Accumulation of lead in the body — as measured by the amount deposited in the outer layer of shin bone — is linked to a greater risk of having high blood pressure that is hard to treat.

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Lead accumulation could be a risk factor for drug-resistant hypertension.

So concludes a study of 475 veterans with high blood pressure that appears in the Journal of the American Heart Association.

The findings not only expand our understanding of how lead buildup in the body might affect the management of high blood pressure, but they could also lead to new treatment targets, note the authors in their study paper.

“Our study,” says lead author Dr. Sung Kyun Park, who is an associate professor of epidemiology and environmental health sciences at the University of Michigan School of Public Health in Ann Arbor, “demonstrates that cumulative lead burden, as measured by cortical bone in the tibia (shin bone), may be an unrecognized risk factor for drug-resistant hypertension.”

Cortical bone is the hard outer layer of bone. The recent findings are the first to suggest that lead buildup in the tibia could be a biomarker for the risk of developing hard-to-treat high blood pressure.

Resistant hypertension is high blood pressure that persists following measures to lower it. These measures include making changes to lifestyle and taking medication.

The American Heart Association (AHA) and American College of Cardiology define resistant hypertension as blood pressure that, despite treatment with three or more drugs from different classes, remains above the goal set in their guidelines.

Doctors also class people who have to take four or more drugs from different classes to bring their blood pressure below the threshold given in the guidelines as having resistant hypertension.

In their study report, Dr. Park and his colleagues cite studies that have found links between blood lead and raised blood pressure and, more recently, suggested that blood lead might be a factor in “cardiovascular-related deaths.”

Others have also proposed various biological mechanisms through which lead in the body can lead to hypertension — for example, by disrupting blood vessel regulation and the progression of atherosclerosis.

However, none of these, Dr. Park and his team note, “have assessed the relationship between cumulative lead exposure and risk of resistant hypertension.”

So, they set out to confirm their theory that researchers could use the lead level in bone as a biomarker of “cumulative lead exposure” that independently influences “the development of resistant hypertension.”

The team analyzed data from the Veterans Affairs Normative Aging Study on 475 “predominantly white” men with high blood pressure.

The dataset included measures of blood pressure, blood pressure medication, and levels of lead in blood, kneecaps (patella), and shin bones (tibia). Of the men, 97 met the criteria for resistant hypertension.

After adjusting for age, race, income, education, weight, smoking status, and further lifestyle, socioeconomic, and demographic factors, the analysis revealed a statistically significant relationship between increasing lead buildup in the shin bone and an increased risk of resistant hypertension.

Every extra 15 micrograms of lead per gram of bone in the tibia linked to a 19 percent higher risk of developing resistant hypertension.

The research team found no such statistically significant links for lead buildup in the kneecaps or blood lead.

The scientists say that more research is now needed to confirm the results of their study, particularly because of its limitations — such as the fact that they only studied men, most of whom were white.

The team also points out that resistant hypertension in the men it studied could have been the result of the participants using over-the-counter medication, or not taking their blood pressure drugs as prescribed.

Other factors that might affect the results include variations in blood pressure measurements due to differences in doctors’ offices.

“Laws limiting lead exposure,” comments Dr. Park, “have been on the books for decades, but, in recent years, it is recognized that lead remains an environmental toxin that is still with us.”

Before the United States phased out the use of lead in gasoline some 30 years ago, breathing road traffic fumes was a primary source of lead exposure. Lead in exhaust fumes was also a major cause of soil contamination near roads, and this type of contamination can persist for decades.

Dr. Park suggests that while lead buildup in the body “likely reflects the after-effects of historically high lead exposures,” another reason could be continuing exposure. He gives the example of “an aging infrastructure where water pipes in many urban areas are older and contain lead.”

Since the lead problems in the drinking water in Flint, Michigan, have surfaced, the issue has become more troubling, especially in older U.S. cities.”

Dr. Sung Kyun Park