Is low-risk hypertension fact or fiction? cardiovascular risk profile in the TROPHY study.

BACKGROUND: The Trial of Preventing Hypertension (TROPHY) Study is designed to establish whether treating high normal blood pressure with a low-dose angiotensin receptor blocker, candesartan cilexetil, for 2 years reduces the rate of progression to hypertension compared with placebo treatment over a 4-year observation period. We are presenting the baseline cardiovascular risk factor profile of the 809 subjects randomized in the TROPHY Study. The risk factors in this analysis were as follows: cholesterol >or=200 mg/dl; LDL-cholesterol >or=160 mg/dL; HDL-cholesterol or=150 mg/dL; body mass index >or=25 kg/m2 (overweight and obese), fasting insulin >or=20 mU/mL; heart rate >or=80 beats/min; hematocrit >or=43.5 % (men) and >or=41.2% (women). METHODS: The TROPHY Study is a 4-year randomized, placebo-controlled, multicenter clinical trial of 809 subjects with high normal blood pressure (BP), which is currently in progress. RESULTS: The participants of the TROPHY study (mean age 49+/-8.1 years) with high normal BP (mean 134+/-4/85+/-4 mm Hg) had additional cardiovascular risk factors. Of the group, 96% had at least one, 81% had two or more, and 13% had five or more additional risk factors. CONCLUSIONS: Our data from individuals with high normal BP suggests clearly that the risk of cardiovascular disease begins to rise before the diagnosis of hypertension is evident. The overall risk in such subjects reflects both the rising BP and other concurring factors. It appears that truly low-risk hypertension only rarely exists.

Trial of preventing hypertension: design and 2-year progress report.

The TRial Of Preventing HYpertension (TROPHY) study is an investigator-initiated trial to examine whether early pharmacological treatment in subjects with "high-normal" blood pressure (BP) might prevent or delay the development of clinical hypertension. This is a 4-year, multicenter, randomized, double-blind study in untreated subjects aged 30 to 65 years with entry BPs of 130 to 139/< or =89 or < or =139/85 to 89. The participants were randomized either to placebo or to a fixed (16 mg once daily) dose of candesartan cilexetil (candesartan). After 2 years, the candesartan group was switched to placebo, and the placebo group continued taking placebo. The main outcome measure was the development of clinical (treatment-requiring) hypertension assessed by an automated (blinded) BP measurement device. We randomized 809 subjects (59% males, average age 49.0+/-SD 8.1 years) in 71 study centers in the United States. The entry BP was 134+/-4.3/84.8+/-3.9 mm Hg. During the first 2 years, 187 subjects (23%) developed clinical hypertension. All have been given antihypertensive treatment, and 170 continue to be followed in study centers. The study dropout rate is 14.8% (120 subjects). The hypertension rates are higher than anticipated, whereas the rates of dropout are within the sample size projections; thus, the study will have sufficient power to evaluate its hypotheses. In this article, we describe baseline characteristics of TROPHY subjects and discuss novel analytical issues and statistical approaches to evaluate the findings in this trial of primary prevention of hypertension.