preserved ejection fraction (HFpEF), even in the presence of increased left ventricular filling pressures. NT-proBNP levels are prognostic in HFpEF and have been used as an inclusion criterion for several recent randomized clinical trials. However, the underlying biologic differences between HFpEF participants with high and low NT-proBNP levels remain to be fully understood. METHODS: We measured 4928 proteins using an aptamer-based proteomic assay (SOMAScan) in available plasma samples from 2 cohorts: (1) Participants with HFpEF enrolled in the PHFS (Penn Heart Failure Study; n=253); (2) TOPCAT (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist Trial) participants in the Americas (n=218). We assessed the relationship between SOMAScan-derived plasma NT-proBNP and levels of other proteins available in the SOMAScan assay version 4 using robust linear regression, with correction for multiple comparisons, followed by pathway analysis. RESULTS: NT-proBNP levels exhibited prominent proteome-wide associations in PHFS and TOPCAT cohorts. Proteins most strongly associated with NT-proBNP in both cohorts included SVEP1 (sushi, von Willebrand factor type-A, epidermal growth factor, and pentraxin domain containing 1; ßTOPCAT=0.539; P<0.0001; ßPHFS=0.516; P<0.0001) and ANGPT2 (angiopoietin 2; ßTOPCAT=0.571; P<0.0001; ßPHFS=0.459; P<0.0001). Canonical pathway analysis demonstrated consistent associations with multiple pathways related to fibrosis and inflammation. These included hepatic fibrosis and inhibition of matrix metalloproteases. Analyses using cut points corresponding to estimated quantitative concentrations of 360 pg/mL (and 480 pg/mL in atrial fibrillation) revealed similar proteomic associations. CONCLUSIONS: Circulating NT-proBNP levels exhibit prominent proteomic associations in HFpEF. Our findings suggest that higher NT-proBNP levels in HFpEF are a marker of fibrosis and inflammation. These findings will aid the interpretation of NT-proBNP levels in HFpEF and may guide the selection of participants in future HFpEF clinical trials.

Prognostic Significance and Biologic Associations of Senescence-Associated Secretory Phenotype Biomarkers in Heart Failure.

BACKGROUND: The role of cellular senescence in human heart failure (HF) remains unclear. The senescence-associated secretory phenotype (SASP) is composed of proteins released by senescent cells. We assessed the prognostic significance and biologic pathways associated with the SASP in human HF using a plasma proteomics approach. METHODS AND RESULTS: We measured 25 known SASP proteins among 2248 PHFS (Penn HF Study) participants using the SOMAScan V4 assay. We extracted the common variance in these proteins to generate SASP factor scores and assessed the relationship between these SASP factor scores and (1) all-cause death and (2) the composite of death or HF hospital admission. We also assessed the relationship of each SASP factor to 4746 other proteins, correcting for multiple comparisons, followed by pathway analyses. Two SASP factors were identified. Both factors were associated with older age, lower estimated glomerular filtration rate, and more advanced New York Heart Association class, among other clinical variables. Both SASP factors exhibited a significant positive association with the risk of death independent of the Meta-Analysis of Global-Group in Chronic HF score and NT-proBNP (N-terminal pro-B-type natriuretic peptide) levels. The 2 identified SASP factors were associated with 1201 and 1554 proteins, respectively, belonging to various pathways including the coagulation system, complement system, acute phase response signaling, and retinoid X receptor-related pathways that regulate cell metabolism. CONCLUSIONS: Increased SASP components are independently associated with adverse outcomes in HF. Biologic pathways associated with SASP are predominantly related to coagulation, inflammation, and cell metabolism.

Proteomic Correlates and Prognostic Significance of Kidney Injury in Heart Failure With Preserved Ejection Fraction.

BACKGROUND: Kidney disease is common in heart failure with preserved ejection fraction (HFpEF). However, the biologic correlates and prognostic significance of kidney injury (KI), in HFpEF, beyond the estimated glomerular filtration rate (eGFR), are unclear. METHODS AND RESULTS: Using baseline plasma samples from the TOPCAT (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist) trial, we measured the following KI biomarkers: cystatin-C, fatty acid-binding protein-3, Beta-2 microglobulin, neutrophil gelatinase-associated lipocalin, and kidney-injury molecule-1. Factor analysis was used to extract the common variability underlying these biomarkers. We assessed the relationship between the KI-factor score and the risk of death or HF-related hospital admission in models adjusted for the Meta-Analysis Global Group in Chronic Heart Failure risk score and eGFR. We also assessed the relationship between the KI factor score and ~5000 plasma proteins, followed by pathway analysis. We validated our findings among HFpEF participants in the Penn Heart Failure Study. KI was associated with the risk of death or HF-related hospital admission independent of the Meta-Analysis Global Group in Chronic Heart Failure risk score and eGFR. Both the risk score and eGFR were no longer associated with death or HF-related hospital admission after adjusting for the KI factor score. KI was predominantly associated with proteins and biologic pathways related to complement activation, inflammation, fibrosis, and cholesterol homeostasis. KI was associated with 140 proteins, which reproduced across cohorts. Findings regarding biologic associations and the prognostic significance of KI were also reproduced in the validation cohort. CONCLUSIONS: KI is associated with adverse outcomes in HFpEF independent of baseline eGFR. Patients with HFpEF and KI exhibit a plasma proteomic signature indicative of complement activation, inflammation, fibrosis, and impaired cholesterol homeostasis.

Urinary Proteomics and Outcomes in Heart Failure With Preserved Ejection Fraction.

BACKGROUND: Although several studies have addressed plasma proteomics in heart failure with preserved ejection fraction, limited data are available on the prognostic value of urinary proteomics. The objective of our study was to identify urinary proteins/peptides associated with death and heart failure admission in patients with heart failure with preserved ejection fraction. METHODS AND RESULTS: The study population included participants enrolled in TOPCAT (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist Trial). The relationship between urine protein levels and the risk of death or heart failure admission was assessed using Cox regression, in both nonadjusted analyses and adjusting for urine creatinine levels, and the MAGGIC (Meta-Analysis Global Group in Chronic Heart Failure) score. A total of 426 (12.4%) TOPCAT participants had urinary protein data and were included. There were 40 urinary proteins/peptides significantly associated with death or heart failure admission in nonadjusted analyses, 21 of which were also significant adjusted analyses. Top proteins in the adjusted analysis included ANGPTL2 (angiopoietin-like protein 2) (hazard ratio [HR], 0.5731 [95% CI, 0.47-0.7]; P=3.13E-05), AMY2A (α amylase 2A) (HR, 0.5496 [95% CI, 0.44-0.69]; P=0.0001), and DNASE1 (deoxyribonuclease-1) (HR, 0.5704 [95% CI, 0.46-0.71]; P=0.0002). Higher urinary levels of proteins involved in fibrosis (collagen VI α-1, collagen XV α-1), metabolism (pancreatic α-amylase 2A/B, mannosidase α class 1A member 1), and inflammation (heat shock protein family D member 1, inducible T cell costimulatory ligand) were associated with a lower risk of death or heart failure admission. CONCLUSIONS: Our study identifies several novel associations between urinary proteins/peptides and outcomes in heart failure with preserved ejection fraction. Many of these associations are independent of clinical risk scores and may aid in risk stratification in this patient population.

Proteomic Associations of Adverse Outcomes in Human Heart Failure.

BACKGROUND: Identifying novel molecular drivers of disease progression in heart failure (HF) is a high-priority goal that may provide new therapeutic targets to improve patient outcomes. The authors investigated the relationship between plasma proteins and adverse outcomes in HF and their putative causal role using Mendelian randomization. METHODS AND RESULTS: The authors measured 4776 plasma proteins among 1964 participants with HF with a reduced left ventricular ejection fraction enrolled in PHFS (Penn Heart Failure Study). Assessed were the observational relationship between plasma proteins and (1) all-cause death or (2) death or HF-related hospital admission (DHFA). The authors replicated nominally significant associations in the Washington University HF registry (N=1080). Proteins significantly associated with outcomes were the subject of 2-sample Mendelian randomization and colocalization analyses. After correction for multiple testing, 243 and 126 proteins were found to be significantly associated with death and DHFA, respectively. These included small ubiquitin-like modifier 2 (standardized hazard ratio [sHR], 1.56; P<0.0001), growth differentiation factor-15 (sHR, 1.68; P<0.0001) for death, A disintegrin and metalloproteinase with thrombospondin motifs-like protein (sHR, 1.40; P<0.0001), and pulmonary-associated surfactant protein C (sHR, 1.24; P<0.0001) for DHFA. In pathway analyses, top canonical pathways associated with death and DHFA included fibrotic, inflammatory, and coagulation pathways. Genomic analyses provided evidence of nominally significant associations between levels of 6 genetically predicted proteins with DHFA and 11 genetically predicted proteins with death. CONCLUSIONS: This study implicates multiple novel proteins in HF and provides preliminary evidence of associations between genetically predicted plasma levels of 17 candidate proteins and the risk for adverse outcomes in human HF.

No shorter telomeres in subjects with a family history of cardiovascular disease in the Asklepios study.

OBJECTIVE: Shorter telomere length is associated with the occurrence of cardiovascular events, but the question of causality is complicated by the intertwined effects of inheritance, aging, and lifestyle factors on both telomere length and cardiovascular disease (CVD). Some studies indicated that healthy offspring of coronary artery disease patients exhibited shorter telomeres than subjects without a family history. Importantly, this result would imply that inheritance of shorter telomeres is a primary abnormality associated with an increased risk of CVD, the so-called Telomere Hypothesis of CVD. Therefore, we aimed at further validating the latter results in the large, population-representative Asklepios Study. METHODS AND RESULTS: Peripheral blood leukocyte telomere length was measured using telomere restriction fragment analysis in the young to middle-aged (≈ 35-55 years old) Asklepios study population, free from overt CVD, and could be successfully combined with data from the Asklepios Family History Database for 2136 subjects. No shorter telomere length could be found in healthy subjects with a family history of CVD compared with those without. CONCLUSIONS: These findings cast serious doubt on the hypothesis that telomere length is shorter in families with an increased risk of CVD and do not support the Telomere Hypothesis of CVD.

Plant sterols and cardiovascular disease: a systematic review and meta-analysis.

The impact of increased serum concentrations of plant sterols on cardiovascular risk is unclear. We conducted a systematic review and meta-analysis aimed to investigate whether there is an association between serum concentrations of two common plant sterols (sitosterol, campesterol) and cardiovascular disease (CVD). We systematically searched the databases MEDLINE, EMBASE, and COCHRANE for studies published between January 1950 and April 2010 that reported either risk ratios (RR) of CVD in relation to serum sterol concentrations (either absolute or expressed as ratios relative to total cholesterol) or serum sterol concentrations in CVD cases and controls separately. We conducted two meta-analyses, one based on RR of CVD contrasting the upper vs. the lower third of the sterol distribution, and another based on standardized mean differences between CVD cases and controls. Summary estimates were derived by fixed and random effects meta-analysis techniques. We identified 17 studies using different designs (four case-control, five nested case-control, three cohort, five cross-sectional) involving 11 182 participants. Eight studies reported RR of CVD and 15 studies reported serum concentrations in CVD cases and controls. Funnel plots showed evidence for publication bias indicating small unpublished studies with non-significant findings. Neither of our meta-analyses suggested any relationship between serum concentrations of sitosterol and campesterol (both absolute concentrations and ratios to cholesterol) and risk of CVD. Our systematic review and meta-analysis did not reveal any evidence of an association between serum concentrations of plant sterols and risk of CVD.

Treatment gaps in the implementation of LDL cholesterol control among high- and very high-risk patients in Europe between 2020 and 2021: the multinational observational SANTORINI study.

Background: European data pre-2019 suggest statin monotherapy is the most common approach to lipid management for preventing cardiovascular (CV) events, resulting in only one-fifth of high- and very high-risk patients achieving the 2019 ESC/EAS recommended low-density lipoprotein cholesterol (LDL-C) goals. Whether the treatment landscape has evolved, or gaps persist remains of interest. Methods: Baseline data are presented from SANTORINI, an observational, prospective study that documents the use of lipid-lowering therapies (LLTs) in patients ≥18 years at high or very high CV risk between 2020 and 2021 across primary and secondary care settings in 14 European countries. Findings: Of 9602 enrolled patients, 9044 with complete data were included (mean age: 65.3 ± 10.9 years; 72.6% male). Physicians reported using 2019 ESC/EAS guidelines as a basis for CV risk classification in 52.0% (4706/9044) of patients (overall: high risk 29.2%; very high risk 70.8%). However, centrally re-assessed CV risk based on 2019 ESC/EAS guidelines suggested 6.5% (308/4706) and 91.0% (4284/4706) were high- and very high-risk patients, respectively. Overall, 21.8% of patients had no documented LLTs, 54.2% were receiving monotherapy and 24.0% combination LLT. Median (interquartile range [IQR]) LDL-C was 2.1 (1.6, 3.0) mmol/L (82 [60, 117] mg/dL), with 20.1% of patients achieving risk-based LDL-C goals as per the 2019 ESC/EAS guidelines. Interpretation: At the time of study enrolment, 80% of high- and very high-risk patients failed to achieve 2019 ESC/EAS guidelines LDL-C goals. Contributory factors may include CV risk underestimation and underutilization of combination therapies. Further efforts are needed to achieve current guideline-recommended LDL-C goals. Trial registration: ClinicalTrials.gov Identifier: NCT04271280. Funding: This study is funded by Daiichi Sankyo Europe GmbH, Munich, Germany.