Shelley Wood

February 04, 2013

BARCELONA, Spain — New results from the Hypertension and Ambulatory Recording Venetia Study (HARVEST) are offering a glimpse at a group typically overlooked in hypertension studies: people who manage to avoid developing the disease over the long term.

Dr Paolo Palatini (University of Padova, Italy) presented the findings here at the 2013 International Conference on Prehypertension and Cardiometabolic Syndrome.

The analysis, he said, may have implications for hypertension guidelines that typically recommend a delay to treatment in the range of several months for patients diagnosed with grade 1 hypertension. The data Palatini presented today detail the characteristics of young adults (mean age 33) diagnosed with grade 1 hypertension whose blood pressure fell to within normal range within the first few months of the study and who then managed to remain normotensive over 15 years of follow-up.

HARVEST was originally designed to examine characteristics of subjects diagnosed with grade 1 hypertension (140–159/90–99 mm Hg) who went on to develop established white-coat, masked, or sustained hypertension over a six-year period.

In the data he presented today, Palatini zeroed in on the 198 subjects whose BP fell to normal (<140/90) in the initial months of HARVEST, as compared with 822 patients who developed hypertension. In this subset, he noted, both systolic and diastolic BP fell sharply between study outset and three months (from grade 1 hypertension to normotensive) and continued to decline over the next decade and a half.

Statistically significant baseline differences included a slightly lower body-mass index (BMI), lower coffee consumption, lower triglycerides, and higher physical-activity levels among patients who remained normotensive. "Overall, they had better metabolic profiles," Palatini said.

Fifteen Years Later, Hypertension Free

Over the 15 years of extended follow-up, mean 24-hour systolic blood pressure in normotensives remained relatively stable but climbed approximately 8 mm Hg in the patients who became hypertensive--a substantial rise by ambulatory BP, Palatini noted. Normotensive subjects also showed significant drops in heart rate, whereas hypertensive patients had heart rates that remained largely unchanged over the course of follow-up.

Of note, the number of subjects with prediabetes after 15 years was nearly double in the hypertensive patients. Also interesting were significant differences in coffee and alcohol consumption between groups--both declined in the two groups, but to a greater degree in the normotensives than in the hypertensives. In a surprising finding, more normotensives reported becoming sedentary over the follow-up period, but this may reflect the fact that hypertensives were more likely to have been urged to keep active by their doctors, as well as the significantly higher levels of physical activity seen in the normotensives at baseline.

Yearly increases in BMI were less than 0.05 kg/m2 in the normotensives as compared with more than 0.16 kg/m2 in the hypertensive patients.

The health effects of these differences were clear at study follow-up, according to Palatini. Prevalence of left ventricular hypertrophy, microalbuminuria, and atrial fibrillation were all significantly higher in the hypertensive patients. None of the normotensive patients experienced a cardiovascular event over the course of the study, as compared with 55 subjects in the hypertensive group (p<0.001).

The analysis may help guideline writers who have typically faced a dearth of data when it comes to recommendations in grade 1 hypertension, Palatini concluded.

"When to initiate antihypertensive treatment in this group is still a matter for debate," he said. The 2007 ESC/ESH guidelines recommend that treatment in grade 1 hypertensives without other risk factors may "be delayed for several months," while the 2009 ESC/ESH guidelines say that drug therapy should be started if BP remains equal to or above 140/90 mm/Hg after "a suitable time period" with appropriate lifestyle changes. "How long this time period should be is difficult to define, but looking again at our data and this progressive decline over 15 years, we could think this time period is much longer than we expected."

"White-Coat Reactors"

In an interview with heartwire , Palatini explained that the initial BP drop seen in the normotensive group was due in part to a higher proportion of "white-coat reactors" in this subset. This group also likely contained people who were at "a particular moment in their lives: problems in the office or at home, stressful situations--we cannot measure this possibility."

Differences in sympathetic activity and genetic background also likely played a role, although these were also not measured in the study. But for example, Palatini said, "there were fewer people with insulin-resistance syndrome [in the normotensive group], and a prediabetic profile is related to sympathetic activity."

The secret to avoiding hypertension is likely complex, Palatini stressed to heartwire .

"Of course we would like to find a single variable that explains everything; instead you have to put together many variables; it's like a mosaic. It would be very naive to think there could be one clear-cut variable, so you have to put together these various things and others--sodium output, renin activity, and so on. We tested some, but we should test them all."

In a discussion panel concluding the session, Dr Stevo Julius (University of Michigan, Ann Arbor, MI) agreed. "I think the group that has not developed hypertension and identifying who these guys are is just as important as or more important than the population who does. We may even provide a way for the clinicians to have a more [information to work with] so they can focus on people who really have higher risk."