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New 'Fingerprinting' May Reveal Causes of High Blood Pressure

April 30, 2008 | by Marla Paul
CHICAGO -- An entirely new approach has been developed that can provide insights about the causes of high blood pressure based on a person's diet and chemicals in the urine. High blood pressure is a leading cause of heart disease and stroke.

Scientists at Northwestern University's Feinberg School of Medicine, in collaboration with colleagues at Imperial College in London, have for the first time identified multiple chemicals in peoples' urine, called metabolites, which have a direct relation to blood pressure. The study was done on population samples from China, Japan, the United Kingdom and the United States.

The study analyzed the adults' metabolic fingerprints from their urine samples. Metabolic fingerprinting looks at the relative levels of many different metabolites, which are the products of metabolism, in a person's blood or urine. Metabolites act as markers which can reveal how diet and lifestyle contribute to risks for certain disease.

Researchers said the approach and the new data point the way to greater understanding of dietary and biological causes of the epidemic of high blood pressure in general populations and possible enhanced ways to prevent and control high blood pressure and cardiovascular disease.

"This is a new set of measurements – metabolomics – that can help to clarify why so many people develop prehypertension and hypertension with increased risk of heart attack, stroke, heart failure, peripheral artery disease and kidney disease, " said Jeremiah Stamler, M.D., coauthor of the study and professor emeritus of preventive medicine at the Feinberg School.

The paper will be published online in the journal Nature April 20.

For the study, researchers analyzed urine samples from 4,630 individuals, ages 40 to 59, from population samples in China, Japan, the United Kingdom and the United States. The individuals were participants in the INTERMAP Study on macro/micronutrients and blood pressure, of which Stamler is the international principal investigator.

Through nuclear magnetic resonance scans of 24-hour urine specimens yielding evidence of thousands of urinary metabolites, coupled with advanced statistics, the scientists have identified three metabolites significantly related to blood pressure. It is anticipated that more metabolites will be identified as the research continues.

The new study reveals that people with increased levels of the amino acid alanine, which is found in many foods but which is particularly high in animal protein, have higher blood pressure and also increased energy intake, levels of dietary cholesterol and body mass index.

People with increased levels of the metabolite formate have lower blood pressure and increased energy intake. Formate arises from the action of microbes in the gut or as a product of metabolism in the body.

Increased levels of hippurate, a by-product of metabolism by microbes in the gut, are found in people with lower blood pressure, lower levels of alcohol intake and higher levels of dietary fiber.

The metabolomics approach can help researchers sharpen understanding about factors underlying the differences in cardiovascular disease patterns across populations.

The research shows that adults in the United Kingdom and the United States, which have similar incidences of high blood pressure and cardiovascular problems, have similar metabolic fingerprints, reflecting similar lifestyles in spite of their geographical distance from one another.

In contrast, although adults in Japan and China have similar genetic profiles, they have very different metabolic fingerprints from one another and from adults in the United Kingdom and the United States, and also have major differences in the incidence of many diseases.

Japanese people living in the United States have metabolic fingerprints that resemble other people in the United States, and dissimilar fingerprints to their counterparts living in Japan. This shows that lifestyle is a dominant feature in determining metabolism.

"With this new approach of exploring urinary metabolites, we now open up a new method that can clarify how different dietary patterns affect metabolism and relate to differences in blood pressure, coronary disease and stroke," Stamler said.
Topics: Research