Khawar Gul

Expert review on coronary calcium

While there is no doubt that high risk patients (those with >20% ten year risk of future cardiovascular event) need more aggressive preventive therapy, a majority of cardiovascular events occur in individuals at intermediate risk (10%–20% ten year risk). Accurate risk assessment may be helpful in decreasing cardiovascular events through more appropriate targeting of preventive measures. It has been suggested that traditional risk assessment may be refined with the selective use of coronary artery calcium (CAC) or other methods of subclinical atherosclerosis measurement. Coronary calcification is a marker of atherosclerosis that can be quantified with the use of cardiac CT and it is proportional to the extent and severity of atherosclerotic disease. The published studies demonstrate a high sensitivity of CAC for the presence of coronary artery disease but a lower specificity for obstructive CAD depending on the magnitude of the CAC. Several large clinical trials found clear, incremental predictive value of CAC over the Framingham risk score when used in asymptomatic patients. Based on multiple observational studies, patients with increased plaque burdens (increased CAC) are approximately ten times more likely to suffer a cardiac event over the next 3–5 years. Coronary calcium scores have outperformed conventional risk factors, highly sensitive C-reactive protein (CRP) and carotid intima media thickness (IMT) as a predictor of cardiovascular events. The relevant prognostic information obtained may be useful to initiate or intensify appropriate treatment strategies to slow the progression of atherosclerotic vascular disease. Current data suggests intermediate risk patients may benefit most from further risk stratification with cardiac CT, as CAC testing is effective at identifying increased risk and in motivating effective behavioral changes. This article reviews information pertaining to the clinical use of CAC for assessing coronary atherosclerosis as a useful predictor of coronary artery disease (CAD) in certain population of patients.

Aged garlic extract supplemented with B vitamins, folic acid and l-arginine retards the progression of subclinical atherosclerosis: A randomized clinical trial

OBJECTIVES Previous studies demonstrated that aged garlic extract reduces multiple cardiovascular risk factors. This study was designed to assess whether aged garlic extract therapy with supplements (AGE+S) favorably affects inflammatory and oxidation biomarkers, vascular function and progression of atherosclerosis as compared to placebo. METHODS In this placebo-controlled, double-blind, randomized trial (conducted 2005-2007), 65 intermediate risk patients (age 60+/-9 years, 79% male) were treated with a placebo capsule or a capsule containing aged garlic extract (250 mg) plus Vitamin B12 (100 microg), folic acid (300 microg), Vitamin B6 (12.5 mg) and l-arginine (100 mg) given daily for a 1 year. All patients underwent coronary artery calcium scanning (CAC), temperature rebound (TR) as an index of vascular reactivity using Digital Thermal Monitoring (DTM), and measurement of lipid profile, autoantibodies to malondialdehyde (MDA)-LDL, apoB-immune complexes, oxidized phospholipids (OxPL) on apolipoprotein B-100 (OxPL/apoB), lipoprotein (a) [Lp (a)], C-reactive protein (CRP), homocysteine were measured at baseline and 12 months. CAC progression was defined as an increase in CAC>15% per year and an increase in TR above baseline was considered a favorable response. RESULTS At 1 year, CAC progression was significantly lower and TR significantly higher in the AGE+S compared to the placebo group after adjustment of cardiovascular risk factors (p<0.05). Total cholesterol, LDL-C, homocysteine, IgG and IgM autoantibodies to MDA-LDL and apoB-immune complexes were decreased, whereas HDL, OxPL/apoB, and Lp (a) were significantly increased in AGE+S to placebo. CONCLUSION AGE+S is associated with a favorable improvement in oxidative biomarkers, vascular function, and reduced progression of atherosclerosis.

Cardiac computed tomographic angiography in an outpatient setting: An analysis of clinical outcomes over a 40-month period

BACKGROUND Cardiac computed tomographic angiography (CTA) provides for accurate noninvasive diagnosis of coronary artery disease (CAD). OBJECTIVES We analyzed the clinical outcomes over 40 months in patients with and without CAD as determined by CTA in an outpatient setting. METHODS Consecutive symptomatic patients (n = 493; mean age, 58 +/- 15 years; 70% men) with an intermediate likelihood of CAD referred for outpatient CTA evaluation were prospectively followed for a mean of 40 +/- 9 months. RESULTS Results of CTA included as normal (defined as normal coronary lumen), found in 32% (157), nonobstructive disease (<50% luminal stenosis) in 41% (204), obstructive disease (>or=50% luminal stenosis) in 19% (93). Eight percent (n = 39) had >or=1 major nondiagnostic coronary artery segment. Follow-up identified 21 patients with myocardial infarction (MI) in the significant obstructive CAD and nondiagnostic group. No patients with either normal coronary arteries or nonobstructive disease experienced an MI during follow-up. The 40-month event-free survival was 100% for both the normal and nonobstructive disease groups, 97.5% for the nondiagnostic study group, and 79% for the group with obstructive CAD. After adjustment for age, sex, diabetes mellitus, hypertension, hypercholesterolemia, and baseline coronary artery calcium (CAC), a stepwise multivariable model (Cox regression) showed that obstructive CAD was an independent predictor of cardiac events and had significant incremental value over clinical risk factors and CAC (HR = 16.6; 95% CI, 4.9-55.2; P = 0.0001). CONCLUSION In symptomatic patients with an intermediate likelihood of CAD referred for CTA, normal coronary arteries or nonobstructive CAD portends an excellent prognosis. The finding of obstructive CAD identifies patients at higher risk of subsequent MI, independent of cardiovascular risk factors and coronary artery calcium.

Diagnostic accuracy of 64 multidetector computed tomographic angiography in peripheral vascular disease.

Background: Previous studies of multidetector CT (MDCT) of the lower extremities for the detection of peripheral vascular disease showed high diagnostic accuracy but were performed with older generation systems. Objective: The purpose of this study was to evaluate the diagnostic accuracy of 64 MDCT for the detection of hemodynamically significant disease within the lower extremity peripheral vasculature as compared to digital subtraction angiography (DSA). Methods: Twenty‐eight consecutive patients with symptomatic lower extremity intermittent claudication and an abnormal ankle‐brachial index (ABI; less than 0.9) were evaluated by both 64 MDCT and DSA. Axial images were acquired with a 64 multidetector general electric light speed VCT scanner. Images were analyzed using a GE Advantage workstation (AW 4.3) capable of advanced image processing and manipulation. The aorto‐iliac and lower extremity arteries were divided into 15 segments per limb (30 segments per patient). Eight hundred forty segments were analyzed in a blinded fashion by physicians with level III CT certification. Segments were classified as grade I (<10% stenosis), grade II (10–49%), grade III (50–99%), and grade IV (occlusion). Results: For all segments evaluated, the overall diagnostic accuracy for detecting grade III and IV lesions was 98% with a sensitivity of 99% and a specificity of 98%. For the aorto‐iliac segments, the diagnostic accuracy was 98% with a sensitivity of 100% and a specificity of 99%. For the femoro‐popliteal segments, the overall accuracy was 98% with a sensitivity of 100% and a specificity of 99%. For the infra‐popliteal segments, the overall accuracy was 98% with a sensitivity of 97% and a specificity of 99%. One segment could not be visualized by MDCT compared to 49 segments that could not be visualized by DSA. Conclusions: This study demonstrates excellent diagnostic accuracy of 64 MDCT in the detection of hemodynamically significant disease of the lower extremities. More segments are visualized using 64 MDCT than DSA, allowing more complete visualization of the vascular tree. CT angiography should be considered in the diagnostic evaluation of symptomatic patients with peripheral vascular disease.

Digital thermal monitoring of vascular function: a novel tool to improve cardiovascular risk assessment

Abstract Digital thermal monitoring (DTM) of vascular function during cuff-occlusive reactive hyperemia relies on the premise that changes in fingertip temperature during and after an ischemic stimulus reflect changes in blood flow. To determine its utility in individuals with and without known coronary heart disease (CHD), 133 consecutive individuals (age 54 ± 10 years, 50% male, 19 with known CHD) underwent DTM during and after 2 minutes of supra-systolic arm cuff inflation. Fingertip temperatures of the occluded and non-occluded fingertips were measured simultaneously. Post-cuff deflation temperature rebound (TR) was lower in the CHD patients and in those with an increased Framingham risk score (FRS) compared to the normal group. After adjustment for age, sex, and cardiac risk factors, TR was significantly lower in those with CHD compared to those without CHD (p < 0.05). This study demonstrates that vascular dysfunction measured by DTM is associated with CHD and an increased FRS, and could potentially be used to identify high-risk patients.

Relations between digital thermal monitoring of vascular function, the Framingham risk score, and coronary artery calcium score

BACKGROUND Digital thermal monitoring (DTM) of vascular function was shown to correlate with the presence of known coronary artery disease (CAD). OBJECTIVE We evaluated whether DTM can identify at-risk, asymptomatic patients with significant coronary artery calcium (CAC) or increased Framingham risk score (FRS). METHODS Two hundred thirty-three consecutive asymptomatic subjects (58 +/- 11 years; 62% men) without known CAD underwent DTM, CAC, and FRS calculation. DTM measurements were obtained during and after a 5-minute suprasystolic arm-cuff occlusion. After cuff-deflation temperature rebound (TR) and area under the temperature curve (AUC) were measured and correlated with FRS and CAC. RESULTS TR was lower in patients with FRS > 20% and CAC >or= 100 as compared with FRS < 10% and CAC < 10, respectively (P < 0.05). After adjustment for age, sex, and traditional cardiac risk factors, the odds ratio of the lowest compared with the upper 2 tertiles of TR was 3.96 for FRS >or= 20% and 2.37 for CAC >or= 100 compared with low-risk cohorts. The area under the receiver operating characteristic (ROC) curve to predict CAC >or= 100 increased significantly from 0.66 for FRS to 0.79 for TR to 0.89 for TR + FRS. CONCLUSIONS Vascular dysfunction measured by DTM strongly correlates with FRS and CAC independent of age, sex, and traditional cardiac risk factors and was superior to FRS for the prediction of significant CAC.

Intravascular thermography: a novel approach for detection of vulnerable plaque.

Atherosclerosis is now an epidemic of developed and developing countries. It is not so important who has atherosclerosis—the question is who has vulnerable plaque and in whom atherosclerosis may result in sudden cardiovascular events. Vulnerable plaques are the underlying cause of myocardial infarction (MI), acute coronary syndrome, and majority of sudden cardiac deaths. Different forms of vulnerable plaques exist. The most common type of vulnerable plaque is rupture-prone plaque. The fact that the majority of culprit atherosclerotic plaques are angiographically invisible and do not impose any significant narrowing or cause hemodynamic disturbance urged cardiovascular investigators worldwide to develop new methods for detection of vulnerable plaque. Today there is little doubt that inflammation plays a central role in development of most vulnerable plaques, particularly rupture-prone plaques. Since inflammatory foci normally produce excessive heat, Casscells et al. for the first time showed ex vivo that living atherosclerotic plaques exhibit thermal heterogeneity. Later, Naghavi et al. developed a multichannel basketshaped thermosensor catheter and confirmed temperature heterogeneity in vivo in atherosclerotic rabbits and dogs. Stefanadis et al., using a single channel thermosensor catheter, showed thermal heterogeneity in coronary arteries of patients with MI and unstable angina. More recently, Verheye et al. have shown that aortic temperature heterogeneity vanishes after discontinuing high fat diet in rabbits. Thermal detection of vulnerable plaque is currently under investigation in clinical trials. This article reviews the current body of knowledge pertaining to thermography for detection of vulnerable plaque. Updated information on detection of vulnerable plaque can be obtained at www.VulnerablePlaque.org or www. vp.org.

Vascular Function Measured by Fingertip Thermal Reactivity Is Impaired in Patients With Metabolic Syndrome and Diabetes Mellitus

Digital thermal monitoring (DTM) of vascular function has already been shown to correlate well with coronary artery calcium (CAC) score and coronary artery disease. To determine its utility in the metabolic syndrome (MS) and diabetes mellitus (DM), 233 asymptomatic patients with DM/MS but without coronary artery disease underwent DTM during and after 5 minutes of supra‐systolic arm cuff inflation, as well as CAC. Post‐cuff deflation adjusted temperature rebound (aTR) was lower in MS and DM compared with the normal group. The odds ratio of lowest vs upper 2 tertiles of aTR was 2.3 for MS and 3.5 for DM compared with the normal group, independent of age, sex, and risk factors. The area under the receiver operating characteristic curve to predict CAC ≥100 was 0.69 for metabolic status (DM/MS), 0.79 for aTR, and 0.87 for both. This study demonstrates that vascular dysfunction measured by DTM is associated with DM/MS and could potentially be used to detect asymptomatic individuals with increased subclinical atherosclerosis.

Digital (Fingertip) Thermal Monitoring of Vascular Function: A Novel, Noninvasive, Nonimaging Test to Improve Traditional Cardiovascular Risk Assessment and Monitoring of Response to Treatments

Digital thermal monitoring (DTM) is a noninvasive, inexpensive, easily performed, operator-independent vascular function test designed to complement the existing, risk-factor based assessment of vascular health and to monitor the vascular response to therapies. It is similar to a blood pressure device, with the addition of adhesive temperature probes on the right and left index fingertips that measure fingertip temperature fall and rebound during a brief (2–5 min), arm-cuff occlusion, and release procedure (reactive hyperemia). The higher the temperature rebound, the better the vascular reactivity. In our studies, we have found that DTM indices of vascular reactivity correlate strongly with the number of cardiovascular risk factors, measured by the Framingham Risk Score (FRS), and with the burden of asymptomatic (subclinical) coronary atherosclerosis, measured by coronary calcium score and CT angiography, as well as with myocardial perfusion defects on nuclear stress testing in symptomatic subjects. Moreover, our studies have shown that DTM provides incremental predictive value over risk factor assessment for the identification of high-risk patients with both subclinical atherosclerosis (Coronary Artery Calcium Score ≥100) and coronary artery stenosis (CT angiography showing ≥ 50% stenosis). Finally, DTM indices of vascular function have shown reproducibility comparable to blood pressure measurements. These very promising findings will require corroboration, particularly in long-term, prospective studies and clinical trials. It is important to emphasize that DTM is not intended to replace measurement of risk factors or advanced imaging tests. Rather, its purpose is to complement them by providing a powerful, noninvasive vascular function assessment of coronary health.