A "Food Is Medicine" Approach to Disease Prevention: Limitations and Alternatives.

This Viewpoint argues that although "food is medicine" programs may help some patients prevent diet-related diseases, changing food industry behavior and ensuring that existing nutrition assistance programs are accessible and health-promoting are better strategies to make a difference.

[Comparison of aspirin treatment strategies for primary prevention of cardiovascular diseases: A decision-analytic Markov modelling study].

OBJECTIVE: To compare the expected population impact of benefit and risk of aspirin treatment strategies for the primary prevention of cardiovascular diseases recommended by different guidelines in the Chinese Electronic Health Records Research in Yinzhou (CHERRY) study. METHODS: A decision-analytic Markov model was used to simulate and compare different strategies of aspirin treatment, including: Strategy ①: Aspirin treatment for Chinese adults aged 40-69 years with a high 10-year cardiovascular risk, recommended by the 2020 Chinese Guideline on the Primary Prevention of Cardiovascular Diseases; Strategy ②: Aspirin treatment for Chinese adults aged 40-59 years with a high 10-year cardiovascular risk, recommended by the 2022 United States Preventive Services Task Force Recommendation Statement on Aspirin Use to Prevent Cardiovascular Disease; Strategy ③: Aspirin treatment for Chinese adults aged 40-69 years with a high 10-year cardiovascular risk and blood pressure well-controlled (< 150/90 mmHg), recommended by the 2019 Guideline on the Assessment and Management of Cardio-vascular Risk in China. The high 10-year cardiovascular risk was defined as the 10-year predicted risk over 10% based on the 2019 World Health Organization non-laboratory model. The Markov model simulated different strategies for ten years (cycles) with parameters mainly from the CHERRY study or published literature. Quality-adjusted life year (QALY) and the number needed to treat (NNT) for each ischemic event (including myocardial infarction and ischemic stroke) were calculated to assess the effectiveness of the different strategies. The number needed to harm (NNH) for each bleeding event (including hemorrhagic stroke and gastrointestinal bleeding) was calculated to assess the safety. The NNT for each net benefit (i.e., the difference of the number of ischemic events could be prevented and the number of bleeding events would be added) was also calculated. One-way sensitivity analysis on the uncertainty of the incidence rate of cardiovascular diseases and probabilistic sensitivity analysis on the uncertainty of hazard ratios of interventions were conducted. RESULTS: A total of 212 153 Chinese adults, were included in this study. The number of people who were recommended for aspirin treatment Strategies ①-③ was 34 235, 2 813, and 25 111, respectively. The Strategy ③ could gain the most QALY of 403 [95% uncertainty interval (UI): 222-511] years. Compared with Strategy ①, Strategy ③ had similar efficiency but better safety, with the extra NNT of 4 (95%UI: 3-4) and NNH of 39 (95%UI: 19-132). The NNT per net benefit was 131 (95%UI: 102-239) for Strategy ①, 256 (95%UI: 181-737) for Strategy ②, and 132 (95%UI: 104-232) for Strategy ③, making Strategy ③ the most favorable option with a better QALY and safety, along with similar efficiency in terms of net benefit. The results were consistent in the sensitivity analyses. CONCLUSION: The aspirin treatment strategies recommended by the updated guidelines on the primary prevention of cardiovascular diseases showed a net benefit for high-risk Chinese adults from developed areas. However, to balance effectiveness and safety, aspirin is suggested to be used for primary prevention of cardiovascular diseases with consideration for blood pressure control, resulting in better intervention efficiency.

New Cardiovascular Risk Assessment Techniques for Primary Prevention: JACC Review Topic of the Week.

Risk factor-based models fail to accurately estimate risk in select populations, in particular younger individuals. A sizable number of people are also classified as being at intermediate risk, for whom the optimal preventive strategy could be more precise. Several personalized risk prediction tools, including coronary artery calcium scoring, polygenic risk scores, and metabolic risk scores may be able to improve risk assessment, pending supportive outcome data from clinical trials. Other tools may well emerge in the near future. A multidimensional approach to risk prediction holds the promise of precise risk prediction. This could allow for targeted prevention minimizing unnecessary costs and risks while maximizing benefits. High-risk individuals could also be identified early in life, creating opportunities to arrest the development of nascent coronary atherosclerosis and prevent future clinical events.

Trends in ICD Implantations and in-Hospital Outcomes After DOJ Investigation.

BACKGROUND: The Department of Justice (DOJ) investigated implantable cardioverter-defibrillators (ICDs) not meeting the Centers for Medicare & Medicaid Services National Coverage Determination (NCD) criteria, resulting in increased adherence to the NCD criteria. Trends of the specific reasons for patients not meeting the NCD criteria and in-hospital outcomes for those patients are not known. METHODS AND RESULTS: We analyzed 300,151 primary-prevention ICDs from 2007-2015 at 1809 hospitals. We calculated the rates of in-hospital adverse events and the proportion of ICDs not meeting the 4 NCD criteria before and after the announcement of the DOJ investigation, stratified by whether hospitals paid settlements to the DOJ. Most reductions in the use of devices in patients not meeting NCD criteria were in patients with recently diagnosed heart failure (15.5%-6.8% for settled; 13.5%-7.3% for nonsettled) and who had had a recent myocardial infarction (8.4%-1.3% for settled; 7.4% to 1.5% for nonsettled). Adverse-event rates were significantly higher for ICDs not meeting NCD criteria (odds ratio 1.26 for settled; P < 0.001; 1.18 for nonsettled; P = 0.001). CONCLUSIONS: After the investigation, there was a rapid reduction in the placement of ICDs in patients with recent acute myocardial infarction or recent diagnosis of heart failure. Patients who did not meet NCD criteria experienced more in-hospital adverse events and higher mortality rates.

The cost implications of a polypill for primary prevention in the TIPS-3 trial.

AIMS: The International Polycap Study 3 (TIPS-3) trial demonstrated that a polypill containing cholesterol- and multiple blood-pressure-lowering drugs reduces cardiovascular events by 20% compared with placebo in people without cardiovascular disease. The polypill plus aspirin led to a 31% relative risk reduction in cardiovascular disease events compared with double placebo. We report regional variations in costs and affordability of a polypill based on the TIPS-3 trial. METHODS AND RESULTS: Countries were categorized using World Bank economic groups: lower-middle-income, upper-middle-income, and high-income countries. Country-specific costs were obtained for hospitalization events, procedures, and non-study medications (2019 US dollars). Polypill price was based on the cheapest equivalent substitute (CES) for each component. For the polypill vs. placebo, the difference in cost over the 4.6 years of the trial was $291 [95% confidence interval (CI): $243-339] per participant in lower-middle-income countries, $1068 (95% CI: $992-1144) in upper-middle-income countries, and $48 (95% CI: -$271 to $367) in high-income countries. Results were similar for the polypill plus aspirin vs. a double placebo. In both cases, the polypill was affordable in all groups using monthly household capacity to pay or a threshold of 4% of the gross national income per capita. CONCLUSION: The use of a polypill (CES) in TIPS-3 increases costs in lower-middle-income countries and upper-middle-income countries but is affordable in countries at various economic levels and is cost neutral (dominant) in high-income countries.

Assessment of Nonfatal Myocardial Infarction as a Surrogate for All-Cause and Cardiovascular Mortality in Treatment or Prevention of Coronary Artery Disease: A Meta-analysis of Randomized Clinical Trials.

Importance: Although nonfatal myocardial infarction (MI) is associated with an increased risk of mortality, evidence validating nonfatal MI as a surrogate end point for all-cause or cardiovascular (CV) mortality is lacking. Objective: To examine whether nonfatal MI may be a surrogate for all-cause or CV mortality in patients with or at risk for coronary artery disease. Data Sources: In this meta-analysis, PubMed was searched from inception until December 31, 2020, for randomized clinical trials of interventions to treat or prevent coronary artery disease reporting mortality and nonfatal MI published in 3 leading journals. Study Selection: Randomized clinical trials including at least 1000 patients with 24 months of follow-up. Data Extraction and Synthesis: Trial-level correlations between nonfatal MI and all-cause or CV mortality were assessed for surrogacy using the coefficient of determination (R2). The criterion for surrogacy was set at 0.8. Subgroup analyses based on study subject (primary prevention, secondary prevention, mixed primary and secondary prevention, and revascularization), era of trial (before 2000, 2000-2009, and 2010 and after), and follow-up duration (2.0-3.9, 4.0-5.9, and ≥6.0 years) were performed. Main Outcomes and Measures: All-cause or CV mortality and nonfatal MI. Results: A total of 144 articles randomizing 1 211 897 patients met the criteria for inclusion. Nonfatal MI did not meet the threshold for surrogacy for all-cause (R2 = 0.02; 95% CI, 0.00-0.08) or CV (R2 = 0.11; 95% CI, 0.02-0.27) mortality. Nonfatal MI was not a surrogate for all-cause mortality in primary (R2 = 0.01; 95% CI, 0.001-0.26), secondary (R2 = 0.03; 95% CI, 0.00-0.20), mixed primary and secondary prevention (R2 = 0.001; 95% CI, 0.00-0.08), or revascularization trials (R2 = 0.21; 95% CI, 0.002-0.50). For trials enrolling patients before 2000 (R2 = 0.22; 95% CI, 0.08-0.36), between 2000 and 2009 (R2 = 0.02; 95% CI, 0.00-0.17), and from 2010 and after (R2 = 0.01; 95% CI, 0.00-0.09), nonfatal MI was not a surrogate for all-cause mortality. Nonfatal MI was not a surrogate for all-cause mortality in randomized clinical trials with 2.0 to 3.9 (R2 = 0.004; 95% CI, 0.00-0.08), 4.0 to 5.9 (R2 = 0.06; 95% CI, 0.001-0.16), or 6.0 or more years of follow-up (R2 = 0.30; 95% CI, 0.01-0.55). Conclusions and Relevance: The findings of this meta-analysis do not appear to establish nonfatal MI as a surrogate for all-cause or CV mortality in randomized clinical trials of interventions to treat or prevent coronary artery disease.

Clinical management and primary prevention of suspected coronary artery disease guided by computed tomography.

AIMS: Despite the well established role of coronary computed tomography angiography (CCTA) as a diagnostic gatekeeper, the yield of subsequent invasive coronary angiographies (ICA) remains low. We evaluated the adherence of CCTA integration in clinical management and primary prevention therapy. METHODS: We retrospectively analyzed patients referred for ICA after CCTA without known coronary artery disease (CAD) or structural cardiac pathologies. Based on computed tomography (CT) findings, patients were classified as appropriately or inappropriately referred to ICA, equaling Coronary Artery Disease - Reporting and Data System (CAD-RADS) categories 0-2 (<50% stenosis) and 3-5 (>50% stenosis), respectively. CT exams were compared regarding invasive findings and revascularizations. Integration of CT results into primary prevention measures was analyzed and compared to measures taken after ICA. RESULTS: Of 1005 patients referred for ICA, 81 (8.1%) had no obstructive CT findings and therefore no ICA indication. ICA inappropriate patients did not differ in symptom characteristics, but had a significantly lower revascularization rate (3.7% vs. 42.1%, P < 0.0001) compared with patients appropriately referred to ICA. In patients with indication for lipid-lowering therapy after the CCTA statin rate was 53.1% and significantly increased after ICA to 76.4% (P < 0.0001). In CCTA, obstructive findings in proximal-only lesions did not increase the revascularization rate (45.6% vs. 42.1%, P = 0.11) but missed nonproximal relevant stenoses (15.0% vs. 2.5%, P < 0.0001) compared with obstructive findings in all segments. CONCLUSION: The overall rate of inappropriateness was low, but there is relevant statin underutilization in eligible patients due to a lack of CT findings integration. Both ICA referrals and primary preventive therapy could be improved by the implementation of CT results based on CAD-RADS recommendations.

Longitudinal Outcomes Associated With Non-Evidence-Based Implantable Cardioverter-Defibrillators Among Medicare Beneficiaries (From the National Cardiovascular Data Registry).

Primary prevention implantable cardioverter-defibrillators (ICDs) in patients with recent myocardial infarction or coronary revascularization and those with newly diagnosed or severe heart failure (HF) are considered non-evidence-based, as defined by pivotal randomized clinical trials. Although non-evidence-based ICDs have been associated previously with greater risk of in-hospital adverse events, longitudinal outcomes are not known. We used Medicare-linked data from the National Cardiovascular Data Registry's ICD Registry to identify patients discharged alive following first-time primary prevention ICD implantations performed between 2010 and 2013. We compared longitudinal outcomes, including all-cause mortality and all-cause hospital readmission among patients receiving non-evidence-based versus evidence-based ICDs, up to 4.75 years after implantation, using multivariable time-to-event analyses. Of 71,666 ICD implantations, 9,609 (13.4%) were classified as non-evidence-based. Compared to patients receiving evidence-based ICDs, non-evidence-based ICD recipients had greater mortality risk at 90 days (HR = 1.44, CI: 1.37 - 1.52, p <0.0001) and at 1 year (HR = 1.19, CI: 1.15 - 1.24, p <0.0001), but similar mortality risk at 3 years (HR = 1.03, CI: 0.98 - 1.08, p = 0.2630). Risk of all-cause hospitalization was higher in patients with non-evidence-based ICDs at 90 days (HR = 1.17, CI: 1.14 - 1.20, p <0.0001), but the difference diminished at 1 year (HR = 1.04, CI 1.00 - 1.07, p = 0.0272) and at 3 years (HR = 0.94, CI: 0.90 - 0.99, p = 0.0105). In conclusion, among patients undergoing primary prevention ICD implantations between 2010 and 2013, those with non-evidence-based ICDs were at increased risk of mortality and readmission during longitudinal follow-up. Differences in the risk of mortality and hospitalization were highest in the first year following device implantation.

Can Cost-effectiveness Analysis Inform Genotype-Guided Aspirin Use for Primary Colorectal Cancer Prevention?

BACKGROUND: Inherited genetic variants can modify the cancer-chemopreventive effect of aspirin. We evaluated the clinical and economic value of genotype-guided aspirin use for colorectal cancer chemoprevention in average-risk individuals. METHODS: A decision analytical model compared genotype-guided aspirin use versus no genetic testing, no aspirin. The model simulated 100,000 adults ≥50 years of age with average colorectal cancer and cardiovascular disease risk. Low-dose aspirin daily starting at age 50 years was recommended only for those with a genetic test result indicating a greater reduction in colorectal cancer risk with aspirin use. The primary outcomes were quality-adjusted life-years (QALY), costs, and incremental cost-effectiveness ratio (ICER). RESULTS: The mean cost of using genotype-guided aspirin was $187,109 with 19.922 mean QALYs compared with $186,464 with 19.912 QALYs for no genetic testing, no aspirin. Genotype-guided aspirin yielded an ICER of $66,243 per QALY gained, and was cost-effective in 58% of simulations at the $100,000 willingness-to-pay threshold. Genotype-guided aspirin was associated with 1,461 fewer polyps developed, 510 fewer colorectal cancer cases, and 181 fewer colorectal cancer-related deaths. This strategy prevented 1,078 myocardial infarctions with 1,430 gastrointestinal bleeding events, and 323 intracranial hemorrhage cases compared with no genetic testing, no aspirin. CONCLUSIONS: Genotype-guided aspirin use for colorectal cancer chemoprevention may offer a cost-effective approach for the future management of average-risk individuals. IMPACT: A genotype-guided aspirin strategy may prevent colorectal cancer, colorectal cancer-related deaths, and myocardial infarctions, while minimizing bleeding adverse events. This model establishes a framework for genetically-guided aspirin use for targeted chemoprevention of colorectal cancer with application toward commercial testing in this population.

Findings from the initial Stepwise Approach to Rabies Elimination (SARE) Assessment in China, 2019.

In 2015, China and other member states of the United Nations adopted the goal of eliminating dog-mediated rabies by 2030. China has made substantial progress in reducing dog-mediated human rabies since peaking with more than 3,300 reported cases in 2007. To further improve coordination and planning, the Chinese Center for Disease Control and Prevention, in collaboration with the United States Centers for Disease Control and Prevention, conducted a Stepwise Approach towards Rabies Elimination (SARE) assessment in March 2019. Assessment goals included outlining progress and identifying activities critical for eliminating dog-mediated rabies. Participants representing national, provincial and local human and animal health sectors in China used the SARE assessment tool to answer 115 questions about the current dog-mediated rabies control and prevention programs in China. The established surveillance system for human rabies cases and availability of post-exposure prophylaxis were identified as strengths. Low dog vaccination coverage and limited laboratory confirmation of rabid dogs were identified gaps, resulting in an overall score of 1.5 on a scale of 0 to 5. Participants outlined steps to increase cross-sectoral information sharing, improve surveillance for dog rabies, increase dog vaccination coverage, and increase laboratory capacity to diagnose rabies at the provincial level. All assessment participants committed to strengthening cross-sector collaboration using a One Health approach to achieve dog-mediated human rabies elimination by 2030.

Fostering Innovation in Prevention and Treatment of Obesity in Youth: Digitally Mediated Physical Play as an Exemplar.

Novel approaches to obesity prevention among youth are needed. Accordingly, the Office of Women's Health, Department of Health and Human Services, sponsored a challenge to create an interactive video game for obesity prevention. Our team took a theory-based, evidence-informed approach to increasing physical activity in girls. Our approach-digitally mediated physical play-allowed us to include computing-based strategies that promote activity without keeping players in front of a screen. Our prize-winning prototype app, Frolic, helps girls choose the perfect game to play in any context, engaging parents for support. The app is used to highlight some opportunities and challenges for interdisciplinary collaboration. However, much work remains to be done to deploy innovative digital obesity interventions and fully capture the contributions of these tools. In order to accelerate advances, funding is needed for projects that combine engineering design principles with traditional obesity research paradigms.

Icosapent Ethyl for Primary Versus Secondary Prevention of Major Adverse Cardiovascular Events in Hypertriglyceridemia: Value for Money Analysis.

BACKGROUND: Icosapent ethyl (IPE) is approved for the prevention of major adverse cardiovascular events (MACE) in patients with hypertriglyceridemia. However, due to budget constraints, access to IPE will inevitably be limited to a fraction of eligible patients. To help maximize value for money spent, we estimated the number of preventable MACE when providing IPE for primary versus secondary prevention. METHODS: The number of preventable MACE was estimated by dividing the available budget by the cost needed to treat (CNT) to prevent one MACE. CNT was calculated as the product of the number needed to treat (NNT) to prevent 1 MACE by therapy cost. NNT values were determined according to the Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention Trial (REDUCE-IT) results. The budget limit was set as the United States' threshold suggested by the Institute for Clinical and Economic Review. Sensitivity analysis was performed regarding the cost of IPE in the United States. RESULTS: The NNT to prevent 1 MACE over 4.9 years in the Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention Trial primary prevention cohort was 59 (95% confidence interval [CI]: 24-∞) versus 14 (11-21) for secondary prevention. At an annual IPE cost of $2915, the CNT to prevent 1 MACE was $842,726 (95% CI: $342,804-∞) and $199,969 ($157,118-$299,953) accordingly. A total of $819 million worth of IPE can avoid 4762 MACE (95% CI: 0-11,707) versus 20,069 (13,379-25,541), when provided as primary versus secondary prevention therapy; P < .001. The number of avoided MACE is sensitive to IPE price. CONCLUSIONS: Prioritizing IPE therapy for patients with an established cardiovascular disease may provide significantly more value for money than primary prevention.

Impact of insurance status on ICD implantation practice patterns: Insights from the NCDR ICD registry.

BACKGROUND: Whether insurance status influences practice patterns in implantable cardioverter-defibrillators (ICDs) and cardiac resynchronization therapy (CRT) defibrillators, when indicated, is not known. METHODS AND RESULTS: We analyzed the NCDR ICD Registry to evaluate associations of insurance status with guidelines-based receipt of CRT, as well as device-type, complication rates, and use of optimal medical therapy defined by guidelines. Among 798,028 patients with de novo ICD implants, we included only patients < 65 years (those older have Medicare) and excluded those admitted before 2006 (n=1,835) or with insurance coverage other than Medicare, Medicaid or private insurance (n=25,695) leaving 286,556 for analysis. Inverse probability of treatment weighting was used to control for imbalances between groups. Mean age was 53 years, 29% were female. Patients with private insurance and Medicare were more likely to receive CRT-D when indicated (79.6%, OR 1.19 95% CI 1.09-1.28, P <.001 and 78.5%, OR 1.11 95% CI 1.01-1.21 P = .03, respectively) compared to the uninsured (76.7%). The uninsured were also more likely than other groups to receive a single-chamber device. Complication rates did not differ. Uninsured patients were, however, more likely to receive optimal medical therapy, particularly in the subgroup receiving the implant for primary prevention. CONCLUSIONS: In propensity-weighted analysis, uninsured patients are less likely to receive CRT when indicated but more likely to be receiving optimal medical therapy at discharge. Reasons for differences in device implantation practices based on insurance status require further study.

Targeting of the diabetes prevention program leads to substantial benefits when capacity is constrained.

OBJECTIVE: Approximately 84 million people in the USA have pre-diabetes, but only a fraction of them receive proven effective therapies to prevent type 2 diabetes. We estimated the value of prioritizing individuals at highest risk of progression to diabetes for treatment, compared to non-targeted treatment of individuals meeting inclusion criteria for the Diabetes Prevention Program (DPP). METHODS: Using microsimulation to project outcomes in the DPP trial population, we compared two interventions to usual care: (1) lifestyle modification and (2) metformin administration. For each intervention, we compared targeted and non-targeted strategies, assuming either limited or unlimited program capacity. We modeled the individualized risk of developing diabetes and projected diabetic outcomes to yield lifetime costs and quality-adjusted life expectancy, from which we estimated net monetary benefits (NMB) for both lifestyle and metformin versus usual care. RESULTS: Compared to usual care, lifestyle modification conferred positive benefits and reduced lifetime costs for all eligible individuals. Metformin's NMB was negative for the lowest population risk quintile. By avoiding use when costs outweighed benefits, targeted administration of metformin conferred a benefit of $500 per person. If only 20% of the population could receive treatment, when prioritizing individuals based on diabetes risk, rather than treating a 20% random sample, the difference in NMB ranged from $14,000 to $20,000 per person. CONCLUSIONS: Targeting active diabetes prevention to patients at highest risk could improve health outcomes and reduce costs compared to providing the same intervention to a similar number of patients with pre-diabetes without targeted selection.

Life Course Health Development in Pediatric Practice.

The development of health is a cumulative, dynamic, and lifelong process responding to a variety of biological and behavioral influences, of which those in childhood are especially influential and, indeed, formative. Reflecting the balance of positive and adverse experiences during childhood, initial trajectories for future health and development emerge. Preventive pediatric care can anticipate and respond to those experiences and the personal and social circumstances in which they occur. These actions can promote better health and prevent chronic illness during adulthood. Building on the life course health development framework, ways to positively affect patterns of individual and population health practice are identified. Maximizing the opportunity to influence children's health over their lifetime will require purposeful partnerships with other entities with which children and their families interact as well as improvements in pediatric care processes. The latter includes expanding the databases that drive service (such as registries, care plans, and referrals) and adopting proactive, strengths-based, patient and family-centered, comprehensive, multidisciplinary models of care.