Albuminuria and cardiovascular risk: A missed opportunity in the 2025 focused update of the ESC/EAS dyslipidaemia guidelines.

Joint statement from the European Atherosclerosis Society and European Society of Vascular Medicine focuses on patients with peripheral arterial disease

Standardization of laboratory lipid profile assessment: A call for action with a special focus on the 2016 ESC/EAS dyslipidemia guidelines – Executive summary: A consensus endorsed by the Cardiovascular Risk and Prevention Group of the Portuguese Internal Medicine Society, the Portuguese Atherosclerosis Society, the Portuguese Society of Cardiology, the Portuguese Society of Laboratory Medicine, and the Portuguese Association of Clinical

Standardization of laboratory and lipid profile evaluation: A call for action with a special focus in 2016 ESC/EAS dyslipidaemia guidelines – Full report

Nutrition interventions to address cardiovascular outcomes in chronic kidney disease

Genetic, experimental, epidemiologic, and clinical data support the causal role of elevated levels of low-density lipoprotein cholesterol (LDL-C) in atherosclerosis and cardiovascular disease (CVD). The recommendations of the 2019 European guidelines are based on the concept of differential CV risk, which in turn defines the LDL-C goals that should be achieved. The 2019 ESC/EAS guidelines for dyslipidaemia use the Systematic COronary Risk Evaluation (SCORE) model to assess CV risk, which provides a 10-year risk of fatal CV event. The SCORE model has recently been updated to reflect current rates of cardiovascular disease in Europe. The new SCORE2 model provides estimates of the 10-year risk of fatal and non-fatal CVD events in people aged 40-69 years, thus improving the identification of individuals at higher risk of a CVD event. However, as in the SCORE age is the main determinant of risk, young people have a relatively low estimated 10-year risk of a CV event even with high levels of one or more causal risk factors. Individuals with familial hypercholesterolaemia, who have elevated LDL-C levels from birth and have a high risk of premature CVD, are one example. The concept of cumulative LDL exposure is thus becoming increasingly important. This is also supported by Mendelian randomisation studies showing that carrying genetic variants associated with lower LDL-C levels reduces CV risk. These observations have introduced the concept of "cholesterol-years", which takes into account both LDL-C levels and time of exposure. It is crucial that future European guidelines pay more attention to this point.

Background/Aim Targeting PCSK9 inhibitors (PCSK9i) to patients with high LDL-cholesterol (LDL-C) as well as a high cardiovascular event rate yields the highest therapeutic effect and is thus reasonable from a health economic perspective. The current European dyslipidaemia guideline determines PCSK9i eligibility solely by LDL-C, whereas guidelines from the US/the UK additionally use a set of clinical risk factors. Such selection criteria require evaluation. Methods We determined the cardiovascular event rate and calculated the cost/preventable cardiovascular event for PCSK9i initiation in the target populations according to three scenarios: (i) European Society of Cardiology (ESC) 2019 dyslipidaemia guideline (PCSK9i recommended for all patients with residual LDL-C >55 mg/dl), (ii) American Heart Association/American College of Cardiology (AHA/ACC) 2018 cholesterol guideline (use of PCSK9i restricted to patients with residual LDL-C >70 mg/dl and clinical risk factors) and (iii) UK National Institute for Health and Care (NICE) recommendation (use of PCSK9i restricted to patients with residual LDL-C >155 mg/dl or >135 mg/dl with clinical risk factors). A Monte Carlo simulation taking into account statin intolerance was used to simulate uptitration of lipid lowering medications according to the different scenarios. Analyses were based on patients with atherosclerotic cardiovascular disease (ASCVD) from a contemporary all-comers cohort recruited at a large tertiary care center in Germany. Major adverse cardiovascular events (MACE, defined as the composite of cardiovascular death, non-fatal myocardial infarction, non-fatal stroke) were recorded over a median follow-up of 4.2 years. Results We included 1922 patients with ASCVD (mean age 69.3 years, median baseline LDL-C 86.0 mg/dl, 75.0% male). Eligibility for PCSK9i was simulated to be 39.6% (ESC 2019), 6.2% (AHA/ACC 2018) and 1.4% (NICE). The 3 year cardiovascular event rates in the corresponding PCSK9i target populations were 11.4%, 13.8% and 13.8% respectively. Event rate differences were driven by a higher rate of non-fatal myocardial infarction in the risk-based target populations (5.2%, 8.2%, 7.2%). Annual cost/preventable event differed by up to a factor 3 (689,000 €, 515,000 € and 215,000 €), driven mainly by pre-PCSK9i LDL-C levels in the different target populations (68.8 mg/dl, 76.0 mg/dl and 182.7 mg/dl). (Table 1) Conclusion The AHA/ACC and NICE guidelines, based on both residual LDL-C and clinical risk factors, reduced the eligibility for PCSK9i as well as the cost/preventable cardiovascular event compared to the ESC guideline. However, the clinical criteria used for risk classification yielded limited discrimination for the identification of subpopulations at highest cardiovascular risk. Development of accurate risk prediction tools and their integration into risk-based allocation strategies, both requisites for a cost-effective use of PCSK9i, remain a challenge.Table 1

South Africa (SA) is home to a heterogeneous population with a wide range of cardiovascular risk factors. Cholesterol reduction in combination with aggressive management of modifiable risk factors, including nutrition, physical activity, blood pressure and smoking, can help to reduce and prevent morbidity and mortality in individuals who are at increased risk of cardiovascular events. This updated consensus guide to management of dyslipidaemia in SA is based on the updated European Society of Cardiology and European Atherosclerosis Society dyslipidaemia guidelines published in 2016. For individuals who are not considered to be at high or very high cardiovascular risk, the decision whether to treat and which interventional strategy to use is based on a cardiovascular risk score calculated using total cholesterol, high-density lipoprotein cholesterol (HDL-C), gender, age and smoking status. The cardiovascular risk score refers to the 10-year risk of any cardiovascular event and includes 4 categories of risk (low, moderate, high and very high). People with established cardiovascular disease, diabetes mellitus, chronic kidney disease and genetic or severe dyslipidaemias are considered to already be at high or very high risk and do not require risk scoring. Therapeutic lifestyle change is the mainstay of management for all patients. The need for and intensity of drug therapy is determined according to baseline low-density lipoprotein (LDL-C) levels and the target LDL-C concentration appropriate to the individual. LDL-C treatment targets are based on pre-treatment risk and are as follows: <3 mmol/L in low- and moderate risk cases; <2.5 mmol/L and a reduction of at least 50% if the baseline concentration is 2.5 - 5.2 mmol/L in high-risk cases; and <1.8 mmol/L and a reduction of at least 50% if the baseline concentration is 1.8 - 3.5 mmol/L in very high-risk cases. A statin is usually recommended first-line; the specific agent is based on the required degree of cholesterol reduction, comorbidities and co-prescribed medication. Special attention should be paid to children with a family history of genetic or severe dyslipidaemia, who should be screened for dyslipidaemia from 8 years of age. In SA, HIV infection is not considered to be a significant cardiovascular risk factor and treatment recommendations for HIV-positive individuals are the same as for the general population, with careful choice of pharmacotherapy to avoid potential adverse drug-drug interactions. The benefit of statins in individuals older than 70 years is uncertain and clinical judgement should be used to guide treatment decisions and to avoid side-effects and overmedication in this group.

South Africa (SA) is home to a heterogeneous population with a wide range of cardiovascular risk factors. Cholesterol reduction in combination with aggressive management of modifiable risk factors, including nutrition, physical activity, blood pressure and smoking, can help to reduce and prevent morbidity and mortality in individuals who are at increased risk of cardiovascular events. This updated consensus guide to management of dyslipidaemia in SA is based on the updated European Society of Cardiology and European Atherosclerosis Society dyslipidaemia guidelines published in 2016. For individuals who are not considered to be at high or very high cardiovascular risk, the decision whether to treat and which interventional strategy to use is based on a cardiovascular risk score calculated using total cholesterol, high-density lipoprotein cholesterol (HDL-C), gender, age and smoking status. The cardiovascular risk score refers to the 10-year risk of any cardiovascular event and includes 4 categories of risk (low, moderate, high and very high). People with established cardiovascular disease, diabetes mellitus, chronic kidney disease and genetic or severe dyslipidaemias are considered to already be at high or very high risk and do not require risk scoring. Therapeutic lifestyle change is the mainstay of management for all patients. The need for and intensity of drug therapy is determined according to baseline low-density lipoprotein (LDL-C) levels and the target LDL-C concentration appropriate to the individual. LDL-C treatment targets are based on pre-treatment risk and are as follows: <3 mmol/L in low- and moderate risk cases; <2.5 mmol/L and a reduction of at least 50% if the baseline concentration is 2.5 - 5.2 mmol/L in high-risk cases; and <1.8 mmol/L and a reduction of at least 50% if the baseline concentration is 1.8 - 3.5 mmol/L in very high-risk cases. A statin is usually recommended first-line; the specific agent is based on the required degree of cholesterol reduction, comorbidities and co-prescribed medication. Special attention should be paid to children with a family history of genetic or severe dyslipidaemia, who should be screened for dyslipidaemia from 8 years of age. In SA, HIV infection is not considered to be a significant cardiovascular risk factor and treatment recommendations for HIV-positive individuals are the same as for the general population, with careful choice of pharmacotherapy to avoid potential adverse drug-drug interactions. The benefit of statins in individuals older than 70 years is uncertain and clinical judgement should be used to guide treatment decisions and to avoid side-effects and overmedication in this group.

The impact of the stepwise implementation of the 2019 European Society of Cardiology (ESC)/European Atherosclerosis Society (EAS) treatment algorithm on low-density lipoprotein cholesterol (LDL-C) goal attainment was simulated in patients from the DA VINCI study. Monte Carlo simulation was used to evaluate treatment optimisation scenarios, based on a patient's risk category: statin intensification (step 1), addition of ezetimibe (step 2), and addition of a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor (step 3). Residual cardiovascular risk and predicted relative and absolute risk reduction (RRR and ARR) in cardiovascular events were assessed. In DA VINCI, 2482 patients did not achieve their 2019 ESC/EAS LDL-C goals and were included in the simulation. In patients without atherosclerotic cardiovascular disease (ASCVD) (n=962), 27.0% (n=259) and 57.0% (n=548) are likely to achieve their LDL-C goals at step 1 and step 2, respectively. Of those at very high risk without ASCVD (n=74), 88.1% (n=65) are likely to achieve their LDL-C goals at step 3. In patients with ASCVD (n=1520), 12.0% (n=183), 42.1% (n=641) and 93.2% (n=1416) are likely to achieve their LDL-C goals at steps 1, 2 and 3, respectively. In patients with and without ASCVD, treatment optimisation may result in mean simulated RRR of 24.0% and 17.7%, respectively, and ARR of 8.1% and 2.6%, respectively. Most patients at high cardiovascular risk are unlikely to achieve LDL-C goals through statin optimisation and ezetimibe, and will require a PCSK9 inhibitor, leading to greater reduction in cardiovascular risk. Amgen.

Purpose Dyslipidemia is a major cardiovascular risk factor and treatment is mostly based on statins and ezetimibe. PCSK-9 inhibitors are monoclonal antibodies that reduce LDL-c levels and have shown significant reduction of cardiovascular risk in high risk patients. Data regarding potential eligibility for PCSK-9, is limited especially when referring to the recent guidelines. Methods Eligibility was calculated using a proprietary adjustable software, which stores data and patient information and thus by using different criteria it can determine potential candidates for PCSK-9 inhibitors. For this purpose, 2000 patients were enrolled prospectively. Our study population was comprised of inpatients diagnosed either with acute coronary syndromes (ACS) or with chronic coronary disease (cCAD) and outpatients from Lipids' Clinic (OLC) (n=407, n=1087, n=506, respectively). In order to test eligibility, three different LDL thresholds were used in our model for high and very high risk groups: a) 70mg/dl and 55mg/dl, respectively, as recommended by the recently updated 2019 ESC/EAS Guidelines for Dyslipidaemia b) 100mg/dl and 70mg/dl, respectively, as recommended by the 2016 ESC/EAS Guidelines for Dyslipidaemias and c) 130mg/dl and 100mg/dl respectively, as mandated by our National Health Care system but also applicable in other countries. Results The eligible percentages for the three thresholds were 18.85%, 9.75% and 2.15%, in the total population (TP) respectively and it varied according to clinical status. Subgroup analysis of eligible population revealed the trends in each group (Figure 1). The increase toward more recent guidelines was mostly attributed to the increasing number of coronary patients who become eligible as our criteria become stricter. Conclusions Our predictive model provides a realistic estimation of PCSK-9 inhibitors potential eligibility in coronary and dyslipidaemic patients and thus it can become a useful tool for the use of PCSK-9 in health care systems. Figure 1 Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Amgen Hellas LTD

Since the introduction of HAART, there was a remarkably change in the natural history of HIV disease, leading to a notable extension of life expectancy, although prolonged metabolic imbalances could significantly act on the longterm prognosis and outcome of HIV-infected persons, and there is an increasing concern about the cardiovascular risk in this population. Current recommendations suggest that HIV-infected perons undergo evaluation and treatment on the basis of the Third National Cholesterol Education Program Expert Panel on Detection, Evaluation and Treatment of High Blood Cholesterol in Adults (NCEP ATP III) guidelines for dyslipidemia, with particular attention to potential drug interactions with antiretroviral agents and maintenance of virologic control of HIV infection. While a hypolipidemic diet and physical activity may certainly improve dyslipidemia, pharmacological treatment becomes indispensable when serum lipid are excessively high for a long time or the patient has a high cardiovascular risk, since the suspension or change of an effective antiretroviral therapy is not recommended. Moreover, the choice of a hypolipidemic drug is often a reason of concern, since expected drug-drug interactions (especially with antiretroviral agents), toxicity, intolerance, effects on concurrent HIV-related disease and decrease patient adherence to multiple pharmacological regimens must be carefully evaluated. Often the lipid goals of patients in this group are not achieved by the therapy recommended in the current lipid guidelines and in this article we describe other possibilities to treat lipid disorders in HIV-infected persons, like rosuvastatin, ezetimibe and fish oil.

Purpose High and very high cardiovascular risk patients are usually possible candidates for PCSK-9 inhibitors. Coronary artery disease (CAD) and Familial Hypercholesterolaemia (FH) patients belong to this group by definition, according to 2019 recent dyslipidaemia guidelines. The real contribution of each group to potential eligibility for PCSK-9 is to be investigated. Methods We enrolled 1892 inpatients prospectively for 12 months, diagnosed either with chronic CAD or with acute coronary syndrome (ACS). In order to test eligibility for PCSK-9 inhibitors, three different LDL thresholds were used in our model for very high and high risk groups: 55mg/dl and 70mg/dl, 70mg/dl and 100mg/dl, 100mg/dl and 130mg/dl, as recommended by the 2019 and 2016 ESC/EAS Guidelines for Dyslipidaemia and the National Health Care system, respectively. A proprietary software was developed and eligibility was determined by using patient clinical information and different criteria. Dutch Lipid Clinic Network criteria were used to determine heterozygous FH population. Results The eligible percentage for the three classifications was 18.6%, 7.7% and 1.8%, in the total CAD population respectively. Definite/ probable FH percentages among our population were 4.8%, 3.4%, 1.4%, respectively. Solely CAD eligible population was 13.8%, 4.3% and 0.4% respectively. The increase of the eligible percentages toward more recent guidelines was mostly attributed to the increasing number of coronary patients who become eligible as our criteria become stricter while the percentage of the eligible CAD/FH population only slightly increases. Conclusions FH is a significant cardiovascular risk factor but stricter criteria and LDL thresholds, favour solely CAD patients. Using real-world data and an adjustable model, we provide a realistic estimation of PCSK-9 eligibility among CAD patients. Funding Acknowledgement Type of funding sources: None. Subgroup analysis of eligible population

Clinical and Economic Impact of Early Rreatment Initiation with Evolocumab in Patients with a Recent Myocardial Infarction in the United States

In the face of the rising incidence of cardiovascular diseases (CVD) and diabetes in low-income and middle-income countries in South Asia, the most cost-effective and equitable strategies for prevention of heart attacks, strokes and vascular complications of diabetes need to be incorporated into primary care services. Health system and resource limitations in these countries call for directing preventive services and pharmacological treatment to people with high cardiovascular risk, identified by risk stratification using hypertension and diabetes as entry points. Absolute cardiovascular risk prediction scores should be used routinely in primary care. Individual management guidelines for hypertension, dyslipidemia and diabetes need to be replaced by integrated and simplified cardiovascular risk management guidelines.

981 CARDIOVASCULAR RISK PROFILE ASSESSMENT AS REPORTED BY INVESTIGATORS AND BY ESC/EAS CRITERIA: EVIDENCE FROM SANTORINI STUDY (THE ITALIAN REALITY))