European Journal of Preventive Cardiology

Almarzooq, Zaid I

doi: 10.1093/eurjpc/zwaa056pmid: 33623990

This editorial refers to ‘The impact of coronary heart disease prevention on work productivity: a ten year analysis’, by Ella Zomer et al., doi: 10.1093/eurjpc/zwaa037. Coronary heart disease (CHD) is the leading cause of death and disability worldwide.1 It has a significant impact on the global economy and productivity, and it continues to worsen.2 The American Heart Association recently published its 2030 Impact Goal that focuses on different measures of health such as health-adjusted life expectancy and aims to raise the bar for healthy life expectancy from 66 years of age to at least 67 years globally by 2030.3 In addition, a recently published position paper from the European Association of Preventive Cardiology stresses the importance of reducing cardiovascular disease costs and discusses some of the evidence behind the cost-effectiveness of primary prevention strategies.4 With increasingly aging populations and rising healthcare costs, it is critical to focus on cost-effective strategies that impact not only direct healthcare costs but also incorporate indirect costs such as productivity while improving the overall well-being of populations. Current guidelines have emphasized the importance of prevention strategies while considering their cost-effectiveness.5 However, the evidence provided in guidelines focuses on direct costs without incorporating indirect costs and, therefore, likely underestimates the impact of CHD. In this issue of the European Journal of Preventive Cardiology, Savira et al. evaluate the impact of cardiovascular prevention on productivity in the Australian working-age population over 10 years using the measure ‘productivity-adjusted life years’ (PALYs). The study sought to evaluate the effect of preventing new cases of CHD on the Australian population’s longevity and productivity. Their study demonstrates several important findings. First, among the total Australian working population, the study projects a life expectancy of ∼133 million and PALYs of ∼83 million. Second, they predicted that the number of working Australians with CHD would increase by 11% over the next ten years, which equates to 39,990 new CHD cases (1.73% of the Australian working-age population). Third, these new cases of CHD will account for 14,202 deaths; 8,228 life years lost; 104,206 PALYs; and total cost of US$14.8 billion that could be avoided if the CHD cases were prevented. Fourth, among the contributors to loss of productivity, labour force dropout (i.e. early retirement) accounted for most of the estimated loss in productivity (69.4%) followed by presenteeism (i.e. at work but not fully functioning, 21%), absenteeism (8.7%), and premature mortality (0.9%). Finally, they identified significant sex differences, with males contributing 61% to the total CHD-related loss in productivity. The authors conclude that these values present important health and economic opportunities for employers and policymakers. Regarding the methods used in this study, the authors had previously used a similar approach, but in closed cohorts, to evaluate the impact of type 2 diabetes and smoking.6,7 The current study constructed a dynamic life table model using the total Australian working population (aged 15–69 years) over 10 years from 2020 to 2029, stratified by CHD status. They included three health states: ‘alive without CHD’, ‘alive with CHD’, and ‘dead’. Absenteeism and presenteeism estimates were derived from prior studies.8,9 A financial value was ascribed to the PALY using the gross domestic product (GDP) per full-time worker. Estimation of life expectancy, PALYs, and cost (GDP per PALYs) were calculated by CHD status. Productivity loss related to CHD was based on prior studies that estimated a loss of 6.7 days of work (range: 1.2–17.8 days) and 16.3 days of unproductive time at work per person per year (range: 0–32.4).8 The authors repeated the model simulation, assuming that all new CHD cases could be prevented, and the differences between the models represented the impact of CHD prevention. Appropriate discounting (∼5% per year) was performed for all outcomes starting after the first year. A sensitivity analysis was performed to account for the risk of mortality associated with CHD, early retirement due to CHD, different base case estimates, different discounting rates including the World Health Organization rate of 3%, and extending the time horizon to 20 years. They used several data sources for this study, including data from the Australian Bureau of Statistics for population-related data including mortality, migration, birth rates, and labour participation and the Australian Institute of Health and Welfare for CHD prevalence rates. This study highlights the important impact of CHD on productivity and the potential economic benefits of prevention. These findings are consistent with prior studies, including a recent study by Schofield et al. that used the measure ‘productivity life years’ to evaluate the impact of chronic health conditions including CHD on older workers in Australia aged 45–64 years using a microsimulation model.2 The authors projected a 62% increase in costs incurred from loss of income, a 35% increase in welfare payments, and a 58% increase in lost income tax revenue due to CHD between the years of 2015–2030 that totals to a loss of US$755 million in GDP for 2015, which increased to US$1082 million in 2030. These studies, however, did not incorporate some of the factors used in the current study, including CHD-related labour force dropout, absenteeism, and presenteeism. This accounts for the different total costs estimated. Another strength of the current study is the use of a dynamic life table method that allowed for movement in and out of the model due to birth, death, migration, and aging beyond the working-age used. Importantly, the measures of labour force participation are not only relevant from an economic standpoint but are also an important indicator of physical functioning and psychological well-being in those with chronic conditions such as CHD. Finally, the mechanisms of lost productivity from CHD are likely multiple and include CHD-related acute hospitalizations, ongoing exertional or resting symptoms of ischaemia, symptoms related to underlying ischaemic cardiomyopathy, and depression related to underlying CHD. The important findings of this study clearly illustrate the economic potential of CHD prevention that could inform the public and policymakers alike. Multiple population-level prevention strategies have proven to be successful and cost-effective (Figure 1).10 Despite the success of individual-level prevention strategies, such as smoking cessation programmes, blood pressure control, and cholesterol reduction therapies, the current study emphasizes the additional need for population-level strategies given the scale of CHD in populations. The European Guidelines on Prevention has recommended a population-level approach that follows the Geoffrey Rose Paradigm, emphasizing that small changes in the risk of disease across a community consistently lead to more significant reductions in disease burden than a large change in high-risk individuals only.5 Multiple initiatives have been successful that governmental and non-governmental agencies could employ. These include policies that promote a healthy diet (e.g., banning of industrial trans fats, taxes on sugar-rich foods and beverages, marketing restrictions), environmental changes to facilitate healthier dietary selection and physical activity, and community-level initiatives (e.g., availability of healthy foods at schools and workplaces, increasing green space and recreational space). The current study’s estimates of indirect costs from CHD suggest that such population-level interventions are likely to be cost-effective when incorporating productivity gains.11 This becomes even more important as government budgets face competing needs from unexpected hazards such as the COVID-19 pandemic and other chronic conditions. Figure 1 Open in new tabDownload slide Impact of coronary heart disease and potential prevention strategies. QALYs, quality-adjusted life years; PALY, productivity-adjusted life years; HALYs, health-adjusted life years; DALYs, disability-adjusted life years. Figure 1 Open in new tabDownload slide Impact of coronary heart disease and potential prevention strategies. QALYs, quality-adjusted life years; PALY, productivity-adjusted life years; HALYs, health-adjusted life years; DALYs, disability-adjusted life years. The results of this study should be interpreted with consideration of a few caveats. First, the estimates presented likely underestimate the incidence of CHD, given that they did not include less severe cases of CHD that do not result in hospitalization. Also, the productivity loss estimates reflected chronic CHD and did not consider acute episodes of CHD that may have a greater loss in productivity, especially in the first year following the event. The authors justify this by findings of prior studies showing that the impact of acute CHD declines with time and plateaus at 1 year.8 Second, estimates of absenteeism and presenteeism related to CHD were derived from a US population, given the absence of these data in the Australian population. To minimize the impact this has on the difference between the two strata of populations (CHD and no CHD), estimates of absenteeism and presenteeism for the population without CHD were also derived from a US population.9 Finally, the generalizability of this study may be limited, given the population selected, and the actual estimates are population specific. Therefore, populations from other countries will need to conduct similar studies to estimate their specific burden of CHD and associated economic impact. Future studies will need to incorporate sociodemographic factors into the model, including race/ethnicity, given the significant disparities that exist in society today. Overall, the study by Savira et al. highlights the substantial opportunities that could be provided by CHD prevention strategies for both public health officials and policymakers. Evaluating these strategies will require the incorporation of indirect costs such as productivity to truly understand the broad scope of their benefits. Conflict of interest: none declared. The opinions expressed in this article are not necessarily those of the Editors of the European Heart Journal or of the European Society of Cardiology. References 1 Roth GA , Johnson C, Abajobir A, Abd-Allah F, Abera SF, Abyu G, Ahmed M, Aksut B, Alam T, Alam K, Alla F, Alvis-Guzman N, Amrock S, Ansari H, Ärnlöv J, Asayesh H, Atey TM, Avila-Burgos L, Awasthi A, Banerjee A, Barac A, Bärnighausen T, Barregard L, Bedi N, Belay Ketema E, Bennett D, Berhe G, Bhutta Z, Bitew S, Carapetis J, Carrero JJ, Malta DC, Castañeda-Orjuela CA, Castillo-Rivas J, Catalá-López F, Choi J-Y, Christensen H, Cirillo M, Cooper L, Criqui M, Cundiff D, Damasceno A, Dandona L, Dandona R, Davletov K, Dharmaratne S, Dorairaj P, Dubey M, Ehrenkranz R, El Sayed Zaki M, Faraon EJA, Esteghamati A, Farid T, Farvid M, Feigin V, Ding EL, Fowkes G, Gebrehiwot T, Gillum R, Gold A, Gona P, Gupta R, Habtewold TD, Hafezi-Nejad N, Hailu T, Hailu GB, Hankey G, Hassen HY, Abate KH, Havmoeller R, Hay SI, Horino M, Hotez PJ, Jacobsen K, James S, Javanbakht M, Jeemon P, John D, Jonas J, Kalkonde Y, Karimkhani C, Kasaeian A, Khader Y, Khan A, Khang Y-H, Khera S, Khoja AT, Khubchandani J, Kim D, Kolte D, Kosen S, Krohn KJ, Kumar GA, Kwan GF, Lal DK, Larsson A, Linn S, Lopez A, Lotufo PA, El Razek HMA, Malekzadeh R, Mazidi M, Meier T, Meles KG, Mensah G, Meretoja A, Mezgebe H, Miller T, Mirrakhimov E, Mohammed S, Moran AE, Musa KI, Narula J, Neal B, Ngalesoni F, Nguyen G, Obermeyer CM, Owolabi M, Patton G, Pedro J, Qato D, Qorbani M, Rahimi K, Rai RK, Rawaf S, Ribeiro A, Safiri S, Salomon JA, Santos I, Santric Milicevic M, Sartorius B, Schutte A, Sepanlou S, Shaikh MA, Shin M-J, Shishehbor M, Shore H, Silva DAS, Sobngwi E, Stranges S, Swaminathan S, Tabarés-Seisdedos R, Tadele Atnafu N, Tesfay F, Thakur JS, Thrift A, Topor-Madry R, Truelsen T, Tyrovolas S, Ukwaja KN, Uthman O, Vasankari T, Vlassov V, Vollset SE, Wakayo T, Watkins D, Weintraub R, Werdecker A, Westerman R, Wiysonge CS, Wolfe C, Workicho A, Xu G, Yano Y, Yip P, Yonemoto N, Younis M, Yu C, Vos T, Naghavi M, Murray C Global, regional, and national burden of cardiovascular diseases for 10 causes, 1990 to 2015 . J Am Coll Cardiol 2017 ; 70 : 1 – 25 . Google Scholar Crossref Search ADS PubMed WorldCat 2 Schofield D , Cunich M , Shrestha R , Passey M , Veerman L , Tanton R , Kelly S. The indirect costs of ischemic heart disease through lost productive life years for Australia from 2015 to 2030: results from a microsimulation model . BMC Public Health 2019 ; 19 : 802 . Google Scholar Crossref Search ADS PubMed WorldCat 3 Angell SY , McConnell MV , Anderson CAM , Bibbins-Domingo K , Boyle DS , Capewell S , Ezzati M , de Ferranti S , Gaskin DJ , Goetzel RZ , Huffman MD , Jones M , Khan YM , Kim S , Kumanyika SK , McCray AT , Merritt RK , Milstein B , Mozaffarian D , Norris T , Roth GA , Sacco RL , Saucedo JF , Shay CM , Siedzik D , Saha S , Warner JJ The American Heart Association 2030 impact goal: a presidential advisory from the American Heart Association . Circulation 2020 ; 141 : e120 – e138 . Google Scholar Crossref Search ADS PubMed WorldCat 4 Piepoli MF , Abreu A , Albus C , Ambrosetti M , Brotons C , Catapano AL , Corra U , Cosyns B , Deaton C , Graham I , Hoes A , Lochen M-L , Matrone B , Redon J , Sattar N , Smulders Y , Tiberi M Update on cardiovascular prevention in clinical practice: a position paper of the European Association of Preventive Cardiology of the European Society of Cardiology . Eur J Prev Cardiol 2020 ; 27 : 181 – 205 . Google Scholar Crossref Search ADS PubMed WorldCat 5 Piepoli MF , Hoes AW , Agewall S , Albus C , Brotons C , Catapano AL , Cooney M-T , Corrà U , Cosyns B , Deaton C , Graham I , Hall MS , Hobbs FDR , Løchen M-L , Löllgen H , Marques-Vidal P , Perk J , Prescott E , Redon J , Richter DJ , Sattar N , Smulders Y , Tiberi M , van der Worp HB , van Dis I , Verschuren WMM , Binno S , ESC Scientific Document Group European Guidelines on cardiovascular disease prevention in clinical practice: the Sixth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (constituted by representatives of 10 societies and by invited experts) Developed with the special contribution of the European Association for Cardiovascular Prevention & Rehabilitation (EACPR ). Eur Heart J 2016 ; 37 : 2315 – 2381 . Google Scholar Crossref Search ADS PubMed WorldCat 6 Owen AJ Maulida SB Zomer E Liew D. Productivity burden of smoking in Australia: a life table modelling study . Tob Control 2019 ; 28 : 297 – 304 . Google Scholar Crossref Search ADS PubMed WorldCat 7 Magliano DJ Martin VJ Owen AJ Zomer E Liew D. The productivity burden of diabetes at a population level . Diabetes Care 2018 ; 41 : 979 – 984 . Google Scholar Crossref Search ADS PubMed WorldCat 8 Goetzel RZ Hawkins K Ozminkowski RJ Wang S. The health and productivity cost burden of the “top 10” physical and mental health conditions affecting six large U.S. employers in 1999 . J Occup Environ Med 2003 ; 45 : 5 – 14 . Google Scholar Crossref Search ADS PubMed WorldCat 9 Stewart WF Ricci JA Chee E Morganstein D. Lost productive work time costs from health conditions in the United States: results from the American Productivity Audit . J Occup Environ Med 2003 ; 45 : 1234 – 1246 . Google Scholar Crossref Search ADS PubMed WorldCat 10 Schwalm JD McKee M Huffman MD Yusuf S. Resource effective strategies to prevent and treat cardiovascular disease . Circulation 2016 ; 133 : 742 – 755 . Google Scholar Crossref Search ADS PubMed WorldCat 11 Grover SA Ho V Lavoie F Coupal L Zowall H Pilote L. The importance of indirect costs in primary cardiovascular disease prevention: can we save lives and money with statins? Arch Intern Med 2003 ; 163 : 333 – 339 . Google Scholar Crossref Search ADS PubMed WorldCat Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: [email protected]. This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model)

Voges, Inga; Krupickova, Sylvia

doi: 10.1093/eurjpc/zwaa017pmid: 33624082

This editorial refers to ‘Physical exercise training in patients with a Fontan circulation: A systematic review’, by E.L. Scheffers et al., doi: 10.1177/2047487320942869 The growing population of single ventricle patients with Fontan circulation requires new strategies about management and treatment of alterations and potential complications in this group of patients. Reduced exercise capacity in Fontan patients is common and it has been shown that exercise performance progressively declines over the years.1 A key factor associated with reduced exercise tolerance is a diminished preload followed by a reduced stroke volume of the single ventricle when exercising, whereas chronotropic response is maintained and corresponds with the exercise intensity.2 Exercise intolerance in Fontan patients may lead to physical inactivity associated with further reduction in exercise capacity and negative effects on physical and psychological well-being (Figure 1).3 Figure 1 Open in new tabDownload slide Positive effects of exercise training in patients with a Fontan circulation. Figure 1 Open in new tabDownload slide Positive effects of exercise training in patients with a Fontan circulation. In this issue, Scheffers et al.4 present a systematic review of various types of exercise training in Fontan patients. Most importantly, they were able to show that exercise training is not only highly likely to be safe, but that it is also associated with improved exercise capacity and quality of life.4 Based on the 22 studies included in this review, they report that peak oxygen consumption (peak VO2) increased in about 60% of the studies. Quality of life was assessed in six studies and it could be demonstrated that training improves self-reported and/or parent-reported quality of life. Similar to previous systematic literature review,5 the authors showed that adverse events during exercise are rare. Only three adverse events in the analysed studies occurred and they were thought to be unrelated to the exercise training.4 Unfortunately, it is difficult to draw a conclusion about the best type of training for patients with a Fontan circulation based on reviewed studies because of the different training types and small number of studies assessing types of the training. However, the conclusion drawn by the authors suggesting a 2-weekly supervised training including a combination of aerobic and resistance training seems to be reasonable. Although this systematic review is very helpful in routine clinical practice for clinicians dealing with Fontan patients, several questions remain and should be addressed in future research. First, are there differences in response to regular exercise between children and adults with a Fontan circulation? Scheffers et al. have addressed this question by giving detailed information about the respective study populations included in each study. They hereby demonstrate the lack of studies focusing on the increasing number of adult Fontan patients who are more likely to be physically limited due to an increasing morbidity with age.6 This leads to the next question. What is the best training type for this more physically limited group of Fontan patients? Those few studies in adult Fontan patients, analysed by Scheffers et al., included patients, who were able to undergo a cardiopulmonary exercise test7–9 suggesting that patients with a worse clinical status were excluded from these studies. The resulting dilemma of this selection effect is the incapability of giving adequate training advice to those patients with more significant physical constraints and Fontan-associated complications. The third question concerns potential differences in exercise capacity and training effects between patients with single right ventricle (RV) and single left ventricle (LV). Especially, the increasing number of patients with hypoplastic left heart syndrome (HLHS) is likely to be different from single LV Fontan patients (e.g. patients with tricuspid atresia or double inlet LV). One reason is that the single RV in HLHS patients or other congenital heart entities must perform significantly more work in the systemic circulation compared to a normal RV in a biventricular system. Right ventricular dysfunction in single RV Fontan patients is therefore common and is likely to be accompanied by physical limitations. We therefore suggest that future studies should address this selection bias by including more uniform patient cohorts with regards to the underlying cardiac disease and the clinical status. Upcoming investigations should also focus on differences between single RV and single LV patients to be able to offer more individualized training advice. Finally, as mentioned by Scheffers et al., the long-term effects of exercise training in Fontan patients are unknown. In particular, the interesting question if regular training in childhood will improve exercise capacity as well as outcome in the adult Fontan patient has not been answered yet. However, referring to the results from other patient populations, it is expected that physical activity and exercise training in Fontan patients will have positive effects on long-term physical and mental health.10 We have little doubt about safety and general positive effects of regular exercise training in Fontan patients as demonstrated by Scheffers et al., especially when it starts early in childhood. But although nowadays cardiologists usually encourage children and adults with a Fontan circulation to participate in sports activities, there are still concerns about possible life-threatening cardiac events. In addition, there is a lack of information about the benefit of sports activities in congenital heart disease patients in schools and other institutions delivering exercise activities. Education of patients and their families, teachers and sports clubs about the overall safety and positive effects of regular exercise on physical and mental health is therefore of great importance to promote exercise training in Fontan patients. Apart from the likely benefit of exercise on general health and well-being, cardiopulmonary exercise testing (CPET) in congenital heart disease patients is also of diagnostic importance and should be part of the regular follow-up. Recent studies have demonstrated that certain CPET markers like peak oxygen uptake and ventilation/carbon dioxide elimination slope as well as oxygen uptake efficiency slope, a newer index of functional capacity, seem to be worse in congenital heart disease patients.11,12 Serial CPET studies, starting in childhood can help to document any deterioration of CPET parameters in Fontan patients and might help to detect patients who have a higher risk for Fontan failure. Efforts should also be made to improve the assessment of physical activity together with regular CPET during long-term follow-up. Ideally, a standard follow-up plan also focusing on physical activities should be available for clinicians dealing with Fontan patients. This will be beneficial for the individual patient but will also help our understanding of exercise capacity during long-term follow-up and will promote further studies. Most likely, highly individualized and supervised exercise programmes considering patients age, underlying morphology, clinical status, and patient’s preference will appear to be the most beneficial in the long-term perspective. Future multicentre studies and data sharing might increase our knowledge about long-term effects of regular physical activity and best approach in the management of Fontan patients. Conflict of interest: none declared. The opinions expressed in this article are not necessarily those of the Editors of the European Journal of Preventive Cardiology or of the European Society of Cardiology. References 1 Giardini A , Hager A, Pace Napoleone C, Picchio FM. Natural history of exercise capacity after the Fontan operation: a longitudinal study . Ann Thorac Surg 2008 ; 85 : 818 – 821 . Google Scholar Crossref Search ADS PubMed WorldCat 2 Claessen G , La Gerche A, Van De Bruaene A, Claeys M, Willems R, Dymarkowski S, Bogaert J, Claus P, Budts W, Heidbuchel H, Gewillig M. Heart rate reserve in Fontan patients: chronotropic incompetence or hemodynamic limitation? J Am Heart Assoc 2019 ; 8 : e012008 . Google Scholar Crossref Search ADS PubMed WorldCat 3 McCrindle BW , Williams RV, Mital S, et al. Physical activity levels in children and adolescents are reduced after the Fontan procedure, independent of exercise capacity, and are associated with lower perceived general health . Arch Dis Child 2007 ; 92 : 509 – 514 . Google Scholar Crossref Search ADS PubMed WorldCat 4 Scheffers EL , vd Berg LE, Ismailova G, et al. Physical exercise training in patients with a Fontan circulation: a systematic review . Eur J Prev Cardiol 2020 . https://doi.org/ 10.1177/2047487320942869 . Google Scholar OpenURL Placeholder Text WorldCat Crossref 5 Sutherland N , Jones B, d'Udekem Y. Should we recommend exercise after the Fontan procedure? Heart Lung Circ 2015 ; 24 : 753 – 768 . Google Scholar Crossref Search ADS PubMed WorldCat 6 Atz AM , Zak V, Mahony L, et al. Longitudinal outcomes of patients with single ventricle after the Fontan procedure . J Am Coll Cardiol 2017 ; 69 : 2735 – 2744 . Google Scholar Crossref Search ADS PubMed WorldCat 7 Cordina RL , O'Meagher S, Karmali A, et al. Resistance training improves cardiac output, exercise capacity and tolerance to positive airway pressure in Fontan physiology . Int J Cardiol 2013 ; 168 : 780 – 788 . Google Scholar Crossref Search ADS PubMed WorldCat 8 Wu FM , Opotowsky AR, Denhoff ER, et al. A pilot study of inspiratory muscle training to improve exercise capacity in patients with Fontan physiology . Semin Thorac Cardiovasc Surg 2018 ; 30 : 462 – 469 . Google Scholar Crossref Search ADS PubMed WorldCat 9 Fritz C , Müller J, Oberhoffer R, et al. Inspiratory muscle training did not improve exercise capacity and lung function in adult patients with Fontan circulation: a randomized controlled trial . Int J Cardiol 2020 ; 305 : 50 – 55 . Google Scholar Crossref Search ADS PubMed WorldCat 10 Dimitri P , Joshi K, Jones N. Moving Medicine for Children Working Group. Moving more: physical activity and its positive effects on long term conditions in children and young people . Arch Dis Child 2020 ; doi:10.1136/archdischild-2019-318017. Google Scholar OpenURL Placeholder Text WorldCat 11 Righini FM , Apostolo A, Heck PB, et al. Exercise physiology in pulmonary hypertension patients with and without congenital heart disease . Eur J Prev Cardiol 2019 ; 26 : 86 – 93 . Google Scholar Crossref Search ADS PubMed WorldCat 12 Hossri CA , Souza IPA, de Oliveira JS, Mastrocola LE. Assessment of oxygen-uptake efficiency slope in healthy children and children with heart disease: Generation of appropriate reference values for the OUES variable . Eur J Prev Cardiol 2019 ; 26 : 177 – 184 . Google Scholar Crossref Search ADS PubMed WorldCat Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: [email protected]. This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model)

Svendsen, Karianne; Vinknes, Kathrine J; Retterstøl, Kjetil; Olsen, Thomas

doi: 10.1093/eurjpc/zwaa008pmid: 33624034

This editorial refers to ‘Non-adherence to established dietary guidelines associated with increased mortality: the Copenhagen General Population Study', by E. Bettina et al., https://doi.org/10.1177/2047487320937491 The general public is constantly assailed by conflicting nutrition claims that can lead to considerable confusion and adverse health outcomes.1,2 These challenges may in part arise from the sensationalism of nutrition research in the media and other outlets. In scientific discourse however, nutrition research, and particularly the field of nutritional epidemiology, is often critizised for being poorly conducted.3 Nevertheless, nutritional epidemiology plays an important role in informing public policies and dietary guidelines, meaning that there is a continuous need for rigorously conducted epidemiological nutrition research to inform the public and to verify that existing guidelines are justified in terms of health outcomes. In this issue of the journal, Ewers et al. investigated the association of non-adherence to national dietary guidelines in the Copenhagen General Population Study, a large cohort consisting of >100 000 participants.4 Using a short food frequency questionnaire (FFQ), they classified participants as either very high, high, intermediate, low, or very low adherers to the dietary guidelines with a specific focus on fat quality, salt intake, fruit and vegetable intakes, and sugar-sweetened beverages. They report a graded relationship between categories of adherence with cardiovascular disease (CVD) mortality, non-CVD mortality, and all-cause mortality, with the strongest adverse effects observed in very low adherers. The authors reported that the population attributable risk (PAR) of all-cause mortality associated with low adherence was ∼12.9%, which is similar to the 13% PAR for acute myocardial infarction associated with low fruit and vegetable intakes in the INTERHEART study.5 This large-scale study is of strong relevance to the public and possesses particular strengths related to the choice of methods and design. First, the choice to include directed acyclic graphs to justify the statistical models facilitates transparency, reproducibility, and confidence because it shows that the authors have given appropriate thought to the causal network underlying the diet–disease relationship that they describe. This method for confounder selection relies on prior epidemiological and biological knowledge compared to largely data-driven methods that can result in significant bias arising from inappropriate adjustment of mediators or so-called colliders.6 Second, the authors should be commended for their inclusion of modern statistical approaches for causal inference such as mediation analysis that can aid in the causal interpretation of the results. In these analyses, mediation effects of LDL-cholesterol, body mass index, or diabetes for low adherence on disease outcomes were not observed. This somewhat surprising finding indicates that other causal mechanisms may be at play and calls for more research into biological mechanisms linking dietary habits to disease outcomes and mortality. As with all observational research, there are some drawbacks to be discussed and considered in light of the results. Measurement errors remain a well-known challenge in nutritional epidemiology and the systematic biases associated with FFQs cannot necessarily be rescued by a large sample, which is otherwise a strength of this study. The short FFQ administered in the present study did not assess intakes of whole-grain products, low-fat dairy and meats, or sugary products outside sweetened beverages, most of which are indeed emphasized in dietary guidelines including the Nordic guidelines.7 The omission of these foods from the FFQ may have affected exposure classification (levels of adherence) and introduced bias in the analyses. The sum of biases inherent in dietary recall instruments can be partially overcome by using a combination of methods for data collection including repeated 24-h recalls in combination with FFQs.8 We therefore argue that more emphasis should be put on collecting accurate dietary data in future cohort studies assessing diet–disease relationships. Despite this drawback, there are likely advantages to administering abbreviated FFQs that sacrifice some precision for convenience for the participants, and the remaining food groups that were indeed included in the FFQ can give a reasonable perspective on diet quality. Furthermore, as the FFQs were administered between 2003 and 2015, they likely reflect current eating habits. This is particularly relevant considering the governmental legislation enforced by Denmark in 2003 imposing restrictions on the contents of industrially produced pro-atherogenic trans fatty acids in all food products.9 Ewers et al. further remind us of the importance of adhering to several dietary factors as opposed to focusing on single nutrients or even food groups to prevent CVD. This is underlined by the findings that very high, high, and intermediate adherences to dietary guidelines were all likely to produce benefits compared to very low adherence in a graded manner. Supporting this notion, other studies collecting data on the same and additional food groups also report inverse associations for high adherence, disease outcomes, and mortality.10,11 In addition, a recent comprehensive meta-analysis showed that foods highlighted by public health nutrition guidelines were inversely associated with all-cause mortality and CVD.12 With this in mind, we argue that a continued focus should be placed on the diet as a whole instead of single nutrients in future research and public health policy. Another point to consider is that the societal and global financial savings are potentially massive,13 further emphasizing the tremendous public, social, and financial benefits of trusting and adhering to dietary guidelines. The authors conclude that the Danish public has good reason to trust the dietary guidelines. In light of the reported findings, the inherent strengths and limitations of the study, and the compliance with the wider literature, we agree with this conclusion. Because dietary guidelines are largely consistent across the world, this means that the findings are likely to be generalizable to other populations. Thus, the message is clear: we can probably remain confident in the public policy dietary guidelines for prevention. Conflict of interest: The authors declare that there are no conflicts of interest. The opinions expressed in this article are not necessarily those of the Editors of the European Journal of Preventive Cardiology or of the European Society of Cardiology. References 1 Nagler RH. Adverse outcomes associated with media exposure to contradictory nutrition messages . J Health Commun 2014 ; 19 : 24 – 40 . Google Scholar Crossref Search ADS PubMed WorldCat 2 Lee CJ Nagler RH Wang N. Source-specific exposure to contradictory nutrition information: documenting prevalence and effects on adverse cognitive and behavioral outcomes . Health Commun 2018 ; 33 : 453 – 461 . Google Scholar Crossref Search ADS PubMed WorldCat 3 Ioannidis JP. Implausible results in human nutrition research . BMJ 2013 ; 347 : f6698 . Google Scholar Crossref Search ADS PubMed WorldCat 4 Ewers B, Marott JL, Schnohr P, Nordestgaard BG, Marckmann P. Non-adherence to established dietary guidelines associated with increased mortality: the Copenhagen General Population Study. European journal of preventive cardiology . Eur J Prev Cardiol . 2020 . 2047487320937491 . 10.1177/2047487320937491 . 32646303. Google Scholar OpenURL Placeholder Text WorldCat Crossref 5 Yusuf S , Hawken S, Ounpuu S, Dans T, Avezum A, Lanas F, McQueen M, Budaj A, Pais TJ., Varigos J, Lisheng. Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): case-control study. 2004;364:937. 10.1016/S0140-6736(04)17018-9 6 VanderWeele TJ. Principles of confounder selection . Eur J Epidemiol 2019 ; 34 : 211 – 219 . Google Scholar Crossref Search ADS PubMed WorldCat 7 Nordic Nutrition Recommendations 2012: Integrating Nutrition and Physical Activity . Copenhagen : Nordic Council of Ministers ; 2012 . Google Scholar Google Preview OpenURL Placeholder Text WorldCat COPAC 8 Carroll J , Midthune D, Subar AF, Shumakovich M, Freedman S, Thompson E, Kipnis V. Taking advantage the strengths 2 different dietary assessment instruments to improve intake estimates for nutritional epidemiology . American Journal of Epidemiology 2012 ; 175 :340. 10.1093/aje/kwr317 Google Scholar OpenURL Placeholder Text WorldCat Crossref 9 Astrup A. The trans fatty acid story in Denmark . Atheroscler Suppl 2006 ; 7 : 43 – 46 . Google Scholar Crossref Search ADS PubMed WorldCat 10 Fresan U Sabate J Martinez-Gonzalez MA , Segovia-Siapco G, de la Fuente-Arrillaga C, Bes-Rastrollo M. Adherence to the 2015 Dietary Guidelines for Americans and mortality risk in a Mediterranean cohort: the SUN project . Prev Med 2019 ;118:317. 10.1016/j.ypmed.2018.11.015 Google Scholar OpenURL Placeholder Text WorldCat 11 Yu D Zhang X Xiang YB , Yang G, Li H, Gao YT, Zheng, W, Shu, XO et al. Adherence to dietary guidelines and mortality: a report from prospective cohort studies of 134,000 Chinese adults in urban Shanghai . Am J Clin Nutr 2014 ; 100 : 693 – 700 . Google Scholar Crossref Search ADS PubMed WorldCat 12 Kwok CS Gulati M Michos ED , Potts J, Wu P, Watson L, Loke YK, Mallen C, Mamas MA et al. Dietary components and risk of cardiovascular disease and all-cause mortality: a review of evidence from meta-analyses . Eur J Prev Cardiol 2019 ; 26 : 1415 – 1429 . Google Scholar Crossref Search ADS PubMed WorldCat 13 Candari CJ Cylus J Nolte E. Assessing the Economic Costs of Unhealthy Diets and Low Physical Activity: An Evidence Review and Proposed Framework . Copenhagen, Denmark: WHO Regional Office for Europe ; 2017 . Google Scholar PubMed OpenURL Placeholder Text Google Preview WorldCat COPAC Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: [email protected]. This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model)

Caro-Codón, Juan; López-Fernández, Teresa; Álvarez-Ortega, Carlos; Zamora Auñón, Pilar; Rodríguez, Isabel Rodríguez; Gómez Prieto, Pilar; Buño Soto, Antonio; Canales Albendea, Miguel; Albaladejo, Ainara; Mediavilla, Guiomar; Feliu Batlle, Jaime; Rodríguez Fraga, Olaia; Martínez Monzonis, Amparo;

Kim, In-Soo; Lee, Byoung Kwon; Yang, Pil-Sung; Joung, Boyoung; Kim, Jong-Youn

doi: 10.1093/eurjpc/zwaa071pmid: 33624094

AimsAlthough the adverse cardiovascular effect of anaemia has been well described, the effect of polycythaemia on the cardiovascular outcomes of the general population remain unclear. The primary objective is to identify the association between polycythaemia and major adverse cardiovascular events (MACE), and the secondary objective is to identify the specific haemoglobin concentration more associated with an increased risk for MACE.Methods and resultsThis was a retrospective cohort study, 451 107 subjects were enrolled who underwent national health examinations from the Korean National Sample Cohort. We estimated the risk of MACE, a composite of cardiovascular mortality, incident myocardial infarction (MI), and stroke according to haemoglobin-based four categories. During 3.8-year of follow-up, polycythaemia group showed higher MACE [hazard ratio (HR) = 1.27 (1.13–1.44) and HR = 1.76 (1.08–2.88); in men and women, respectively], incident MI [HR = 1.37 (1.05–1.79) and HR = 3.46 (1.06–14.00)], and incident ischaemic stroke [HR = 1.27 (1.10–1.46) and HR = 1.72 (1.02–2.91)] than normal haemoglobin group (P < 0.001 in all cases). In the normal haemoglobin and polycythaemia groups, a 1 g/dL increase in haemoglobin level was associated with increased risks of MACE [HR = 1.04 (1.01–1.07) and HR = 1.05 (1.01–1.10) in men and women, each P < 0.05]. To investigate the specific haemoglobin concentration related to greater MACE incidence, we analysed the sensitivity/specificity of different haemoglobin levels: ≥16.5 g/dL in men and ≥15.0 g/dL in women showed the highest Youden’s index (sensitivity + specificity − 1), with c-indices of 0.82 (0.81–0.83) and 0.83 (0.82–0.84), respectively.ConclusionEven in the Korean general population, polycythaemia was significantly associated with higher rates of MACE, incident MI, and incident ischaemic stroke. Especially, subjects with haemoglobin levels ≥15.0 g/dL in women and ≥16.5 g/dL among men were associated with increased risks of MACE.

Brotons, Carlos

doi: 10.1093/eurjpc/zwaa111pmid: 33624077

This editorial refers to ‘Parental cardiovascular health predicts time to onset of cardiovascular disease in offspring’, by J.M. Muchira et al. doi:10.1093/eurjpc/zwaa072 According to the European Cardiovascular Disease Statistics 2017 of the European Heart Network, cardiovascular diseases (CVDs) are the leading causes of death in many European countries, accounting for 1.8 million deaths across Europe. Every year, there are more than 3 million new cases of coronary heart disease (CHD) and more than 600 000 cases of stroke in the European Union (EU), and 17 million EU citizens live with a heart attack or stroke.1,2 In many European countries, stroke, heart attack, and other CVD take up a large, if not the biggest, proportion of healthcare spending. Across the EU, hospitalizations for CVD, including heart attack and stroke, are responsible for 53% of healthcare expenditure. Combined with indirect costs, CVD cost the EU health system a total of €210 billion in 2015.1 The number of people at risk of a heart attack or stroke is likely to rise, which poses a threat to social and economic sustainability of healthcare in European countries. The number of people at high risk of cardiovascular or cerebrovascular disease will rise, driven by ageing populations and endemic lifestyle and behavioural risk factors, such as physical inactivity and unhealthy diet. 3. It has also become clear that many CVDs with ultimate outcomes in adulthood actually have their origins during childhood. Unfortunately, there are disturbing trends of increasing obesity, and increasing prevalence of hypertension and type 2 diabetes mellitus in the paediatric population. The American Heart Association (AHA)4 defined the concept of ideal cardiovascular health (CVH), by the presence of both ideal health behaviours (non-smoking, body mass index <25 kg/m2, physical activity at goal levels, and healthy diet) and ideal health factors (total cholesterol <200 mg/dL, blood pressure <120/<80 mmHg, and fasting glucose <100 mg/dL). With the use of levels that span the entire range of the same metrics, CVH status for the whole population is defined as poor, intermediate, or ideal. These metrics can be very useful to determine the changing prevalence of CVH status of the population. Transmission of cardiovascular risk factors from parent to offspring can be explained by three mechanisms: pregnancy complications, genetic inheritance, and shared environmental risk factors after pregnancy. A factor that has received increased attention is the idea of developmental programming during foetal life. The Barker hypothesis stated that low birth weight (LBW) serves as proxy not just for foetal but also adult health. Today, LBW is associated with a host of chronic diseases ranging from CHD, type 2 diabetes mellitus, cancer, and osteoporosis to various psychiatric illnesses.5 When facing with the adversity of malnutrition or pregnancy complications such as preeclampsia, a foetus will undergo an adaptation in order to survive to a stressful environment. It must be recognized, however, that over time, this evolutionary advantage of plasticity is lost, and one’s response to environmental or pathological challenges becomes constrained. This phenomenon, known as programming, refers to the fact that stimuli, when applied during early development, generate permanent changes that persist throughout one’s lifespan. Programming is not just limited to the in utero environment, but extends into childhood, where different organs and systems continue to adapt to various cues.6 Heritability studies have identified genetic variants for certain cardiovascular risk factors such as excessive fatness7 or familial hypercholesterolaemia caused by mutations in the LDL receptor gene, PCSK9 and ApoB.8 Also, there is evidence that adverse maternal cardiovascular risk factors such as body mass index and blood pressure are strongly associated with corresponding adverse cardiovascular risk factors in offspring at the age of 9 years after pregnancy, regardless of pregnancy complications and environmental risk factors.9 Shared environmental risk factors such as diet and exposure to smoking may be also involved in the pathway of tracking cardiovascular risk factors from parents to children. Previous studies have shown that parents’ diet quality and energy intake and smoking are associated with those of their offspring.10,11 Another recent study that conducted a series of cross-sectional analyses of the Framingham Heart Study (FHS) has shown that parental CVH was positively associated with offspring CVH. Interestingly, investigators found that intergenerational CVH gains from declining smoking rates, cholesterol and blood pressure were offset by increasing obesity and elevated glucose levels among the offspring.12 Also, clustering of shared exposure to CVD within families is attributable to interactions among genetic, environmental and behavioural factors, and socioeconomic status. It has been shown that among individuals at high genetic risk, a favourable lifestyle was associated with a nearly 50% lower relative risk of coronary artery disease than was an unfavourable lifestyle.13 There has been a significant increase in the number of epigenetics studies investigating cardiovascular risk factors and outcomes in relation to DNA methylation, histone posttranslational modifications, alteration of RNA expression but still it is not well understood the underlying cause and biological implications.14 In this issue of the journal, Muchira et al.15 make further steps, analysing the association between parental CVH and time to onset of CVD in the offspring, using the longest running cohorts of the FHS, the Original Cohort (Parents) and Offspring Cohort. They derived a CVH score (out of 14) based on 7 CVH metrics according to AHA criteria described above. They included a good sample size with 1989 offspring, 1989 mothers, and 1989 fathers and used time to event duration from baseline to first occurrence of fatal or non-fatal CVD event in the offspring. They found that parental with ideal CVH had a greater CVD-free survival, being maternal CVH a more robust predictor than parental CVH. This is a worthwhile investigation contributing to the knowledge of intergenerational transmission of cardiovascular risk factors from parents to children. Even though this study was restricted to predominantly white Caucasian participants, the findings that maternal CVH have stronger positive association with offspring's CVD-free survival than fathers are not surprising and may also apply to other populations. Mothers have had an important role in families in terms of shaping dietary patterns and other lifestyle habits, and even environmental factors. However, nowadays this might have changed since in many Western societies fathers and mothers equally share child-care responsibilities. The study of Muchira et al. is a valuable investigation and emphasizes the importance community prevention programmes focusing on families. It is of paramount importance to prevent the development of risk factors specially on childhood and adolescence. It makes sense that avoidance of adverse levels of risk factors in the first place may be the most effective means for avoiding clinical events during the remaining lifespan. This is the meaning of primordial prevention, a concept introduced by Strasser16 in 1978. It refers to a strategy to prevent whole societies from experiencing epidemics of the risk factors, and at the individual level is to prevent the development of risk factors in the first place, while primary prevention refers to the efforts aimed at individuals who already have adverse levels of known risk factors. Thus, primordial prevention has relevance in many nations of today given the substantial burden of obesity and diabetes, and adverse health behaviours such as unhealthy diet and sedentary lifestyle, and environmental factors that often begin in childhood. One limitation of this study acknowledged by authors is that nowadays we have new risk factors outside the traditional ones and also new technologies for detection of CVD. Future intergenerational epidemiological studies should further integrate new biological, behavioural, or environmental factors as well as new diagnostic tools. The take-home message from this study is that cardiovascular prevention measures should be family-centred because of the intergenerational transmission of behavioural and risk factors from parents (mostly from mothers) to children. It is also important not to forget the importance of population-level strategies to the prevention of CVD, and both national and local authorities should create and encourage healthier environments in cities, schools, worksites, and other community settings. The opinions expressed in this article are not necessarily those of the Editors of the European Journal of Preventive Cardiology or of the European Society of Cardiology. Funding The author did not receive any funding for this research. Conflict of interest: none declared. References 1 European Heart Network. European Cardiovascular Disease Statistics. Brussels : European Heart Network ; 2017 . 2 Eurostat . Causes of deaths - deaths by country of residence and occurrence. 2016 . http://appsso.eurostat.ec.europa.eu/nui/submitViewTableAction.do (4 May 2020). 3 Kotseva K De Bacquer D Jennings C , et al. Time trends in lifestyle, risk factor control, and use of evidence-based medications in patients with coronary heart disease in Europe: results from 3 EUROASPIRE surveys, 1999–2013 . Global Heart 2016 ; 12:315-322.e3. doi:10.1016/j.gheart.2015.11.003 Google Scholar OpenURL Placeholder Text WorldCat 4 Lloyd-Jones DM Hong Y Labarthe D Mozaffarian D Appel LJ Van Horn L Greenlund K Daniels S Nichol G Tomaselli GF Arnett DK Fonarow GC Ho PM Lauer MS Masoudi FA Robertson RM Roger V Schwamm LH Sorlie P Yancy CW Rosamond WD; American Heart Association Strategic Planning Task Force and Statistics Committee. Defining and setting national goals for cardiovascular health promotion and disease reduction: the American Heart Association's strategic Impact Goal through 2020 and beyond . Circulation 2010 ; 121 : 586 – 613 . Google Scholar Crossref Search ADS PubMed WorldCat 5 Barker DJ Osmond C Kajantie E Eriksson J. Growth and chronic disease: findings in the Helsinki Birth Cohort . Ann Hum Biol 2009 ; 36 : 445 – 458 . Google Scholar Crossref Search ADS PubMed WorldCat 6 Calkins K Devaskar SU. Fetal origins of adult disease . Curr Probl Pediatr Adolesc Health Care 2011 ; 41 : 158 – 176 . Google Scholar Crossref Search ADS PubMed WorldCat 7 Pate RR O'Neill JR Liese AD Janz KF Granberg EM Colabianchi N Harsha DW Condrasky MM O'Neil PM Lau EY Taverno Ross SE. Factors associated with development of excessive fatness in children and adolescents: a review of prospective studies . Obes Rev 2013 ; 14 : 645 – 658 . Google Scholar Crossref Search ADS PubMed WorldCat 8 Damani SB Topol EJ. Future use of genomics in coronary artery disease . J Am Coll Cardiol 2007 ; 50 : 1933 – 1940 . Google Scholar Crossref Search ADS PubMed WorldCat 9 Benschop L Schalekamp-Timmermans S Roeters van Lennep JE Jaddoe VWV Steegers EAP Kamran Ikram M. Cardiovascular risk factors track from mother to child . J Am Heart Assoc 2018 ; 7 : e009536 . Google Scholar Crossref Search ADS PubMed WorldCat 10 Robson SM Couch SC Peugh JL Glanz K Zhou C Sallis JF Saelens BE. Parent diet quality and energy intake are related to child diet quality and energy intake . J Acad Nutr Diet 2016 ; 116 : 984 – 990 . Google Scholar Crossref Search ADS PubMed WorldCat 11 Vuolo M Staff J. Parent and child cigarette use: a longitudinal, multigenerational study . Pediatrics 2013 ; 132 : e568 – e577 . Google Scholar Crossref Search ADS PubMed WorldCat 12 Muchira JM Gona PN Mogos MF Stuart-Shor E Leveille SG Piano MR Hayman L . Temporal trends and familial clustering of ideal cardiovascular health in parents and offspring over the life course: an investigation using the Framingham Heart Study . J Am Heart Assoc 2020 ; 9 : e016292 . Google Scholar Crossref Search ADS PubMed WorldCat 13 Khera AV Emdin CA Drake I Natarajan P Bick AG Cook NR Chasman DI Baber U Mehran R Rader DJ Fuster V Boerwinkle E Melander O Orho-Melander M Ridker PM Kathiresan S. Genetic risk, adherence to a healthy lifestyle, and coronary disease . N Engl J Med 2016 ; 375 : 2349 – 2358 . Google Scholar Crossref Search ADS PubMed WorldCat 14 Piepoli MF Abreu A Albus C Ambrosetti M Brotons C Catapano AL Corra U Cosyns B Deaton C Graham I Hoes A Lochen M-L Matrone B Redon J Sattar N Smulders Y Tiberi M. Update on cardiovascular prevention in clinical practice: a position paper of the European Association of Preventive Cardiology of the European Society of Cardiology . Eur J Prev Cardiol 2020 ; 27 : 181 – 205 . Google Scholar Crossref Search ADS PubMed WorldCat 15 Muchira JM Gona PN Mogos MF Stuart-Shor E Leveille SG Piano MR Hayman L . Parental cardiovascular health predicts time to onset of cardiovascular disease in offspring . Eur J Prev Cardio 2020 ; Google Scholar OpenURL Placeholder Text WorldCat 16 Strasser T. Reflections on cardiovascular diseases . Interdiscip Sci Rev 1978 ; 3 : 225 – 230 . Google Scholar Crossref Search ADS WorldCat Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: [email protected]. This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model)

Muchira, James M; Gona, Philimon N; Mogos, Mulubrhan F; Stuart-Shor, Eileen; Leveille, Suzanne G; Piano, Mariann R; Hayman, Laura L

doi: 10.1093/eurjpc/zwaa072pmid: 33624039

BackgroundCardiovascular disease (CVD) risk factors are transmitted from parents to children. We prospectively examined the association between parental cardiovascular health (CVH) and time to onset of CVD in the offspring.Methods and resultsThe study consisted of a total of 5967 offspring–mother–father trios derived from the Framingham Heart Study. Cardiovascular health score was defined using the seven American Heart Association’s CVH metrics attained at ideal levels: poor (0–2), intermediate (3–4), and ideal CVH (5–7). Multivariable-adjusted Cox proportional hazards regression models, Kaplan–Meier plots, and Irwin’s restricted mean were used to examine the association and sex-specific differences between parental CVH and offspring’s CVD-free survival. In a total of 71 974 person-years of follow-up among the offspring, 718 incident CVD events occurred. The overall CVD incidence rate was 10 per 1000 person-years [95% confidence interval (CI) 9.3–10.7]. Offspring of mothers with ideal CVH lived 9 more years free of CVD than offspring of mothers with poor CVH (P < 0.001). Maternal poor CVH was associated with twice as high hazard of early onset of CVD compared with maternal ideal CVH (adjusted Hazard Ratio 2.09, 95% CI 1.50–2.92). No statistically significant association was observed in the hazards of CVD-free survival by paternal CVH categories.ConclusionsWe found that offspring of parents with ideal CVH had a greater CVD-free survival. Maternal CVH was a more robust predictor of offspring’s CVD-free survival than paternal CVH, underscoring the need for clinical and policy interventions that involve mothers to break the intergenerational cycle of CVD-related morbidity and mortality.

Gencer, Baris; Morrow, David A; Braunwald, Eugene; Goodrich, Erica L; Hilvo, Mika; Kauhanen, Dimple; Sabatine, Marc S; Laaksonen, Reijo; O’Donoghue, Michelle L

doi: 10.1093/eurjpc/zwaa143pmid: 33624052