Portal de Periódicos da CAPES

Is 2015 the Primetime Year for Prehypertension? Prehypertension: A Cardiovascular Risk Factor or Simply a Risk Marker?

2015; Wiley; Volume: 4; Issue: 2 Linguagem: Inglês

10.1161/jaha.115.001792

2047-9980

Gabriel B. Habib, Salim S. Virani, Hani Jneid,

Sodium Intake and Health

HomeJournal of the American Heart AssociationVol. 4, No. 2Is 2015 the Primetime Year for Prehypertension? Prehypertension: A Cardiovascular Risk Factor or Simply a Risk Marker? Open AccessEditorialPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citations ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toOpen AccessEditorialPDF/EPUBIs 2015 the Primetime Year for Prehypertension? Prehypertension: A Cardiovascular Risk Factor or Simply a Risk Marker? Gabriel B. HabibSr, Salim S. Virani and Hani Jneid Gabriel B. HabibSrGabriel B. HabibSr Cardiology/Medicine, Michael E. DeBakey VA Medical Center, Houston, TX , Salim S. ViraniSalim S. Virani Cardiology/Medicine, Michael E. DeBakey VA Medical Center, Houston, TX and Hani JneidHani Jneid Cardiology/Medicine, Michael E. DeBakey VA Medical Center, Houston, TX Originally published24 Feb 2015https://doi.org/10.1161/JAHA.115.001792Journal of the American Heart Association. 2015;4:e001792How Important is Hypertension for World Health?The Comparative Risk Assessment module of the World Health Organization's Global Burden of Disease 2000 study1 conducted a systematic assessment of changes in population health resulting from modifying exposure to 26 risk factors. These included atherosclerotic risk factors such as high blood pressure, smoking history, high cholesterol, high body mass index and physical inactivity, which were examined in over 55 million inhabitants of dozens of developing and developed regions of the world.1 The message was clear: Hypertension is the single most important contributor to the global burden of mortality and morbidity in both developed and developing countries and the most important cardiovascular (CV) risk factor.Why is Hypertension the Leading Risk Factor for World Health?The relationship of systolic blood pressure (BP) to CV mortality was evaluated in the Prospective Studies Collaboration, the largest meta‐analysis of its kind encompassing 1 million participants 40 to 89 years of age. Systolic BP was shown to be a powerful risk factor for stroke and ischemic heart disease mortality with doubling of fatal CV disease for every 20 mm Hg increment in SBP across fourth through 8 decades of life.2 Most importantly, the aforementioned meta‐analysis informed us that systolic BP is strongly and directly related to vascular and overall mortality, without a threshold effect down to a BP of 115/75 mm Hg.2Is it Time for Change?A 50‐year‐old man with a BP of 135/80 mm Hg is twice as likely to die from a stroke as his counterpart with a BP of 115/80 mmHg. However, both subjects are considered non‐hypertensive since the arbitrary cutoff for hypertension of 140/90 mm Hg is not reached. So, how can we better differentiate between these 2 subjects with different CV prognoses?Over 12 years ago, the Seventh Report of the Joint National Committee on Prevention, Diagnosis, Evaluation and Treatment of High BP (JNC 7)3 defined a new BP category, prehypertension, a BP between 120/80 and 139/89 mm Hg that specifically identifies a higher‐risk subject with BP higher than optimal BP but yet lower than the arbitrary cutoff for hypertension.Why Should we Recognize Prehypertensive Subjects With a Separate BP Category Compared to Normotensive Subjects?First, they are likely to become hypertensive over time, especially if they are of African‐American descent.4, 5 Second, they have a higher CV risk compared with normotensive subjects with a BP 8‐fold in hypertensive and >3‐fold in prehypertensive subjects—compared with just 2.4 and 1.5‐fold, respectively, in white Americans.10 However, the small sample size of the Asian and Pacific Islanders in this study (2.4% of the entire population) contributed to the failure of these large differences in CV risks to translate into clinically significant differences in outcome. These findings are, however, both surprising and difficult to reconcile with the conclusions of the meta‐analysis by Huang et al7Is Prehypertension an Independent Causative Risk Factor for CHD or Simply a Risk Marker?Cohort studies are observational studies and are important in evaluating associations between risk markers or risk factors—the exposure of interest—and incidence of the disease of interest. However, to demonstrate causality, a variety of criteria should be satisfied.13We critically review below the classical and widely acceptable Bradford Hill's causality criteria as they apply to the association between prehypertension and CHD outcomes: Strength of association: "A strong association is more likely to have a causal component than is a modest association." For Western studies, the magnitude of the association ranges from 17% to a >100% excess risk across individual studies and amount to an overall 70% excess CHD risk, supporting a strong association. However, the modest 25% excess CHD risk among Asians with prehypertension is not consistent with a strong association, especially when we factor in unknown confounders and possible residual confounding effect after multivariate risk adjustment.Consistency: "A relationship is observed repeatedly." Here lies the major drawback for Asian studies: many individual Asian studies did not report statistically significant associations between prehypertension and CHD risk.Specificity: "A factor influences specifically a particular outcome or population." Specificity of the association of prehypertension and CHD is supported by multivariate risk‐adjusted analyses which tease out known confounders of the association of prehypertension and CHD but unknown confounders cannot be adjusted for in observational studies.Temporality: "The factor must precede the outcome it is assumed to affect." Temporality is supported by cohort studies in which subjects had no CV disease at study entry: only 4 of the included studies excluded such patients but study conclusions were similar with or without baseline CV disease.Biological gradient: "The outcome increases monotonically with increasing dose of the exposure or according to a function predicted by a substantive theory." Greater relative risks (RR) of CHD with high‐range prehypertension compared with low‐range hypertension supports a biological gradient. However, the difference in RR between low‐ and high‐range prehypertension is small—1.27 (95% CI of 1.07 to 1.50) versus 1.58 (95% CI of 1.24 to 2.02)—and non‐significant.Plausibility: "The observed association can be plausibly explained by substantive matter (eg, biological) explanations." The relation between prehypertension and CHD has not been well explained. Studies on atheroma progression are small, few and inconsistent in confirming the plausibility of this association.14, 15Coherence: "A causal conclusion should not fundamentally contradict present substantive knowledge." The association between prehypertension and CHD is supported by the previously reported consistent and strong relation between BP and CHD risk down to a BP of 115/75 mm Hg.2Experiment: "Causation is more likely if evidence is based on randomized experiments." This criterion is not fulfilled: the few randomized controlled clinical trials in prehypertension have reported inconsistent effects on atheroma progression14, 15 and no randomized clinical trials have evaluated hard clinical outcome endpoints in prehypertension.Analogy: "For analogous exposures and outcomes an effect has already been shown." Susser16 interpreted this criterion as follows: "when one class of causal agents is known to have produced an effect, the standards for evidence that another agent of that class produces a similar effect can be reduced." The wealth of the evidence supporting the association of hypertension with CHD2 favors an association between a similar (or analogous) exposure—prehypertension—and CHD.We therefore conclude—based on the totality of evidence—that the association between prehypertension and CHD is stronger and more compelling among Westerners than among Asians and is not—in our judgment—a causal association, especially among Asians. Thus, prehypertension is a CHD risk marker especially among Westerners but not a CHD risk factor.So, What are the Clinical Implications of This Recent Meta‐Analysis?Should a prehypertensive subject be monitored more closely? The answer is yes. It is reasonable to monitor BP more closely in prehypertensive subjects since a significant proportion of them will later develop hypertension3, 17, 18Should a prehypertensive subject start any specific treatment? The answer is yes: lifestyle changes generally recommended in the overall population3 should be further emphasized in these subjects,3 in our opinion. The JNC 7 guideline recommendation for lifestyle changes in prehypertension is supported by the recent meta‐analysis since prehypertension is a marker for an increased CHD risk, especially among Westerners. However, no pharmacological treatment is currently recommended by any medical society in the general population with prehypertension,3, 6, 17, 18 a recommendation that is supported by our conclusion that prehypertension—albeit a CHD risk marker—has not been proven to be a causal CHD risk factor requiring specific treatment per se. Tempting as it might be to initiate pharmacologic therapy in prehypertensive subjects, the published clinical trials have cast doubt to any long‐term benefit from a short‐term pharmacologic intervention.14, 15 Overall, the risk‐benefit ratio and the value of such treatment in this subpopulation remain controversial.Should we wait for BP to exceed the arbitrary cutoff of 140/90 mm Hg to start pharmacologic treatment to reduce CV risk? The answer is yes. The JNC 8 panel6 recommends starting antihypertensive drug therapy if BP is ≥140/90 mm Hg in patients ≤60 years and if BP is ≥150/90 mm Hg in patients >60 years.6So, is 2015 the primetime year for prehypertension? The answer is yes. We are READY and SET but we do not have the evidence to GO with no proven therapy in sight for prehypertension. We should await considerably more research, particularly randomized controlled interventional clinical trials in prehypertensive subjects before recommending anything beyond BP monitoring and therapeutic lifestyle change as was initially recommended in JNC 7 over 12 years ago.DisclosuresDr Habib and Dr Jneid have no conflict of interest to disclose. Dr Virani has no conflict of interest to disclose but receives grant support from the Department of Veterans Affairs, American Heart Association, American Diabetes Association, and Baylor College of Medicine's Center for Globalization.Footnotes*Correspondence to: Gabriel B. Habib Sr, MS, MD, FACC, FCCP, FAHA, Michael E. DeBakey VA Medical Center, 2002 Holcombe Blvd., Houston, TX 77030‐4298. E‐mail: [email protected]comThe opinions expressed in this article are not necessarily those of the editors or of the American Heart Association.References1 Ezzati M, Lopez AD, Rodgers A, Vander Hoorn S, Murray CJ; Comparative Risk Assessment Collaborating Group . Selected major risk factors and global and regional burden of disease. Lancet. 2002; 360:1347–1360.CrossrefMedlineGoogle Scholar2 Lewington S, Clarke R, Qizilbash N, Peto R, Collins R; Prospective Studies Collaboration . Age‐specific relevance of usual blood pressure to vascular mortality: a meta‐analysis of individual data for one million adults in 61 prospective studies. Lancet. 2002; 360:1903–1913.CrossrefMedlineGoogle Scholar3 Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL, Jones DW, Materson BJ, Oparil S, Wright JT, Roccella EJ; National Heart, Lung, and Blood Institute Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure; National High Blood Pressure Education Program Coordinating Committee . The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure: the JNC 7 report. JAMA. 2003; 289:2560–2572.CrossrefMedlineGoogle Scholar4 Robinson S, Brucer M. Range of normal blood pressure: a statistical and clinical study of 11,383 persons. Arch Intern Med. 1939; 64:409–444.CrossrefGoogle Scholar5 Selassie A, Wagner CS, Laken ML, Ferguson ML, Ferdinand KC, Egan BM. Progression is accelerated from prehypertension to hypertension in blacks. Hypertension. 2011; 58:579–587.LinkGoogle Scholar6 James PA, Oparil S, Carter BL, Cushman WC, Dennison‐Himmelfarb C, Handler J, Lackland DT, LeFevre ML, MacKenzie TD, Ogedegbe O, Smith SC, Svetkey LP, Taler SJ, Townsend RR, Wright JT, Narva AS, Ortiz E. 2014 evidence‐based guideline for the management of high blood pressure in adults: report from the panel members appointed to the Eighth Joint National Committee (JNC 8). JAMA. 2014; 311:507–520.CrossrefMedlineGoogle Scholar7 Huang Y, Cai X, Liu C, Zhu D, Hua J, Hu Y, Peng J, Xu D. Prehypertension and the risk of coronary heart disease in Asians and Westerners: a meta‐analysis. J Am Heart Assoc. 2015; 4:e001519 doi: 10.1161/JAHA.114.001519.LinkGoogle Scholar8 Qureshi AI, Suri MF, Kirmani JF, Divani AA, Mohammad Y. Is prehypertension a risk factor for cardiovascular diseases?Stroke. 2005; 36:1859–1863.LinkGoogle Scholar9 Kshirsagar AV, Carpenter M, Bang H, Wyatt SB, Colindres RE. Blood pressure usually considered normal is associated with an elevated risk of cardiovascular disease. Am J Med. 2006; 119:133–141.CrossrefMedlineGoogle Scholar10 Hsia J; Margolis KL, Eaton CB, Wenger NK, Allison M, Wu L, LaCroix AZ, Black HR; Women's Health Initiative Investigators . Prehypertension and cardiovascular disease risk in the Women's Health Initiative. Circulation. 2007; 115:855–860.LinkGoogle Scholar11 Lee ET, Howard BV, Wang W, Welty TK, Galloway JM, Best LG, Fabsitz RR, Zhang Y, Yeh J, Devereux RB. Prediction of coronary heart disease in a population with high prevalence of diabetes and albuminuria: the Strong Heart Study. Circulation. 2006; 113:2897–2905.LinkGoogle Scholar12 Huang Y, Cai X, Li Y, Su L, Mai W, Wang S, Hu Y, Wu Y, Xu D. Prehypertension and the risk of stroke: a meta‐analysis. Neurology. 2014; 82:1153–1161.CrossrefMedlineGoogle Scholar13 Hill AB. The environment and disease: association or causation?Proc R Soc Med. 1965; 58:295–300.CrossrefMedlineGoogle Scholar14 Sipahi I, Tuzcu EM, Schoenhagen P, Wolski KE, Nicholls SJ, Balog C, Crowe TD, Nissen SE. Effects of normal, pre‐hypertensive and hypertensive blood pressure levels on progression of coronary atherosclerosis. J Am Coll Cardiol. 2006; 48:833–838.CrossrefMedlineGoogle Scholar15 Nicholls SJ, Bakris GL, Kastelein JJ, Menon V, Williams B, Armbrecht J, Brunel P, Nicolaides M, Hsu A, Hu B, Fang H, Puri R, Uno K, Kataoka Y, Bash D, Nissen SE. Effect of Aliskiren on progression of coronary disease in patients with prehypertension: the AQUARIUS randomized clinical trial. JAMA. 2013; 310:1135–1144.CrossrefMedlineGoogle Scholar16 Susser M. What is a cause and how do we know one? A grammar for pragmatic epidemiology. Am J Epidemiol. 1991; 7:635–648.CrossrefGoogle Scholar17 Mancia G, Fagard R, Narkiewicz K, Redon J, Zanchetti A, Böhm M, Christiaens T, Cifkova R, De Backer G, Dominiczak A, Galderisi M, Grobbee DE, Jaarsma T, Kirchhof P, Kjeldsen SE, Laurent S, Manolis AJ, Nilsson PM, Ruilope LM, Schmieder RE, Sirnes PA, Sleight P, Viigimaa M, Waeber B, Zannad F, Redon J, Dominiczak A, Narkiewicz K, Nilsson PM, Burnier M, Viigimaa M, Ambrosioni E, Caufield M, Coca A, Olsen MH, Schmieder RE, Tsioufis C, van de Borne P, Zamorano JL, Achenbach S, Baumgartner H, Bax JJ, Bueno H, Dean V, Deaton C, Erol C, Fagard R, Ferrari R, Hasdai D, Hoes AW, Kirchhof P, Knuuti J, Kolh P, Lancellotti P, Linhart A, Nihoyannopoulos P, Piepoli MF, Ponikowski P, Sirnes PA, Tamargo JL, Tendera M, Torbicki A, Wijns W, Windecker S, Clement DL, Coca A, Gillebert TC, Tendera M, Rosei EA, Ambrosioni E, Anker SD, Bauersachs J, Hitij JB, Caulfield M, De Buyzere M, De Geest S, Derumeaux GA, Erdine S, Farsang C, Funck‐Brentano C, Gerc V, Germano G, Gielen S, Haller H, Hoes AW, Jordan J, Kahan T, Komajda M, Lovic D, Mahrholdt H, Olsen MH, Ostergren J, Parati G, Perk J, Polonia J, Popescu BA, Reiner Z, Rydén L, Sirenko Y, Stanton A, Struijker‐Boudier H, Tsioufis C, van de Borne P, Vlachopoulos C, Volpe M, Wood DA. 2013 ESH/ESC Guidelines for the management of arterial hypertension: the Task Force for the management of Arterrial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). Eur Heart J. 2013; 34:2159–2219.CrossrefMedlineGoogle Scholar18 Weber MA, Schiffrin EL, White WB, Mann S, Lindholm LH, Kenerson JG, Flack JM, Carter BL, Materson BJ, Ram CV, Cohen DL, Cadet JC, Jean‐Charles RR, Taler S, Kountz D, Townsend R, Chalmers J, Ramirez AJ, Bakris GL, Wang J, Schutte AE, Bisognano JD, Touyz RM, Sica D, Harrap SB. Clinical practice guidelines for the management of hypertension in the community: a statement by the American Society of Hypertension and the International Society of Hypertension. J Hypertens. 2014; 32:3–15.CrossrefMedlineGoogle Scholar Previous Back to top Next FiguresReferencesRelatedDetailsCited By Saif-Ur-Rahman K, Chiang C, Weldegerima Gebremariam L, Haregot Hilawe E, Hirakawa Y, Aoyama A and Yatsuya H (2021) Association of anthropometric indices of obesity with hypertension among public employees in northern Ethiopia: findings from a cross-sectional survey, BMJ Open, 10.1136/bmjopen-2021-050969, 11:9, (e050969), Online publication date: 1-Sep-2021. Wu J, Duan W, Jiao Y, Liu S, Zheng L, Sun Y and Sun Z (2021) The Association of Stage 1 Hypertension, Defined by the 2017 ACC/AHA Guidelines, With Cardiovascular Events Among Rural Women in Liaoning Province, China, Frontiers in Cardiovascular Medicine, 10.3389/fcvm.2021.710500, 8 Duan W, Wu J, Liu S, Jiao Y, Zheng L, Sun Y and Sun Z (2020) Impact of Prehypertension on the Risk of Major Adverse Cardiovascular Events in a Chinese Rural Cohort, American Journal of Hypertension, 10.1093/ajh/hpaa019, 33:5, (465-470), Online publication date: 29-Apr-2020. Wang Z, Hao G, Wang X, Chen Z, Zhang L, Zhang Z, Hu H, Weintraub W and Gao R (2019) Clinical outcomes and economic impact of the 2017 ACC/AHA guidelines on hypertension in China, The Journal of Clinical Hypertension, 10.1111/jch.13609, 21:8, (1212-1220), Online publication date: 1-Aug-2019. Nsanya M, Kavishe B, Katende D, Mosha N, Hansen C, Nsubuga R, Munderi P, Grosskurth H and Kapiga S (2019) Prevalence of high blood pressure and associated factors among adolescents and young people in Tanzania and Uganda, The Journal of Clinical Hypertension, 10.1111/jch.13502, 21:4, (470-478), Online publication date: 1-Apr-2019. Cao C, Cai W, Niu X, Fu J, Ni J, Lei Q, Niu J, Zhou X and Li Y (2018) Prehypertension during pregnancy and risk of small for gestational age: a systematic review and meta-analysis, The Journal of Maternal-Fetal & Neonatal Medicine, 10.1080/14767058.2018.1519015, (1-8) Rahman M, Zaman M, Islam J, Chowdhury J, Ahsan H, Rahman R, Hassan M, Hossain Z, Alam B and Yasmin R (2017) Prevalence, treatment patterns, and risk factors of hypertension and pre-hypertension among Bangladeshi adults, Journal of Human Hypertension, 10.1038/s41371-017-0018-x, 32:5, (334-348), Online publication date: 1-May-2018. Peltzer K, Pengpid S, Sychareun V, Ferrer A, Low W, Huu T, Win H, Rochmawati E and Turnbull N (2017) Prehypertension and psychosocial risk factors among university students in ASEAN countries, BMC Cardiovascular Disorders, 10.1186/s12872-017-0666-3, 17:1, Online publication date: 1-Dec-2017. Jackson H, Yates B, Blanchard S, Zimmerman L, Hudson D and Pozehl B (2016) Behavior-Specific Influences for Physical Activity Among African American Women, Western Journal of Nursing Research, 10.1177/0193945916640724, 38:8, (992-1011), Online publication date: 1-Aug-2016. Lei Q, Zhou X, Zhou Y, Mai C, Hou M, Lv L, Duan D, Wen J, Lin X, Wang P, Ling X, Li Y and Niu J (2016) Prehypertension During Normotensive Pregnancy and Postpartum Clustering of Cardiometabolic Risk Factors, Hypertension, 68:2, (455-463), Online publication date: 1-Aug-2016.Mozaffarian D, Benjamin E, Go A, Arnett D, Blaha M, Cushman M, Das S, de Ferranti S, Després J, Fullerton H, Howard V, Huffman M, Isasi C, Jiménez M, Judd S, Kissela B, Lichtman J, Lisabeth L, Liu S, Mackey R, Magid D, McGuire D, Mohler E, Moy C, Muntner P, Mussolino M, Nasir K, Neumar R, Nichol G, Palaniappan L, Pandey D, Reeves M, Rodriguez C, Rosamond W, Sorlie P, Stein J, Towfighi A, Turan T, Virani S, Woo D, Yeh R and Turner M (2015) Heart Disease and Stroke Statistics—2016 Update, Circulation, 133:4, (e38-e360), Online publication date: 26-Jan-2016. Xu T and Huang Y (2015) Prehypertension—new insights for health risks, Nature Reviews Cardiology, 10.1038/nrcardio.2015.17-c1, 12:7, (440-440), Online publication date: 1-Jul-2015. January 30, 2015Vol 4, Issue 2Article InformationMetrics © 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.https://doi.org/10.1161/JAHA.115.001792PMID: 25699997 Originally publishedFebruary 24, 2015 Keywordsmeta‐analysiscoronary heart diseaseEditorialshypertensionprehypertensionPDF download SubjectsClinical Studies