Is the Relation of Systolic Blood Pressure to Risk of Cardiovascular Disease Continuous and Graded, or Are There Critical Values?
2003; Lippincott Williams & Wilkins; Volume: 42; Issue: 4 Linguagem: Inglês
10.1161/01.hyp.0000093382.69464.c4
ISSN1524-4563
AutoresWilliam B. Kannel, Ramachandran S. Vasan, Daniel Levy,
Tópico(s)Hormonal Regulation and Hypertension
ResumoHomeHypertensionVol. 42, No. 4Is the Relation of Systolic Blood Pressure to Risk of Cardiovascular Disease Continuous and Graded, or Are There Critical Values? Free AccessReview ArticlePDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessReview ArticlePDF/EPUBIs the Relation of Systolic Blood Pressure to Risk of Cardiovascular Disease Continuous and Graded, or Are There Critical Values? William B. Kannel, Ramachandran S. Vasan and Daniel Levy William B. KannelWilliam B. Kannel From the National Heart, Lung, and Blood Institute's Framingham Study and the Department of Preventive Medicine, Boston University, Boston, Mass. , Ramachandran S. VasanRamachandran S. Vasan From the National Heart, Lung, and Blood Institute's Framingham Study and the Department of Preventive Medicine, Boston University, Boston, Mass. and Daniel LevyDaniel Levy From the National Heart, Lung, and Blood Institute's Framingham Study and the Department of Preventive Medicine, Boston University, Boston, Mass. Originally published15 Sep 2003https://doi.org/10.1161/01.HYP.0000093382.69464.C4Hypertension. 2003;42:453–456Other version(s) of this articleYou are viewing the most recent version of this article. Previous versions: September 15, 2003: Previous Version 1 Because epidemiologic data indicate a continuous incremental risk of cardiovascular disease (CVD) in relation to blood pressure (BP), hypertension treatment guidelines now recommend treating high-normal and mild BP elevations.1 Port and coworkers,2 analyzing Framingham Study data, challenge this assertion. They claim that Framingham data in actuality "contradict the concept that lower pressures imply lower risk and the idea that 140 mm Hg is a useful cut-off value for hypertension for all adults." They suggest that there is an age- and sex-dependent threshold for "hypertension" and that a substantial proportion of the population currently deemed at increased risk are, in fact, not.Their conclusion derives from the use of "logistic splines" methodology to examine the relation of systolic blood pressure (SBP) to CVD and all-cause mortality. They contend that previous linear logistic analysis depicting a continuous, graded relation is misleading and that there is actually a threshold at the 70th percentile of SBP for a person at a given age and sex. They also suggest that because BP increases steadily with age, the threshold also increases with age.2 By inference, Port et al seem to suggest that we to return to the discarded concept that a "normal" systolic pressure is, roughly, "100+ years of age mm Hg." They focus on all-cause mortality because "it is most free of misclassifications and, importantly the number of events is sufficiently high to allow accurate estimates of the shape of the relation with systolic blood pressure." However, the more relevant outcome is CVD mortality and the CVD events promoted by hypertension unconfounded by non-CVD mortality, which could be associated with low BP. Furthermore, even a focus on CVD mortality, excluding the large majority of nonfatal events, needlessly reduces the amount of data on which to determine the shape of the BP–CVD incidence curve.Normal BP for AgeA review of the evidence for a continuous, graded influence of BP on the incidence and mortality of CVD appears to be in order. The first consideration is the issue of what constitutes a "normal" BP. It is evident that in most developed countries, SBP rises with age.3 Diastolic blood pressure (DBP) rises with age until age 55 years, after which it declines in both sexes.4 However, in some less-developed countries where obesity and high salt intake are uncommon, adults experience little increase in BP with age.3 It is well established that the disproportionate rise in SBP relative to DBP with age is a consequence of a pathologic reduction in arterial compliance: as elastic fibers fragment, the elastic lamellae disrupt, and the collagen-to-elastin ratio in the arterial wall is altered.5Usual Versus Optimal BPThe current concept of "desirable" BP is based not on what BP level is "usually" but rather on what is "optimal" (ie, associated with a low rate of hypertension-related CVD). It is clear from the Framingham Study and other prospective, epidemiologic data that at all ages, the risk of developing a CVD event increases with SBP and that at any given BP, the absolute vascular risk is substantially greater in the elderly (Table 1). The elderly do not endure their higher average BP well. Although their relative risk of suffering a CVD event might be a bit lower, this is offset by a much higher absolute age-adjusted risk. Examination of the SBPs at which CVD events occurred in Framingham Study male participants not on treatment indicates that 45% occurred at a SBP <140 mm Hg, the value that the logistic splines analysis of Port et al suggests as the threshold of increased risk.6TABLE 1. Average Annual Incidence of CVD by SBP: Framingham Study 30-Year Follow-UpSBP, mm HgAnnual Rate per 1000Men, Age Range, yWomen, Age Range, y35–4445–5455–6465–7475–8435–4445–5455–6465–7475–84All SBP CVD incidence trends are significant except for ages 35–44 in women.Source: Cupples and D'Agostino.674–119381616331361217120–1395111823381591742140–15971931374939162233160–179132943529109242047180–300103562781121016364552Incremental BP Risk at FraminghamFramingham Study data, based on 30 years of biennial, prospective surveillance of a cohort for CVD in relation to components of BP, concluded that there is a continuous, graded relation of SBP to the rate of development of CVD at all ages. Without resorting to any type of statistical modeling, no clear indication of a critical BP was discerned in any group from age 35 to 84 years (Table 1). Similar graded relations of BP to coronary heart disease (CHD) and all-cause mortality have been reported in several other cohorts.7–9A large data set is required to obtain a precise estimate of the trend in CVD incidence at lower BP levels (eg, 350 000 male screenees followed up for CVD mortality.10 Data from MRFIT confirm a continuous and graded influence of SBP on CHD mortality extending down into the range of SBP <140 mm Hg (Table 2). Perusal of the age-adjusted rates (without statistical modeling) based on 6122 events occurring at SBPs <140 mm Hg shows a stepwise increase in CHD mortality with each 10-mm Hg increment in pressure. The data show no indication of a threshold below which BP is unassociated with a lower CHD death rate. Age-specific data from this MRFIT study indicate a fairly consistent gradient of CHD mortality risk per mm Hg increment in SBP at all ages from 35 to 57 years.10 Based on the similar size of the regression coefficients for each age decade, there is little to suggest a shifting threshold of risk in relation to BP with advancing age in men (Table 3). TABLE 2. Association of SBP and CHD Mortality in 347 978 Men Screened for MRFITSBP, mm HgMen, nCHD Deaths, nAge-Adjusted RateAge-Adjusted Relative RiskRelative risk was estimated by proportional-hazards regression model stratified by clinic and adjusted for age, race, income, cholesterol, cigarettes, and diabetes.Source: Neaton et al.10 2103284482.66.40 (4.74–8.65)TABLE 3. Impact of SBP on CHD Mortality in Men Screened for MRFITAge, yBeta Coefficient (SE)**Increment in log hazard ratio per mm Hg increase in SBP. Risk was estimated by proportional-hazards regression stratified by clinic and adjusted for age, race, income, cholesterol, cigarettes, and diabetes. SE indicates standard error.Source: Neaton et al.1035–440.0232 (0.0022)40–440.0257 (0.0014)45–490.0234 (0.0010)50–540.0208 (0.0008)55–570.0214 (0.0010)All ages0.0222 (0.0005)An even more definitive demonstration of the continuous, graded influence of BP on CVD risk comes from a recent meta-analysis of data from 61 prospective studies involving almost 1 million participants and 56 000 vascular deaths.11 This Prospective Studies Collaboration found that BP is related to vascular mortality, without any indication of a threshold down to 115/75 mm Hg. Persons aged 40 to 69 years had a doubling of risk of stroke or coronary mortality with every 20-mm Hg increment in SBP (or 10-mm Hg higher DBP) throughout the entire range of BP.Incremental Risk Within Normal to High-Normal RangeFurthermore, recent analysis of the relation of nonhypertensive BP to development of CVD in the Framingham Study found a significant, graded influence of BP from optimal (<120/80 mm Hg) to normal (120 to 129/80 to 84 mm Hg) to high-normal (130 to 139/85 to 89 mm Hg) Joint National Committee VI stages among untreated men and women (Table 4). This incremental risk at nonhypertensive BPs was seen in age-adjusted analyses and was also noted after adjustment for coexistent risk factors. Compared with optimal BP, high-normal BP conferred a 1.6- to 2.5-fold risk of a "hard" CVD event.12TABLE 4. Relation of Nonhypertensive BP Categories to Development of Hard CVD in Framingham Study Subjects, Ages 35–90 YearsBP Category (mm Hg)10-Year Cumulative IncidenceWomenMenAge-Adjusted RateHR*Age-Adjusted RateHR*Stratified by exam. HR indicates hazard ratio adjusted for age, body mass index, cholesterol, diabetes, and smoking.*Values represent 95% confidence intervals.Source: Vasan et al.12Optimal (<120/80)1.9%1.05.8%1.0Normal (120–129/80–84)2.8%1.5 (0.9–2.5)7.6%1.3 (1.0–1.9)High-normal (130–139/85–89)4.4%2.5 (1.6–4.1)10.1%1.6 (1.1–2.2)P for trend across categories<0.01<0.001Impact of Long-Term Antecedent BP on CVD RiskAssessment of the true CVD risk gradient associated with increased BP must take into account the biologic as well as the analytic coefficient of variation. Recent analysis of Framingham Study data examined the relation of casual BP to subsequent risk of CVD, comparing the impact of a single current BP, the average of all readings over 10 years, and the average for all available values 11 to 20 years before baseline.13 It was found that antecedent SBP is an important determinant of future CVD events above and beyond current SBP. In particular, it was demonstrated that in nonhypertensive subjects (<140/90 mm Hg and not on treatment) in the 60-, 70-, and 80-year age groups, each standard deviation increase in current, recent, and remote SBP increased the risk of CVD by 12% to 45%, (ie, there was a continuous gradient of CVD risk).Likewise, the stroke risk in relation to increments in antecedent, current, recent, and remote long-term BP was recently examined in the Framingham Study. Models for antecedent long-term BP influence were adjusted for smoking, diabetes, and baseline BP, thereby reflecting the additional, independent, long-term BP impact. It was determined that in nonhypertensive persons (<140/90 mm Hg), the stroke risk increased substantially with each standard deviation increase in SBP in men and women at the current ages of 60 and 70 years.14 It thus appears from Framingham Study data that there is a significant and lingering gradient of risk in relation to SBPs below the alleged 140-mm Hg threshold suggested by the analysis of Port et al.Antecedent BP and HypertensionAntecedent BP within the normal range has also been shown to be a determinant of future hypertension. Recent data from the Framingham Study indicate that development of hypertension over 4 years of observation in subjects aged <65 years occurred 7 times more often in subjects with high-normal than optimal BPs and over that age, at 3 times the rate.15 This is another reason for concern about even minimally elevated (nonhypertensive) BP.Role of Pulse PressureThe influence of SBP on CVD should be evaluated, taking the accompanying DBP into account. Data from the Framingham Study indicate that at SBPs of 120 to 139 mm Hg in the elderly, the relative risk of CHD increases the lower accompanying DBP.16 Hence, pulse pressure appears to emerge as an important BP determinant of CVD incidence in the elderly.17 Perusal of Framingham Study data indicates a continuous, graded influence of pulse pressure on CVD incidence (Table 5).18 Thus, rather than the threshold for BP risk changing with advancing age, as alleged by the spline analysis of Port et al, it appears that it is the influence of the different components of BP that changes. TABLE 5. Risk of CV Events by Pulse Pressure: 30-Year Follow-Up of the Framingham StudyPulse pressure, mm HgAge-Adjusted Rate per 1000Age 35–64 YearsAge 65–94 YearsMenWomenMenWomenSource: Kannel.18 7033165832Increment per 10 mm Hg19.7%20.9%23.4%10.5%PerspectivesThere is overwhelming evidence of a continuous, graded influence of SBP on CVD morbidity and mortality at all ages in both sexes. An optimal BP for avoiding CVD is <140/90 mm Hg, and there is no clearly defined critical BP that distinguishes normal from abnormal. It is the level of BP that kills, not arbitrarily defined hypertension. Because the hazard of CVD increases in a continuous, graded fashion in relation to BP, a population approach as advocated by Rose19 must accompany efforts to detect and treat elevated values. For cost-effective treatment of persons with prehypertension and stage 1 hypertensive BPs, multivariable risk stratification is required, and the goal of therapy should be to improve the global risk.1,20 The hazard of any level of BP elevation is increased when there is concomitant dyslipidemia, proteinuria, diabetes, or already existing overt renal disease, coronary disease, or peripheral artery disease.1 The importance of what appear to be trivial differences in BP, even within the high-normal BP range, should not be underestimated. The extra effort needed to lower the BP down to the recommended goals for avoiding CVD is worthwhile. Further clinical trials are needed to address the unanswered question about the efficacy of individualized treatment of patients whose BPs are <160 mm Hg systolic and 90 mm Hg diastolic by using global risk assessment to set goals for BP lowering.Framingham Study Research is supported by National Institutes of Health/National Heart, Lung, and Blood Institute contract NO1-HC-25195, and the Framingham Visiting Scientist Program is supported by Servier Amerique.FootnotesCorrespondence to William B. Kannel, MD, Framingham Heart Study, 73 Mt Wayte Ave, Suite 2, Framingham, MA 01702-5827. E-mail [email protected] References 1 Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL, Jones DW, Materson BJ, Oparil S, Wright JT Jr, Roccella EJ. 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 Scholar2 Port S, Demer L, Jennrich R, Walter D, Garfinkel A. Systolic blood pressure and mortality. Lancet. 2000; 355: 175–180.CrossrefMedlineGoogle Scholar3 Rodriguez BL, Labarthe DR, Huang B, Lopez-Gomez J. Rise of blood pressure with age: new evidence of population differences. Hypertension. 1994; 24: 779–785.LinkGoogle Scholar4 Kannel WB, Wolf PA, Verter J, McNamara PM. Epidemiologic assessment of the role of blood pressure in stroke. JAMA. 1970; 214: 301–310.CrossrefMedlineGoogle Scholar5 Avolio A, Jones D, Taffazoli-Shadpour M. Quantification of alterations in structure and function of elastin in the arterial media. Hypertension. 1998; 32: 170–175.CrossrefMedlineGoogle Scholar6 Cupples LA, D'Agostino RB. Some risk factors related to the annual incidence of cardiovascular disease and death using pooled repeated biennial measurements: 30-year follow-up. In: Kannel WB, Wolf PA, eds. The Framingham Study: An Epidemiological Investigation of Cardiovascular Disease. Washington, DC: NHLBI National Printing Office; 1971: section 34.Google Scholar7 Lew EA. High blood pressure, other risk factors and longevity: the insurance viewpoint. Am J Med. 1973; 55: 281–294.CrossrefMedlineGoogle Scholar8 Yano K, McGee D, Reed DM. The impact of elevated blood pressure upon 10-year mortality among Japanese men in Hawaii: the Honolulu Heart Program. J Chronic Dis. 1983; 36: 569–579.CrossrefMedlineGoogle Scholar9 The Pooling Project Research Group. Relationship of blood pressure, serum cholesterol, smoking habit, relative weight and ECG abnormalities to incidence of major coronary events: final report of the Pooling Project. J Chronic Dis. 1978; 31: 201–206.CrossrefMedlineGoogle Scholar10 Neaton JD, Kuller L, Stamler J, Wentworth DN. Impact of systolic and diastolic blood pressure on cardiovascular mortality. In: Laragh JH, Brenner BM, eds. Hypertension: Pathophysiology, Diagnosis, and Management, 2nd ed. New York, NY: Raven Press Ltd; 1995:127–144.Google Scholar11 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 Scholar12 Vasan RS, Larson MG, Leip EP, Evans JC, O'Donnell CJ, Kannel WB, Levy D. Impact of high-normal blood pressure on the risk of cardiovascular disease. N Engl J Med. 2001; 345: 1291–1297.CrossrefMedlineGoogle Scholar13 Vasan RS, Massaro JM, Wilson PWF, Seshadri S, Wolf PA, Levy D, D'Agostino RB. Antecedent blood pressure and risk of cardiovascular disease: the Framingham Study. Circulation. 2002; 105: 48–53.LinkGoogle Scholar14 Seshadri S, Wolf PA, Beiser A, Vasan R, Wilson PWF, Kase CS, Kelly-Hays M, Kannel WB, D'Agostino RB. Elevated midlife blood pressure increases stroke risk in elderly persons: the Framingham Study. Arch Intern Med. 2001; 161: 2343–2350.CrossrefMedlineGoogle Scholar15 Vasan RS, Larson MG, Leip EP, Kannel WB, Levy D. Assessment of frequency of progression to hypertension in non-hypertensive participants in the Framingham Study: a cohort study. Lancet. 2001; 358: 1682–1686.CrossrefMedlineGoogle Scholar16 Franklin SS, Kahn SA, Wong ND, Larson MG, Levy D. Is pulse pressure useful in predicting risk for coronary heart disease? the Framingham Study. Circulation. 1999; 100: 354–360.CrossrefMedlineGoogle Scholar17 Franklin SS, Larson MG, Kahn SA, Wong ND, Leip EP, Kannel WB, Levy D. Does the relation of blood pressure to coronary heart disease risk change with aging? the Framingham Heart Study. Circulation. 2001; 103: 1245–1249.CrossrefMedlineGoogle Scholar18 Kannel WB. Elevated systolic blood pressure as a cardiovascular risk factor. Am J Cardiol. 2000; 85: 251–255.CrossrefMedlineGoogle Scholar19 Rose G. Sick individuals and sick populations. Int J Epidemiol. 1985; 14: 32–38.CrossrefMedlineGoogle Scholar20 Kannel WB. Risk stratification in hypertension: new insights from the Framingham Study. Am J Hypertens. 2000; 13: 3S–10S.CrossrefMedlineGoogle Scholar Previous Back to top Next FiguresReferencesRelatedDetailsCited ByElfassy T, German C, Muntner P, Choi E, Contreras G, Shimbo D and Yang E (2023) Blood Pressure and Cardiovascular Disease Mortality Among US Adults: A Sex-Stratified Analysis, 1999–2019, Hypertension, 80:7, (1452-1462), Online publication date: 1-Jul-2023. Soria-Contreras D, Oken E, Tellez-Rojo M, Rifas-Shiman S, Perng W and Chavarro J (2022) History of infertility and long-term weight, body composition, and blood pressure among women in Project Viva, Annals of Epidemiology, 10.1016/j.annepidem.2022.06.033, 74, (43-50), Online publication date: 1-Oct-2022. 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