Free oxygen radicals in whole blood correlate strongly with high-sensitivity C-reactive protein.

BACKGROUND: Increased concentrations of reactive oxygen molecules are believed to be a driving force in inflammation. Although evident in tissue culture and animal models, it has been difficult to link reactive oxygen species (ROS) and inflammatory markers in humans. In patients recruited to represent a broad spectrum of risk factors, we investigated the relationship between the plasma concentration of oxygen radicals and high-sensitivity C-reactive protein (hs-CRP), utilizing a new chemistry with an easily oxidized chromophore. METHODS: ROS and hs-CRP were measured in blood from 59 fasting subjects selected to have variable risk predicted by classical risk factors. ROS were determined using the free oxygen radical monitor, which is an indirect colorimetric assay for the concentration of hydroperoxides in whole blood. RESULTS: Using log transformation, the correlation between ROS and hs-CRP was r = 0.505 (P < 0.0001). This relationship between ROS and hs-CRP was comparable (r = 0.527, P = 0.001) in the subgroup not currently on statin therapy (n = 39). ROS were not correlated with Framingham risk, r = -0.027 (P = 0.84). CONCLUSION: ROS directly measured in human blood correlates strongly with hs-CRP.

Usefulness of arterial compliance in the thigh in predicting exercise capacity in individuals without coronary heart disease.

This study examined the relation between arterial compliance of the lower extremities and aerobic capacity in patients with a broad spectrum of cardiovascular risk but without overt coronary heart disease (CHD). Local arterial compliance was noninvasively measured in the thigh and calf in 104 men and 99 women using air plethysmography. Subjects also underwent maximal exercise treadmill testing as a measure of aerobic capacity. In univariate analysis, age (r = -0.49, p <0.001), systolic blood pressure at rest (r = -0.27, p <0.001), pulse pressure (r = -0.39, p <0.001), total cholesterol (r = -0.25, p <0.001), triglycerides (r = -0.025, p <0.001), non-high-density lipoprotein cholesterol (r = -0.23, p <0.001), high-sensitivity C-reactive protein (r = -0.21, p = 0.002), and low-density lipoprotein cholesterol (r = -0.15, p = 0.03) all demonstrated a significant inverse association with treadmill time. Thigh and calf compliance demonstrated a significant positive association with treadmill time (r = 0.48, p <0.001; r = 0.46, p <0.001). In multivariate analysis, thigh compliance (p = 0.003), age (p <0.001), gender (p = 0.005), and triglycerides (p = 0.017) were independent predictors of treadmill time. In conclusion, thigh compliance measured with a simple-to-use, fully automated device independently predicts aerobic fitness in patients with a wide range of cardiovascular risk but without CHD.

Comparison of the relation of triglyceride-rich lipoproteins and muscular artery compliance in healthy women versus healthy men.

To determine whether structural features or concentrations of plasma lipoproteins are predictive of arterial compliance in healthy women versus healthy men, cohorts of 111 men and 112 women with a wide range of 10-year risks for coronary artery disease were selected using assessments based on the Framingham Heart Study. Age ranges were restricted to 35 to 69 years for men and 45 to 79 years for women. Lipid-lowering drugs or any evidence of vascular disease was cause for exclusion. Fasting lipoprotein analysis and arterial compliance measurements in thigh and calf were completed in all patients. Plasma triglyceride levels were the most powerful predictor of compliance in women. Weaker but significant relations were observed between plasma non-high-density lipoprotein cholesterol, apolipoprotein-B, and apolipoprotein-CIII. In contrast, the only significant predictor of compliance in men was body weight. Thus, the major lipid predictors of arterial stiffness in women are concentrations of triglyceride-rich lipoproteins. These results are consistent with previous findings that triglyceride measurements are more strongly related to clinical vascular events in women than in men.

Simvastatin improved arterial compliance in high-risk patients.

Reduced arterial compliance is associated with arteriosclerosis. In some arteries, this is due in part to abnormal vascular tone, which can be altered by low-density lipoprotein (LDL) cholesterol reduction and statin therapy. We tested the effectiveness of statin therapy in improving arterial compliance in patients with manifest coronary disease (CAD) and/or diabetes. Simvastatin (40 mg/day) was administered to 10 patients with proven CAD for 4 months. As measured by air plethysmography, compliance of the arterial segments in the thigh improved in every patient after 2 months, increasing by 34% by the fourth month. Compliance at the calf was not affected. These results suggest that compliance in the thigh is controlled by smooth muscle tone. Compliance measurements in the thigh and calf may be a useful measurement in evaluating high-risk patients and monitoring cholesterol-lowering therapy.

Ankle/Brachial index in the primary care setting.

Peripheral arterial disease (PAD) is an underdiagnosed circulatory problem in the primary care setting. Individuals are at increased risk for cardiovascular disease; therefore, there is the need for a technique capable of early identification and detection of patients with PAD. The focus of this study was to compare the accuracy of a new operator-independent method of measuring ankle brachial index (ABI) with the traditional Doppler ultrasound method of determining ABI. In 246 limbs the authors compared ankle systolic pressures and ABI measured by a new automated oscillatory method called the ABIgram with those measured by standard Doppler ultrasound. In phase 1, the 2 methods for measuring ankle systolic pressure had a mean difference of 2 mm Hg with a standard deviation of 6.7 mm Hg. In phase 2 the mean difference was 3.1 mm Hg with a standard deviation of 5.1 mm Hg. Further, ABI as measured by the 2 methods fell within 1% and demonstrated a 5% error in reproducibility. These numbers pass the SP-10 standard for medical devices established by the FDA. The ABIgram module of the Vasocor Vascular Diagnostic Center offers primary care physicians the ability to rapidly obtain ABI measurements comparable to the standard technique. Further, the ABIgram may be operated by staff commonly found in the primary care setting.

Polyunsaturated fatty acids acutely suppress antibodies to malondialdehyde-modified lipoproteins in patients with vascular disease.

Antibodies to malondialdehyde (MDA)-modified low-density lipoprotein (LDL) are transiently reduced during the postprandial period in patients with atherosclerotic heart disease. Previous experiments using mixed meals high in fat have found reductions of approximately 20% within 2 hours. This study was designed to reveal if this phenomenon was due uniquely to saturated fats. Using a standardized immunoassay for the detection of circulating levels of autoantibodies (AAbs) against MDA-modified LDL, we examined the acute changes in AAb levels during 6 hours of postprandial lipemia in 10 men with known atherosclerotic heart disease. Each subject was given 4 meals 1 week apart. Three of the meals differed in content of saturated fat, monounsaturated fat, and polyunsaturated fat. A fat-free meal with equivalent carbohydrate and equivalent protein was also administered. The study was double blinded and the meals were administered in random order. Only the meal enriched with polyunsaturated fatty acids caused the reduction in antibodies to MDA-LDL. This decrease was statistically significant from baseline at 1 hour (p <0.05), 2 hours (p <0.004), and 3 hours (p <0.02), with the nadir occurring at 2 hours. Polyunsaturated fatty acids are the major stimulus for causing a reduction in the AAbs to MDA-LDL during postprandial lipemia. These results strongly suggest that fat in chylomicrons may be a major source of oxidized lipids in the blood of patients with arteriosclerosis.