Studies Support Earlier Intervention

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NEW YORK - Three new studies suggest that early therapeutic approaches may be appropriate for patients with pre-diabetes, pre-hypertension, or both conditions. 

“Diabetes and hypertension have reached epidemic status, not only in the U.S., but across the globe,” said Henry Black, MD, President of the American Society of Hypertension. “We are encouraged by research that sheds light on early indicators of cardiovascular disease which may lead to better methods of predicting, and ultimately preventing, these devastating illnesses.”

In one study, Louisiana researchers examined 1999-2006 data from disease-free adults in the National Health and Nutrition Examination Survey (NHANES) database and diagnosed pre-hypertension and pre-diabetes using criteria established by the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) and the American Diabetes Association (systolic BP 120-139 and/or diastolic BP 80-89 mm Hg; fasting blood sugar 100-125 mg/dL).

One in three apparently healthy adults had pre-hypertension and one in four had pre-diabetes. One in 10 had both pre-hypertension and pre-diabetes. Adults who have both pre-hypertension and pre-diabetes were also overweight, had a larger waist circumference (abdominal obesity), higher “whole body” inflammation, and higher insulin levels.

In addition, these subjects had higher pulse pressures (the difference between systolic and diastolic pressure), higher total cholesterol, higher triglycerides, lower HDL cholesterol levels, and higher LDL cholesterol levels. The investigators concluded that all of these measures, individually and collectively, indicate an early high risk for heart attack and stroke.

“We would like to propose that pre-hypertension (BP above 120/80 mmHg) and pre-diabetes (blood glucose levels higher than 100 mg/dL) occurring together should be a red flag for urgent further evaluation,” said lead author Alok Gupta, MD, Assistant Professor of Clinical Research at the Pennington Biomedical Research Center, Louisiana State University, Baton Rouge.

Findings suggest that identifying and treating patients with pre-diabetes and pre-hypertension could help reduce the number of patients who end up with end-stage renal disease, he said. Emerging evidence supports early intervention in patients who have these conditions.

“Nephrologists can help their primary care colleagues by bringing up this issue of early intervention,” Dr. Gupta told Renal & Urology News. “By doing this I think everyone would benefit because it would hopefully lower the number of cases of end-stage renal disease.”

In a separate study, researchers in Minnesota found that pre-diabetes, even in patients with no apparent cardiovascular disease (CVD), was associated with changes in vascular and structural function and abnormalities in the heart.  The investigators compared 369 asymptomatic subjects with pre-diabetes (mean glucose of 106.3 mg/dL) with 1,277 asymptomatic subjects with normoglycemia (mean glucose 88.5 mg/dL) in a primary prevention program. All subjects underwent non-invasive screening for early CVD.

The screening program consisted of the assessment of large and small artery elasticity based on the diastolic pulse contour analysis of the radial artery waveform, measurement of resting BP, and exercise BP after a three minute treadmill test. The screening program also included retinal photography, an ultrasound derived carotid artery intimal-media thickness, a urine test for microalbuminuria, an electrocardiogram, an ultrasound of the left ventricle for wall thickness and dimensions, and a left ventricular mass calculation. Each test was scored 0 if normal, 1 if borderline, and 2 if abnormal.  The investigators used the Rasmussen disease score, which is the sum of all the scores of each test as a predictor of cardiovascular morbid events. The investigators also calculated a Framingham risk score.

In the group with pre-diabetes, the Rasmussen disease score was significantly higher than in the normoglycemic group even after adjusting for age, gender, and BMI. This was not the case for the Framingham risk score, however. The researchers say these results clearly showed that the pre-diabetic subjects had early manifestations of CVD despite being asymptomatic.

“Our findings strengthen the case for early intervention to prevent diabetes,” said study investigator Daniel Duprez, MD, PhD, Professor of Medicine at the Rasmussen Center for Cardiovascular Disease Prevention Center Cardiovascular Division at the University of Minnesota in Minneapolis. “We recommend non-invasive screening for patients with pre-diabetes to detect cases of early cardiovascular disease, when patients may be likely to respond to lifestyle changes and effective pharmacotherapy.”

In another study, California researchers evaluated pre-hypertensive patients for increased markers of inflammation and glucose metabolism. Investigators determined that pre-hypertensive patients who were not obese or diabetic displayed altered metabolic and inflammatory functions, which are currently known to be elevated in hypertensive patients.  In addition, they found that an angiotensin II receptor type 1 (AGTR1) polymorphism, which was previously found to be associated with hypertension, could predict pre-hypertension.

The researchers recruited 405 subjects from the University of California-San Diego (UCSD) Twin Study. Those with hypertension, diabetes, or obesity were excluded. Investigators collected fasting plasma to measure inflammatory markers, including leptin, interleukin-6 (IL-6), C-reactive protein, and insulin. Pre-hypertensive subjects tended to be older and had greater BMIs than those with normal BP. After adjusting for multiple possible confounders, these pre-hypertensive individuals continued to display greater plasma glucose, insulin, leptin, and IL-6 levels.

“We conclude that pre-hypertensive subjects already exhibit early pathophysiologic changes that place them at risk of future cardiovascular disease with metabolic and inflammatory consequences, and that AGTR1 may also contribute to this increased risk,” said study investigator Maple Fung, MD, Assistant Professor of Medicine at UCSD. “Further, investigation is needed to confirm these findings and their precise molecular mechanisms of action.”

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