MedPageToday.com

Published: Sep 2, 2014

By Nancy Walsh, Senior Staff Writer, MedPage Today

Action Points

• Normotensive participants were followed for a median of 7 years for the development of hypertension (systolic blood pressure) in order to determine the relationship of fat distribution with incident hypertension.
• Increased visceral adiposity, as determined by imaging studies, but not total or subcutaneous adiposity, was significantly associated with incident hypertension.

Visceral adipose tissue, rather than body mass index (BMI) or overall subcutaneous fat, was associated with the development of hypertension, researchers found.

In a multivariate analysis, BMI initially was associated with incident hypertension, with a relative risk of 1.24 (95% CI 1.12-1.36, P<0.0001) per standard deviation increase, according to Aslan T. Turer, MD, and colleagues from the University of Texas Southwestern Medical Center in Dallas.

However, after visceral adiposity and subcutaneous fat were included in the model, only visceral adipose tissue remained significant, with a relative risk of 1.22 (95% CI 1.07-1.39, P=0.004) for each standard deviation increase, the researchers reported in the Journal of the American College of Cardiology.

“There is growing evidence that [visceral adipose tissue] represents a pathological adipose tissue depot, which accumulates when subcutaneous depots are overwhelmed or otherwise unavailable for storage. Relative to [subcutaneous adipose tissue], visceral fat is more sensitive to lipolysis and secretes higher amounts of inflammatory cytokines,” Turer and colleagues wrote.

The central mystery that the investigators sought to address is that hypertension has been clearly linked with obesity, yet not all obese individuals develop high blood pressure.

To see if the distribution, rather than quantity, of body fat could be implicated, the researchers analyzed data from theDallas Heart Study, in which 903 participants had an initial evaluation between 2000 and 2002.

This consisted of blood pressure measurements, imaging studies to quantify adipose tissue at various sites in the abdomen and lower body, and laboratory assessment of relevant biomarkers.

Follow-up studies were then done between 2007 and 2009.

During the intervening 7 years, 230 individuals — one-quarter of the cohort — were diagnosed with hypertension.

Those who became hypertensive were older (43 versus 39), more commonly had already developed diabetes (7% versus 2%) and more often were black (56% versus 33%).

They also had higher BMI and had more subcutaneous fat and visceral adipose tissue, including intraperitoneal and retroperitoneal fat.

In the main model of visceral fat and hypertension, the significant association persisted with additional adjustment for inflammatory markers such as C-reactive protein, adipokines such as leptin, kidney function, and insulin resistance.

An additional model replaced visceral adipose tissue with liver fat, retroperitoneal fat, and intraperitoneal fat, and found significant associations for liver fat (RR 1.13 per standard deviation, 95% CI 1.02-1.25, P=0.02) and retroperitoneal fat (RR 1.09, 95% CI 1.05-1.13, P<0.0001).

Then, in a quartile analysis, increasingly higher risks were seen for higher levels of retroperitoneal fat, with adjusted relative risk ratios of 1.48 (95% CI 0.98-2.22) for the second versus the first (referent) quartile, and 1.84 (95% CI 1.20-2.84) for the highest versus the referent quartile.

The researchers considered it interesting “that the most significant associations between visceral adiposity and hypertension were observed with retroperitoneal fat. To our knowledge, this observation has not been reported previously but, if validated, suggests that there may be local effects from fat surrounding the kidneys that influence the development of hypertension.”

In an accompanying editorial, Lawrence R. Krakoff, MD, of the Icahn School of Medicine at Mount Sinai in New York City, wrote, “The new observation that retroperitoneal fat is the highest correlate with incident hypertension in this prospective study suggests that perirenal fat or perhaps periadrenal fat might be the substrate for blood pressure-raising renal and/or adrenal mechanisms.”

However, he cautioned, “At present, it is unclear as to whether increased retroperitoneal fat is a cause or result of mechanisms that increase blood pressure associated with obesity.”

The study authors also noted that their analysis was unable to affirm causality, as the study was observational. An additional limitation was that the subtypes of visceral fat were measured only once, at baseline, and could have changed over time.

They concluded, “These data are consistent with a growing body of literature implicating [visceral adipose tissue], rather than generalized adiposity, in the aggregation of cardiovascular risk factors that eventually drive adverse clinical events.”