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High-Normal Blood Pressure and the Risk of Cardiovascular Disease

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High-Normal Blood Pressure and the Risk of Cardiovascular Disease REVIEW Circ J 2009; 73: 1381 – 1385 High-Normal Blood Pressure and the Risk of Cardiovascular Disease Yoshihiro Kokubo, MD; Kei Kamide, MD* The guidelines of the Joint National Committee 7 from the USA on hypertension have unified the normal and high-normal blood pressure categories into a single entity termed ‘prehypertension’. In contrast, The European Guidelines for the management of hypertension in 2007 considered ‘prehypertensive’ to be divided into normal and high-normal blood pressure. These patients with high-normal blood pressure or prehypertension might prog- ress to hypertension over time. Previous studies have shown that high-normal blood pressure is a risk factor for cardiovascular disease (CVD) in Western countries and Japan. The combination of high-normal blood pressure and other cardiovascular risk factors increases the risks of CVD. Recently, metabolic syndrome has also been shown to be a risk factor for CVD. In Japan, the association between metabolic syndrome and CVD was also found to be significant. The risks for CVD incidence were similar among participants who had the same number of components, regardless of the presence of abdominal obesity. In the Japanese guidelines for the management of hypertension published in 2009, patients are considered to be in a high-risk group if they have diabetes, chronic kidney disease, 3 or more risk factors, target organ damage or CVD, even if they have only high-normal blood pressure, and appropriate antihypertensive therapy should be initiated. (Circ J 2009; 73: 1381 – 1385) Key Words: Blood pressure category; Cardiovascular diseases; General population; Prospective studies; Risk factors ypertension is a strong risk factor for cardiovascu- 1–3 High-Normal Blood Pressure lar disease (CVD) worldwide. Approximately, and Prehypertension H 50% in men and 30% in women with CVD inci- dence could be described as excessive incidence because In 2003, the JNC 7 on hypertension unified the normal and of higher blood pressure (≥120/80 mmHg).4 A decline in the high-normal blood pressure categories into a single entity annual stroke incidence has been observed over a long period termed ‘prehypertension’.11 This change was based on in the Framingham Heart Study, the Hisayama Study, and evidence from the Framingham Heart Study that the chance other cohorts1,2,5–7 in response to lowering blood pressure of developing hypertension is higher in these ‘prehyperten- and decreasing the smoking rate.8 sive’ patients than in those with optimal blood pressure Recently, slightly elevated blood pressure has been found (<120/80 mmHg) at all ages.12,13 It has been estimated that to be associated with the incidence of CVD.4,7,9 To prevent 31% of the general adult population in USA16 falls into the CVD, blood pressure should be kept as low as possible. prehypertensive category, as do 38% of men and 33% of The European Society of Hypertension and the European women in a general urban Japanese population.4 Society of Cardiology (ESH-ESC) guidelines for the man- Previous studies have reported that individuals with agement of arterial hypertension consider prehypertensive high-normal blood pressure have a higher progression rate to be categorized into ‘normal blood pressure’ (systolic and risk of hypertension, compared with those with normal blood pressure (SBP) 120 to 129 mmHg or diastolic blood blood pressure.14,15 In 2007, the ESH-ESC Committee has pressure (DBP) 80 to 84 mmHg) and ‘high-normal blood decided not to use the term ‘prehypertension’ for the fol- pressure’ (SBP 130 to 139 mmHg or DBP 85 to 89 mmHg).10 lowing reasons: (1) even in the Framingham Heart study, In contrast, the guidelines of the Joint National Committee the risk of developing hypertension was definitely higher 7 from the USA (JNC 7) on hypertension have unified the in patients with high-normal blood pressure than in those normal and high-normal blood pressure categories into a with normal blood pressure;9,14 (2) because of the serious single entity termed ‘prehypertension’.11 In this article, high- meaning of the word hypertension for general populations, normal blood pressure is compared with prehypertension, the term ‘prehypertension’ might create anxiety and lead to and this category is reviewed as a risk factor for CVD. unnecessary consultations with a doctor; (3) this category is a highly differentiated one in practice, with the extremes (Received May 12, 2009; revised manuscript received May 20, 2009; consisting of patients in no need of any intervention as well accepted May 21, 2009; released online July 14, 2009) as of those with a very high-risk profile such as diabetes, Department of Preventive Cardiology, National Cardiovascular Cen- chronic kidney disease (CKD), or hyperlipidemia for whom ter, *Department of Geriatric Medicine, Osaka University Graduate drug treatment is required, although lifestyle changes School of Medicine, Suita, Japan recommended by the JNC 7 for all prehypertensive indi- Mailing address: Yoshihiro Kokubo, MD, Department of Preventive 11 Cardiology, National Cardiovascular Center, 5-7-1 Fujishiro-dai, Suita viduals can be a valuable population strategy. 565-8565, Japan. E-mail: [email protected] All rights are reserved to the Japanese Circulation Society. For permis- sions, please e-mail: [email protected] Circulation Journal Vol.73, August 2009 1382 KOKUBO Y et al. High-Normal Blood Pressure Progression years. High-normal blood pressure has also been associated with increased risk of carotid atherosclerosis,33 altered to Hypertension cardiac morphological features,27 and diastolic ventricular Optimal, normal, and high-normal blood pressure might dysfunction,26 all of which might be precursors of CVD. progress to hypertension over time. In the Framingham Heart Study, the progression rates to hypertension over a High-Normal Blood Pressure 4-year period were 5%, 18%, and 37% for the younger age (aged 35 to 64 years) groups with optimal, normal, and and CVD in Japan high-normal blood pressure, and were 16%, 26%, and 50% Of the prospective studies examining the incidence of for the older (aged 65 to 94 years) age groups with optimal, CVD in Japanese populations, the Suita study showed that normal, and high-normal blood pressure, respectively.14 the risks of myocardial infarction and stroke for high-normal Clinical trial data from patients with high-normal blood blood pressure and hypertension (Stage ≥1 group) were pressure showed that 40% over 2 years and 63% over 4 observed in men (hazard ratio =2.3, 95% confidence inter- years developed hypertension,17 which is consistent with vals: 1.0–5.3 and hazard ratio =3.4, 95% confidence inter- the Framingham Heart study.14 There are several potential vals: 1.6–6.8 for myocardial infarction; hazard ratios =2.0, reasons for progression to hypertension in individuals with 95% confidence intervals: 1.0–4.2 and hazard ratios =3.3, high-normal blood pressure relative to optimal and normal 95% confidence intervals: 1.8–6.2 for stroke, respectively). blood pressure groups. First, individuals with high-normal The multivariable hazard ratio of CVD incidence in women blood pressure require a smaller increment of blood pres- was 2.1 (95% confidence intervals: 1.3–3.6) for the hyper- sure on follow-up to progress to hypertension than the other tension (Stage ≥1 groups).4 groups.14 Second, risk factors for hypertension are more The Ohasama study showed that high-normal blood pres- common in the high-normal blood pressure group.18 sure is a risk factor for stroke by using home blood pressure rather than causal blood pressure.34 The Hisayama study, High-Normal Blood Pressure which observed the natural course of untreated hyperten- sion in a general Japanese elderly population over a 32-year and Precursors of CVD period, indicated that high-normal blood pressure is not a Elevated concentrations of C-reactive protein,19,20 tumor risk factor for cerebral infarction.35 This cohort was approx- necrosis factor-α,20 homocysteine,21,22 oxidized low-density imately half the size of the participants of the Suita study, lipoprotein,23 gamma-glutamyltransferase,24 microalbumin- and the patients were older and observed for longer periods. uria,25 and other inflammatory markers20,23 are associated Hypertensive risk for CVD decreased with advancing age.36 with higher blood pressure. High-normal blood pressure has Over very long periods, confounding factors, including been associated with increased carotid intima and media advancing age, menopause, lifestyle modifications, and thickness,26 altered cardiac morphological features,26 and medication, might affect the blood pressure classification. diastolic ventricular dysfunction,27 which might be precur- The Tanno-Sobetu Study determined that high-normal blood sors of cardiovascular events. The additive effect of more pressure, determined according to the 1999 World Health than 1 risk factor on the risk of CVD has been well estab- Organization/International Society of Hypertension (WHO/ lished.28,29 Thus, high-normal blood pressure is considered ISH) criteria, is not a risk factor for CVD in comparison to to be associated with an increased risk of ischemic heart optimal and normal blood pressures, because of the small disease and stroke compared with optimal blood pres- sample size.37 sure.9,13,30 Some prospective studies have looked at mortality from CVD in Japanese populations. Murakami et al have sum- High-Normal Blood Pressure marized a relationship between prehypertension and overall mortality by performing a meta-analysis of data from and CVD in Caucasians 13 population-based cohort studies conducted in Japan The Framingham Heart study has indicated that men and (176,389 participants).38 In this study, the interactions women with high-normal blood pressure have a more than between age and SBP for all causes of mortality were 2-fold increase in relative risk for CVD compared with statistically significant (P for interaction =0.01 for men and those who have optimal blood pressure.9 This finding was 0.02 for women).
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