The Biggest Unmet Needs in Cardiovascular Disease Prevention in 2023.

BACKGROUND: While the major causes of atherosclerotic cardiovascular disease (CVD) are known, clinical audits continue to show inadequate risk factor control, even in the highest risk subjects. More effective risk estimation methods may help, and advances in this field are outlined. There exist excellent guidelines on CVD prevention, but their very length and complexity may limit their use. Other factors inhibiting guideline implementation are explored. SUMMARY: While new medications continue to be developed, the real challenges to effective CVD prevention are societal and political. Both nationally and at European levels, cohesive, integrated strategies with defined responsibilities and accountability are needed, together with empowerment of people to understand the concept of risk and what they can do about it. KEY MESSAGES: There are profound health inequalities between and within countries that need to be addressed.

New Way to "SCORE" Risk: Updates on the ESC Scoring System and Incorporation into ESC Cardiovascular Prevention Guidelines.

PURPOSE OF REVIEW: Prior European Society of Cardiology (ESC) guidelines endorsed the SCORE 10-year cardiovascular disease (CVD) risk calculator to inform the total risk approach to CVD prevention, including the use of preventive interventions like lipid lowering therapies. However, SCORE was released in 2003, did not allow for estimation of fatal and non-fatal CVD events, and was limited to adults aged 40 to 70 years. The ESC's Cardiovascular Risk Collaboration (CRC) was tasked with updating SCORE (SCORE2) and with extending the upper age range of adults eligible for risk estimation (SCORE2-OP). This review summarises these two deliverables. RECENT FINDINGS: Published in 2021, these updated risk scores allow for estimation of 10 year total (fatal + non-fatal) risks of a first atherosclerotic cardiovascular event in adults (SCORE2) and older persons (SCORE2-OP), calibrated for use in four European risk regions. The models account for competing risk of non-CVD death. These were extensively validated with excellent calibration and C-statistics ranging from 0.67 to 0.81. SCORE2 and SCORE2-OP have informed the 2021 ESC Guidelines on cardiovascular disease prevention in clinical practice. In addition to endorsing these two updated risk calculators, these guidelines have, for the first time, recommended the use of age-related risk categories. This change was motivated to prevent overreliance on age when making CVD prevention decisions.

Management of Dyslipidemias in Europe and the USA: Same Evidence, Different Conclusions? Can We Find Common Ground?

PURPOSE OF REVIEW: An examination of the current ACC/AHA and ESC/EAS Guidelines on the management of dyslipidemias for common ground and differences. RECENT FINDINGS: There is much common ground. Both note that ASCVD is, in most people, the product of a number of risk factors, notably tobacco exposure, hyperlipidemia, hypertension, inactivity, overweight and diabetes. They stress that risk calculators can help in the assessment of risk in apparently healthy persons. Persons with established ASCVD and many with diabetes or renal impairment are at high to very high risk and warrant intensive risk factor advice. The ACC/AHA Guidelines favor the universal use of statins in all high-risk subjects. In contrast, the ESC/EAS Guidelines favor a goal approach based on total risk and baseline LDL cholesterol level. Perhaps the most important challenges are to stress similarities rather than differences and to simplify communications with both healthcare professionals and the public. Subjects with established vascular disease and renal impairment and many with diabetes are at high to very high risk and need intensive risk factor management. A risk chart or calculator is recommended to assess total risk in apparently healthy persons. The higher the risk, the more intense the risk factor management.

Comparison of application of the ACC/AHA guidelines, Adult Treatment Panel III guidelines, and European Society of Cardiology guidelines for cardiovascular disease prevention in a European cohort.

IMPORTANCE: The 2013 American College of Cardiology/American Heart Association (ACC/AHA) guidelines introduced a prediction model and lowered the threshold for treatment with statins to a 7.5% 10-year hard atherosclerotic cardiovascular disease (ASCVD) risk. Implications of the new guideline's threshold and model have not been addressed in non-US populations or compared with previous guidelines. OBJECTIVE: To determine population-wide implications of the ACC/AHA, the Adult Treatment Panel III (ATP-III), and the European Society of Cardiology (ESC) guidelines using a cohort of Dutch individuals aged 55 years or older. DESIGN, SETTING, AND PARTICIPANTS: We included 4854 Rotterdam Study participants recruited in 1997-2001. We calculated 10-year risks for "hard" ASCVD events (including fatal and nonfatal coronary heart disease [CHD] and stroke) (ACC/AHA), hard CHD events (fatal and nonfatal myocardial infarction, CHD mortality) (ATP-III), and atherosclerotic CVD mortality (ESC). MAIN OUTCOMES AND MEASURES: Events were assessed until January 1, 2012. Per guideline, we calculated proportions of individuals for whom statins would be recommended and determined calibration and discrimination of risk models. RESULTS: The mean age was 65.5 (SD, 5.2) years. Statins would be recommended for 96.4% (95% CI, 95.4%-97.1%; n = 1825) of men and 65.8% (95% CI, 63.8%-67.7%; n = 1523) of women by the ACC/AHA, 52.0% (95% CI, 49.8%-54.3%; n = 985) of men and 35.5% (95% CI, 33.5%-37.5%; n = 821) of women by the ATP-III, and 66.1% (95% CI, 64.0%-68.3%; n = 1253) of men and 39.1% (95% CI, 37.1%-41.2%; n = 906) of women by ESC guidelines. With the ACC/AHA model, average predicted risk vs observed cumulative incidence of hard ASCVD events was 21.5% (95% CI, 20.9%-22.1%) vs 12.7% (95% CI, 11.1%-14.5%) for men (192 events) and 11.6% (95% CI, 11.2%-12.0%) vs 7.9% (95% CI, 6.7%-9.2%) for women (151 events). Similar overestimation occurred with the ATP-III model (98 events in men and 62 events in women) and ESC model (50 events in men and 37 events in women). The C statistic was 0.67 (95% CI, 0.63-0.71) in men and 0.68 (95% CI, 0.64-0.73) in women for hard ASCVD (ACC/AHA), 0.67 (95% CI, 0.62-0.72) in men and 0.69 (95% CI, 0.63-0.75) in women for hard CHD (ATP-III), and 0.76 (95% CI, 0.70-0.82) in men and 0.77 (95% CI, 0.71-0.83) in women for CVD mortality (ESC). CONCLUSIONS AND RELEVANCE: In this European population aged 55 years or older, proportions of individuals eligible for statins differed substantially among the guidelines. The ACC/AHA guideline would recommend statins for nearly all men and two-thirds of women, proportions exceeding those with the ATP-III or ESC guidelines. All 3 risk models provided poor calibration and moderate to good discrimination. Improving risk predictions and setting appropriate population-wide thresholds are necessary to facilitate better clinical decision making.

Personalized lifetime prediction of survival and treatment benefit in patients with heart failure with reduced ejection fraction: The LIFE-HF model.

AIMS: Although trials have proven the group-level effectiveness of various therapies for heart failure with reduced ejection fraction (HFrEF), important differences in absolute effectiveness exist between individuals. We developed and validated the LIFEtime-perspective for Heart Failure (LIFE-HF) model for the prediction of individual (lifetime) risk and treatment benefit in patients with HFrEF. METHODS AND RESULTS: Cox proportional hazards functions with age as the time scale were developed in the PARADIGM-HF and ATMOSPHERE trials (n = 15 415). Outcomes were cardiovascular death, heart failure (HF) hospitalization or cardiovascular death, and non-cardiovascular mortality. Predictors were age, sex, New York Heart Association class, prior HF hospitalization, diabetes mellitus, extracardiac vascular disease, systolic blood pressure, left ventricular ejection fraction, N-terminal pro-B-type natriuretic peptide, and glomerular filtration rate. The functions were combined in life-tables to predict individual overall and HF hospitalization-free survival. External validation was performed in the SwedeHF registry, ASIAN-HF registry, and DAPA-HF trial (n = 51 286). Calibration of 2- to 10-year risk was adequate, and c-statistics were 0.65-0.74. An interactive tool was developed combining the model with hazard ratios from trials to allow estimation of an individual's (lifetime) risk and treatment benefit in clinical practice. Applying the tool to the development cohort, combined treatment with a mineralocorticoid receptor antagonist, sodium-glucose cotransporter 2 inhibitor, and angiotensin receptor-neprilysin inhibitor was estimated to afford a median of 2.5 (interquartile range [IQR] 1.7-3.7) and 3.7 (IQR 2.4-5.5) additional years of overall and HF hospitalization-free survival, respectively. CONCLUSION: The LIFE-HF model enables estimation of lifelong overall and HF hospitalization-free survival, and (lifetime) treatment benefit for individual patients with HFrEF. It could serve as a tool to improve the management of HFrEF by facilitating personalized medicine and shared decision-making.

Atherosclerotic cardiovascular disease risk assessment: An American Society for Preventive Cardiology clinical practice statement.

Risk for atherosclerotic cardiovascular disease (ASCVD) shows considerable heterogeneity both in generally healthy persons and in those with known ASCVD. The foundation of preventive cardiology begins with assessing baseline ASCVD risk using global risk scores based on standard office-based measures. Persons at low risk are generally recommended for lifestyle management only and those at highest risk are recommended for both lifestyle and pharmacologic therapy. Additional "risk enhancing" factors, including both traditional risk factors and novel biomarkers and inflammatory factors can be used to further assess ASCVD risk, especially in those at borderline or intermediate risk. There are also female-specific risk enhancers, social determinants of health, and considerations for high-risk ethnic groups. Screening for subclinical atherosclerosis, especially with the use of coronary calcium screening, can further inform the treatment decision if uncertain based on the above strategies. Persons with pre-existing ASCVD also have variable risk, affected by the number of major ASCVD events, whether recurrent events have occurred recently, and the presence of other major risk factors or high-risk conditions. Current guidelines define high to very high risk ASCVD accordingly. Accurate ASCVD risk assessment is crucial for the appropriate targeting of preventive therapies to reduce ASCVD risk. Finally, the clinician-patient risk discussion focusing on lifestyle management and the risks and benefits of evidence-based pharmacologic therapies to best lower ASCVD risk is central to this process. This clinical practice statement provides the preventive cardiology specialist with guidance and tools for assessment of ASCVD risk with the goal of appropriately targeting treatment approaches for prevention of ASCVD events.

Total cardiovascular disease risk assessment: a review.

PURPOSE OF REVIEW: The high risk strategy for the prevention of cardiovascular disease (CVD) requires an assessment of an individual's total CVD risk so that the most intensive risk factor management can be directed towards those at highest risk. Here we review developments in the assessment and estimation of total CVD risk. RECENT FINDINGS: Recent advances have focused on newer approaches to expressing risk, including lifetime risk and risk age; these are particularly useful in communicating risk to younger individuals. Additionally, increased emphasis has been placed on the role of body weight and abdominal obesity in CVD risk. Several recent large studies have clarified a number of issues relevant to the management of CVD risk, a matter of growing global concern. SUMMARY: Simple risk estimation systems utilizing only easily measured variables have a role in improving the accessibility and cost effectiveness of risk estimation. The addition of newer variables to risk estimation systems may be particularly useful for those at intermediate risk, in order to more correctly reclassify such individuals into appropriate risk categories.

Medication details documented on hospital discharge: cross-sectional observational study of factors associated with medication non-reconciliation.

AIMS: Movement into or out of hospital is a vulnerable period for medication safety. Reconciling the medication a patient is using before admission with the medication prescribed on discharge, and documenting any changes (medication reconciliation) is recommended to improve safety. The aims of the study were to investigate the factors contributing to medication reconciliation on discharge, and identify the prevalence of non-reconciliation. METHODS: The study was a cross-sectional, observational survey using consecutive discharges from purposively selected services in two acute public hospitals in Ireland. Medication reconciliation, potential for harm and unplanned re-admission were investigated. RESULTS: Medication non-reconciliation was identified in 50% of 1245 inpatient episodes, involving 16% of 9569 medications. The majority of non-reconciled episodes had potential to result in moderate (63%) or severe (2%) harm. Handwritten rather than computerized discharges (adjusted odds ratio (adjusted OR) 1.60, 95% CI 1.11, 2.99), increasing number of medications (adjusted OR 1.26, 95% CI 1.21, 1.31) or chronic illness (adjusted OR 2.08, 95% CI 1.33, 3.24) were associated with non-reconciliation. Omission of endocrine, central nervous system and nutrition and blood drugs was more likely on discharge, whilst omission on admission and throughout inpatient care, without documentation, was more likely for obstetric, gynaecology and urinary tract (OGU) or respiratory drugs. Documentation in the discharge communication that medication was intentionally stopped during inpatient care was less likely for cardiovascular, musculoskeletal and OGU drugs. Errors involving the dose were most likely for respiratory drugs. CONCLUSIONS: The findings inform strategies to facilitate medication reconciliation on discharge from acute hospital care.

Integrin α(IIb)ß3 exists in an activated state in subjects with elevated plasma homocysteine levels.

Elevated levels of plasma homocysteine (Hcy) are an independent risk factor for cardiovascular disease and thrombosis. The molecular basis for this phenomenon is not known but may relate to modification of cell surface thiols. The platelet specific integrin α(IIb)ß3 is a cysteine-rich cell adhesion molecule that plays a critical role in platelet aggregation and adhesion in haemostasis and thrombosis. In this study, we looked for evidence of a homocysteine-induced modification of α(IIb)ß3 using a fluorescently labeled PAC-1 antibody that recognizes the activated conformation of the integrin on the platelet surface. We show that exogenous Hcy (10-100 µM) and homocysteine thiolactone (HcyTL) (10-100 µM) increased PAC-1 binding to platelets in a concentration dependent manner in vitro. In parallel, we show subjects with clinical hyperhomocysteinemia exhibit a greater degree of activation of α(IIb)ß3 compared to age-matched controls. These findings demonstrate that circulating Hcy can modulate the activation state of the platelet integrin α(IIb)ß3, a key player in platelet aggregation and thrombosis.

Systematic Coronary Risk Evaluation (SCORE): JACC Focus Seminar 4/8.

Clinical estimation of the combined effect of several risk factors is unreliable and this resulted in the development of a number of risk estimation systems to guide clinical practice. Here, after defining general principles of risk estimation, the authors describe the evolution of the European Society of Cardiology's (ESC) Systematic COronary Risk Evaluation (SCORE) risk estimation system and some learnings from the data. They move on to describe the establishment of the ESC's Cardiovascular Risk Collaboration and outline its proposed research directions. First among these is the evolution of SCORE 2, which provides updated, calibrated risk estimates for total cardiovascular events for low, moderate, high, and very high-risk regions of Europe. The authors conclude by considering that the future of risk estimation may be to express risk as years of exposure to a cardiovascular risk factor profile rather than risk over a fixed time period, such as 10 years, and how advances in genetics may permit individualized lifetime risk estimation from childhood on.

Optimising implementation of European guidelines on cardiovascular disease prevention in clinical practice: what is needed?

Cardiovascular disease is a model example of a preventable condition for which practice guidelines are particularly important. In 2016, the joint task force created by the European Society of Cardiology (ESC) together with 10 other societies released the new version of the European guidelines on cardiovascular disease prevention. To facilitate the implementation of the ESC guidelines, a dedicated prevention implementation committee has been established within the European Association of Preventive Cardiology. The paper will first explore potential barriers to the guidelines' implementation. It then develops a discussion that seeks to inform the future development of the committee's work, including a new definition of the guidelines' stakeholders (health policy-makers, healthcare professionals and health educators, patient organisations, entrepreneurs and the general public), future activities within four specific areas: strengthening awareness of the guidelines among stakeholders; supporting organisational changes to facilitate the guidelines' implementation; motivating stakeholders to utilise the guidelines; and present ideas on new implementation strategies. Providing multifaceted cooperation between healthcare professionals, healthcare management executives and health policy-makers, the novel approach proposed in this paper should contribute to a wider use of the 2016 ESC guidelines and produce desired effects of less cardiovascular disease morbidity and mortality. Furthermore, the solutions presented within the paper may constitute a benchmark for the implementation of practice guidelines in other medical disciplines.

Elevated resting heart rate is an independent risk factor for cardiovascular disease in healthy men and women.

BACKGROUND: Elevated resting heart rate (RHR) is known to be associated with reduced survival but inconsistencies remain, including lack of significance in most studies of healthy women, lack of independence from systolic blood pressure (SBP) in some, and the suggestion that RHR is merely functioning as a marker of physical inactivity or other comorbidities. We aimed to clarify these inconsistencies. METHODS: We analyzed the effect of RHR on end points in the National FINRISK Study; a representative, prospective study using Cox proportional hazards model. Ten-thousand five-hundred nineteen men and 11,334 women were included, excluding those with preexisting coronary heart disease, angina, heart failure, or on antihypertensive therapy. RESULTS: The hazard ratios for cardiovascular disease (CVD) mortality for each 15 beats/min increase in RHR were 1.24 (1.11-1.40) in men and 1.32 (1.08-1.60) in women, adjusted for age, gender, total cholesterol, physical activity (categorical), SBP, body mass index, and high-density lipoprotein cholesterol. This relationship remained significant after exclusion of those with comorbidities and events occurring within first 2 years of observation. Relationship with coronary mortality was stronger and with total mortality was slightly weaker. Inclusion of nonfatal end points weakened the relationship. CONCLUSIONS: A strong, graded, independent relationship between RHR and incident CVD was demonstrated. This was consistent in healthy men and women. We have clarified that the relationship is independent of SBP and that the temporal sequence would be compatible with a causal relationship. New findings include independence from both a validated measure of physical activity and comorbidities and the demonstration of a stronger effect for fatal than nonfatal events, supporting increased arrhythmogenicity of one of the mechanisms.

Italian cardiovascular mortality charts of the CUORE project: are they comparable with the SCORE charts?

BACKGROUND: The aim of this study was to build risk charts for the assessment of cardiovascular mortality of the CUORE project, an Italian longitudinal study, and to compare them with the systematic coronary risk evaluation (SCORE) project charts for low risk European countries. DESIGN: Random population samples enrolled in the 1980s and 1990s in Italy were included in the analysis: 7,520 men and 13,127 women aged 35-69 years without previous cardiovascular events and with a mean follow-up period of 10 years for cardiovascular disease. ICD-9 codes of death certificates similar to those of the SCORE project were considered when they appear as first cause of death. METHODS: Sex-stratified Cox proportional hazard model including age, systolic blood pressure, ratio between total and HDL cholesterol, and smoking habit as risk factors was used to assess cardiovascular mortality. RESULTS: Analysis showed that all risk factors included in the model were statistically significant. The corresponding area under the receiver operating characteristic curve was 0.825 (95% confidence interval: 0.803-0.846) for men and 0.850 (0.823-0.877) for women. The CUORE project charts yielded similar results to the corresponding charts of the SCORE project: Lin's coefficient was 0.929 for men and 0.935 for women. CONCLUSION: The comparison between CUORE and SCORE mortality risk charts shows that SCORE charts reflect quite well the Italian cardiovascular mortality and, correspondingly, Italian cohorts of the CUORE project are quite representative of European countries at low risk for cardiovascular mortality.

Assessment of cardiovascular risk.

Atherosclerotic cardiovascular disease (CVD) is the most common cause of death worldwide. Usually atherosclerosis is caused by the combined effects of multiple risk factors. For this reason, most guidelines on the prevention of CVD stress the assessment of total CVD risk. The most intensive risk factor modification can then be directed towards the individuals who will derive the greatest benefit. To assist the clinician in calculating the effects of these multiple interacting risk factors, a number of risk estimation systems have been developed. This review address several issues regarding total CVD risk assessment: Why should total CVD risk be assessed? What risk estimation systems are available? How well do these systems estimate risk? What are the advantages and disadvantages of the current systems? What are the current limitations of risk estimation systems and how can they be resolved? What new developments have occurred in CVD risk estimation?

Comparison of Transatlantic Approaches to Lipid Management: The AHA/ACC/Multisociety Guidelines vs the ESC/EAS Guidelines.

The 2018 American Heart Association/American College of Cardiology/Multisociety (AHA/ACC) guidelines and the 2019 European Society of Cardiology/European Atherosclerosis Society (ESC/EAS) guidelines on lipid management were published less than a year apart. Both guidelines focus on reducing cardiovascular risk, but they follow different approaches in terms of methods of risk estimation, definitions of at-risk groups, and treatment goals to achieve this common underlying objective. Both recommend achieving risk-based percentage reductions of low-density lipoprotein cholesterol (LDL-C) levels with statin therapy. The ESC/EAS guidelines additionally recommend target LDL-C levels and are more liberal in supporting the use of both statin and nonstatin therapies across broader patient groups. The AHA/ACC guidelines may be considered more conservative, reserving the addition of nonstatins to maximally tolerated statins for only select patient groups based on specific LDL-C thresholds. One of the main reasons for these differences is incorporation of cost value considerations by the AHA/ACC guidelines, whereas the ESC/EAS guidelines consider an ideal setting with unlimited resources while making recommendations. In this review, we discuss similarities and differences between the 2 lipid guidelines to help clinicians become more cognizant of these recommendations and provide the best individualized patient care.

Homocysteine increases the risk associated with hyperlipidaemia.

BACKGROUND: The European Concerted Action Project 'Homocysteine and Vascular Disease' showed that an elevated homocysteine is associated with a substantially increased risk of cardiovascular disease, and particularly when combined with other factors such as smoking, hypertension and hypercholesterolaemia. The purpose of this study was to examine the potential interactions between homocysteine and individual lipid subfractions. In addition, it was hypothesized that HDL cholesterol may protect against hyperhomocysteinaemia because HDL cholesterol is associated with the enzyme paroxonase, which reduces oxidization of homocysteine to the harmful metabolite, homocysteine thiolactonase. METHODS: Data from a multicentre European case-control study (750 cases and 800 controls) were used for analysis. The risks of vascular disease associated with homocysteine, total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides, apoprotein A1 and apoprotein B were established. The effect of elevated homocysteine on the cardiovascular risk associated with each lipid subfraction was then examined. RESULTS: As expected, homocysteine, total cholesterol, LDL cholesterol, triglycerides and apolipoprotein B were associated with cardiovascular risk. HDL cholesterol was inversely related to risk. Homocysteine increased the risk associated with all lipid measures. In contrast, a low plasma cholesterol does not seem to confer protection against the risk associated with a raised plasma homocysteine. Hyperhomocysteinaemia is associated with an increased risk at all levels of HDL cholesterol, conversely, in those with elevated homocysteine HDL cholesterol levels result in reduced risk. CONCLUSION: In general, the increased cardiovascular risk associated with elevated homocysteine is evident across the spectrum cholesterol subfraction levels.