Increased tissue factor activity in monocytes from obese young adults.

1. The relationship between inflammation, obesity-related proteins and tissue factor (TF), the major initiator of the extrinsic clotting cascade, is not well understood. We examined if basal and stimulated peripheral blood mononuclear cell (PBMC) TF-procoagulant activity (PCA) was higher in obese subjects and examined the effects of leptin, resistin and serum amyloid A (SAA). 2. PBMC from 12 obese (six male, aged 29±4years, body mass index 46.0±8.7kg/m(2) ) and 12 age- and sex-matched lean controls were cultured either unstimulated or stimulated by lipopolysaccharide (LPS; 10ρg/mL and 100ng/mL, for 4-16h) or SAA (1 ng/mL, 25ng/mL, 250ng/mL, for 4h). Separately, PBMC from lean subjects were cultured unstimulated with leptin (100ρg/mL, 1ng/mL, 10ng/mL, 100ng/mL, 1 µg/mL), resistin (0.1ng/mL, 1ng/mL, 10ng/mL, 100ng/mL) or leptin (100ng/mL) plus LPS (100ρg/mL). TF-PCA was determined by a 1-stage plasma recalcification assay. 3. Four-hour unstimulated PBMC TF-PCA was greater in the obese (90.4±16.5 vs 39.9±4.7mu TF/10(6) PBMC, P=0.01). After 4h stimulation with SAA or LPS the TF-PCA was similar. Unstimulated TF-PCA correlated with log serum high sensitivity C- reactive protein (hs-CRP) (r=0.42, P=0.04) and insulin (r=0.44, P=0.048), but not with log serum SAA (r=0.192, P=0.55). Physiological concentrations of leptin or resistin and leptin plus LPS did not increase TF-PCA in PBMC from lean subjects. 4. Basal PBMC TF-PCA is higher in the obese and is associated with serum hs-CRP. The obesity-related proteins SAA, leptin and resistin are unlikely to play a major role in increasing PBMC TF-PCA.

Vascular risk factors correlate to the extent as well as the severity of coronary atherosclerosis.

BACKGROUND: Because most acute coronary events result from thrombosis at sites of minor plaque, the extent of non-obstructive coronary artery disease (CAD), rather than simply the number of severe stenoses, might be clinically relevant. OBJECTIVE: To examine the relationship between vascular risk factors and a novel extent score for CAD that measures the percentage of the coronary tree involved with atheromatous plaque, as judged by coronary angiography. METHODS: We assessed the extent and severity of CAD and the presence of vascular risk factors of 429 consecutive eligible patients (296 men, aged 61 +/- 11 years) who presented for elective coronary angiography. Detailed analyses of lipid levels were performed for 126 subjects. RESULTS: The mean extent score was 54 (range 0-100). The presence of diabetes (P < 0.001), current or former smoking (P < 0.005) and a history of hypertension (P < 0.001) were all strongly associated with the CAD extent score, as was severity of disease. For the 283 patients with one or no severe stenosis, diabetes was associated with a greater extent score (57 versus 41%, P < 0.005), as was smoking (49 versus 34%, P < 0.005). For the 126 patients with detailed data on lipid levels, extent of coronary artery disease was independently correlated to age (P < 0.005), male sex (P < 0.05), presence of diabetes (P < 0.05), hypertension (P < 0.05), level of lipoprotein (a) (P < 0.005) and low-density:high-density lipoprotein ratio (P < 0.01) in multivariable analysis. CONCLUSIONS: Extent of CAD, as well as its severity, is significantly associated with traditional vascular risk factors. Because most acute coronary events occur at sites of minor plaque, this might explain the mechanism whereby risk factors confer adverse prognostic significance.

ST monitoring for myocardial ischemia during and after coronary angioplasty.

We performed 12-lead electrocardiographic monitoring in 97 patients during coronary angioplasty (PTCA) of a single vessel to correlate ischemic ST changes with clinical, angiographic and coronary hemodynamic variables and to determine the optimum lead or combination of leads for their detection. Ischemia (chest pain or ST change, group A) occurred in 79 patients (80%), but in only 15 of 23 patients (65%) with collaterals (p less than 0.05). Ischemia occurred more often in left anterior descending and left circumflex PTCA than right coronary PTCA, but pain was the only manifestation more often in left circumflex and right coronary PTCA. Ischemic ST change was silent in 16% and this proportion did not differ in clinical or angiographic groups except for diabetes with 3 of 5 (60%) having silent ischemia (p less than 0.05). Patients in group A (ischemia) compared to group B (no ischemia) had less severe lesions (85 +/- 9 vs 91 +/- 7%, p less than 0.01), higher transstenotic gradients (62 +/- 19 vs 53 +/- 9 mm Hg, p less than 0.05) and lower distal occluded pressures (24 +/- 11 vs 33 +/- 10 mm Hg, p less than 0.01), suggesting less collateral flow. Compared with a 12-lead electrocardiogram, the best single lead for detecting ST change during PTCA in each artery had a sensitivity of 80% and this increased to 93% using the best 2 leads. The best 3 leads (V3/III/V5 for left anterior descending and III/V2/V5 for right coronary and left circumflex) increased sensitivity to 100%.(ABSTRACT TRUNCATED AT 250 WORDS)

Clinical significance of silent ischemia in unstable angina pectoris.

In a prospective study the significance of silent ischemia was evaluated in 66 patients with a clinical diagnosis of unstable angina (no requirement for reversible ST-T changes during pain on 12-lead electrocardiograms before entry), and the results of continuous 2-channel electrocardiographic (ECG) recordings, begun within 24 hours of admission, were compared with other clinical and ECG predictors of adverse outcome. Ischemic changes were detected in 7 patients (11%) during a mean of 41 hours of recording. There were 37 episodes of transient ST-segment change (16 ST elevation, 21 ST depression) of which 11 (30%) were symptomatic and 26 (70%) were silent. All 7 patients had at least 1 silent episode and 5 also had symptomatic episodes during the recording but only 2 patients had exclusively silent episodes. During a mean follow-up of 13.3 months, 3 patients died, 5 had a nonfatal myocardial infarction and 32 required revascularization. Although transient myocardial ischemia during the continuous ECG recording, whether silent or symptomatic, was a specific predictor of subsequent nonfatal myocardial infarction or death (specificity 92%), its sensitivity for these events was low (25%). In contrast, recurrent rest pain (greater than or equal to 1 episode) occurred in all patients with these serious adverse events (sensitivity 100%, specificity 49%). Transient ischemia occurs infrequently during continuous ECG recordings in patients with unstable angina not selected by reversible ST-T changes on a 12-lead electrocardiogram at entry. Recurrent rest pain after hospital admission is a more sensitive predictor of serious events in this group.

Validation of a real-time electrocardiographic monitor for detection of myocardial ischemia secondary to coronary artery disease.

A new real-time electrocardiographic (ECG) monitor (QMED Monitor OneTM) was evaluated to assess its accuracy in detecting ischemic ST-segment changes in 43 patients (34 men, 9 women, mean age 56 +/- 11 years) during exercise stress testing. The output of QMED was compared with ST-segment measurements from a Marquette CASE-II computer (ECGM) using a bipolar lead CM5, defining a positive ECG as at least 1 mm of planar or downsloping ST depression. Results were concordant in 33 patients, 15 with both positive and 18 both negative responses, yielding an accuracy (expressed as sensitivity, specificity, positive and negative predictive accuracy) of 83%, 72%, 68% and 86%, respectively. Seven false-positive QMED episodes occurred: 4 due to excess baseline wander or noise in the control ECG, which may have been prevented by reapplication of electrodes, and all 7 episodes were correctly discounted by inspection of the sample ischemic ECG output, yielding an accuracy of 81%, 100%, 100% and 85%. Mean duration and maximal magnitude of ST depression in patients with a positive ECG response was 7.9 +/- 7 minutes and 1.7 +/- 0.6 mm for QMED and 8.9 +/- 7 minutes and 2.2 +/- 0.7 mm for ECGM. The 3 false-negative QMED events were relatively brief and mild ischemic episodes and slight differences in electrode placement between the 2 systems may account for this discrepancy in 2 of the patients. Real-time ST monitoring with QMED is sufficiently reliable for clinical use. Optimal specificity depends on the ability to inspect sample ECG traces to verify a stable baseline and confirm episodes of ischemic ST-segment shift.