Cardiovascular Health and Protection Against CVD: More Than the Sum of the Parts? Donald M. Lloyd-Jones Circulation. published online October 1, 2014; Circulation is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231 Copyright © 2014 American Heart Association, Inc. All rights reserved. Print ISSN: 0009-7322. Online ISSN: 1524-4539
The online version of this article, along with updated information and services, is located on the World Wide Web at: http://circ.ahajournals.org/content/early/2014/10/01/CIRCULATIONAHA.114.012869
Permissions: Requests for permissions to reproduce figures, tables, or portions of articles originally published in Circulation can be obtained via RightsLink, a service of the Copyright Clearance Center, not the Editorial Office. Once the online version of the published article for which permission is being requested is located, click Request Permissions in the middle column of the Web page under Services. Further information about this process is available in the Permissions and Rights Question and Answer document. Reprints: Information about reprints can be found online at: http://www.lww.com/reprints Subscriptions: Information about subscribing to Circulation is online at: http://circ.ahajournals.org//subscriptions/
Downloaded from http://circ.ahajournals.org/ at New York University/ Medical Center--New York on October 14, 2014
DOI: 10.1161/CIRCULATIONAHA.114.012869
Cardiovascular Health and Protection Against CVD: More Than the Sum of the Parts?
Running title: Lloyd-Jones; Mechanisms of CV health protection
Donald M. Lloyd-Jones, MD, ScM, FAHA
Department of Preventive Medicine and the Division of Cardiology, Department of Medicine, Northwestern Medicine, Chicago, No orthw rth estern University Feinberg rg School School of Medic icine, ic e, C hicago, IL
Address Ad ddr dres esss for es for Correspondence: Coorr rres e pond es pond nden e ce ce: Donald M.. Ll Lloyd-Jones, MD, ScM Donald Dona ld M Lloy oydd-JJone Jones, s, M D, S D, cM M Department Preventive Medicine D epartme t ntt off P re enti ti e M edi diciine Northwestern University Feinberg School of Medicine 680 N. Lake Shore Dr., Suite 1400 Chicago, IL 60611 Tel: 312-908-1718 Fax: 312-908-9588 E-mail: [email protected] Journal Subject Code: Etiology:[8] Epidemiology
Key words:Editorial, cardiovascular outcomes, risk factor, health status
1 Downloaded from http://circ.ahajournals.org/ at New York University/ Medical Center--New York on October 14, 2014
DOI: 10.1161/CIRCULATIONAHA.114.012869
Five years ago, the American Heart Association (AHA) launched a bold new initiative to begin promoting “cardiovascular health” in individuals and the population, in addition to continuing its decades-long fight to reduce cardiovascular and stroke mortality and decrease cardiovascular disease (CVD) risk. This shift in priorities came as a result of a “quiet revolution,”1 turning the adverse-outcomes-oriented and risk-focused perspective on its head, and instead focusing on creating the opportunity for promoting and preserving attributes associated with healthy, CVDfree longevity. The first-ever formal definition for this construct of cardiovascular health, published in 2010,2 was based on a broad review of the literature designed to determine groups of factors associated with excellent prognosis in long-term CVD-free survival and quality of life. Itt was designed to be simple, accessible and actionable, allowing all patients, cli clinicians inici ciian ns an andd communities to focus on improving cardiovascular health. And it was crafted in a way so that it could co oul uldd be m measured e sure ea reed in i the broad US population an andd m major ajor subgroup subgroups, u s, m up monitored on onitored over time, and influenced nfllue u nced by AH AHA AHA’s A’s po A’s portfolio ortfo rttfo foli lioo off pprograms. li rogra rog grams..2 A Although ltho houghh the ho the en entire nti tirre sspectrum p ct pe ctru um of ccardiovascular arrdi diov o asccula ov cular a health heal he alth al th hw was as ccaptured aptu aptu ureed (f (from fro om bi birth irt r h th thro through roug ro ug gh li livi living ving vi ng gw with ith CV ith CVD), VD) D),, a cr crit critical ittic ical al oobservation bser bser e vaatiion o w was as the thee recognition ecognition off aan n “i “ideal ide d al car cardiovascular ardi ar diov di ov vas ascu cu ula l r he heal health” alth al th” ph th phen phenotype enot en o yp ot ypee th that att co cons consisted sis i te tedd of tthe hee ssimultaneous imul im ulta ul t neous presence of ideal levels of seven health behaviors and health factors: smoking status, physical activity, eating pattern, body weight, and blood cholesterol, blood glucose and blood pressure levels. In the five years since the publication of the definition of cardiovascular health, numerous investigators have examined the prevalence of levels of ideal cardiovascular health in diverse populations from around the globe.3-8 In countries with more developed economies, it seems to be a universal finding that the prevalence of truly ideal cardiovascular health in adults is rare, often less than 1%. Whereas it appears that most of us are born with the potential for ideal
2 Downloaded from http://circ.ahajournals.org/ at New York University/ Medical Center--New York on October 14, 2014
DOI: 10.1161/CIRCULATIONAHA.114.012869
cardiovascular health, in the US fewer than half of all adolescents have retained at least five of the seven metrics at ideal levels, with steady declines in prevalence thereafter, until ideal cardiovascular health is vanishingly rare above age 60 years.9 Recent data suggest that this is much more a function of the loss of healthy lifestyle and behavior attributes during young adulthood, rather than an inevitable consequence of aging or heredity. There are even positive indications that improving lifestyle can make a large difference in preserving ideal cardiovascular health, that small changes can have an impact, and that it is never too late, although earlier implementation is clearly better.10-12 A number of studies have also examined the prospective associations of different levels of cardiovascular health with short-and long-term cardiovascular and non-cardiov non-cardiovascular ov vasscu ula larr outcomes. Table 1 provides a summary of the outcomes favorably associated with greater cardiovascular ca ard dio iovvasc vasccul ulaar hhealth ealt ea lth to date. Findings have cons consistently nsiisttently demons ns demonstrated str trated ed d tthat hat having more of the seven components levels with lower and eveen compon nen ntss aatt id iideal eal le eal leve vels ve ls iiss aassociated sso socciated ed d wit th lowe werr ri we risk skk ffor or ffatal atal at all an nd nnon-fatal nd on-ffatal on-f cardiovascular with ca ard rdio iova io v sc va scul ular ul ar events eve vent ntss inn all all l race/sex rac a e/ e/se sexx subgroups se suubg gro roup upss studied, up sttud udie i d, d w ithh ex it eextremely trem trem mel elyy low low incidence inci in c de ci denncee rates rate ra tess in those ideal health metrics levels). hose with ide deeal ccardiovascular ardi ar d ov di ovas a cu cula lar he la heal allth t ((i.e., i e. i. e.,, al alll se sseven venn me ve etr tric icss at iideal ic d al le de leve vels ve ls). ls ) IIntriguing ). ntri nt r gu ri guin ing data alsoo in reveal associations with lower risk for incident cancer, better cognition in younger and older adults, less depression, better quality of life, enhanced compression of morbidity, and even lower healthcare charges, among other outcomes.4,7,13-18 It is certainly intuitive that lower levels of cardiovascular risk factors and better health behaviors should be associated with lower risk for CVD. And yet: one of the tantalizing impressions when one examines data on this ideal cardiovascular health concept is that the whole may indeed be greater than the sum of the parts. In this issue of Circulation, Xanthakis et al.,19 from the Framingham investigators, provide the latest pieces of evidence linking greater cardiovascular health construct to favorable
3 Downloaded from http://circ.ahajournals.org/ at New York University/ Medical Center--New York on October 14, 2014
DOI: 10.1161/CIRCULATIONAHA.114.012869
outcomes with regard to CVD incidence. The major contribution these authors make is in filling some of the gaps in our understanding about the mechanisms underlying the association of greater cardiovascular health with lower disease incidence. One may legitimately ask: do people with better cardiovascular health over time simply develop less subclinical disease (atherosclerosis, or vascular or myocardial damage), and therefore they are at lower CVD risk simply because of that? Or is there possibly more to it? Xanthakis et al. characterized 2680 mostly middle-aged Framingham Study participants with regard to their cardiovascular health status on all seven metrics at baseline. Consistent with the approach taken by many other investigators, they created a simple score from 0 to 7 points, indicating levels. ndicating how many cardiovascular health metrics each participant had at ideall le leve velss. Th ve They ey tthen hen examined associations of the score with various serologic markers of inflammation, coagulation, and target-organ cardiovascular an nd ta targ rget rg et-o et -org -o rggan n ddamage, am amage, as well as measures off ssubclinical ubclinical cardi diov o asscular ul disease, including increased ncrrea e sed carotid caro otiid intima-media intiima ma-m -med -m edia ed iaa thickness thiick kness or stenosis, sttenoosiis, evidence eviden evi iden nce ce ooff left left vventricular en ntr tric icuular ic ular hhypertrophy ypperrtrrophy ophy h or systolic yst stol olic ol ic dysfunction, dys ysfu func fu ncttioon, on, microalbuminuria, microa micr oalb lbum lb um min inuuria uriaa, or low low w ankle-brachial ankl nkle-b -b bra rach chiaal index. ch in ndeex. x As As expected, expe ex pect pe c ed ct d, most most of mos of the th he serum erum biomarkers biomar arrke kers rss were werre within wiith thin in normative nor o ma m tiive ranges ran ange gess inn this ge thi h s sample, samp sa mple mp lee, on o average. ave vera rage ra ge.. Having ge Havi Ha ving vi ng a higher cardiovascular health score was significantly associated with modestly lower levels of aldosterone, C-reactive protein, D-dimer, fibrinogen, growth-differentiation factor 15, homocysteine, and plasminogen activator-inhibitor 1. In other words, greater cardiovascular health was associated with lower levels of adverse biomarkers. An interesting finding was a positive association of the cardiovascular health score with natriuretic peptide levels within the normative range, which the authors plausibly suggest may be due to enrichment of the sample at higher scores for those with lower BMI and more women, two factors that are associated with higher natriuretic peptide levels.19
4 Downloaded from http://circ.ahajournals.org/ at New York University/ Medical Center--New York on October 14, 2014
DOI: 10.1161/CIRCULATIONAHA.114.012869
A higher cardiovascular health score was also associated with lower odds of having subclinical disease. For each one point higher in the score, the odds of having any subclinical disease measure were 23% lower. Higher scores were even less likely to be associated with evidence for multiple aspects of subclinical disease. It may come as no surprise, therefore, that Xanthakis et al. observed a significantly lower risk for CVD events (coronary heart disease, stroke or transient ischemic attack, heart failure, or claudication) among those with higher cardiovascular health scores, with a hazard ratio of 0.77 per 1-point higher on the cardiovascular health score and a generally linear relationship across the range of scores.19 In this study, compared to someone with 0 points, someone with 1 point was on average at 23% lower risk for CVD over 16 years; someone with 2 points was at 41% (1- (0.77*0.77) lower risk; ris isk; k; and andd so so on. on. However, the innovative aspect of the authors’ analysis is that they then adjusted for the significant ignnif ific ican ic an nt biom bbiomarkers iomar arkkers ar ke and subclinical disease measures, mea e sures, which might mig i htt be be expected to completely attenuate attteenu n ate the as ass association sociat atio i n be io betw between tw ween een th thee car ccardiovascular ardio ovaascuulaar he health ealth alth h sco score corre aand nd d iincident nccid den entt CV CVD, VD, D, ssince i ce in ce tthey heyy he represent epr pres essen e t likely liike kely ly intermediary intter erme medi d aryy factors di fact fa ctor ct orss inn the or the pathway patthway way from frrom m cardiovascular car ardi diov di ov vas ascu c lar cu lar health heal he a th to al to disease. di eas dise ase. e. But Butt even after adjustment adj djus ustm us tm men entt fo for th the he bi biom biomarkers omar om arke ar keers r aand nd ssubclinical ubcl ub clin cl in nic ical al ddisease i ea is ease se m measures, e su ea sure res, re s, tthe hee ccardiovascular ardi ar d ov di o ascular health score remained independently and significantly associated with lower risk for CVD (hazard ratio 0.87, 95% confidence interval 0.78 – 0.97 for each 1 point higher in the score). What are we to make of this? To be sure, we must be cautious and recognize the potential for residual confounding. The vast majority of CVD events are of course preceded by evidence of vascular or myocardial alterations or damage, and the measures available to the authors for this analysis incompletely represent all of the causal pathways involved in the transition from cardiovascular health to CVD. Nonetheless, the Framingham investigators have provided the most interesting data to date examining potential mechanisms underlying the construct of
5 Downloaded from http://circ.ahajournals.org/ at New York University/ Medical Center--New York on October 14, 2014
DOI: 10.1161/CIRCULATIONAHA.114.012869
cardiovascular health. Their data suggest that there might be additional intangible benefits of the cardiovascular health phenotype, perhaps related to other aspects of a healthy lifestyle, or the tendency for longer exposure to favorable levels of cardiovascular health metrics among those with greater cardiovascular health (since it is easier and more common to preserve it than restore it). Such speculations require further investigation. In the meantime, these data provide yet more strong and compelling evidence that, regardless of the mechanism, promotion of cardiovascular health must be advanced immediately and forcefully as a key part of the national agenda, at every level of policymaking, across all healthcare and public health systems, and for all segments of the population. Only with maximal effort can we blunt the substantial substa taant ntia i l burden ia burd bu rden rd en ooff CVD and CVD-related costs that are impending over the next decades.20 To promote and achieve a cu ult ltur uree of hhealth ur ealt ltth in which all Americans, and pa part ticularly our yyouth, o th ou h, ca cann achieve healthy culture particularly longevity, onggev e ity, whe where here ree ccardiovascular arrdi d ovvas ascu cu ula larr he hea health alth alth h iiss po poor, oorr, w wee m must usst im improve mprrov ovee iit; t; wh whe where ere it is is intermediate, in nte t rmed rmed e ia iate te,, we we must mu ust restore res e to tore re iit; t; and andd where whe here re ideal, ide deal de all, we m must ustt preserve us pres pr eser erve er vee it. it. t
Conflict of Interest Disclosures: None.
References: 1. Labarthe DR. From cardiovascular disease to cardiovascular health: a quiet revolution? Circ Cardiovasc Qual Outcomes. 2012;5:e86-92. 2. 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. 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;121:586613. 3. Del Brutto OH, Dong C, Rundek T, Elkind MS, Del Brutto VJ, Sacco RL. Cardiovascular Health Status Among Caribbean Hispanics Living in Northern Manhattan and Ecuadorian
6 Downloaded from http://circ.ahajournals.org/ at New York University/ Medical Center--New York on October 14, 2014
DOI: 10.1161/CIRCULATIONAHA.114.012869
Natives/Mestizos in Rural Coastal Ecuador. J Community Health. 2013;38:634-641. 4. Laitinen TT, Pahkala K, Magnussen CG, Viikari JS, Oikonen M, Taittonen L, Mikkila V, Jokinen E, Hutri-Kahonen N, Laitinen T, Kahonen M, Lehtimaki T, Raitakari OT, Juonala M. Ideal cardiovascular health in childhood and cardiometabolic outcomes in adulthood. Circulation. 2012;125:1971-1978. 5. Shay CM, Ning H, Allen NB, Carnethon MR, Chiuve SE, Greenlund KJ, Daviglus ML, Lloyd-Jones DM. Status of cardiovascular health in US adults. Circulation. 2012;125:45-56. 6. Vetrano DL, Martone AM, Mastropaolo S, Tosato M, Colloca G, Marzetti E, Onder G, Bernabei R, Landi F. Prevalence of the seven cardiovascular health metrics in a Mediterranean country: results from a cross-sectional study. Eur J Pub Health. 2013;23:858-862. 7. Yang Q, Cogswell ME, Flanders WD, Hong Y, Zhang Z, Loustalot F, Gillespie C, Merritt R, Hu FB. Trends in cardiovascular health metrics and associations with all-cause and CVD mortality among US adults. JAMA. 2012;307:1273-1283. Q,, Wu S S,, Zhao 8. Zhang Q, Zhou Y, Gao X, Wang C, Zhang S, Wang A, Li N, Bian L, Wu J, JJia iaa Q Zh intracerebral hemorrhagic X. Ideal cardiovascular health metrics and the risks of ischemic and intracerebra al he hemo morr mo rrha rr hagi ha gicc gi stroke. troke. Stroke. 2013;44:2451-2456. Roger VL, Benjamin EJ, Borden WB, 9.. R ogeer og er V L, Goo AS, AS Lloyd-Jones DM, Benjam min E J, Berry JD, B orde deen W B, Bravata DM, Dai Ford ES, Fox CS,, Fu Fullerton Gillespie Hailpern Heit Howard VJ,, Ki Kissela S,, F ordd ES S, F oxx CS C ull ller erto er t n HJ to HJ,, Gi Gill lles espi piee C, H ailperrn SM ail SM, He eit it JJA, A, H owar ow ardd VJ V Kiss sssel e a BM, B , BM Kittner Lackland DT, Lichtman Marelli K itttne n r SJ, La ack kla land nd D T, L iccht htma maan JH, JH H, Lisabeth Lisaabeeth LD, LD, Makuc Mak akuuc uc DM, DM, M, Marcus Marrcu us GM GM, Ma Mare r ll re lli A, A, Matchar DB, Moy CS, Mozaffarian Mussolino ME, Nichol G,, P Paynter NP, Soliman EZ, M attchar tc DB B, Mo oy CS S, Moz M ozaffar ff ria i n D, M usssoolino oM E, N icho ic ho ol G aynnteer er N P, S ollim man nE Z, Sorlie PD, Sotoodehnia N,, Tu Turan Virani SS, Wong MB. Heart Sorl So rlie rl iee P D,, S otoo ot ooodeehn hnia ia N Tura an TN TN,, Vi Vira ranni S ra S W S, onng ND ND, Wo Wooo D, D Turner Turnerr M B.. H eaart ddisease iseeasse is se Circulation. 2012;125:e2-e220. andd stroke stro st r ke sstatistics--2012 tati t st s iccss--2 -20112 update. uppda date te. Circul ulat atio ion. n 20 2012;1 ;125 25:ee22-e2 e2200. 10. Li K, D Daviglus ML, Lo Loria CM, Co Colangelo DM. 10 Liuu K avig av iglu luss ML Lori riaa CM Cola lang ngel eloo LA, LA Spring Spr prin ingg B, B Moller Mol olle lerr AC, AC Lloyd-Jones Lloy Ll oydd-Jo Jone ness DM Healthy lifestyle through young adulthood and the presence of low cardiovascular disease risk profile in middle age. Circulation. 2012;125:996-1004. 11. Spring B, Moller AC, Colangelo LA, Siddique J, Roehrig M, Daviglus ML, Polak JF, Reis JP, Sidney S, Liu K. Healthy lifestyle change and subclinical atherosclerosis in young adults. Circulation. 2014;130:10-17. 12. Laitinen TT, Pahkala K, Venn A, Woo JG, Oikonen M, Dwyer T, Mikkila V, Hutri-Kahonen N, Smith KJ, Gall SL, Morrison JA, Viikari JS, Raitakari OT, Magnussen CG, Juonala M. Childhood lifestyle and clinical determinants of adult ideal cardiovascular health. Int J Cardiol. 2013;169:126-132. 13. Dong C, Rundek T, Wright CB, Anwar Z, Elkind MS, Sacco RL. Ideal cardiovascular health predicts lower risks of myocardial infarction, stroke, and vascular death across whites, blacks, and hispanics. Circulation. 2012;125:2975-2984.
7 Downloaded from http://circ.ahajournals.org/ at New York University/ Medical Center--New York on October 14, 2014
DOI: 10.1161/CIRCULATIONAHA.114.012869
14. Folsom AR, Yatsuya H, Nettleton JA, Lutsey PL, Cushman M, Rosamond WD, Investigators AS. Community prevalence of ideal cardiovascular health, by the American Heart Association definition, and relationship with cardiovascular disease incidence. J Am Coll Cardiol. 2011;57:1690-1696. 15. Kulshreshtha A, Vaccarino V, Judd SE, Howard VJ, McClellan WM, Muntner P, Hong Y, Safford MM, Goyal A, Cushman M. Life's Simple 7 and risk of incident stroke. Stroke. 2013;44:1909-1914. 16. Rasmussen-Torvik LJ, Shay CM, Abramson JG, Friedrich CA, Nettleton JA, Prizment AE, Folsom AR. Ideal cardiovascular health is inversely associated with incident cancer. Circulation. 2013;127:1270-1275. 17. Reis JP, Loria CM, Launer LJ, Sidney S, Liu K, Jacobs DR, Jr., Zhu N, Lloyd-Jones DM, He K, Yaffe K. Cardiovascular health through young adulthood and cognitive functioning in midlife. Ann Neurol. 2013;73:170-179. 18. Wilkins JT, Ning H, Berry J, Zhao L, Dyerr AR, Lloyd-Jones DM. Lifetime risk skk aand nd yyears ears ea rs lived ived free of total cardiovascular disease. JAMA. 2012;308:1795-1801. 19. Xanthakis V, Enserro DM, Murabito JM, Polak JF, Wollert KC, Januzzi JL, Wang TJ, Tofler G, Vasan RS. S Ideal cardiovascular health: associations with biomarkers and subclinical disease, and an nd impact imppact im pact on on incidence in nci ciddence of cardiovascular disease diseas asee in as in the Framingham Framinggha h m Offspring Offs Of f pring Study. Circulation. Circ Ci cul ulation. 2014;130:XX-XXX. 20144;1 2014 ; 30 30:X :XX:X X XX XXXX. X. 20. PA, Dracup K,, Ez Ezekowitz Finkelstein 20 0. Heidenreich Heidenre reic ich PA A, Trogdon Troogdo doon JG JG, Khavjou K avj Kh avjou OA OA, Butler Butl Bu tler err JJ,, Dr D acupp K zekowit i z MD, MD, F innkelssteein EA, D,, EA A, Hong Hongg Y, Y, Johnston John Jo hnst hn ston onn SC, SC, C Khera Kheera A, A, Lloyd-Jones Lloy oydoy d-Joone dn s DM, DM, Nelson Nellson Ne on SA, SA, A Nichol Nich ichol hol G, G Orenstein Oreens nsteein in D Wilson United States: Wils lson on PW, PW, W Woo Woo o YJ. YJ. Forecasting Forrec e as asti tingg the the future fut utur uree of cardiovascular cardiiov ovas ascu cula larr disease diise seas asee in tthe he U nite ni t d St S attes es:: a statement the American Heart Association. Circulation. 2011;123:933-944. policy stateme meent ffrom rom ro m th he Am Amer ric ican an nH e rt A ea ssoc ss ocia oc iati ia tiion o . Ci Circ rcul rc ullat atio i n. 20 2011 11;1 11 ;123 ;1 233:9 933 33-9 -9 944 4 .
Table 1. Domains of improved outcomes with which greater levels of cardiovascular health (as defined by the American Heart Association2) have been associated prospectively. All-cause (total) mortality -CVD, coronary, stroke mortality Non-fatal CVD events -Coronary heart disease -Stroke Incident cancer Venous thromboembolism
End-stage renal disease Atherosclerosis and arterial stiffness in younger adults Cognitive function in younger and older adults Depression Quality of life Compression of morbidity Medicare charges
8 Downloaded from http://circ.ahajournals.org/ at New York University/ Medical Center--New York on October 14, 2014
The online version of this article, along with updated information and services, is located on the World Wide Web at: http://circ.ahajournals.org/content/early/2014/10/01/CIRCULATIONAHA.114.012869
Permissions: Requests for permissions to reproduce figures, tables, or portions of articles originally published in Circulation can be obtained via RightsLink, a service of the Copyright Clearance Center, not the Editorial Office. Once the online version of the published article for which permission is being requested is located, click Request Permissions in the middle column of the Web page under Services. Further information about this process is available in the Permissions and Rights Question and Answer document. Reprints: Information about reprints can be found online at: http://www.lww.com/reprints Subscriptions: Information about subscribing to Circulation is online at: http://circ.ahajournals.org//subscriptions/
Downloaded from http://circ.ahajournals.org/ at New York University/ Medical Center--New York on October 14, 2014
DOI: 10.1161/CIRCULATIONAHA.114.012869
Cardiovascular Health and Protection Against CVD: More Than the Sum of the Parts?
Running title: Lloyd-Jones; Mechanisms of CV health protection
Donald M. Lloyd-Jones, MD, ScM, FAHA
Department of Preventive Medicine and the Division of Cardiology, Department of Medicine, Northwestern Medicine, Chicago, No orthw rth estern University Feinberg rg School School of Medic icine, ic e, C hicago, IL
Address Ad ddr dres esss for es for Correspondence: Coorr rres e pond es pond nden e ce ce: Donald M.. Ll Lloyd-Jones, MD, ScM Donald Dona ld M Lloy oydd-JJone Jones, s, M D, S D, cM M Department Preventive Medicine D epartme t ntt off P re enti ti e M edi diciine Northwestern University Feinberg School of Medicine 680 N. Lake Shore Dr., Suite 1400 Chicago, IL 60611 Tel: 312-908-1718 Fax: 312-908-9588 E-mail: [email protected] Journal Subject Code: Etiology:[8] Epidemiology
Key words:Editorial, cardiovascular outcomes, risk factor, health status
1 Downloaded from http://circ.ahajournals.org/ at New York University/ Medical Center--New York on October 14, 2014
DOI: 10.1161/CIRCULATIONAHA.114.012869
Five years ago, the American Heart Association (AHA) launched a bold new initiative to begin promoting “cardiovascular health” in individuals and the population, in addition to continuing its decades-long fight to reduce cardiovascular and stroke mortality and decrease cardiovascular disease (CVD) risk. This shift in priorities came as a result of a “quiet revolution,”1 turning the adverse-outcomes-oriented and risk-focused perspective on its head, and instead focusing on creating the opportunity for promoting and preserving attributes associated with healthy, CVDfree longevity. The first-ever formal definition for this construct of cardiovascular health, published in 2010,2 was based on a broad review of the literature designed to determine groups of factors associated with excellent prognosis in long-term CVD-free survival and quality of life. Itt was designed to be simple, accessible and actionable, allowing all patients, cli clinicians inici ciian ns an andd communities to focus on improving cardiovascular health. And it was crafted in a way so that it could co oul uldd be m measured e sure ea reed in i the broad US population an andd m major ajor subgroup subgroups, u s, m up monitored on onitored over time, and influenced nfllue u nced by AH AHA AHA’s A’s po A’s portfolio ortfo rttfo foli lioo off pprograms. li rogra rog grams..2 A Although ltho houghh the ho the en entire nti tirre sspectrum p ct pe ctru um of ccardiovascular arrdi diov o asccula ov cular a health heal he alth al th hw was as ccaptured aptu aptu ureed (f (from fro om bi birth irt r h th thro through roug ro ug gh li livi living ving vi ng gw with ith CV ith CVD), VD) D),, a cr crit critical ittic ical al oobservation bser bser e vaatiion o w was as the thee recognition ecognition off aan n “i “ideal ide d al car cardiovascular ardi ar diov di ov vas ascu cu ula l r he heal health” alth al th” ph th phen phenotype enot en o yp ot ypee th that att co cons consisted sis i te tedd of tthe hee ssimultaneous imul im ulta ul t neous presence of ideal levels of seven health behaviors and health factors: smoking status, physical activity, eating pattern, body weight, and blood cholesterol, blood glucose and blood pressure levels. In the five years since the publication of the definition of cardiovascular health, numerous investigators have examined the prevalence of levels of ideal cardiovascular health in diverse populations from around the globe.3-8 In countries with more developed economies, it seems to be a universal finding that the prevalence of truly ideal cardiovascular health in adults is rare, often less than 1%. Whereas it appears that most of us are born with the potential for ideal
2 Downloaded from http://circ.ahajournals.org/ at New York University/ Medical Center--New York on October 14, 2014
DOI: 10.1161/CIRCULATIONAHA.114.012869
cardiovascular health, in the US fewer than half of all adolescents have retained at least five of the seven metrics at ideal levels, with steady declines in prevalence thereafter, until ideal cardiovascular health is vanishingly rare above age 60 years.9 Recent data suggest that this is much more a function of the loss of healthy lifestyle and behavior attributes during young adulthood, rather than an inevitable consequence of aging or heredity. There are even positive indications that improving lifestyle can make a large difference in preserving ideal cardiovascular health, that small changes can have an impact, and that it is never too late, although earlier implementation is clearly better.10-12 A number of studies have also examined the prospective associations of different levels of cardiovascular health with short-and long-term cardiovascular and non-cardiov non-cardiovascular ov vasscu ula larr outcomes. Table 1 provides a summary of the outcomes favorably associated with greater cardiovascular ca ard dio iovvasc vasccul ulaar hhealth ealt ea lth to date. Findings have cons consistently nsiisttently demons ns demonstrated str trated ed d tthat hat having more of the seven components levels with lower and eveen compon nen ntss aatt id iideal eal le eal leve vels ve ls iiss aassociated sso socciated ed d wit th lowe werr ri we risk skk ffor or ffatal atal at all an nd nnon-fatal nd on-ffatal on-f cardiovascular with ca ard rdio iova io v sc va scul ular ul ar events eve vent ntss inn all all l race/sex rac a e/ e/se sexx subgroups se suubg gro roup upss studied, up sttud udie i d, d w ithh ex it eextremely trem trem mel elyy low low incidence inci in c de ci denncee rates rate ra tess in those ideal health metrics levels). hose with ide deeal ccardiovascular ardi ar d ov di ovas a cu cula lar he la heal allth t ((i.e., i e. i. e.,, al alll se sseven venn me ve etr tric icss at iideal ic d al le de leve vels ve ls). ls ) IIntriguing ). ntri nt r gu ri guin ing data alsoo in reveal associations with lower risk for incident cancer, better cognition in younger and older adults, less depression, better quality of life, enhanced compression of morbidity, and even lower healthcare charges, among other outcomes.4,7,13-18 It is certainly intuitive that lower levels of cardiovascular risk factors and better health behaviors should be associated with lower risk for CVD. And yet: one of the tantalizing impressions when one examines data on this ideal cardiovascular health concept is that the whole may indeed be greater than the sum of the parts. In this issue of Circulation, Xanthakis et al.,19 from the Framingham investigators, provide the latest pieces of evidence linking greater cardiovascular health construct to favorable
3 Downloaded from http://circ.ahajournals.org/ at New York University/ Medical Center--New York on October 14, 2014
DOI: 10.1161/CIRCULATIONAHA.114.012869
outcomes with regard to CVD incidence. The major contribution these authors make is in filling some of the gaps in our understanding about the mechanisms underlying the association of greater cardiovascular health with lower disease incidence. One may legitimately ask: do people with better cardiovascular health over time simply develop less subclinical disease (atherosclerosis, or vascular or myocardial damage), and therefore they are at lower CVD risk simply because of that? Or is there possibly more to it? Xanthakis et al. characterized 2680 mostly middle-aged Framingham Study participants with regard to their cardiovascular health status on all seven metrics at baseline. Consistent with the approach taken by many other investigators, they created a simple score from 0 to 7 points, indicating levels. ndicating how many cardiovascular health metrics each participant had at ideall le leve velss. Th ve They ey tthen hen examined associations of the score with various serologic markers of inflammation, coagulation, and target-organ cardiovascular an nd ta targ rget rg et-o et -org -o rggan n ddamage, am amage, as well as measures off ssubclinical ubclinical cardi diov o asscular ul disease, including increased ncrrea e sed carotid caro otiid intima-media intiima ma-m -med -m edia ed iaa thickness thiick kness or stenosis, sttenoosiis, evidence eviden evi iden nce ce ooff left left vventricular en ntr tric icuular ic ular hhypertrophy ypperrtrrophy ophy h or systolic yst stol olic ol ic dysfunction, dys ysfu func fu ncttioon, on, microalbuminuria, microa micr oalb lbum lb um min inuuria uriaa, or low low w ankle-brachial ankl nkle-b -b bra rach chiaal index. ch in ndeex. x As As expected, expe ex pect pe c ed ct d, most most of mos of the th he serum erum biomarkers biomar arrke kers rss were werre within wiith thin in normative nor o ma m tiive ranges ran ange gess inn this ge thi h s sample, samp sa mple mp lee, on o average. ave vera rage ra ge.. Having ge Havi Ha ving vi ng a higher cardiovascular health score was significantly associated with modestly lower levels of aldosterone, C-reactive protein, D-dimer, fibrinogen, growth-differentiation factor 15, homocysteine, and plasminogen activator-inhibitor 1. In other words, greater cardiovascular health was associated with lower levels of adverse biomarkers. An interesting finding was a positive association of the cardiovascular health score with natriuretic peptide levels within the normative range, which the authors plausibly suggest may be due to enrichment of the sample at higher scores for those with lower BMI and more women, two factors that are associated with higher natriuretic peptide levels.19
4 Downloaded from http://circ.ahajournals.org/ at New York University/ Medical Center--New York on October 14, 2014
DOI: 10.1161/CIRCULATIONAHA.114.012869
A higher cardiovascular health score was also associated with lower odds of having subclinical disease. For each one point higher in the score, the odds of having any subclinical disease measure were 23% lower. Higher scores were even less likely to be associated with evidence for multiple aspects of subclinical disease. It may come as no surprise, therefore, that Xanthakis et al. observed a significantly lower risk for CVD events (coronary heart disease, stroke or transient ischemic attack, heart failure, or claudication) among those with higher cardiovascular health scores, with a hazard ratio of 0.77 per 1-point higher on the cardiovascular health score and a generally linear relationship across the range of scores.19 In this study, compared to someone with 0 points, someone with 1 point was on average at 23% lower risk for CVD over 16 years; someone with 2 points was at 41% (1- (0.77*0.77) lower risk; ris isk; k; and andd so so on. on. However, the innovative aspect of the authors’ analysis is that they then adjusted for the significant ignnif ific ican ic an nt biom bbiomarkers iomar arkkers ar ke and subclinical disease measures, mea e sures, which might mig i htt be be expected to completely attenuate attteenu n ate the as ass association sociat atio i n be io betw between tw ween een th thee car ccardiovascular ardio ovaascuulaar he health ealth alth h sco score corre aand nd d iincident nccid den entt CV CVD, VD, D, ssince i ce in ce tthey heyy he represent epr pres essen e t likely liike kely ly intermediary intter erme medi d aryy factors di fact fa ctor ct orss inn the or the pathway patthway way from frrom m cardiovascular car ardi diov di ov vas ascu c lar cu lar health heal he a th to al to disease. di eas dise ase. e. But Butt even after adjustment adj djus ustm us tm men entt fo for th the he bi biom biomarkers omar om arke ar keers r aand nd ssubclinical ubcl ub clin cl in nic ical al ddisease i ea is ease se m measures, e su ea sure res, re s, tthe hee ccardiovascular ardi ar d ov di o ascular health score remained independently and significantly associated with lower risk for CVD (hazard ratio 0.87, 95% confidence interval 0.78 – 0.97 for each 1 point higher in the score). What are we to make of this? To be sure, we must be cautious and recognize the potential for residual confounding. The vast majority of CVD events are of course preceded by evidence of vascular or myocardial alterations or damage, and the measures available to the authors for this analysis incompletely represent all of the causal pathways involved in the transition from cardiovascular health to CVD. Nonetheless, the Framingham investigators have provided the most interesting data to date examining potential mechanisms underlying the construct of
5 Downloaded from http://circ.ahajournals.org/ at New York University/ Medical Center--New York on October 14, 2014
DOI: 10.1161/CIRCULATIONAHA.114.012869
cardiovascular health. Their data suggest that there might be additional intangible benefits of the cardiovascular health phenotype, perhaps related to other aspects of a healthy lifestyle, or the tendency for longer exposure to favorable levels of cardiovascular health metrics among those with greater cardiovascular health (since it is easier and more common to preserve it than restore it). Such speculations require further investigation. In the meantime, these data provide yet more strong and compelling evidence that, regardless of the mechanism, promotion of cardiovascular health must be advanced immediately and forcefully as a key part of the national agenda, at every level of policymaking, across all healthcare and public health systems, and for all segments of the population. Only with maximal effort can we blunt the substantial substa taant ntia i l burden ia burd bu rden rd en ooff CVD and CVD-related costs that are impending over the next decades.20 To promote and achieve a cu ult ltur uree of hhealth ur ealt ltth in which all Americans, and pa part ticularly our yyouth, o th ou h, ca cann achieve healthy culture particularly longevity, onggev e ity, whe where here ree ccardiovascular arrdi d ovvas ascu cu ula larr he hea health alth alth h iiss po poor, oorr, w wee m must usst im improve mprrov ovee iit; t; wh whe where ere it is is intermediate, in nte t rmed rmed e ia iate te,, we we must mu ust restore res e to tore re iit; t; and andd where whe here re ideal, ide deal de all, we m must ustt preserve us pres pr eser erve er vee it. it. t
Conflict of Interest Disclosures: None.
References: 1. Labarthe DR. From cardiovascular disease to cardiovascular health: a quiet revolution? Circ Cardiovasc Qual Outcomes. 2012;5:e86-92. 2. 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. 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;121:586613. 3. Del Brutto OH, Dong C, Rundek T, Elkind MS, Del Brutto VJ, Sacco RL. Cardiovascular Health Status Among Caribbean Hispanics Living in Northern Manhattan and Ecuadorian
6 Downloaded from http://circ.ahajournals.org/ at New York University/ Medical Center--New York on October 14, 2014
DOI: 10.1161/CIRCULATIONAHA.114.012869
Natives/Mestizos in Rural Coastal Ecuador. J Community Health. 2013;38:634-641. 4. Laitinen TT, Pahkala K, Magnussen CG, Viikari JS, Oikonen M, Taittonen L, Mikkila V, Jokinen E, Hutri-Kahonen N, Laitinen T, Kahonen M, Lehtimaki T, Raitakari OT, Juonala M. Ideal cardiovascular health in childhood and cardiometabolic outcomes in adulthood. Circulation. 2012;125:1971-1978. 5. Shay CM, Ning H, Allen NB, Carnethon MR, Chiuve SE, Greenlund KJ, Daviglus ML, Lloyd-Jones DM. Status of cardiovascular health in US adults. Circulation. 2012;125:45-56. 6. Vetrano DL, Martone AM, Mastropaolo S, Tosato M, Colloca G, Marzetti E, Onder G, Bernabei R, Landi F. Prevalence of the seven cardiovascular health metrics in a Mediterranean country: results from a cross-sectional study. Eur J Pub Health. 2013;23:858-862. 7. Yang Q, Cogswell ME, Flanders WD, Hong Y, Zhang Z, Loustalot F, Gillespie C, Merritt R, Hu FB. Trends in cardiovascular health metrics and associations with all-cause and CVD mortality among US adults. JAMA. 2012;307:1273-1283. Q,, Wu S S,, Zhao 8. Zhang Q, Zhou Y, Gao X, Wang C, Zhang S, Wang A, Li N, Bian L, Wu J, JJia iaa Q Zh intracerebral hemorrhagic X. Ideal cardiovascular health metrics and the risks of ischemic and intracerebra al he hemo morr mo rrha rr hagi ha gicc gi stroke. troke. Stroke. 2013;44:2451-2456. Roger VL, Benjamin EJ, Borden WB, 9.. R ogeer og er V L, Goo AS, AS Lloyd-Jones DM, Benjam min E J, Berry JD, B orde deen W B, Bravata DM, Dai Ford ES, Fox CS,, Fu Fullerton Gillespie Hailpern Heit Howard VJ,, Ki Kissela S,, F ordd ES S, F oxx CS C ull ller erto er t n HJ to HJ,, Gi Gill lles espi piee C, H ailperrn SM ail SM, He eit it JJA, A, H owar ow ardd VJ V Kiss sssel e a BM, B , BM Kittner Lackland DT, Lichtman Marelli K itttne n r SJ, La ack kla land nd D T, L iccht htma maan JH, JH H, Lisabeth Lisaabeeth LD, LD, Makuc Mak akuuc uc DM, DM, M, Marcus Marrcu us GM GM, Ma Mare r ll re lli A, A, Matchar DB, Moy CS, Mozaffarian Mussolino ME, Nichol G,, P Paynter NP, Soliman EZ, M attchar tc DB B, Mo oy CS S, Moz M ozaffar ff ria i n D, M usssoolino oM E, N icho ic ho ol G aynnteer er N P, S ollim man nE Z, Sorlie PD, Sotoodehnia N,, Tu Turan Virani SS, Wong MB. Heart Sorl So rlie rl iee P D,, S otoo ot ooodeehn hnia ia N Tura an TN TN,, Vi Vira ranni S ra S W S, onng ND ND, Wo Wooo D, D Turner Turnerr M B.. H eaart ddisease iseeasse is se Circulation. 2012;125:e2-e220. andd stroke stro st r ke sstatistics--2012 tati t st s iccss--2 -20112 update. uppda date te. Circul ulat atio ion. n 20 2012;1 ;125 25:ee22-e2 e2200. 10. Li K, D Daviglus ML, Lo Loria CM, Co Colangelo DM. 10 Liuu K avig av iglu luss ML Lori riaa CM Cola lang ngel eloo LA, LA Spring Spr prin ingg B, B Moller Mol olle lerr AC, AC Lloyd-Jones Lloy Ll oydd-Jo Jone ness DM Healthy lifestyle through young adulthood and the presence of low cardiovascular disease risk profile in middle age. Circulation. 2012;125:996-1004. 11. Spring B, Moller AC, Colangelo LA, Siddique J, Roehrig M, Daviglus ML, Polak JF, Reis JP, Sidney S, Liu K. Healthy lifestyle change and subclinical atherosclerosis in young adults. Circulation. 2014;130:10-17. 12. Laitinen TT, Pahkala K, Venn A, Woo JG, Oikonen M, Dwyer T, Mikkila V, Hutri-Kahonen N, Smith KJ, Gall SL, Morrison JA, Viikari JS, Raitakari OT, Magnussen CG, Juonala M. Childhood lifestyle and clinical determinants of adult ideal cardiovascular health. Int J Cardiol. 2013;169:126-132. 13. Dong C, Rundek T, Wright CB, Anwar Z, Elkind MS, Sacco RL. Ideal cardiovascular health predicts lower risks of myocardial infarction, stroke, and vascular death across whites, blacks, and hispanics. Circulation. 2012;125:2975-2984.
7 Downloaded from http://circ.ahajournals.org/ at New York University/ Medical Center--New York on October 14, 2014
DOI: 10.1161/CIRCULATIONAHA.114.012869
14. Folsom AR, Yatsuya H, Nettleton JA, Lutsey PL, Cushman M, Rosamond WD, Investigators AS. Community prevalence of ideal cardiovascular health, by the American Heart Association definition, and relationship with cardiovascular disease incidence. J Am Coll Cardiol. 2011;57:1690-1696. 15. Kulshreshtha A, Vaccarino V, Judd SE, Howard VJ, McClellan WM, Muntner P, Hong Y, Safford MM, Goyal A, Cushman M. Life's Simple 7 and risk of incident stroke. Stroke. 2013;44:1909-1914. 16. Rasmussen-Torvik LJ, Shay CM, Abramson JG, Friedrich CA, Nettleton JA, Prizment AE, Folsom AR. Ideal cardiovascular health is inversely associated with incident cancer. Circulation. 2013;127:1270-1275. 17. Reis JP, Loria CM, Launer LJ, Sidney S, Liu K, Jacobs DR, Jr., Zhu N, Lloyd-Jones DM, He K, Yaffe K. Cardiovascular health through young adulthood and cognitive functioning in midlife. Ann Neurol. 2013;73:170-179. 18. Wilkins JT, Ning H, Berry J, Zhao L, Dyerr AR, Lloyd-Jones DM. Lifetime risk skk aand nd yyears ears ea rs lived ived free of total cardiovascular disease. JAMA. 2012;308:1795-1801. 19. Xanthakis V, Enserro DM, Murabito JM, Polak JF, Wollert KC, Januzzi JL, Wang TJ, Tofler G, Vasan RS. S Ideal cardiovascular health: associations with biomarkers and subclinical disease, and an nd impact imppact im pact on on incidence in nci ciddence of cardiovascular disease diseas asee in as in the Framingham Framinggha h m Offspring Offs Of f pring Study. Circulation. Circ Ci cul ulation. 2014;130:XX-XXX. 20144;1 2014 ; 30 30:X :XX:X X XX XXXX. X. 20. PA, Dracup K,, Ez Ezekowitz Finkelstein 20 0. Heidenreich Heidenre reic ich PA A, Trogdon Troogdo doon JG JG, Khavjou K avj Kh avjou OA OA, Butler Butl Bu tler err JJ,, Dr D acupp K zekowit i z MD, MD, F innkelssteein EA, D,, EA A, Hong Hongg Y, Y, Johnston John Jo hnst hn ston onn SC, SC, C Khera Kheera A, A, Lloyd-Jones Lloy oydoy d-Joone dn s DM, DM, Nelson Nellson Ne on SA, SA, A Nichol Nich ichol hol G, G Orenstein Oreens nsteein in D Wilson United States: Wils lson on PW, PW, W Woo Woo o YJ. YJ. Forecasting Forrec e as asti tingg the the future fut utur uree of cardiovascular cardiiov ovas ascu cula larr disease diise seas asee in tthe he U nite ni t d St S attes es:: a statement the American Heart Association. Circulation. 2011;123:933-944. policy stateme meent ffrom rom ro m th he Am Amer ric ican an nH e rt A ea ssoc ss ocia oc iati ia tiion o . Ci Circ rcul rc ullat atio i n. 20 2011 11;1 11 ;123 ;1 233:9 933 33-9 -9 944 4 .
Table 1. Domains of improved outcomes with which greater levels of cardiovascular health (as defined by the American Heart Association2) have been associated prospectively. All-cause (total) mortality -CVD, coronary, stroke mortality Non-fatal CVD events -Coronary heart disease -Stroke Incident cancer Venous thromboembolism
End-stage renal disease Atherosclerosis and arterial stiffness in younger adults Cognitive function in younger and older adults Depression Quality of life Compression of morbidity Medicare charges
8 Downloaded from http://circ.ahajournals.org/ at New York University/ Medical Center--New York on October 14, 2014
