Majority of patients who appear healthy may be at risk for cardiovascular disease

Three separate studies announced today at the American Society of Hypertension Inc.'s 25th Annual Scientific Meeting and Exposition (ASH 2010) examined the cardiovascular consequences of relatively healthy patients - those who were asymptomatic and not classified as hypertensive or diabetic - and found that many patients who appear healthy may still be at risk for cardiovascular disease.

While not meeting the criteria for a diagnosis of hypertension or diabetes, patients in these studies did meet criteria for prediabetes and/or prehypertension. These studies address and measure various cardiovascular risk factors and indicators to identify structural and functional changes that occur early in the hypertension and diabetes disease progression cycle.

"Diabetes and hypertension have reached epidemic status, not only in the U.S., but across the globe," Henry R. Black, MD, President of ASH. "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."

Apparently Healthy U.S. Adults with Coexisting Prehypertension and Prediabetes Prone for Early Cardiovascular Events (OR-31)
In the first study, researchers examined data on disease-free adults in the NHANES database (1999-2006) and diagnosed pre-hypertensive and pre-diabetic patients using the JNC 7 and ADA criteria (SBP 120-139 and/or DBP 80-89 mm Hg; FBS 100-125 mg/dL).

Researchers found that one in three apparently healthy adults had prehypertension and one in four of otherwise healthy individuals had prediabetes. Collectively, one in ten had both prehypertension and prediabetes. Adults who had both prehypertension and prediabetes were also overweight, had a larger waist circumference (abdominal obesity), higher "whole body" inflammation and insulin (a hormone that reduces blood glucose). These subjects also had higher pulse pressure (the difference between the systolic and diastolic blood pressure), higher total cholesterol, triglycerides, higher "bad cholesterol" along with lower "good cholesterol." These total, bad and good cholesterol levels made their "risk ratios" above desirable levels. All of these measures individually, and collectively, indicate an early high risk for heart attack or stroke.

"We would like to propose that prehypertension (blood pressure above120/80 mm Hg) and prediabetes (blood sugar of more than 100 mg/dL) occurring together, should be a red flag for urgent further evaluation," said lead author, Alok K. Gupta, M.D., assistant professor with Clinical Research, Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge. "Resting blood pressure and spot finger stick sugar tests (more than 140 mg/dL 2 hours after a meal which may indicate prediabetes) are obtained for every patient who visits a doctor's office. This early recognition and subsequent intervention with lifestyle measures may prevent high blood pressure and diabetes from occurring later in life - reducing risk in otherwise healthy adults."

Prediabetes Associated with Functional and Structural Cardiovascular Abnormalities ( PO-198)
Additional data presented at ASH 2010 demonstrated that prediabetes, even in patients with no apparent cardiovascular disease (CVD), is associated with changes in vascular and structural function and abnormalities in the heart.

Researchers compared 369 asymptomatic subjects with prediabetes (mean glucose 106.3 ± 5.8 mg/dl) with 1,277 asymptomatic subjects with normoglycemia (mean glucose 88.5 ± 7.0 mg/dl) in a primary prevention program. All subjects underwent a non-invasive screening for early cardiovascular disease. This 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 blood pressure and exercise blood pressure after a 3 minute treadmill test, retinal photography, ultrasound derived carotid artery intimal-media thickness (IMT), urine test for micro-albuminuria, ECG, ultrasound of the left ventricle for wall thickness and dimensions, left ventricular mass calculation and a venous blood sample for NT-proBNP. Each test was scored 0 if normal, 1 if borderline and 2 if abnormal. The Rasmussen disease score is the sum of the all the scores of each test as a predictor of cardiovascular morbid events. Framingham risk score was calculated as well.

Researchers found that in the group with prediabetes, the Rasmussen disease score was significantly higher in the prediabetic group than in the normoglycemic group even after adjustment for age, gender and body mass index, while this was not the case for the Framingham risk score. These results clearly showed that these prediabetic subjects had early manifestations of cardiovascular disease despite being asymptomatic. Moreover the classical biostatistical risk approach (Framingham) would still classify these prediabetic subjects in a low risk to low intermediate risk category.

"Our findings strengthen the case for early intervention to prevent diabetes," said Daniel Duprez, M.D., Ph.D., professor of medicine at the Rasmussen Center for Cardiovascular Disease Prevention Center Cardiovascular Division, University of Minnesota. "We recommend non-invasive screening for patients with prediabetes to detect cases of early cardiovascular disease, when patients may be likely to respond to lifestyle changes and effective pharmacotherapy."

Early inflammatory and metabolic changes in association with AGTR1 polymorphisms in prehypertensive subjects (OR-17)

A separate study evaluated prehypertensive patients for increased markers of inflammation and glucose metabolism. Investigators determined that prehypertensive patients who were otherwise healthy (non-obese and non-diabetic) displayed altered metabolic and inflammatory functions, which are currently known to be elevated in hypertensive patients. Further, they found that an angiotensin II receptor type 1 (AGTR1) polymorphism, previously associated with hypertension, could predict prehypertension.

Researchers recruited 405 white subjects from the USCD Twin Study. Those with hypertension, diabetes, or obesity were excluded. Fasting plasma was collected for inflammatory markers, including leptin, IL-6, CRP, and insulin. Sex and age were used as covariates in all analyses. Investigators evaluated the relationships between prehypertensive blood pressure, metabolic traits, and three common variants within AGTR1 (A1166C (rs5186), Leu191Leu (rs5182), and intron-2 A/G(rs2276736)).

We found that prehypertensive subjects were older with greater BMI than those with normal blood pressure, and after adjusting for multiple confounders, continued to display greater plasma glucose, insulin, leptin and interleukin-6. The common AGTR1 A1166C (rs5186) polymorphism in the 3'-UTR region, particularly the presence of the 1166C allele which fails to downregulate gene expression, predicted higher systolic blood pressure and greater likelihood of being in the prehypertension group. A lesser-studied polymorphism in intron-2 of AGTR1 (A/G; rs2276736) was associated with plasma leptin and HDL.

"We conclude that prehypertensive 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 Maple M. Fung, M.D., assistant professor of medicine, University of California, San Diego. "Further investigation is needed to confirm these findings and their precise molecular mechanisms of action."