An Overview of the Expanded Definition and Classification of Hypertension Part 5/5

Strategies for and the Clinical Implications of Treating Patients Along a Continuum of Global Cardiovascular Risk

The paradigm shift in viewing elevated BP as a marker for hypertension and hypertension as a progressive CVD syndrome has important implications for treating patients in the clinical setting. The risk-based approach proposed by the HWG will lead to reclassifying patients who were previously designated prehypertensive (based on JNC 7 criteria) to either HWG normal or stage 1 hypertension.^[4] In terms of treatment, lowering BP remains an important goal of antihypertensive therapy, yet ultimately the overarching objective is to prevent CV complications.^[9] Treatment of other CV risk factors is therefore equally important. Moreover, CV risk factors, including elevated BP, are not only precipitators, but also continuous pathogenic components at every stage of progression of CVD.^[9] Clinical strategies, therefore, need to focus on detecting and treating patients at risk at every stage along the continuum, from preventing target-organ damage and interrupting CVD progression in patients with early-stage hypertension, to making aggressive efforts to slow further disease progression and avoid CV events in patients with late-stage hypertension.
Evidence for the benefit of antihypertensive treatment in early-stage hypertension (HWG stage 1 or JNC 7 prehypertension category) has only recently become available. The Trial of Preventing Hypertension (TROPHY) study has shown that antihypertensive therapy may help prevent the development of elevated BP levels among individuals with BP lower than 140/90 mm Hg who are at high risk for frank hypertension (due to the presence of multiple CV risk factors).^[17] In line with the HWG paradigm, patients in this study had high-normal SBP/DBP levels of 130-139/85-89 mm Hg at baseline, yet had a strikingly high rate of CV risk factors other than elevated BP.^[17] Among the TROPHY patients, 96% had at least 1 additional CV risk factor, includingvarious measures of dyslipidemia, insulin resistance, and obesity, as well as elevatedhematocrit and heart rate; 81% had 2 or more additional risk factors; and33% had 4 or more additional risk factors. The most prevalent risk factor in thecohort as being overweight.^[2,17] Patients were randomized to receive treatment with the angiotensin receptor blocker candesartan or placebo for 2 years, followed by an additional 2 years of placebo-only therapy; all patients were instructed to make changes in lifestyle to reduce BP throughout the trial.^[17] After 2 years, hypertension haddeveloped in 154 patients in the placebo group and 53 patients in the angiotensin receptor blockergroup, representing a significant 63% relative risk reduction with pharmacotherapy (P < .001). After 4 years, hypertension had developed in 240 patients assigned to placeboand 208 patients assigned to active treatment (relative risk reduction, 15.6%;P < .007). Serious adverse events occurred in 3.5% of patients who received active treatment and in 5.9% of those who received placebo. As the authors noted, the absolute difference between active treatment and placebo at 2 years in TROPHY, 26.8%, is much higher than the 8% absolute difference observed in the Trials of Hypertension Prevention,^[18] the only trial of lifestyle modification with a similar duration, suggesting that drug therapy plus lifestyle modification is more effective than lifestyle modification alone in early hypertension.^[17]
The benefit of treatment with antihypertensive agents in patients classified as normotensive by conventional standards also is supported by the Perindopril Protection Against Recurrent Stroke Study (PROGRESS).^[19] In this study, antihypertensive treatment in subjects without elevated BP (mean BP, 136/79 mm Hg) but with a history of target-organ damage -- in this case, a history of transient ischemic attacks or stroke -- was associated with a significant 27% reduction in the relative risk for stroke compared with placebo (P < .01), similar to the 32% reduction observed in patients designated as hypertensive.^[19] Moreover, intensive BP reduction with combination therapy was associated with better outcomes than less-intensive BP reduction with single-agent therapy, regardless of hypertension status. Because individuals similar to those considered normotensive in PROGRESS would be classified as having stage 2 hypertension (based on the presence of target-organ damage) in the HWG paradigm, results of this study highlight the importance of considering comprehensive risk factor assessment, including the presence of target-organ damage, when defining and staging patients with hypertension.
Whether all individuals with early-stage hypertension, as defined by the HWG, should be treated with antihypertensive therapy requires further study. As the group emphasized in their 2005 report, characterizing hypertension as a complex CV disorder associated with, but not exclusively defined by, high BP is best viewed as a transitional strategy that is intended to generate further clinical research into improved strategies for detecting, treating, and possibly preventing the disease.^[4]

Summary

The key points advanced by the HWG in their updated hypertension position paper are that BP serves as a biomarker for the disease hypertension and, as such, elevated BP is not synonymous with hypertension. Some individuals may exhibit elevated BP in the absence of hypertension, whereas other individuals with the same levels of BP might be classified into different stages of hypertension.^[6] Therefore, for purposes of calculating total CV risk and staging patients as normal or hypertensive, BP should be evaluated in the context of other CV risk factors and disease markers. Ultimately, it is hoped that the risk-based approach to defining and staging hypertension, as proposed by the HWG, will lead to earlier identification of individuals with hypertensive CVD. Preliminary data, such as that described by the TROPHY Investigators, suggest that lowering BP with pharmacologic therapy can prevent or delay the progression of hypertensive CVD even at early stages (ie, HWG stage 1 hypertension/JNC 7 prehypertension). Additional research is necessary to confirm these findings and identify cost-effective methods to detect and measure early CVD markers in clinical practice.