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.

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.

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.

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.

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.

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.

Current guidelines on prevention with a focus on dyslipidemias.

Examination of the current the American College of Cardiology/American Heart Association (ACC/AHA) and European Society of Cardiology/European Atherosclerosis Society (ESC/EAS) guidelines on the prevention of cardiovascular disease and the management of dyslipidemias finds much common ground. Both note that Atherosclerotic cardiovascular disease (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 and guideline-based preventive therapies. The ACC/AHA guidelines favor the universal use of statins in all high-risk subjects and in primary prevention where the global risk exceeds 7.5% in 10 years, with a percentage reduction in low-density lipoprotein cholesterol (LDL-C) based on statin intensity as the "goal". In contrast, the ESC/EAS guidelines favor a goal or percentage-based reduction in LDL-C based on total risk and baseline LDL-C level. Both guidelines consider certain imaging and other measures to stratify risk as well as the use of non-statin therapies in those not achieving recommended targets. Perhaps the most important challenges are to stress similarities rather than differences, and to simplify communications with both healthcare professionals and the public.

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.

Simplifying the audit of risk factor recording and control: A report from an international study in 11 countries.

BACKGROUND: To simplify the assessment of the recording and control of coronary heart disease risk factors in different countries and regions. DESIGN: The SUrvey of Risk Factors (SURF) is an international clinical audit. METHODS: Data on consecutive patients with established coronary heart disease from countries in Europe, Asia and the Middle East were collected on a one-page collection sheet or electronically during routine clinic visits. Information on demographics, diagnostic category, risk factors, physical and laboratory measurements, and medications were included and key variables summarized in a Cardiovascular Health Index Score. RESULTS: Coronary heart disease patients (N = 10,186; 29% women) were enrolled from 79 centres in 11 countries. Recording of risk factors varied considerably: smoking was recorded in over 98% of subjects, while about 20% lacked data on laboratory measurements relevant to cardiovascular disease risk. Sixteen per cent of participants reported smoking, 29% were obese, and 46% had abdominal obesity. Sixty per cent of participants had blood pressure <140/90 mmHg (140/80 mmHg for diabetics), 48% had HbA1c<7%, 30% had low-density lipoprotein <1.8 mmol/l and 17% had a good cardiovascular health index score. There were substantial regional variations. Less than 3% of patients attended cardiac rehabilitation in Asia or the Middle East, compared with 45% in Europe. In Asia, 15% of patients had low-density lipoprotein cholesterol <1.8 mmol/l compared with 33% in Europe and 36% in the Middle East. Variations in medications were noted, with lower use of statins in Asia. CONCLUSIONS: SURF proved to be practical in daily practice. Results indicated poor control of risk factors with substantial variation between countries, calling for development and implementation of clinical standards of secondary prevention of coronary heart disease.

Cardiovascular risk estimation in older persons: SCORE O.P.

AIMS: Estimation of cardiovascular disease risk, using SCORE (Systematic COronary Risk Evaluation) is recommended by European guidelines on cardiovascular disease prevention. Risk estimation is inaccurate in older people. We hypothesized that this may be due to the assumption, inherent in current risk estimation systems, that risk factors function similarly in all age groups. We aimed to derive and validate a risk estimation function, SCORE O.P., solely from data from individuals aged 65 years and older. METHODS AND RESULTS: 20,704 men and 20,121 women, aged 65 and over and without pre-existing coronary disease, from four representative, prospective studies of the general population were included. These were Italian, Belgian and Danish studies (from original SCORE dataset) and the CONOR (Cohort of Norway) study. The variables which remained statistically significant in Cox proportional hazards model and were included in the SCORE O.P. model were: age, total cholesterol, high-density lipoprotein cholesterol, systolic blood pressure, smoking status and diabetes. SCORE O.P. showed good discrimination; area under receiver operator characteristic curve (AUROC) 0.74 (95% confidence interval: 0.73 to 0.75). Calibration was also reasonable, Hosmer-Lemeshow goodness of fit test: 17.16 (men), 22.70 (women). Compared with the original SCORE function extrapolated to the ≥65 years age group discrimination improved, p = 0.05 (men), p < 0.001 (women). Simple risk charts were constructed. On simulated external validation, performed using 10-fold cross validation, AUROC was 0.74 and predicted/observed ratio was 1.02. CONCLUSION: SCORE O.P. provides improved accuracy in risk estimation in older people and may reduce excessive use of medication in this vulnerable population.

Lack of efficacy of resveratrol on C-reactive protein and selected cardiovascular risk factors--Results from a systematic review and meta-analysis of randomized controlled trials.

INTRODUCTION: Numerous studies have suggested that oral supplementation with resveratrol exerts cardioprotective effects, but evidence of the effects on C-reactive protein (CRP) plasma levels and other cardiovascular (CV) risk factors is inconclusive. Therefore, we performed a meta-analysis to evaluate the efficacy of resveratrol supplementation on plasma CRP concentrations and selected predictors of CV risk. METHODS: The search included PUBMED, Cochrane Library, Web of Science, Scopus, and EMBASE (up to August 31, 2014) to identify RCTs investigating the effects of resveratrol supplementation on selected CV risk factors. Quantitative data synthesis was performed using a random-effects model, with weighted mean difference (WMD) and 95% confidence intervals (CI) as summary statistics. RESULTS: Meta-analysis of data from 10 RCTs (11 treatment arms) did not support a significant effect of resveratrol supplementation in altering plasma CRP concentrations (WMD: -0.144 mg/L, 95% CI: -0.968-0.680, p = 0.731). Resveratrol supplementation was not found to alter plasma levels of total cholesterol (WMD: 1.49 mg/dL, 95% CI: -14.96-17.93, p = 0.859), low density lipoprotein cholesterol (WMD: -0.31 mg/dL, 95% CI: -9.57-8.95, p = 0.948), triglycerides (WMD: 2.67 mg/dL, 95% CI: -28.34-33.67, p = 0.866), and glucose (WMD: 1.28 mg/dL, 95% CI: -5.28-7.84, p = 0.703). It also slightly reduced high density lipoprotein cholesterol concentrations (WMD: -4.18 mg/dL, 95% CI: -6.54 to -1.82, p = 0.001). Likewise, no significant effect was observed on systolic (WMD: 0.82 mmHg, 95% CI: -8.86-10.50, p = 0.868) and diastolic blood pressure (WMD: 1.72 mm Hg, 95% CI: -6.29-9.73, p=0.674). CONCLUSIONS: This meta-analysis of available RCTs does not suggest any benefit of resveratrol supplementation on CV risk factors. Larger, well-designed trials are necessary to confirm these results.

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.

A comparison of the herbicide tolerances of rare and common plants in an agricultural landscape.

Declining plant biodiversity in agroecosystems has often been attributed to escalating use of chemical herbicides, but other changes in farming systems, including the clearing of seminatural habitat fragments, confound the influence of herbicides. The present study introduces a new approach to evaluate the impacts of herbicide pollution on plant communities at landscape or regional scales. If herbicides are in fact a key factor shaping agricultural plant diversity, one would expect to see the signal of past herbicide impacts in the current plant community composition of an intensively farmed region, with common, successful species more tolerant to widely used herbicides than rare or declining species. Data from an extensive field survey of plant diversity in Lancaster County, Pennsylvania, USA, were compared with herbicide bioassay experiments in a greenhouse to test the hypothesis that common species possess higher herbicide tolerances than rare species. Five congeneric pairs of rare and common species were treated with 3 commonly used herbicide modes of action in bioassay experiments, and few significant differences were found in the tolerances of rare species relative to common species. These preliminary results suggest that other factors beyond herbicide exposure may be more important in shaping the distribution and abundance of plant species diversity across an agricultural landscape.

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.