Angiographic changes in saphenous vein grafts are predictors of clinical outcomes

Background Previous studies have suggested that angiographic evidence of disease progression in coronary arteries increases the risk of subsequent coronary clinical events. This study ascertained whether patients enrolled in the Post Coronary Artery Bypass Graft Clinical Trial (POST CABG) who had substantial progression of atherosclerosis in ≥1 saphenous vein grafts (on the basis of assessment of baseline and follow-up angiograms obtained 4-5 years after study entry), but who had not reported clinical symptoms before follow-up angiography, were at a higher risk of subsequent events than patients who did not have substantial progression of atherosclerosis (decrease ≥0.6 mm in lumen diameter at site of greatest change from baseline). Methods All 1351 patients enrolled in the trial underwent baseline angiography; only the 961 patients who had follow-up angiography and no coronary events before the follow-up study were included in this analysis. The clinical center staff contacted patients to ascertain the events that had occurred after follow-up angiography (approximately 3.4 years later). Results Sixty-nine patients had died; 870 patients or relatives were interviewed, and 22 patients could not be contacted. Univariable estimates of relative risk associated with substantial progression ranged from 2.2 (P < .001) for cardiovascular death or nonfatal myocardial infarction to 3.3 (P < .001) for revascularization. Multivariable and univariable estimates of risk were similar. Conclusions The findings provide evidence that patients who had substantial progression of atherosclerosis in vein grafts are at an increased risk for subsequent coronary events and suggest that angiographic changes in vein grafts are appropriate surrogate measures for clinical outcomes. (Am Heart J 2003;145:262-9.)     

Determination of in vivo velocity and endothelial shear stress patterns with phasic flow in human coronary arteries: a methodology to predict progression of coronary atherosclerosis

Background Although the coronary arteries are equally exposed to systemic risk factors, coronary atherosclerosis is focal and eccentric, and each lesion evolves in an independent manner. Variations in shear stress elicit markedly different humoral, metabolic, and structural responses in endothelial cells. Areas of low shear stress promote atherosclerosis, whereas areas of high shear stress prevent atherosclerosis. Characterization of the shear stresses affecting coronary arteries in humans in vivo may permit prediction of progression of coronary disease, prediction of which plaques might become vulnerable to rupture, and prediction of sites of restenosis after percutaneous coronary intervention. Methods To determine endothelial shear stress, the 3-dimensional anatomy of a segment of the right coronary artery was determined immediately after directional atherectomy by use of a combination of intracoronary ultrasound and biplane coronary angiography. The geometry of the segment was represented in curvilinear coordinates and a computational fluid dynamics technique was used to investigate the detailed phasic velocity profile and shear stress distribution. The results were analyzed with several conventional indicators and one novel indicator of disturbed flow. Results Our methodology identified areas of minor flow reversals, significant swirling, and large variations of local velocity and shear stress—temporally, axially, and cirumferentially—within the artery, even in the absence of significant luminal obstruction. Conclusions We have described a system that permits, for the first time, the in vivo determination of pulsatile local velocity patterns and endothelial shear stress in the human coronary arteries. The flow phenomena exhibit characteristics consistent with the focal nature of atherogenesis and restenosis. (Am Heart J 2002;143:931-9.)     

Sarpogrelate treatment reduces restenosis after coronary stenting

Background Sarpogrelate, a serotonin blocker, has been reported to inhibit the serotonin-induced proliferation of rat aortic smooth muscle cells. The aim of this study was to investigate whether sarpogrelate reduces restenosis after coronary stenting as a result of prevention of intimal hyperplasia. Methods We examined 79 patients with stable angina undergoing elective coronary stenting on de novo lesions of native coronary arteries in a prospective, randomized trial. All enrolled patients received aspirin and ticlopidine, and one third of the patients were assigned to receive oral sarpogrelate. Results Treatment with sarpogrelate in addition to aspirin and ticlopidine caused no major adverse cardiovascular events or hemorrhagic adverse effects during the 6-month follow-up period. The restenosis rate in the group of patients receiving sarpogrelate was 4.3%, which was significantly lower than the 28.6% rate found in the group of patients not receiving sarpogrelate. Conclusions Sarpogrelate treatment reduces restenosis after coronary stenting, which suggests that serotonin released from activated platelets may play an important role in stent restenosis. (Am Heart J 2003:145:e16.)     

Rationale and design of a study assessing treatment strategies of atrial fibrillation in patients with heart failure: the Atrial Fibrillation and Congestive Heart Failure (AF-CHF) trial

Background Nonrandomized studies suggest that atrial fibrillation is independently associated with increased mortality in patients with heart failure. Whether restoring and maintaining sinus rhythm will have a beneficial impact on cardiovascular mortality in patients with heart failure has never been tested in an adequately powered randomized trial. Objective The primary objective of the Atrial Fibrillation and Congestive Heart Failure (AF-CHF) trial is to determine whether restoring and maintaining sinus rhythm significantly reduces cardiovascular mortality compared with a rate-control strategy in patients with atrial fibrillation and CHF. Methods AF-CHF is a prospective multicenter trial (109 centers in Canada, United States, South America, Europe, and Israel), that will randomize 1450 patients with CHF with left ventricular ejection fraction ≤35% and atrial fibrillation to 1 of 2 treatment strategies: (1) rhythm control with the use of electrical cardioversion combined with antiarrhythmic drugs (amiodarone or other class III agents), (2) rate control with the use of β-blockers, digoxin, or pacemaker and AV nodal ablation. Cardiovascular mortality is the primary end point and the intention-to-treat approach the primary method of analysis. We anticipate an 18.75% 2-year cardiovascular mortality in the rate control arm with a 25% mortality reduction in the rhythm control group. Results As of August 13, 2002, 334 patients have been enrolled from 68 participating centers. Enrollment is expected to be concluded in May 2003 with a minimum follow-up of 2 years. Conclusion The results of this trial should provide definitive information concerning 2 widely applicable treatment strategies of atrial fibrillation in a large cohort of patients with CHF. (Am Heart J 2002;144:597-607.)     

High-sensitivity C-reactive protein in the prediction of coronary events in patients with premature coronary artery disease

Background and Methods Inflammation plays an important role in the initiation and progression of atherosclerosis and in the pathogenesis of acute cardiovascular events. Recent studies have indicated a possible association between C-reactive protein (CRP) and the clinical outcome of coronary artery disease (CAD). We studied prospectively in a group of 125 patients with premature CAD whether plasma levels of CRP as measured with a high-sensitivity assay predict risk for future coronary events. All patients had stable CAD at time of blood sampling but had originally been seen with unstable angina or myocardial infarction. The mean follow-up time after blood collection was 54 months, and death, myocardial infarction, need for coronary revascularization, or admission to hospital with angina pectoris were defined as clinical end points. Results Patients in the highest tertile of CRP levels had a >3.8-fold risk (risk ratio 3.82, 95% CI 1.19-12.17) for death, myocardial infarction, or need for coronary revascularization compared with the patients in the first tertile. The relative risk for patients in the second tertile was 3.5-fold higher (95% CI 1.04-11.56). CRP levels in the third tertile independently predicted risk after adjustment for lipids and other clinical risk factors. Conclusion In patients with clinically stable conditions who have a positive history for acute coronary syndromes before age 50 years, plasma levels of CRP higher than 1.6 mg/L are predictors of future coronary events and therefore indicate the role of underlying chronic inflammation for the clinical course of CAD. Accordingly, reference limits for prediction of risk in CAD have to be lower in this specific patient group than in middle-aged or elderly patients. (Am Heart J 2002;144:449-55.)     

Intravascular ultrasound for the evaluation of therapies targeting coronary atherosclerosis.

Many cardiovascular events are clinical manifestations of underlying atherosclerotic disease. The progression of atherosclerosis, traditionally measured by angiography, is predictive of future clinical events and is a valid surrogate marker of cardiovascular (CV) disease. There is growing interest in using novel surrogate end points in clinical trials to expedite the development of new CV therapies. Innovative imaging technologies, such as intravascular ultrasound (IVUS), may carry advantages for the evaluation of coronary atherosclerotic burden and disease progression. Unlike angiography, which displays only the opacified luminal "silhouette," IVUS provides transmural imaging of the entire arterial wall and permits both detection of early-stage atherosclerosis and accurate cross-sectional and even 3-dimensional quantification of plaques. Intravascular ultrasound is now used to guide therapeutic interventions and for diagnostic purposes, primarily for the evaluation of ambiguous lesions and left main coronary artery disease. In addition, clinical studies are using IVUS serially to measure plaque progression, which appears to be related to future CV events. Although the probative force of clinical end point studies still is stronger, IVUS is catching up. Currently, several trials of CV therapies use IVUS-determined plaque progression as the end point. The rationale for using IVUS-based surrogate end points in clinical trials is discussed in the present review. Key advantages of using IVUS-based surrogate end points versus clinical outcome include smaller patient numbers and substantially shorter trial durations; this reduces costs and may expedite the development and testing of new drugs. We expect in the near future a further increase of the use of IVUS-based surrogate end points in trials that evaluate novel CV therapies targeting on coronary atherosclerosis.     

Impact of geographic miss on adjacent coronary artery segments in diffuse in-stent restenosis with beta-radiation therapy: angiographic and intravascular ultrasound analysis

Background The impacts of geographic miss on edge restenosis have not been sufficiently evaluated. Methods β-Radiation therapy with rhenium 188-filled balloon after rotational atherectomy for diffuse in-stent restenosis was performed in 50 patients. We evaluated the impacts of geographic miss on adjacent coronary artery segments beyond the stent by angiographic (QCA) and intravascular ultrasound (IVUS) analysis in 50 irradiated lesions and 100 edges. Serial IVUS and QCA comparisons between postradiation and 6 months' follow-up were available in 44 and 47 of 50 patients, respectively. QCA measurements of minimal lumen diameter (MLD) and IVUS analysis were performed in the reference and radiation segments. Edges that were touched by the angioplasty balloon but were not adequately covered by radiation constituted the geographic miss edges. Results Geographic miss was observed in 55.6% and 52.6% in QCA and IVUS analysis, respectively. Edge restenosis after radiation therapy in 3 patients was associated with geographic miss. In contrast to uninjured edges (postradiation 2.9 ± 0.6 mm to follow-up 2.8 ± 0.6 mm, P = .292), MLD in the radiation segment by QCA analysis significantly decreased from 2.7 ± 0.4 mm to 2.4 ± 0.6 mm in geographic miss edges (P = .002). IVUS analysis showed that significant positive remodeling in the radiation segment occurred in uninjured edges (vessel area from 15.4 ± 4.4 mm² to 15.8 ± 4.4 mm², P = .001) but not in geographic miss edges (vessel area from 12.8 ± 3.6 mm² to 13.0 ± 3.6 mm², P = .119). Conclusion The geographic miss might be one of the predictors, which resulted in decreased MLD at follow-up in β-radiation therapy. Sufficient lesion coverage with radiation might be associated with positive remodeling in the radiation segment. (Am Heart J 2002;143:327-33.)     

Relationships between reduced heart rate variability and pre-clinical cardiovascular disease in patients with type 2 diabetes

Aims

Reduced heart rate variability (HRV), an early sign of diabetic cardiovascular autonomic neuropathy (CAN), is associated with worse cardiovascular outcomes. The objective was to evaluate relationships between HRV parameters and three pre-clinical cardiovascular disease markers (left ventricular hypertrophy [LVH], aortic stiffness and carotid atherosclerosis) in type 2 diabetes.

Methods

In a cross-sectional study, 313 patients with type 2 diabetes performed 24-h Holter monitoring, carotid ultrasonography (intima-media thickness and plaques measurements), aortic pulse wave velocity measurement and echocardiography (left ventricular mass index [LVMI] measurement). Time-domain HRV parameters were the standard deviation of all normal RR intervals (SDNN), the standard deviation of the averaged normal RR intervals for all 5 min segments (SDANN), the root mean square of differences between adjacent R-R intervals (rMSSD), and the percentage of adjacent R-R intervals that varied by >50 ms (pNN50). Multivariate linear and logistic regressions assessed associations between HRV parameters and the three markers of pre-clinical cardiovascular disease.

Results

Patients with reduced HRV had longer diabetes duration, greater prevalences of microvascular complications, lower physical fitness, and higher heart rate, glycated hemoglobin, albuminuria and LVMI than patients with normal HRV. On multivariate regressions, after adjustments for several confounders, reduced SDNN and SDANN were independently associated with LVH and aortic stiffness. No HRV parameter was associated with carotid atherosclerosis.

Conclusions

Two reduced HRV parameters, SDNN and SDANN, which reflect cardiovascular autonomic imbalance, were associated with LVH and aortic stiffness, markers of pre-clinical cardiovascular disease. These findings may offer insights into physiopathological mechanisms linking CAN to worse cardiovascular prognosis.     

Serum glucose and lipid levels in adult congenital heart disease patients

Atherosclerosis has been correlated with known cardiovascular risk factors such as serum glucose or lipid levels. Because congenital heart disease patients tend to survive until adulthood, atherosclerosis has also become a matter of concern in these patients. One hundred fifty-eight congenital heart disease patients and 152 patients selected at random from the population were studied and compared to determine serum glucose, total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein cholesterol, and triglycerides levels. Both groups had similar socioeconomic status levels and the same environmental influences. Significant differences were seen between congenital heart disease patients and the control group, after sex, age, and body mass index adjustment, in fasting plasma glucose (97.7 [94.2-101.2] vs 86.9 [83.2-90.7], P < .001), total cholesterol (171.5 [165.7-177.3] vs 199.8 [90.7-206.0], P < .001), LDL cholesterol (103.9 [98.8-108.8] vs 123.8 [118.5-129.1], P < .001), and high-density lipoprotein cholesterol (48.1 [46.2-50.0] vs 54.2 [52.1-56.2], P < .001) levels. Nonsignificant differences were seen in triglycerides concentrations. Those patients with ventricular septal defect, coarctation of the aorta, and cyanosis had the lowest total cholesterol and LDL cholesterol concentrations. Congenital heart disease patients have lower plasma cholesterol concentrations and higher serum glucose levels than noncongenital ones.     

Prognostic significance of coronary artery calcium in asymptomatic subjects with usual cardiovascular risk

Background Coronary calcium detected noninvasively is an attractive way to diagnose atherosclerosis before the development of symptoms. This study examines the prognostic value of coronary calcium in asymptomatic subjects with usual cardiovascular risk. Methods and Results In 425 asymptomatic subjects, 229 men (aged 45.1 ± 14 years) and 196 women (aged 42.7 ± 13 years), coronary calcium presence was studied by digital cinefluoroscopy. The majority (76%) had no or at most one risk factor. Subjects were followed up for 58.4 ± 12.7 months for cardiac events. Coronary calcium was present in 76 of 425 (17.9%) subjects. Cardiac events were observed in 21 subjects: 2 cardiac deaths, 7 acute myocardial infarctions, 3 coronary artery bypass grafts, 3 coronary angioplasty procedures, 3 events of unstable angina, and 10 events of stable angina pectoris. Survival curve analysis showed significant differences in all the studied end points between subjects with and those without calcium. Coronary calcium was an independent predictor of all events (3.6-fold increase, P < .008), cardiac death/myocardial infarction/revascularization (13.9-fold increase, P < .02), and stable angina (7.4-fold increase, P < .007). However, calcium did not independently predict cardiac death/myocardial infarction or acute coronary syndromes. Conclusions Coronary calcium in asymptomatic subjects with usual cardiovascular risk adds significant incremental information to risk factors information for the development of symptomatic coronary artery disease. (Am Heart J 2003;145:542-8.)     

Impact of deep vessel wall injury and vessel stretching on subsequent arterial remodeling after balloon angioplasty: a serial intravascular ultrasound study

Background Arterial remodeling has been shown to be responsible for lumen narrowing after nonstent interventions. Methods To examine the impact of deep vessel wall injury (DI) after balloon angioplasty on the subsequent vessel remodeling process, we performed serial intravascular ultrasound (IVUS) analysis in 47 native coronary artery lesions that underwent balloon angioplasty. An IVUS study was performed before and after balloon angioplasty and repeated at follow-up. Vessel and lumen area were measured at the narrowest site before intervention. Plaque area was calculated as vessel area minus lumen area. DI was defined as the presence of plaque/vessel wall fracture deep in the medial layer (sonolucent zone by IVUS) after angioplasty. Results After angioplasty, DI was present in 18 (38%, DI group) and absent in 29 (62%, non-DI group) of lesions. During follow-up, changes in vessel area in the DI group were significantly larger than in the non-DI group (P = .007). There were no significant differences in changes in plaque area. A trend toward greater late lumen loss was observed in the non-DI group (P = .05). In the DI group, changes in lumen area correlated better with changes in vessel area (r = 0.81, P < .0001) than with changes in plaque area (r = 0.32, P = .20). However, in the non-DI group, changes in lumen area correlated with changes in plaque area (r = −0.55, P = .002), but not with changes in vessel area (r = 0.30, P = .11). Conclusions Deep vessel wall injury after balloon angioplasty is associated with the magnitude of the subsequent vessel remodeling process. The differences in the remodeling process may have implications regarding adjunctive therapies to prevent restenosis after balloon angioplasty. (Am Heart J 2002;144:323-8.)     

An updated meta-analysis of calcium-channel blockers in the prevention of restenosis after coronary angioplasty

Background In 1994, a meta-analysis of 5 small randomized trials reported a 30% reduction in the odds of angiographic restenosis when calcium-channel blockers (CCB) were given after percutaneous coronary intervention. Recently, the results of 2 large similar trials (Nisoldipine In Coronary Artery Disease in Leuven [NICOLE], and Coronary AngioPlasty Amlodipine in REstenosis Study [CAPARES]) were published. An extended meta-analysis including the results of the latter trials was performed. Methods A total of 2380 patients were analyzed. Statistical analysis included calculation of odds ratios for each trial, common odds ratio, and homogeneity for treatment effects across trials. Results The incidence of angiographic restenosis was 36% in the CCB-treated group and 42% in the placebo group. The odds ratio of restenosis with CCB therapy was 0.78 (95% CI 0.64-0.95) compared with control patients (P = .01). Treatment effects were homogeneous across the trials. For the combined end point of death, coronary artery bypass grafting, repeat percutaneous transluminal coronary angioplasty, and myocardial infarction, 126 of 626 events occurred in the CCB group and 191 of 655 in the placebo group (odds ratio 0.61 [95% CI 0.47-0.80], P < .001). Conclusions This extended meta-analysis confirmed a reduction in the odds of restenosis and clinical events when CCBs were added to standard therapy after percutaneous coronary intervention. (Am Heart J 2003; 145:404-8.)     

Antiplatelet effects of angiotensin-converting enzyme inhibitors compared with aspirin and clopidogrel: a pilot study with whole-blood aggregometry

Background Although specific antiplatelet drugs are well-established and effective in atherosclerosis prevention, recent clinical trials have also shown that use of angiotensin-converting enzyme (ACE) inhibitors results in a decrease in cardiovascular events. Therefore, in this study, we sought to assess the coagulative activity of patients with cardiovascular disease grouped for treatment with either ACE inhibitors, aspirin, clopidogrel/aspirin, or none of these medications. Methods Blood samples from 303 patients with cardiovascular disease were analyzed with whole-blood aggregometry. Platelet aggregation was determined by the increase in impedance across paired electrodes in response to the aggregatory agents adenosine diphosphate (ADP) or collagen. Results As the central finding, platelet aggregation was attenuated by ACE inhibitors and by aspirin or clopidogrel/aspirin, which was indicated by a lower impedance increase compared with no medication. With ACE inhibition, platelet aggregation decreased by 33% (P = .042) after ADP induction. No significant antithrombotic effect was seen with aspirin alone (17%, P = 1.0), whereas a decrease in ADP-induced platelet aggregation was extensive with clopidogrel/aspirin (85%, P = .001). After collagen induction, platelet aggregation was reduced by 16% (P = .028) in the presence of ACE inhibitor therapy, whereas inhibition with aspirin and clopidogrel/aspirin was 23% (P = .004) and 35% (P = .026), respectively, compared with participants who were not treated. Conclusions These ex vivo data on whole-blood aggregometry provide direct evidence that ACE inhibitors decrease platelet aggregation, whereas aspirin and clopidogrel are confirmed as established antithrombotics. Pleiotropic effects of ACE inhibition on platelet function may contribute to the clinical benefit observed with this drug class on major cardiovascular end points. (Am Heart J 2003;145:343-8.)     

Intravascular ultrasound for the evaluation of therapies targeting coronary atherosclerosis

Many cardiovascular events are clinical manifestations of underlying atherosclerotic disease. The progression of atherosclerosis, traditionally measured by angiography, is predictive of future clinical events and is a valid surrogate marker of cardiovascular (CV) disease. There is growing interest in using novel surrogate end points in clinical trials to expedite the development of new CV therapies. Innovative imaging technologies, such as intravascular ultrasound (IVUS), may carry advantages for the evaluation of coronary atherosclerotic burden and disease progression. Unlike angiography, which displays only the opacified luminal "silhouette," IVUS provides transmural imaging of the entire arterial wall and permits both detection of early-stage atherosclerosis and accurate cross-sectional and even 3-dimensional quantification of plaques. Intravascular ultrasound is now used to guide therapeutic interventions and for diagnostic purposes, primarily for the evaluation of ambiguous lesions and left main coronary artery disease. In addition, clinical studies are using IVUS serially to measure plaque progression, which appears to be related to future CV events. Although the probative force of clinical end point studies still is stronger, IVUS is catching up. Currently, several trials of CV therapies use IVUS-determined plaque progression as the end point. The rationale for using IVUS-based surrogate end points in clinical trials is discussed in the present review. Key advantages of using IVUS-based surrogate end points versus clinical outcome include smaller patient numbers and substantially shorter trial durations; this reduces costs and may expedite the development and testing of new drugs. We expect in the near future a further increase of the use of IVUS-based surrogate end points in trials that evaluate novel CV therapies targeting on coronary atherosclerosis.     

Angiopoietin-like protein 4 significantly predicts future cardiovascular events in coronary patients

Background: Angiopoietin-like protein 4 (ANGPTL4) has been associated with cardiometabolic disorders including dyslipidemia and atherosclerosis in animal studies; in humans, however, its impact on metabolic traits and cardiovascular risk remains unclear. Methods: We examined the association of plasma ANGPTL4 levels with the metabolic syndrome (harmonized consensus definition), with angiographically determined coronary artery disease (CAD), and with the risk of future cardiovascular events in a cohort of 490 patients undergoing coronary angiography for the evaluation of stable CAD. In addition, we investigated the influence of the tagging single nucleotide polymorphisms (SNPs) rs4076317, rs2278236, rs1044250, and rs11672433 as well as variant rs116843064 (E40K) of the ANGPTL4 gene on cardiovascular risk in a larger sample of 983 angiographied coronary patients including the above mentioned 490 subjects. Results: Plasma ANGPTL4 was significantly higher in patients with the metabolic syndrome than in subjects without the metabolic syndrome (26.0 ± 19.4 ng/ml vs. 22.2 ± 19.7 ng/ml; p = 0.008). No significant association was found between ANGPTL4 and angiographically characterized coronary atherosclerosis. Prospectively, however, plasma ANGPTL4 significantly predicted future cardiovascular events both univariately (HR1.45 [1.16–1.82], p = 0.001) and after adjustment for standard cardiovascular risk factors (1.26 [1.01–1.58]; p = 0.045). Concordantly, rs4076317, rs2278236, and rs1044250 significantly affected the risk of future cardiovascular events (adjusted HRs 0.70 [0.54–0.90]; p = 0.005, 0.76 [0.61–0.94]; p = 0.012, and 1.30 [1.03–1.62]; p = 0.025, respectively). Conclusions: We conclude that plasma ANGPTL4 levels as well as ANGPTL4 variants significantly predict cardiovascular events independently of conventional cardiovascular risk factors.     

Effects of Statins on Progression of Coronary Artery Disease as Measured by Intravascular Ultrasound

J Clin Hypertens (Greenwich). 2011;13:492–496.©2011 Wiley Periodicals, Inc.Intravascular ultrasound (IVUS) is a novel technique that provides an accurate and reproducible method to measure atheroma burden. Statin drugs reduce both atherogenic lipoproteins and cardiovascular morbidity and mortality. Studies assessing the effect of statin treatment on atheroma burden have shown conflicting results. Hence, this meta‐analysis was conducted to evaluate the impact of statin therapy on coronary atherosclerosis progression. A systematic search using PubMed, EMBASE, and Cochrane Library databases was performed. Heterogeneity of the studies was analyzed by Cochran’s Q statistics. The significance of common treatment effect was assessed by computing common mean difference between the control and treatment groups. A two‐sided α error of <0.05 was considered statistically significant (P<.05). Eight trials composed of 919 patients including a placebo group with 458 patients and a treatment group with 461 patients were used. Characteristics of both groups at baseline were similar without any significant difference between them. In the pooled analysis, the common mean difference of coronary atheroma volume between statin therapy and the placebo arm was −3.573 (confidence interval, −4.46 to −2.68; P<.01). This meta‐analysis demonstrates that treatment with statins not only slows atherosclerotic plaque progression but may also lead to plaque regression.

Therapy with high doses of 3‐hydroxy 3‐methylglutaryl coenzyme A reductase (HMG CoA) inhibitors (statins) reduces both atherogenic lipoproteins and cardiovascular morbidity and mortality. ¹ , ² Studies have shown that intensive statin therapy is more effective than moderate therapy in reducing the progression of atherosclerosis as determined by measuring carotid intimal medial thickness or assessing atheroma burden using intravascular ultrasound (IVUS). ³ , ⁴ , ⁵ Angiography plays a pivotal role in the selection of patients for revascularization and has been widely used to measure the efficacy of anti‐atherosclerotic drug therapies. ⁶ , ⁷ , ⁸ However, angiography depicts a silhouette of the coronary lumen and does not directly image the atheroma within the vessel wall, where anti‐atherosclerotic therapies show their effects. The recent application of IVUS in progression‐regression trials enabled systematic assessment of the effects of such therapies on various components of the vessel, including the atheroma itself. ⁴ , ⁹ , ¹⁰ , ¹¹ IVUS provides an accurate and reproducible method to measure atheroma burden and can be used to evaluate progression of coronary atherosclerosis. IVUS is a particularly good method for assessing atherosclerosis because it allows measurement of atheroma burden, not just luminal narrowing. ¹² IVUS allows the earlier stage of eccentric growth and intramural atheroma formation to be quantified and followed. ¹³ Therefore, many recent studies have used this tool to measure the effects of various anti‐atherosclerotic therapies on coronary atheroma burden.However, studies assessing the effect of statin treatment on atheroma burden have shown conflicting results. Hence, this meta‐analysis was conducted to evaluate the impact of statin therapy on coronary atherosclerosis progression.     

An Approach to the Rational Use of Revascularization in Heart Failure Patients

The most common cause of heart failure with reduced ejection fraction (HFrEF) is coronary artery disease. A multitude of factors come into play when deciding whether a patient with HFrEF and coronary artery disease should have coronary artery bypass graft (CABG) surgery, percutaneous coronary intervention, or medical therapy alone. For candidates for percutaneous coronary intervention and CABG, evidence from large registries would suggest that patients with 2-vessel coronary artery diseases and proximal left anterior descending disease and all patients with 3-vessel coronary artery disease do better with CABG. For patients that are candidates for medical therapy with or without CABG, the results of the Surgical Treatment for Ischemic Heart Failure (STICH) trial indicate that with CABG, the reduction of mortality is not statistically significant (hazard ratio [HR], 0.86; P = 0.12). However, CABG is superior in reducing cardiovascular deaths (HR, 0.81; P = 0.05), and the combination of cardiovascular deaths and cardiovascular hospitalizations (HR, 0.74; P < 0.001). Patients undergoing CABG have an upfront risk that is eliminated by 2 years and thereafter do better. The assessment of cardiac viability or reversible ischemia does not appear to be helpful in determining which individuals will improve more with CABG. Patients with severe mitral regurgitation who undergo CABG appear to benefit from simultaneous valve repair but not from the addition of surgical ventricular reconstruction of the left ventricle, although in specific patients this might be considered. The totality of evidence would thus suggest that patients with HFrEF should be evaluated for the possibility of coronary revascularization if they are candidates for CABG.     

Effect of beta2-adrenergic receptor functioning and increased norepinephrine on the hypercoagulable state with mental stress

Background Procoagulant stress responses may contribute to atherosclerosis development and acute coronary thrombosis. In the present study, we examined the role of β₂-adrenergic receptor function and plasma catecholamines in the stress-induced increase in the 2 hypercoagulability markers thrombin-antithrombin III (TAT) complex and fibrin D-dimer (DD). Methods Lymphocyte β₂-adrenoreceptor sensitivity and density were assessed at rest, and plasma levels of TAT, DD, epinephrine, and norepinephrine were measured at rest and in response to a standardized mental stress task in 19 normotensive and mildly hypertensive nonmedicated subjects (mean age 38 years, age range 29 to 48 years). Results The stressor elicited a significant increase in TAT (P = .024), DD (P = .026), and norepinephrine (P = .005). Resting β₂-adrenoreceptor sensitivity (isoproterenol-stimulated cyclic adenosine monophosphate production) plus the norepinephrine change scores (stress minus rest) accounted for 59% of the variance in the absolute TAT increase in response to stress (P = .001). Hypertension status and demographic variables such as sex did not influence the results. Conclusions Acute mental stress may trigger a hypercoagulable state evidenced by increased thrombin activity and increased fibrin turnover. β₂-Adrenergic receptor sensitivity and plasma catecholamine activity may mediate the procoagulant response to acute stressors. These mechanisms may help explain the adverse impact of mental stress on the cardiovascular system. (Am Heart J 2002;144:68-72.)     

Arterial stiffness in patients with non-alcoholic fatty liver disease is related to fibrosis stage and epicardial adipose tissue thickness

Objective: Non-alcoholic fatty liver disease (NAFLD) is associated with atherosclerosis and reduced vascular compliance. The purpose of this study was to examine the relationships between arterial stiffness measures, the histological severity of NAFLD, and epicardial fat thickness (EFT). Methods: A total of 100 patients with biopsy-proven NAFLD and 50 age- and sex-matched controls were enrolled. The histological severity was assessed in all NAFLD patients. Measurements of arterial stiffness [pulse-wave velocity (PWV) and augmentation index (AIx)] were carried out using a Mobil-O-Graph arteriograph system. EFT was assessed by means of echocardiography. Results: Compared with controls, NAFLD patients had significantly higher PWV and AIx values. Stepwise linear regression analysis demonstrated that the liver fibrosis score and EFT were independent predictors of both PWV and AIx values in NAFLD patients. Conclusions: Patients with NAFLD have an increased arterial stiffness, which reflects both the severity of liver fibrosis and increased EFT values.     

CD14 gene -159C/T polymorphism is not associated with coronary artery disease and myocardial infarction

Background Monocyte differentiation antigen CD14 is considered an important cell-activating mediator of inflammatory responses that may result in atherosclerosis, coronary artery disease (CAD), thrombus formation, and myocardial infarction (MI). We assessed the possibility that a C → T nucleotide substitution polymorphism in the promoter (position −159) of the gene encoding CD14 constitutes a risk factor for CAD and MI. Methods Consecutive patients with significant, angiographically documented coronary stenoses but without symptoms or signs of old or acute MI constituted the group with CAD (n = 998). Consecutive patients with angiographic examination with old or acute MI constituted the group with MI (n = 793). Subjects matched with patients for age and gender but without angiographic evidence of CAD and without symptoms or signs of MI (n = 340) and a group of healthy blood donors (n = 104) served as controls. Results Genotype distributions of the −159C/T polymorphism were similar across the groups; CC:CT:TT was 26.9%:51.0%:22.1% in blood donors, 25.9%:52.0%:22.1% in matched control subjects, 27.4%:49.9%:22.7% in patients with CAD, and 29.2%:49.2%:21.6% in patients with MI. The lack of association persisted also after adjustment for the presence of conventional cardiovascular risk factors. In addition, no significant differences were found between genotype distributions of control subjects and selected subgroups of patients with CAD or MI. Conclusion These findings indicate that, in the sample of patients examined in this study, the −159C/T polymorphism of the CD14 gene is not related to CAD or MI. (Am Heart J 2002;143:971-6.)