Impact of psychological status on cardiovascular diseases: Is it time for upgrading risk score charts?

The global burden of cardiovascular diseases (CVDs) still represents a challenging issue. Global Burden of Disease (GBD) Study 2019 estimated a 2-fold increase in CVDs prevalence and about 50% increase in the overall CVD deaths worldwide from 1990 to 2019 [[1]Roth G.A. Mensah G.A. Johnson C.O. Addolorato G. Ammirati E. Baddour L.M. Barengo N.C. Beaton A.Z. Benjamin E.J. Benziger C.P. Bonny A. Brauer M. Brodmann M. Cahill T.J. Carapetis J. Catapano A.L. Chugh S.S. Cooper L.T. Coresh J. Criqui M. DeCleene N. Eagle K.A. Emmons-Bell S. Feigin V.L. Fernández-Solà J. Fowkes G. Gakidou E. Grundy S.M. He F.J. Howard G. Hu F. Inker L. Karthikeyan G. Kassebaum N. Koroshetz W. Lavie C. Lloyd-Jones D. Lu H.S. Mirijello A. Temesgen A.M. Mokdad A. Moran A.E. Muntner P. Narula J. Neal B. Ntsekhe M. Moraes de Oliveira G. Otto C. Owolabi M. Pratt M. Rajagopalan S. Reitsma M. Ribeiro A.L.P. Rigotti N. Rodgers A. Sable C. Shakil S. Sliwa-Hahnle K. Stark B. Sundström J. Timpel P. Tleyjeh I.M. Valgimigli M. Vos T. Whelton P.K. Yacoub M. Zuhlke L. Murray C. Fuster V. GBD-NHLBI-JACC Global Burden of Cardiovascular Diseases Writing GroupGlobal burden of cardiovascular diseases and risk factors, 1990-2019: update from the GBD 2019 study.J. Am. Coll. Cardiol. 2020; 76: 2982-3021Crossref PubMed Scopus (1396) Google Scholar].Recent trials dealing with new pharmacological treatments for counteracting progression of CVDs outlined that cumulative incidence of cardiovascular (CV) events did not decrease below 2.5% at 1-year follow-up, thus pointing out that about 25 patients every thousand suffer from major cardiovascular events (MACE) despite the optimization of therapies [2Sabatine M.S. Giugliano R.P. Keech A.C. Honarpour N. Wiviott S.D. Murphy S.A. Kuder J.F. Wang H. Liu T. Wasserman S.M. Sever P.S. Pedersen T.R. FOURIER steering committee and investigators. Evolocumab and clinical outcomes in patients with cardiovascular disease.N. Engl. J. Med. 2017; 376: 1713-1722Crossref PubMed Scopus (3005) Google Scholar, 3Eikelboom J.W. Connolly S.J. Bosch J. Dagenais G.R. Hart R.G. Shestakovska O. Diaz R. Alings M. Lonn E.M. Anand S.S. Widimsky P. Hori M. Avezum A. Piegas L.S. Branch K.R.H. Probstfield J. Bhatt D.L. Zhu J. Liang Y. Maggioni A.P. Lopez-Jaramillo P. O'Donnell M. Kakkar A.K. Fox K.A.A. Parkhomenko A.N. Ertl G. Störk S. Keltai M. Ryden L. Pogosova N. Dans A.L. Lanas F. Commerford P.J. Torp-Pedersen C. Guzik T.J. Verhamme P.B. Vinereanu D. Kim J.H. Tonkin A.M. Lewis B.S. Felix C. Yusoff K. Steg P.G. Metsarinne K.P. Cook Bruns N. Misselwitz F. Chen E. Leong D. Yusuf S. COMPASS InvestigatorsRivaroxaban with or without aspirin in stable cardiovascular disease.N. Engl. J. Med. 2017; 377: 1319-1330Crossref PubMed Scopus (1316) Google Scholar, 4Schwartz G.G. Steg P.G. Szarek M. Bhatt D.L. Bittner V.A. Diaz R. Edelberg J.M. Goodman S.G. Hanotin C. Harrington R.A. Jukema J.W. Lecorps G. Mahaffey K.W. Moryusef A. Pordy R. Quintero K. Roe M.T. Sasiela W.J. Tamby J.F. Tricoci P. White H.D. Zeiher A.M. ODYSSEY OUTCOMES committees and investigators. Alirocumab and cardiovascular outcomes after acute coronary syndrome.N. Engl. J. Med. 2018; 379: 2097-2107Crossref PubMed Scopus (1461) Google Scholar, 5Zinman B. Wanner C. Lachin J.M. Fitchett D. Bluhmki E. Hantel S. Mattheus M. Devins T. Johansen O.E. Woerle H.J. Broedl U.C. Inzucchi S.E. EMPA-REG OUTCOME investigators. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes.N. Engl. J. Med. 2015; 373: 2117-2128Crossref PubMed Scopus (6811) Google Scholar, 6Ridker P.M. Everett B.M. Thuren T. MacFadyen J.G. Chang W.H. Ballantyne C. Fonseca F. Nicolau J. Koenig W. Anker S.D. Kastelein J.J.P. Cornel J.H. Pais P. Pella D. Genest J. Cifkova R. Lorenzatti A. Forster T. Kobalava Z. Vida-Simiti L. Flather M. Shimokawa H. Ogawa H. Dellborg M. Rossi P.R.F. Troquay R.P.T. Libby P. Glynn R.J. CANTOS Trial GroupAntiinflammatory therapy with canakinumab for atherosclerotic disease.N. Engl. J. Med. 2017; 377: 1119-1131Crossref PubMed Scopus (4355) Google Scholar, 7Cannon C.P. Blazing M.A. Giugliano R.P. McCagg A. White J.A. Theroux P. Darius H. Lewis B.S. Ophuis T.O. Jukema J.W. De Ferrari G.M. Ruzyllo W. De Lucca P. Im K. Bohula E.A. Reist C. Wiviott S.D. Tershakovec A.M. Musliner T.A. Braunwald E. Califf R.M. IMPROVE-IT investigators. Ezetimibe added to statin therapy after acute coronary syndromes.N. Engl. J. Med. 2015; 372: 2387-2397Crossref PubMed Scopus (2682) Google Scholar]. Therefore, the need for the identification of the full spectrum of residual CV risk factors of the patients is fundamental for better implementing therapies and improving the performance of common risk score charts [[8]DeFilippis A.P. Young R. Carrubba C.J. McEvoy J.W. Budoff M.J. Blumenthal R.S. Kronmal R.A. McClelland R.L. Nasir K. Blaha M.J. An analysis of calibration and discrimination among multiple cardiovascular risk scores in a modern multiethnic cohort.Ann. Intern. Med. 2015; 162: 266-275Crossref PubMed Scopus (337) Google Scholar].Psychological health and dedicated interventions might influence the CV outcome of patients [9Krittanawong C. Maitra N.S. Hassan Virk H.U. Fogg S. Wang Z. Kaplin S. Gritsch D. Storch E.A. Tobler P.N. Charney D.S. Levine G.N. Association of optimism with cardiovascular events and all-cause mortality: systematic review and meta-analysis.Am. J. Med. 2022; 135: 856-863.e2Abstract Full Text Full Text PDF PubMed Scopus (1) Google Scholar, 10Song X. Song J. Shao M. Gao X. Ji F. Tian H. Xu Y. Zhuo C. Depression predicts the risk of adverse events after percutaneous coronary intervention: a meta-analysis.J. Affect. Disord. 2020; 266: 158-164Crossref PubMed Scopus (11) Google Scholar, 11Richards S.H. Anderson L. Jenkinson C.E. Whalley B. Rees K. Davies P. Bennett P. Liu Z. West R. Thompson D.R. Taylor R.S. Psychological interventions for coronary heart disease.Cochrane Database Syst. Rev. 2017; 4: CD002902PubMed Google Scholar] although there are concerns about implementing psychological evaluation in daily clinical evaluation of patients at risk for CVDs.In this issue, Sun et al. [[12]Sun Y. Zhang H. Wang B. Chen C. Chen Y. Chen Y. Xia F. Tan X. Zhang J. Li Q. Qi L. Lu Y. Wang N. Joint exposure to positive affect, life satisfaction, 1 broad depression, and neuroticism and risk of cardiovascular diseases: a prospective cohort study.Atherosclerosis. 2022; (in press)https://doi.org/10.1016/j.atherosclerosis.2022.08.007Abstract Full Text Full Text PDF Scopus (1) Google Scholar] tried to shed lights on this topic by highlighting the relationship between psychological factors – namely happiness, life satisfaction, broad depression, and neuroticism – and the occurrence of CV outcomes (coronary heart disease [CHD], stroke, and heart failure [HF]), as well as the association with genetic susceptibility for CVDs occurrence.In this study, a large population of 126,255 participants were recruited from the UK Biobank if they did not experience previous CHD, stroke or HF events, had data on four psychological wellbeing factors - happiness, life satisfaction, broad depression, and neuroticism - and had genetic data on single nucleotide polymorphisms (SNPs) associated with CHD, stroke and HF. Authors generated a psychological wellbeing score, which included the previous four variables: higher scores were related to healthier psychological wellbeing. Meanwhile, a weighted genetic risk score (GRS) was derived from using SNPs associated with each CV outcome [[12]Sun Y. Zhang H. Wang B. Chen C. Chen Y. Chen Y. Xia F. Tan X. Zhang J. Li Q. Qi L. Lu Y. Wang N. Joint exposure to positive affect, life satisfaction, 1 broad depression, and neuroticism and risk of cardiovascular diseases: a prospective cohort study.Atherosclerosis. 2022; (in press)https://doi.org/10.1016/j.atherosclerosis.2022.08.007Abstract Full Text Full Text PDF Scopus (1) Google Scholar]. Patients underwent a median follow-up of 11.5 years. Sun et al. [[12]Sun Y. Zhang H. Wang B. Chen C. Chen Y. Chen Y. Xia F. Tan X. Zhang J. Li Q. Qi L. Lu Y. Wang N. Joint exposure to positive affect, life satisfaction, 1 broad depression, and neuroticism and risk of cardiovascular diseases: a prospective cohort study.Atherosclerosis. 2022; (in press)https://doi.org/10.1016/j.atherosclerosis.2022.08.007Abstract Full Text Full Text PDF Scopus (1) Google Scholar] demonstrated that lower psychological wellbeing scores (=0) were related to a 51% increase in CVD risk as compared to patients with score 3–4. Furthermore, patients with both higher-risk psychological status and higher GRS score showed a 2.7-fold increase in CHD occurrence, 1.23-fold increase in stroke events, and 1.67-fold increase in HF. Such results were consistent during the follow-up period even after adjusting for confounding factors.These data are interesting and impressive, although some criticisms and prospective insights are needed.The work from Sun et al. [[12]Sun Y. Zhang H. Wang B. Chen C. Chen Y. Chen Y. Xia F. Tan X. Zhang J. Li Q. Qi L. Lu Y. Wang N. Joint exposure to positive affect, life satisfaction, 1 broad depression, and neuroticism and risk of cardiovascular diseases: a prospective cohort study.Atherosclerosis. 2022; (in press)https://doi.org/10.1016/j.atherosclerosis.2022.08.007Abstract Full Text Full Text PDF Scopus (1) Google Scholar] is one of the largest population-based cohorts that assessed for wellbeing status and contextually evaluated MACE, as well as genetic predisposition to CV adverse events. Identification of the variations in therapies and the consistency of the results through specified follow-up periods give useful insights to the readers.Literature lacks a definite score for the assessment of the wellbeing status of individuals in relation to their CV risk profile and genetics. Sun et al. [[12]Sun Y. Zhang H. Wang B. Chen C. Chen Y. Chen Y. Xia F. Tan X. Zhang J. Li Q. Qi L. Lu Y. Wang N. Joint exposure to positive affect, life satisfaction, 1 broad depression, and neuroticism and risk of cardiovascular diseases: a prospective cohort study.Atherosclerosis. 2022; (in press)https://doi.org/10.1016/j.atherosclerosis.2022.08.007Abstract Full Text Full Text PDF Scopus (1) Google Scholar] considered a combined indicator for this purpose. The idea to use multiple measures of well-being is innovative as it provides a multiparametric approach to psychological status in patients at CV risk. Nevertheless, the need for validation of this score should be better considered and performed in further dedicated researches to be able to reproduce the results worldwide. This would be the premix for the development of upgraded CV risk score charts, able to fully stratify individuals' CV risk.Furthermore, by demonstrating that higher CV genetic risk in patients with worse control of their psychological wellbeing status steadily increased the overall incidence in MACE (HR: 2.70 [2.25–3.24] for CHD occurrence; HR: 1.67 [1.22–2.28] for HF occurrence), authors proved the need for a comprehensive evaluation of patients at risk for CVDs, which should include evaluation of CV risk factors, genetic predisposition, and psychological assessment. The recent European Society of Cardiology guidelines on cardiovascular disease prevention in clinical practice [[13]Visseren F.L.J. Mach F. Smulders Y.M. Carballo D. Koskinas K.C. Bäck M. Benetos A. Biffi A. Boavida J.M. Capodanno D. Cosyns B. Crawford C. Davos C.H. Desormais I. Di Angelantonio E. Franco O.H. Halvorsen S. Hobbs F.D.R. Hollander M. Jankowska E.A. Michal M. Sacco S. Sattar N. Tokgozoglu L. Tonstad S. Tsioufis K.P. van Dis I. van Gelder I.C. Wanner C. Williams B. ESC national cardiac societies; ESC scientific document group. 2021 ESC guidelines on cardiovascular disease prevention in clinical practice.Eur. Heart J. 2021; 42: 3227-3337Crossref PubMed Scopus (579) Google Scholar] rightly potentiated the recommendations for the assessment of psychological status in patients at risk for CV events (class of recommendation I level of evidence C) as a general rule for identifying potential further residual risk factors in this subset of patients. The combination of genetics to psychological status and general CV assessment would certainly improve the CV risk stratification of patients.Indeed, social factors and socio-economic positions might influence wellbeing as well as the occurrence of MACE [[14]Sullivan S. Young A. Garcia M. Almuwaqqat Z. Moazzami K. Hammadah M. Lima B.B. Driggers E.G. Levantsevych O. Alkhalaf M. Jajeh M.N. Alkhoder A. Elon L. Gooding H. Lewis T.T. Shah A.J. Bremner J.D. Quyyumi A.A. Vaccarino V. Gender disparities between neighborhood social vulnerability and psychological distress among patients with heart disease.J. Womens Health (Larchmt). 2022 Aug 12; (Epub ahead of print)https://doi.org/10.1089/jwh.2021.0505Crossref PubMed Google Scholar,[15]Mulle J.G. Vaccarino V. Cardiovascular disease, psychosocial factors, and genetics: the case of depression.Prog. Cardiovasc. Dis. 2013; 55: 557-562Crossref PubMed Scopus (37) Google Scholar]. Literature is scant about this challenging issue and, unfortunately, the work from Sun et al. [[12]Sun Y. Zhang H. Wang B. Chen C. Chen Y. Chen Y. Xia F. Tan X. Zhang J. Li Q. Qi L. Lu Y. Wang N. Joint exposure to positive affect, life satisfaction, 1 broad depression, and neuroticism and risk of cardiovascular diseases: a prospective cohort study.Atherosclerosis. 2022; (in press)https://doi.org/10.1016/j.atherosclerosis.2022.08.007Abstract Full Text Full Text PDF Scopus (1) Google Scholar] did not fully address such a specific point. This could be considered as a limitation of the paper. Further insights should address this specific point for the sake of a comprehensive evaluation of CV risk of individuals. The global burden of cardiovascular diseases (CVDs) still represents a challenging issue. Global Burden of Disease (GBD) Study 2019 estimated a 2-fold increase in CVDs prevalence and about 50% increase in the overall CVD deaths worldwide from 1990 to 2019 [[1]Roth G.A. Mensah G.A. Johnson C.O. Addolorato G. Ammirati E. Baddour L.M. Barengo N.C. Beaton A.Z. Benjamin E.J. Benziger C.P. Bonny A. Brauer M. Brodmann M. Cahill T.J. Carapetis J. Catapano A.L. Chugh S.S. Cooper L.T. Coresh J. Criqui M. DeCleene N. Eagle K.A. Emmons-Bell S. Feigin V.L. Fernández-Solà J. Fowkes G. Gakidou E. Grundy S.M. He F.J. Howard G. Hu F. Inker L. Karthikeyan G. Kassebaum N. Koroshetz W. Lavie C. Lloyd-Jones D. Lu H.S. Mirijello A. Temesgen A.M. Mokdad A. Moran A.E. Muntner P. Narula J. Neal B. Ntsekhe M. Moraes de Oliveira G. Otto C. Owolabi M. Pratt M. Rajagopalan S. Reitsma M. Ribeiro A.L.P. Rigotti N. Rodgers A. Sable C. Shakil S. Sliwa-Hahnle K. Stark B. Sundström J. Timpel P. Tleyjeh I.M. Valgimigli M. Vos T. Whelton P.K. Yacoub M. Zuhlke L. Murray C. Fuster V. GBD-NHLBI-JACC Global Burden of Cardiovascular Diseases Writing GroupGlobal burden of cardiovascular diseases and risk factors, 1990-2019: update from the GBD 2019 study.J. Am. Coll. Cardiol. 2020; 76: 2982-3021Crossref PubMed Scopus (1396) Google Scholar]. Recent trials dealing with new pharmacological treatments for counteracting progression of CVDs outlined that cumulative incidence of cardiovascular (CV) events did not decrease below 2.5% at 1-year follow-up, thus pointing out that about 25 patients every thousand suffer from major cardiovascular events (MACE) despite the optimization of therapies [2Sabatine M.S. Giugliano R.P. Keech A.C. Honarpour N. Wiviott S.D. Murphy S.A. Kuder J.F. Wang H. Liu T. Wasserman S.M. Sever P.S. Pedersen T.R. FOURIER steering committee and investigators. Evolocumab and clinical outcomes in patients with cardiovascular disease.N. Engl. J. Med. 2017; 376: 1713-1722Crossref PubMed Scopus (3005) Google Scholar, 3Eikelboom J.W. Connolly S.J. Bosch J. Dagenais G.R. Hart R.G. Shestakovska O. Diaz R. Alings M. Lonn E.M. Anand S.S. Widimsky P. Hori M. Avezum A. Piegas L.S. Branch K.R.H. Probstfield J. Bhatt D.L. Zhu J. Liang Y. Maggioni A.P. Lopez-Jaramillo P. O'Donnell M. Kakkar A.K. Fox K.A.A. Parkhomenko A.N. Ertl G. Störk S. Keltai M. Ryden L. Pogosova N. Dans A.L. Lanas F. Commerford P.J. Torp-Pedersen C. Guzik T.J. Verhamme P.B. Vinereanu D. Kim J.H. Tonkin A.M. Lewis B.S. Felix C. Yusoff K. Steg P.G. Metsarinne K.P. Cook Bruns N. Misselwitz F. Chen E. Leong D. Yusuf S. COMPASS InvestigatorsRivaroxaban with or without aspirin in stable cardiovascular disease.N. Engl. J. Med. 2017; 377: 1319-1330Crossref PubMed Scopus (1316) Google Scholar, 4Schwartz G.G. Steg P.G. Szarek M. Bhatt D.L. Bittner V.A. Diaz R. Edelberg J.M. Goodman S.G. Hanotin C. Harrington R.A. Jukema J.W. Lecorps G. Mahaffey K.W. Moryusef A. Pordy R. Quintero K. Roe M.T. Sasiela W.J. Tamby J.F. Tricoci P. White H.D. Zeiher A.M. ODYSSEY OUTCOMES committees and investigators. Alirocumab and cardiovascular outcomes after acute coronary syndrome.N. Engl. J. Med. 2018; 379: 2097-2107Crossref PubMed Scopus (1461) Google Scholar, 5Zinman B. Wanner C. Lachin J.M. Fitchett D. Bluhmki E. Hantel S. Mattheus M. Devins T. Johansen O.E. Woerle H.J. Broedl U.C. Inzucchi S.E. EMPA-REG OUTCOME investigators. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes.N. Engl. J. Med. 2015; 373: 2117-2128Crossref PubMed Scopus (6811) Google Scholar, 6Ridker P.M. Everett B.M. Thuren T. MacFadyen J.G. Chang W.H. Ballantyne C. Fonseca F. Nicolau J. Koenig W. Anker S.D. Kastelein J.J.P. Cornel J.H. Pais P. Pella D. Genest J. Cifkova R. Lorenzatti A. Forster T. Kobalava Z. Vida-Simiti L. Flather M. Shimokawa H. Ogawa H. Dellborg M. Rossi P.R.F. Troquay R.P.T. Libby P. Glynn R.J. CANTOS Trial GroupAntiinflammatory therapy with canakinumab for atherosclerotic disease.N. Engl. J. Med. 2017; 377: 1119-1131Crossref PubMed Scopus (4355) Google Scholar, 7Cannon C.P. Blazing M.A. Giugliano R.P. McCagg A. White J.A. Theroux P. Darius H. Lewis B.S. Ophuis T.O. Jukema J.W. De Ferrari G.M. Ruzyllo W. De Lucca P. Im K. Bohula E.A. Reist C. Wiviott S.D. Tershakovec A.M. Musliner T.A. Braunwald E. Califf R.M. IMPROVE-IT investigators. Ezetimibe added to statin therapy after acute coronary syndromes.N. Engl. J. Med. 2015; 372: 2387-2397Crossref PubMed Scopus (2682) Google Scholar]. Therefore, the need for the identification of the full spectrum of residual CV risk factors of the patients is fundamental for better implementing therapies and improving the performance of common risk score charts [[8]DeFilippis A.P. Young R. Carrubba C.J. McEvoy J.W. Budoff M.J. Blumenthal R.S. Kronmal R.A. McClelland R.L. Nasir K. Blaha M.J. An analysis of calibration and discrimination among multiple cardiovascular risk scores in a modern multiethnic cohort.Ann. Intern. Med. 2015; 162: 266-275Crossref PubMed Scopus (337) Google Scholar]. Psychological health and dedicated interventions might influence the CV outcome of patients [9Krittanawong C. Maitra N.S. Hassan Virk H.U. Fogg S. Wang Z. Kaplin S. Gritsch D. Storch E.A. Tobler P.N. Charney D.S. Levine G.N. Association of optimism with cardiovascular events and all-cause mortality: systematic review and meta-analysis.Am. J. Med. 2022; 135: 856-863.e2Abstract Full Text Full Text PDF PubMed Scopus (1) Google Scholar, 10Song X. Song J. Shao M. Gao X. Ji F. Tian H. Xu Y. Zhuo C. Depression predicts the risk of adverse events after percutaneous coronary intervention: a meta-analysis.J. Affect. Disord. 2020; 266: 158-164Crossref PubMed Scopus (11) Google Scholar, 11Richards S.H. Anderson L. Jenkinson C.E. Whalley B. Rees K. Davies P. Bennett P. Liu Z. West R. Thompson D.R. Taylor R.S. Psychological interventions for coronary heart disease.Cochrane Database Syst. Rev. 2017; 4: CD002902PubMed Google Scholar] although there are concerns about implementing psychological evaluation in daily clinical evaluation of patients at risk for CVDs. In this issue, Sun et al. [[12]Sun Y. Zhang H. Wang B. Chen C. Chen Y. Chen Y. Xia F. Tan X. Zhang J. Li Q. Qi L. Lu Y. Wang N. Joint exposure to positive affect, life satisfaction, 1 broad depression, and neuroticism and risk of cardiovascular diseases: a prospective cohort study.Atherosclerosis. 2022; (in press)https://doi.org/10.1016/j.atherosclerosis.2022.08.007Abstract Full Text Full Text PDF Scopus (1) Google Scholar] tried to shed lights on this topic by highlighting the relationship between psychological factors – namely happiness, life satisfaction, broad depression, and neuroticism – and the occurrence of CV outcomes (coronary heart disease [CHD], stroke, and heart failure [HF]), as well as the association with genetic susceptibility for CVDs occurrence. In this study, a large population of 126,255 participants were recruited from the UK Biobank if they did not experience previous CHD, stroke or HF events, had data on four psychological wellbeing factors - happiness, life satisfaction, broad depression, and neuroticism - and had genetic data on single nucleotide polymorphisms (SNPs) associated with CHD, stroke and HF. Authors generated a psychological wellbeing score, which included the previous four variables: higher scores were related to healthier psychological wellbeing. Meanwhile, a weighted genetic risk score (GRS) was derived from using SNPs associated with each CV outcome [[12]Sun Y. Zhang H. Wang B. Chen C. Chen Y. Chen Y. Xia F. Tan X. Zhang J. Li Q. Qi L. Lu Y. Wang N. Joint exposure to positive affect, life satisfaction, 1 broad depression, and neuroticism and risk of cardiovascular diseases: a prospective cohort study.Atherosclerosis. 2022; (in press)https://doi.org/10.1016/j.atherosclerosis.2022.08.007Abstract Full Text Full Text PDF Scopus (1) Google Scholar]. Patients underwent a median follow-up of 11.5 years. Sun et al. [[12]Sun Y. Zhang H. Wang B. Chen C. Chen Y. Chen Y. Xia F. Tan X. Zhang J. Li Q. Qi L. Lu Y. Wang N. Joint exposure to positive affect, life satisfaction, 1 broad depression, and neuroticism and risk of cardiovascular diseases: a prospective cohort study.Atherosclerosis. 2022; (in press)https://doi.org/10.1016/j.atherosclerosis.2022.08.007Abstract Full Text Full Text PDF Scopus (1) Google Scholar] demonstrated that lower psychological wellbeing scores (=0) were related to a 51% increase in CVD risk as compared to patients with score 3–4. Furthermore, patients with both higher-risk psychological status and higher GRS score showed a 2.7-fold increase in CHD occurrence, 1.23-fold increase in stroke events, and 1.67-fold increase in HF. Such results were consistent during the follow-up period even after adjusting for confounding factors. These data are interesting and impressive, although some criticisms and prospective insights are needed. The work from Sun et al. [[12]Sun Y. Zhang H. Wang B. Chen C. Chen Y. Chen Y. Xia F. Tan X. Zhang J. Li Q. Qi L. Lu Y. Wang N. Joint exposure to positive affect, life satisfaction, 1 broad depression, and neuroticism and risk of cardiovascular diseases: a prospective cohort study.Atherosclerosis. 2022; (in press)https://doi.org/10.1016/j.atherosclerosis.2022.08.007Abstract Full Text Full Text PDF Scopus (1) Google Scholar] is one of the largest population-based cohorts that assessed for wellbeing status and contextually evaluated MACE, as well as genetic predisposition to CV adverse events. Identification of the variations in therapies and the consistency of the results through specified follow-up periods give useful insights to the readers. Literature lacks a definite score for the assessment of the wellbeing status of individuals in relation to their CV risk profile and genetics. Sun et al. [[12]Sun Y. Zhang H. Wang B. Chen C. Chen Y. Chen Y. Xia F. Tan X. Zhang J. Li Q. Qi L. Lu Y. Wang N. Joint exposure to positive affect, life satisfaction, 1 broad depression, and neuroticism and risk of cardiovascular diseases: a prospective cohort study.Atherosclerosis. 2022; (in press)https://doi.org/10.1016/j.atherosclerosis.2022.08.007Abstract Full Text Full Text PDF Scopus (1) Google Scholar] considered a combined indicator for this purpose. The idea to use multiple measures of well-being is innovative as it provides a multiparametric approach to psychological status in patients at CV risk. Nevertheless, the need for validation of this score should be better considered and performed in further dedicated researches to be able to reproduce the results worldwide. This would be the premix for the development of upgraded CV risk score charts, able to fully stratify individuals' CV risk. Furthermore, by demonstrating that higher CV genetic risk in patients with worse control of their psychological wellbeing status steadily increased the overall incidence in MACE (HR: 2.70 [2.25–3.24] for CHD occurrence; HR: 1.67 [1.22–2.28] for HF occurrence), authors proved the need for a comprehensive evaluation of patients at risk for CVDs, which should include evaluation of CV risk factors, genetic predisposition, and psychological assessment. The recent European Society of Cardiology guidelines on cardiovascular disease prevention in clinical practice [[13]Visseren F.L.J. Mach F. Smulders Y.M. Carballo D. Koskinas K.C. Bäck M. Benetos A. Biffi A. Boavida J.M. Capodanno D. Cosyns B. Crawford C. Davos C.H. Desormais I. Di Angelantonio E. Franco O.H. Halvorsen S. Hobbs F.D.R. Hollander M. Jankowska E.A. Michal M. Sacco S. Sattar N. Tokgozoglu L. Tonstad S. Tsioufis K.P. van Dis I. van Gelder I.C. Wanner C. Williams B. ESC national cardiac societies; ESC scientific document group. 2021 ESC guidelines on cardiovascular disease prevention in clinical practice.Eur. Heart J. 2021; 42: 3227-3337Crossref PubMed Scopus (579) Google Scholar] rightly potentiated the recommendations for the assessment of psychological status in patients at risk for CV events (class of recommendation I level of evidence C) as a general rule for identifying potential further residual risk factors in this subset of patients. The combination of genetics to psychological status and general CV assessment would certainly improve the CV risk stratification of patients. Indeed, social factors and socio-economic positions might influence wellbeing as well as the occurrence of MACE [[14]Sullivan S. Young A. Garcia M. Almuwaqqat Z. Moazzami K. Hammadah M. Lima B.B. Driggers E.G. Levantsevych O. Alkhalaf M. Jajeh M.N. Alkhoder A. Elon L. Gooding H. Lewis T.T. Shah A.J. Bremner J.D. Quyyumi A.A. Vaccarino V. Gender disparities between neighborhood social vulnerability and psychological distress among patients with heart disease.J. Womens Health (Larchmt). 2022 Aug 12; (Epub ahead of print)https://doi.org/10.1089/jwh.2021.0505Crossref PubMed Google Scholar,[15]Mulle J.G. Vaccarino V. Cardiovascular disease, psychosocial factors, and genetics: the case of depression.Prog. Cardiovasc. Dis. 2013; 55: 557-562Crossref PubMed Scopus (37) Google Scholar]. Literature is scant about this challenging issue and, unfortunately, the work from Sun et al. [[12]Sun Y. Zhang H. Wang B. Chen C. Chen Y. Chen Y. Xia F. Tan X. Zhang J. Li Q. Qi L. Lu Y. Wang N. Joint exposure to positive affect, life satisfaction, 1 broad depression, and neuroticism and risk of cardiovascular diseases: a prospective cohort study.Atherosclerosis. 2022; (in press)https://doi.org/10.1016/j.atherosclerosis.2022.08.007Abstract Full Text Full Text PDF Scopus (1) Google Scholar] did not fully address such a specific point. This could be considered as a limitation of the paper. Further insights should address this specific point for the sake of a comprehensive evaluation of CV risk of individuals. The author declares that he has no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Joint exposure to positive affect, life satisfaction, broad depression, and neuroticism and risk of cardiovascular diseases: A prospective cohort studyAtherosclerosisVol. 359PreviewPsychologic wellbeing can impact cardiovascular health. We aimed to evaluate the joint association of multiple psychologic wellbeing factors with cardiovascular diseases (CVD) and examine whether this association was modified by genetic susceptibility. Full-Text PDF