Diastolic pressure above optimal is the most important predictor of subsequent hypertension in normotensive patients younger 50 years

In this issue of the Journal, Kanegae and colleagues1 from Japan have published a long-term observational study of normotensive industrial workers, addressing the issue of which components of normal blood pressure (BP) predict subsequent hypertension. Japanese health and safety laws require employers to provide annual medical checkups for employees, and this study is from a single large urban provider of this service. Participants were individuals who had a checkup in 2005 and were normotensive at that visit, and were then followed at subsequent annual visits for up to 8 years (mean 4.9 years). Normotension was defined as resting BP <140/90 mm Hg at the baseline visit and not taking antihypertensive drugs. Of 141 041 individuals screened in 2005 (and after various exclusions including age younger than 18 years, preexisting cardiac or cerebrovascular disease, and inadequate follow-up data), 93 303 normotensive individuals were identified, just over half of whom were men, with a mean age of 41.1 years. Among these normotensive participants, baseline BP was divided into to seven categories: (1) <120/80 mm Hg (optimal); (2) 120–129/<80 mm Hg (isolated systolic normal); (3) <120/80–84 mm Hg (isolated diastolic normal); (4) 120–129/80–84 mm Hg (systolic diastolic normal); (5) 130–139/<85 mm Hg (isolated systolic high-normal); (6) <130/85–89 (isolated diastolic high-normal); and (7) 130–139/85–89 mm Hg (systolic diastolic high-normal). At a mean follow-up of 4.9 years, 14 590 of the originally normotensive 93 303 patients developed hypertension (4.8%). Incidence of new-onset hypertension (in cases per 1000 person-years) was 8.8 in individuals younger than 30 years, 19.7 for those 30 to 39 years, 36.6 for those 40 to 49 years, 56.5 for those 50 to 59 years, and 84 for those 60 years and older. New isolated diastolic hypertension was more common than isolated systolic hypertension and systolic diastolic hypertension in patients younger than 50 years compared with those older than 50 years, in whom isolated systolic hypertension was more common. Although higher age at baseline was the strongest predictor of subsequent hypertension, there were significant differences in baseline BP components and the risk of subsequent hypertension between younger and older patients. The impact of diastolic BP on the risk of developing hypertension compared with optimal BP (systolic BP <120 and diastolic BP <80 mm Hg) was significantly greater than that of systolic BP in patients younger than 50 years (hazard ratio, 17.5 for isolated diastolic high-normal vs 10.5 for isolated systolic high-normal [P<.001] and 8.0 for isolated diastolic normal vs 4.1 for isolated systolic normal [P<.001]). The principal conclusion of the study is that in individuals younger than 50 years, baseline diastolic BP ≥80 mm Hg is a much stronger predictor of subsequent hypertension than baseline systolic BP ≥120 mm Hg. Whereas in individuals 50 years and older, this differential is no longer evident. Prehypertension was defined in the JNC 7 guidelines2 as a resting systolic BP of 120 to 139 mm Hg and/or a diastolic BP of 80 to 89 mm Hg. The significance of this definition was that although most individuals with BP in this range do not warrant antihypertensive drug therapy, compared with those with optimal BP, they are at significantly higher risk of progression to hypertension, and are also at higher cardiovascular risk, even while their BP remains in the prehypertension range. Other investigations have used 130 to 139 mm Hg/80 to 89 mm Hg as the definition of prehypertension, as was the case in the Trial of Preventing Hypertension (TROPHY),3 which remains the only randomized controlled trial to date of antihypertensive therapy vs placebo in prehypertension. In this trial, nearly two thirds of untreated patients with prehypertension progressed to hypertension in 2 years. There is clear evidence from other studies of a significant incidence of progression from prehypertension to hypertension of 5% to 15% annually, depending on the definition of prehypertension, and with higher rates in older populations.4-6 Rather than prehypertension, some investigators have used the terms “normal” (120–129±80–84 mm Hg) and “high-normal” (130–130±85–89 mm Hg)7 to differentiate from “optimal” (<120/80 mm Hg), and it is clear that cardiovascular risk is increased, even in the “normal” group. The point of difference of the study by Kanegae and colleagues is that with the benefit of the large numbers and the subdivision of “normal” BP into seven categories (and prehypertension into six categories), the investigators were able to focus in detail on the precursor BP profiles of individuals destined to progress to hypertension. The most interesting finding, and this has not been previously reported, is that in individuals younger than 50 years, normal diastolic BP above “optimal” (<80 mm Hg), ie, 80 to 89 mm Hg, have approximately double the risk of progressing to hypertension over 4.9 years than those with normal systolic pressure above “optimal” (<120 mm Hg). This may allow identification of younger normotensive individuals who are at higher risk of developing hypertension. Specifically in the age group of individuals younger than 50 years, resting diastolic BP in the 80 to 89 mm Hg range may identify a group at higher risk of hypertension, perhaps triggering early intervention with lifestyle change and/or medication to halt or delay this progression.8 What is not in doubt is the growing human and financial burden of hypertension worldwide.9 Identification of individuals at higher risk of developing hypertension may allow effective preventive strategies to be implemented, and this study identifies a possible such group among younger individuals. It is in younger people, after all, in whom effective intervention in the precursor stages of hypertension will likely yield the highest long-term cost benefits. None.

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