The Trial of Preventing Hypertension (TROPHY) As Seen Through the Eyes of the Hypertension Writing Group's Expanded Definition of Hypertension

The recently published results of the Trial of Preventing Hypertension (TROPHY) ¹ represent a milestone in the evolving therapy of hypertension. The study population had blood pressures (Bps) ranging from 130 to 139 mm Hg systolic and 85 to 89 mm Hg diastolic. A total of 809 subjects were randomized to receive either the angiotensin II receptor blocker candesartan or placebo. The primary end point of the trial was the development of stage 1 hypertension, defined by the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) as a BP of >140/90 mm Hg.

During the first 2 years of the trial, Bps of >140/90 mm Hg occurred at least three times in 154 participants in the placebo group and in 53 of those in the candesartan group (relative risk reduction, 66.3%; p<0.001). Office and home Bps were determined. The time course of BP demonstrated a significant reduction in BP that was approximately 10 mm Hg at 2 years of therapy (Figure 1). After discontinuation of active treatment, an increase in BP occurred in the candesartan group (208 participants developed a BP >140/90 mm Hg on the last visit), while 240 increased to stage 1 levels in the placebo group (relative risk reduction, 15.6%; p<0.007). Serious adverse events occurred in 3.5% of the participants assigned to candesartan and 5.9% of those receiving placebo.

Figure 1.

The time course of systolic blood pressure (SBP) showing the change in the blood pressure (ABP) that reaches approximately 10 mm Hg after 2 years. Data derived from Nesbitt SD, Julius S, Leonard D, et al., for the Trial of Preventing Hypertension (TROPHY) Study Investigators. Is low‐risk hypertension factor fiction? Cardiovascular risk profile in the TROPHY Study. Am J Hypertens. 200S;18:980–98S

Participants in TROPHY had “prehypertension” as defined by JNC 7. ² In addition, most of the participants had other cardiovascular risk factors (Figure 2). Thus, according to the new, expanded definition of hypertension as proposed by the Hypertension Writing Group at the American Society of Hypertension meeting in 2005, ³ the subjects in TROPHY had stage 1 hypertension (Table). As discussed by the writing group, there is no threshold level of BP that defines cardiovascular risk down to levels <115/70 mm Hg. ⁴ Thus, the definition of hypertension does not depend on the level of BP alone but on global cardiovascular risk as well. A person with no cardiovascular risk factors and a BP of 135/85 mm Hg is at a different level of risk than someone with the same BP plus dyslipidemia, obesity, diabetes, or a history of smoking.

Figure 2.

Cardiovascular risk factor profile according to the Trial of Preventing Hypertension (TROPHY). It is clear that many of these participants would fall into the category of stage 1 hypertension as proposed by the Hypertension Writing Group. Adapted with permission from Nesbitt SD, Julius S, Leonard D, et al., for the TROPHY Study Investigators. Is low‐risk hypertension factor fiction? Cardiovascular risk profile in the TROPHY study. Am J Hypertens. 2005;18:980–985.

Table.

American Society of Hypertension Writing Group Definition and Classification of Hypertension

Classification	Normal	Stage 1 Hypertension	Stage 2 Hypertension	Stage 3 Hypertension
Descriptive category	Normal BP or rare BP elevations AND no identifiable CVD*	Occasional or intermittent BP elevations OR early CVD*	Sustained BP elevations OR progressive CVD*	Marked and sustained BP elevations OR advanced CVD*
Cardiovascular risk factors	None or few	Several	Many	Many
Early disease markers	None	Usually present	Overtly present	Overtly present with progression
Target organ disease	None	None	Early signs present	Overtly present with or without CVD events
BP=blood pressure; *cardiovascular disease (CVD) designation is determined by the constellation of risk factors, early disease markers, and target organ disease. Reproduced with permission from J Clin Hypertens (Greenwich). 2005;7:505—512. 3

In TROPHY, virtually all participants had some cardiovascular risk factors. Not reported were values for waist circumference or high‐sensitivity C‐reactive protein, factors that are known to predict increases in BP. Clearly, many subjects in TROPHY had the constellation of abnormalities that constitute the metabolic syndrome.

BP is a “test” of cardiovascular function and a “target” for therapy when the BP level begins to participate in the pathophysiology of cardiovascular disease. The observation that BP continued to increase in the placebo group of the TROPHY study validates the concept of using BP to monitor cardiovascular function. In addition, the data demonstrate that treatment may prevent the rise in BP; this is true antihypertensive therapy. Attention to treatment of all of the modifiable risk factors, both pharmacologic and nonpharmacologic, is clearly required for optimal benefit of patients.

While the use of a cut point of >140/90 mm Hg to define hypertension has served us well in the past, it is time to rid ourselves of the addiction to specific numbers in deciding which of our patients require treatment, and the treatment need not be pharmacologic. Equally as important is recognizing that some patients with Bps similar to those in this recent study are considered normal and need not bear the label of hypertension.