Biomedical subjects

Jean-Claude Tardif

Publications and source records attributed to Jean-Claude Tardif.

At least 19 recordsLinked to original sources

PubMed2025

GWAS of CRP response to statins further supports the role of APOE in statin response: A GIST consortium study.

Statins are first-line treatments in the primary and secondary prevention of cardiovascular disease. Clinical studies show statins act independently of lipid-lowering mechanisms to decrease C-reactive protein (CRP), an inflammation marker. We aim to elucidate genetic loci associated with CRP statin response. CRP statin response is the change in log-CRP between off-treatment and on-treatment measurements. Cohort-level Genome-Wide Association Studies (GWAS) of CRP response were performed using 1000 Genomes imputed data, testing ∼10 million common genetic variants. GWAS meta-analysis combined results from seven cohorts and clinical trials totalling 14,070 statin-treated individuals of European ancestry within the GIST consortium. Secondary analyses included statin-by-placebo interaction analyses, and lookups in African ancestry cohorts. Our GWAS identified two genome-wide significant (P < 5e-8) loci: APOE and HNF1A for CRP statin response corrected for baseline CRP. The missense lead variant rs429358 at APOE, contributing to the APOE-E4 haplotype, is a risk locus for dyslipidaemia, Alzheimer's and coronary artery disease (CAD). The HNF1A locus is associated with diabetes, cholesterol levels, and CAD. Both loci are also associated with baseline CRP levels, and neither locus achieved a significant (P < 0.05) result from the statin v. placebo interaction meta-analysis using randomized clinical trial data. However, the interaction result (P-int=0.09) for APOE was suggestive and possibly underpowered. The APOE-E4 signal may therefore be associated with both CRP and LDL-cholesterol statin response. Combined with suggestions in the literature that APOE also leads to differential statin benefit in Alzheimer's, the APOE locus warrants further investigation for potential genetic effects on healthcare with statin treatment.

Humans↗

PubMed2007

Effects of the antioxidant succinobucol (AGI-1067) on human atherosclerosis in a randomized clinical trial.

BACKGROUND: The antioxidant AGI-1067 was shown to reduce experimental atherosclerosis. The present study originally intended to study restenosis as a primary endpoint but was subsequently modified to primarily investigate the effects of AGI-1067 on coronary atherosclerosis. METHODS AND RESULTS: This placebo-controlled randomized trial assessed the effects of AGI-1067 280 mg qd started before percutaneous coronary intervention (PCI) and administered for 12 months after PCI on atherosclerosis progression as assessed by coronary intravascular ultrasound (IVUS). Among patients with IVUS examinations considered technically adequate both at baseline and follow-up upon central laboratory assessments (n=232), plaque volume was not significantly modified with placebo (least squares mean change: -0.4mm(3), P=0.85 versus baseline), but was significantly reduced by -4.0mm(3) at end of treatment in the AGI-1067 group (P=0.001 versus baseline, P=0.12 versus placebo). LDL-cholesterol varied by -9% and +4% in the placebo and AGI-1067 groups, respectively (P<0.05 between groups), and HDL-cholesterol was reduced by 1% with placebo and 14% with AGI-1067 (P<0.05 between groups). Plasma myeloperoxidase was reduced by 6% with AGI-1067 (P<0.05) but hs-CRP was not significantly different between groups. CONCLUSIONS: Atherosclerosis regression (-4.0mm(3)) was observed in patients treated with AGI-1067, although this was not significantly different from placebo. The anti-inflammatory effect of AGI-1067 is supported by reduced levels of myeloperoxidase.

Aged↗

PubMed2006

Alterations in the endothelial G-protein coupled receptor pathway in epicardial arteries and subendocardial arterioles in compensated left ventricular hypertrophy.

The present study was designed to compare alterations of endothelium-dependent vasorelaxation in coronary epicardial arteries and subendocardial arterioles occurring in left ventricular hypertrophy (LVH) secondary to 60 days of aortic banding in a porcine model. Development of LVH was documented by echocardiogram and the endothelial function of subendocardial and epicardial vessels was studied by constructing concentration-response curves in a pressure myograph and standard organ chambers, respectively. 5-HT induced relaxations were reduced (p<0.05) in both vessel types isolated from pigs with LVH. Dilations of subendocardial arterioles and epicardial vessels to UK14304 were depressed by LVH. In the presence of Nomega-nitro-L-arginine (L-NNA), EDHF solely accounts for BK-induced relaxations; it fully compensates for the loss of NO in arterioles, but only partially in epicardial arteries isolated from LVH swine. Endothelium-independent relaxations induced by SNP were not altered in both vessel types from the LVH group. In a porcine model of LVH secondary to 60 days of aortic banding, the associated coronary endothelial dysfunction preferentially involves Gi-protein mediated relaxations in arterioles and arteries but also affects Gq-protein mediated relaxations in epicardial coronary arteries.

Animals↗

PubMed2006

Targeted ablation of ILK from the murine heart results in dilated cardiomyopathy and spontaneous heart failure.

A requirement for integrin-mediated adhesion in cardiac physiology is revealed through targeted deletion of integrin-associated genes in the murine heart. Here we show that targeted ablation of the integrin-linked kinase (ILK) expression results in spontaneous cardiomyopathy and heart failure by 6 wk of age. Deletion of ILK results in disaggregation of cardiomyocytes, associated with disruption of adhesion signaling through the beta1-integrin/FAK (focal adhesion kinase) complex. Importantly, the loss of ILK is accompanied by a reduction in cardiac Akt phosphorylation, which normally provides a protective response against stress. Together, these results suggest that ILK plays a central role in protecting the mammalian heart against cardiomyopathy and failure.

Animals↗

PubMed2006

Vascular biomarkers and surrogates in cardiovascular disease.

Cardiovascular biomarker research efforts have resulted in the identification of new risk factors and novel drug targets, as well as the establishment of treatment guidelines. Government agencies, academic research institutions, diagnostic industries, and pharmaceutical companies all recognize the importance of biomarkers in advancing therapies to improve public health. In drug development, biomarkers are used to evaluate early signals of efficacy and safety, to select dose, and to identify the target population. The United States Food and Drug Administration has relied on biomarkers to support clinical applications in many therapeutic fields, including cardiovascular disease. The appropriate application of cardiovascular biomarkers requires an understanding of disease natural history, the mechanism of the intervention, and the characteristics and limitations of the biomarker. Channels of communication among researcher, developer, and regulator must remain open to maximize the success of future biomarker efforts. In 2003, 2004, and 2005, an international panel of cardiovascular biomarker experts convened at the "Cardiovascular Biomarker and Surrogate Endpoints Symposia" held in Bethesda, Md, to discuss the use of biomarkers in the development of improved cardiovascular diagnostics and therapeutics. The information presented in the present report summarizes the authors' perspective distilled from these proceedings.

Atherosclerosis↗

PubMed2006

Effect of atherosclerotic regression on total luminal size of coronary arteries as determined by intravascular ultrasound.

We assessed vascular changes during atherosclerosis regression. Compensatory enlargement of coronary arteries accommodates plaque burden during atherosclerosis development. Lipid-lowering therapy has altered the natural history of coronary atherosclerosis, but the arterial changes that occur during disease regression need to be clarified. Intravascular ultrasound was performed at baseline and after approximately 18 months in 432 patients with coronary disease. Mean plaque, lumen, and total vessel area were computed in a 30-mm coronary segment of interest. Mean low-density lipoprotein cholesterol level was 2.4 mmol/L, and 88% of patients received statins. Overall, changes in plaque and total vessel areas were highly correlated (r = 0.82, p <0.0001). Among the 227 patients with plaque regression, the plaque area decrease was -0.58 +/- 0.54 mm(2), and changes in total vessel and lumen areas were -1.02 +/- 1.10 and -0.44 +/- 0.86 mm(2), respectively. The decrease in plaque area correlated better with the change in total vessel area (r = 0.64, p <0.0001) than with the change in lumen area (r = 0.20, p = 0.003). The relation between plaque regression and decrease in total vessel area was significantly better (p = 0.019) for patients with a >40% atheroma area (r = 0.72; p <0.0001) than for those with <or=40% (r = 0.48; p = 0.0004). In conclusion, regression of atherosclerotic plaque is generally accompanied by a decrease in total vessel size, without an increase in luminal dimensions. This reverse vascular remodeling may be responsible for the "regression paradox," whereby secondary prevention is associated with clinical benefits despite minimal improvement in coronary lumen dimensions.

Acetamides↗

PubMed2006

Circulating 4-hydroxynonenal-protein thioether adducts assessed by gas chromatography-mass spectrometry are increased with disease progression and aging in spontaneously hypertensive rats.

Oxidative stress has been implicated in numerous degenerative diseases of aging, including heart diseases. However, there is still a need to identify biomarkers of oxidative stress-related events, such as protein modification by the lipid peroxidation product 4-hydroxynonenal (HNE) in these diseases in humans. The objective of this study was to assess if circulating levels of HNE-protein adducts (i) can be assessed with precision by GCMS and (ii) vary with disease progression and aging in a model of cardiomyopathy that displays enhanced oxidative stress, namely the spontaneously hypertensive rats (SHR). We modified a previously published isotope dilution GCMS method that quantifies HNE and its inactive metabolite, 1,4-dihydroxynonene (DHN), bound to thiol proteins following treatment with NaB(2)H(4) and Raney nickel, to increase its sensitivity (20-fold), precision, and robustness. Levels of these adducts were measured in blood and plasma collected from SHR and control Wistar rats at 7, 15, 22, and 30 weeks of age. Levels of protein-bound HNE, which were quantitated with good precision in the nanomolar range in blood, but not in plasma, were significantly increased by disease (SHR) and age (P < 0.0001 for both). Compared to Wistar rats, SHR showed greater blood levels of HNE-protein adducts at 22 and 30 weeks. Levels of protein-bound DHN, which were detected in blood and in plasma, were not affected by disease or age. Collectively, the results of this study conducted in an animal model of cardiomyopathy demonstrate that changes in blood HNE-protein thioether adducts with disease progression and aging can be assessed with good precision by the described GCMS method. This method may prove to be useful in evaluating the occurrence and impact of oxidative stress-related events involving bioactive HNE in heart diseases and aging in humans.

Aging↗

PubMed2006

Effect of very high-intensity statin therapy on regression of coronary atherosclerosis: the ASTEROID trial.

CONTEXT: Prior intravascular ultrasound (IVUS) trials have demonstrated slowing or halting of atherosclerosis progression with statin therapy but have not shown convincing evidence of regression using percent atheroma volume (PAV), the most rigorous IVUS measure of disease progression and regression. OBJECTIVE: To assess whether very intensive statin therapy could regress coronary atherosclerosis as determined by IVUS imaging. DESIGN AND SETTING: Prospective, open-label blinded end-points trial (A Study to Evaluate the Effect of Rosuvastatin on Intravascular Ultrasound-Derived Coronary Atheroma Burden [ASTEROID]) was performed at 53 community and tertiary care centers in the United States, Canada, Europe, and Australia. A motorized IVUS pullback was used to assess coronary atheroma burden at baseline and after 24 months of treatment. Each pair of baseline and follow-up IVUS assessments was analyzed in a blinded fashion. PATIENTS: Between November 2002 and October 2003, 507 patients had a baseline IVUS examination and received at least 1 dose of study drug. After 24 months, 349 patients had evaluable serial IVUS examinations. INTERVENTION: All patients received intensive statin therapy with rosuvastatin, 40 mg/d. MAIN OUTCOME MEASURES: Two primary efficacy parameters were prespecified: the change in PAV and the change in nominal atheroma volume in the 10-mm subsegment with the greatest disease severity at baseline. A secondary efficacy variable, change in normalized total atheroma volume for the entire artery, was also prespecified. RESULTS: The mean (SD) baseline low-density lipoprotein cholesterol (LDL-C) level of 130.4 (34.3) mg/dL declined to 60.8 (20.0) mg/dL, a mean reduction of 53.2% (P<.001). Mean (SD) high-density lipoprotein cholesterol (HDL-C) level at baseline was 43.1 (11.1) mg/dL, increasing to 49.0 (12.6) mg/dL, an increase of 14.7% (P<.001). The mean (SD) change in PAV for the entire vessel was -0.98% (3.15%), with a median of -0.79% (97.5% CI, -1.21% to -0.53%) (P<.001 vs baseline). The mean (SD) change in atheroma volume in the most diseased 10-mm subsegment was -6.1 (10.1) mm3, with a median of -5.6 mm3 (97.5% CI, -6.8 to -4.0 mm3) (P<.001 vs baseline). Change in total atheroma volume showed a 6.8% median reduction; with a mean (SD) reduction of -14.7 (25.7) mm3, with a median of -12.5 mm3 (95% CI, -15.1 to -10.5 mm3) (P<.001 vs baseline). Adverse events were infrequent and similar to other statin trials. CONCLUSIONS: Very high-intensity statin therapy using rosuvastatin 40 mg/d achieved an average LDL-C of 60.8 mg/dL and increased HDL-C by 14.7%, resulting in significant regression of atherosclerosis for all 3 prespecified IVUS measures of disease burden. Treatment to LDL-C levels below currently accepted guidelines, when accompanied by significant HDL-C increases, can regress atherosclerosis in coronary disease patients. Further studies are needed to determine the effect of the observed changes on clinical outcome. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00240318.

Aged↗

PubMed2006

Randomized trial of hormone therapy in women after coronary bypass surgery. Evidence of differential effect of hormone therapy on angiographic progression of disease in saphenous vein grafts and native coronary arteries.

Clinical trials indicate that hormone therapy (HT) does not decrease cardiovascular disease events or angiographic coronary disease progression. The effects of HT on SVG vessels are unknown. To determine whether postmenopausal hormone therapy started after coronary bypass surgery (CABG) decreases saphenous vein graft (SVG) disease, we conducted a multicenter randomized placebo-controlled angiographic study of estradiol+/-medroxyprogesterone started within 6 months of CABG in 83 postmenopausal women. Angiographic and intravascular ultrasound (IVUS) assessment at 6 and 42 months was planned to assess SVG disease progression. The study was stopped early following publication of the Women's Health Initiative Estrogen/Progestin study. Eighty-three subjects underwent a 6-month angiogram with 63 undergoing IVUS. Forty-five subjects completed the 42-month angiogram (20 underwent 42-month IVUS). In analysis of paired 6- and 42-month angiogram and IVUS studies, HT slowed angiographic progression of SVG disease assessed by mean percent stenosis (p<0.001), minimal lumen diameter (p=0.029), and total plaque volume (p=0.006). In contrast, HT accelerated disease progression in non-bypassed native coronary arteries (minimum lumen diameter, p=0.01). SVG disease and closure occurred in 38% subjects within 1-year post-CABG. The groups had similar frequency of cardiovascular events expect for angioplasty that occurred in eight HT compared to one placebo subject (p<0.05). In HT subjects angioplasty was indicated for native coronary arterial stenoses while in the placebo subject angioplasty was indicated for SVG stenosis. This study suggests that hormone treatment may slow SVG disease progression while accelerating atherosclerosis in non-bypassed native coronary arteries.

Coronary Angiography↗

PubMed2006

Left and right ventricular diastolic dysfunction as predictors of difficult separation from cardiopulmonary bypass.

PURPOSE: As the evaluation of diastolic function can be complex in the setting of a busy cardiac operating room, its assessment may benefit from an algorithmic approach using transesophageal echocardiography. We developed a diagnostic algorithm which was then applied in a series of cardiac surgery patients to determine whether moderate to severe left ventricular diastolic dysfunction (LVDD) and right ventricular diastolic dysfunction (RVDD) can predict difficult separation from cardiopulmonary bypass (DSB). METHODS: An algorithm using pulsed-wave Doppler interrogation of the mitral and tricuspid valve, the pulmonary and hepatic venous flow, and tissue Doppler interrogation of the mitral and tricuspid annulus was developed. The study was divided in two phases involving two groups of patients undergoing cardiac surgery. In phase I, echocardiographic evaluations of patients (n = 74) were used to test the reproducibility of the algorithm and to evaluate inter-observer variability using Cohen's kappa values which were calculated in three specific periods. In phase II, the algorithm was applied to a second group of patients (validation group, n = 179) to explore its prognostic significance. The primary end-point in phase II was DSB. RESULTS: In phase I, the kappa coefficients for LVDD and RVDD algorithms were 0.77 and 0.82, respectively. In phase II, moderate or severe degrees of LVDD were observed in 29 patients (16%) and moderate to severe RVDD was observed in 18 patients (10%) before cardiac surgery. Both moderate and severe LVDD (P = 0.017) and RVDD (P = 0.049) before surgery were observed more frequently in patients with DSB. CONCLUSION: Moderate and severe LVDD and RVDD can be identified with very good reproducibility, and both degrees of diastolic dysfunction are associated with DSB.

Aged↗

PubMed2006

The metabolic syndrome and its components and the long-term risk of death in patients with coronary heart disease.

BACKGROUND: The metabolic syndrome confers an increased risk of major cardiovascular events in individuals initially free from coronary heart disease (CHD). Presently, approximately 25% of the US population possesses the metabolic syndrome as defined using the National Cholesterol Education Program (NCEP) criteria. We sought to assess the impact of the metabolic syndrome and its individual components on intermediate-term and long-term outcomes in patients with CHD. METHODS: The CASS registry represents a database of 24,958 patients with suspected or proven CHD who underwent cardiac catheterization between 1974 and 1979. Mean long-term follow-up was 12.6 +/- 5.1 years. Metabolic syndrome was defined using modified definitions of the NCEP and World Health Organization (WHO) because high-density lipoprotein cholesterol measures were not available. RESULTS: We identified 3279 and 1080 patients with metabolic syndrome using our modified NCEP and WHO definitions, respectively. Adjusted long-term all-cause death was higher in patients with metabolic syndrome (hazard ratio [HR] 1.21, 95% CI 1.14-1.29; HR 1.56, 95% CI 1.43-1.70 for NCEP and WHO criteria, respectively). Similarly, long-term adjusted risk of cardiovascular death and intermediate-term risk of morbidity and mortality were higher in patients with the metabolic syndrome. Fasting blood glucose > or = 110 mg/dL was responsible for most of the increased risk associated with the metabolic syndrome (adjusted HR 1.47, 95% CI 1.39-1.56). CONCLUSIONS: The metabolic syndrome confers a higher risk of long-term death in patients with preexisting CHD, and dysglycemia appears to be responsible for most of the associated risk.

Analysis of Variance↗

PubMed2006

Quantification of the risk and predictors of hyperkalemia in patients with left ventricular dysfunction: a retrospective analysis of the Studies of Left Ventricular Dysfunction (SOLVD) trials.

BACKGROUND: Limited data are available to predict the occurrence of hyperkalemia. Risk assessment is complicated by the lack of consistency of definition between trials. METHODS: We conducted a retrospective analysis of the SOLVD to evaluate the incidence of hyperkalemia and the value of several baseline characteristics as predictors of hyperkalemia in patients with left ventricular dysfunction. RESULTS: The incidence of hyperkalemia was 6.0% and 1.1% using a definition of > or = 5.5 and > or = 6.0 mmol/L, respectively. Independent predictors of hyperkalemia (> or = 5.5 mmol/L) were randomization to enalapril, baseline serum creatinine, serum potassium, New York Heart Association functional class III or IV, a history of diabetes, and atrial fibrillation (all P < .05). The use of loop diuretics was also associated with an increased risk of hyperkalemia but only in patients included in the SOLVD prevention trial. Similar results were obtained when renal function was evaluated using the estimated creatinine clearance. CONCLUSIONS: The definition of hyperkalemia is important when evaluating its incidence in clinical trials. Renal dysfunction, baseline serum potassium, diabetes, atrial fibrillation, New York Heart Association functional class, and treatment with an angiotensin-converting enzyme inhibitor are factors associated with the development of hyperkalemia in patients with left ventricular dysfunction. More specifically, our results suggests that before initiating drugs that can cause hyperkalemia in patients with heart failure, a strong consideration should be given to calculate creatinine clearance and that patients with a creatinine clearance < 60 mL/min should undergo a close monitoring of their serum potassium to prevent the development of hyperkalemia.

Aged↗

PubMed2006

Temporal increases in subclinical levels of inflammation are associated with adverse clinical outcomes in patients with left ventricular dysfunction.

BACKGROUND: The implication of various cytokines in a subclinical inflammatory process has been documented in heart failure (HF). The role of temporal changes of more conventional markers of inflammation, such as the white blood cell (WBC) count, on clinical outcomes remains largely unknown. METHODS AND RESULTS: We performed a retrospective analysis of patients included in the Studies Of Left Ventricular Dysfunction that had documented eligibility at the baseline visit, a documented WBC count at baseline and at least 1 measurement during follow-up. We evaluated the association between variations in WBC count, WBC subfractions and mortality and non-fatal events. An increase in WBC count during follow-up compared with baseline was associated with a significantly higher risk of all-cause and cardiovascular (CV) mortality, HF mortality and arrhythmic death (all P < .05). A relative increase in the neutrophil count was associated with higher risk of all-cause and CV mortality, HF mortality and cardiac ischemic events (all P < .05). No significant interaction was present in regards to the etiology of HF. CONCLUSIONS: Temporal increases in WBC and neutrophil counts are associated with increased risks of death and CV events. This relationship appears to be independent of HF etiology.

Aged↗

PubMed2006

Biventricular diastolic filling patterns after coronary artery bypass graft surgery.

OBJECTIVE: We sought to study the evolution of biventricular filling properties after coronary artery bypass grafting. BACKGROUND: The evolution of diastolic function as defined with newer echocardiographic modalities after coronary artery bypass grafting surgery is unknown in patients with preoperative left ventricular diastolic dysfunction. METHODS: Transthoracic echocardiography was performed preoperatively and 48 hours and 6 months after coronary artery bypass grafting in 49 patients (randomized to milrinone [n = 25]) or placebo [n = 24]) with preoperative left ventricular diastolic dysfunction classified according to published criteria. Mild right ventricular diastolic dysfunction was defined as the ratio of early to atrial filling velocity of less than 1 in transtricuspid flow or the velocity of reversed atrial flow of greater than 50% of that of systolic flow in hepatic venous flow or the ratio of tricuspid annulus velocity during early and atrial filling of less than 1 if both the ratio of early to atrial filling velocity and the ratio of systolic to diastolic velocity was greater than 1 in hepatic venous flow. Moderate right ventricular diastolic dysfunction was diagnosed when there was a ratio of early to atrial filling velocity of greater than 1 with a ratio of systolic to diastolic velocity of less than 1. Severe right ventricular diastolic dysfunction was defined as a ratio of early to atrial filling velocity of greater than 1 associated with reversed systolic wave in hepatic venous flow. RESULTS: Moderate and severe left ventricular diastolic dysfunction increased from preoperatively to 48 hours after coronary artery bypass grafting from 8.2% to 53.7% and from 2.0% to 9.7%, respectively (P < .0001, 48 hours vs preoperatively for both), and the patterns at 6 months were similar to those observed preoperatively. Similar evolution over time was found for right ventricular diastolic dysfunction. CONCLUSIONS: In patients with preoperative left ventricular diastolic dysfunction, biventricular filling patterns are impaired initially but return to preoperative status 6 months after coronary artery bypass grafting.

Aged↗

PubMed2006

Dynamic right ventricular outflow tract obstruction in cardiac surgery.

BACKGROUND: Right ventricular outflow tract obstruction can be a cause of hemodynamic instability but it has not been described in non-congenital cardiac surgery. METHODS: The prevalence of right ventricular outflow tract obstruction was retrospectively studied in 670 consecutive patients undergoing cardiac surgery. Significant right ventricular outflow tract obstruction was diagnosed if the right ventricular systolic to pulmonary artery peak gradient was more than 25 mm Hg. The diagnosis was based on measurement of the right ventricular and pulmonary artery systolic pressure through the paceport and distal opening of the pulmonary artery catheter. To further validate the prevalence and the importance of right ventricular outflow tract obstruction, 130 patients were prospectively studied over a 12-month period. RESULTS: In the retrospective cohort, 6 patients (1%) undergoing various types of cardiac surgical procedures were found to have significant dynamic right ventricular outflow tract obstruction with a mean gradient of 31 +/- 4 mm Hg (26 to 35 mm Hg). In the prospective study significant dynamic right ventricular outflow tract obstruction was identified in 5 patients (4%) (average peak: 37 +/- 15 mm Hg; range: 27 to 60 mm Hg). The typical transesophageal echocardiography finding was end-systolic obliteration of the right ventricular outflow tract. In patients with significant dynamic right ventricular outflow tract obstruction, hemodynamic instability was present in 10/11 patients (91%). CONCLUSIONS: Right ventricular outflow tract obstruction is easily diagnosed using the paceport of the pulmonary artery catheter and should be considered as a potential cause of hemodynamic instability especially when transesophageal echocardiography reveals systolic right ventricular cavity obliteration.

Aged↗

PubMed2006

Cardiac investigation in patients with diabetes.

Most patients with type 2 diabetes die from heart disease. Screening for the presence of myocardial ischemia is of clinical importance in the management of this population. The pain response to ischemia can be either absent or blunted in diabetes, resulting in the absence of symptoms or an atypical presentation. Exercise electrocardiogram (ECG) should be the initial test in men who are able to exercise and have a normal resting ECG. Stress cardiac imaging should be the initial test in diabetic men with an abnormal resting ECG or who are not able to exercise. More widespread use of cardiac imaging is probably justified in diabetic women and patients with suspected coronary artery disease. Official guidelines for appropriate and cost-effective cardiac investigation should help physicians manage diabetic patients.

Coronary Artery Disease↗

PubMed2006

Antioxidants: the good, the bad and the ugly.

Inflammation has a fundamental role in mediating all stages of atherosclerotic disease. The key role of oxidation in linking lipids and inflammation to atherosclerosis is compelling and is supported by experimental evidence. However, the relevance of the antioxidant hypothesis for the treatment of patients with atherosclerosis has not been definitively proven. Results of randomized trials with 'antioxidant' vitamins have been disappointing, and there are potentially important problems associated with their use, including their potential pro-oxidant effects. Probucol has reduced postpercutaneous coronary intervention (PCI)-restenosis and progression of carotid atherosclerosis in clinical trials. The antioxidant vascular protectant AGI-1067 has also been effective at preventing atherosclerosis in all tested animal models. The nonintervened reference coronary segments of the PCI vessel demonstrated improvements with AGI-1067 in the Canadian Antioxidant Restenosis Trial-1 (CART-1), evidence supportive of a clinical effect on slowing atherosclerosis progression. Two trials test the antioxidant/anti-inflammatory hypothesis with AGI-1067; CART-2 assesses its value for the reduction of both atherosclerosis progression and post-PCI restenosis, and Aggressive Reduction of Inflammation Stops Events (ARISE), which is evaluating its effects on hard cardiovascular outcomes.

Angioplasty, Balloon, Coronary↗

PubMed2006

Prevention challenges: the era of atherosclerosis regression.

Statins slow atherosclerosis progression and can even induce atherosclerosis regression. The reduction of cardiovascular events with statins by approximately one-third demonstrates not only their clinical efficacy but also the unmet clinical need. The aging of the population and the epidemics of the metabolic syndrome and diabetes contribute to the increasing burden of atherosclerosis in society, and fuel the need for novel complementary therapies to further improve clinical outcomes. Some targets, such as acyl-coenzyme A:cholesterol acyltransferase inhibition, have yielded disappointing clinical results. In contrast, there is strong evidence linking lower high density lipoprotein (HDL) cholesterol levels and greater cardiovascular risk, thus providing the rationale for targeting HDL in the prevention and treatment of cardiovascular diseases. Therapeutic approaches include direct infusions of HDL cholesterol or HDL-mimetic agents, as well as the inhibition of cholesteryl ester transfer protein (CETP). CETP inhibition appears to be one particularly promising strategy. The CETP inhibitor torcetrapib increases plasma HDL cholesterol levels by 40% to 60%, while modestly decreasing low density lipoprotein (LDL) cholesterol. Combining the HDL cholesterol-elevating properties of a CETP inhibitor with the LDL cholesterol-lowering properties of a statin may offer improved outcomes over targeting LDL cholesterol alone. This hypothesis is being extensively evaluated in a comprehensive program that involves several imaging studies and a large-scale clinical end point trial. The additional cardiovascular protection required for patients with atherosclerosis or risk equivalents will likely be provided by therapies that go beyond LDL reduction.

Acyl Coenzyme A↗