Dark Chocolate Improves Coronary Vasomotion and Reduces Platelet Reactivity

Further information: Medical Treatment of Stable Angina from Cardiovascular Medicine, 3rd Edn*

Reported in this study [1] are the results of a double-blind, and investigator-initiated controlled study examining the effect of flavonoid-rich dark chocolate or flavonoid–free control chocolate on coronary endothelial vasomotion and platelet function in 22 heart transplant recipients. Using quantitative coronary angiography and cold-pressor testing, the authors assessed coronary vasomotion before and 2 hours after giving the participants 40 g of flavonoid-rich dark chocolate or cocoa-free chocolate.

Two hours after ingestion of flavonoid-rich chocolate, coronary artery diameter was increased significantly (from 2.36±0.51 to 2.51±0.59 mm, P<0.01), whereas it remained unchanged after control chocolate. Endothelium-dependent coronary vasomotion improved significantly after dark chocolate (4.5±11.4% vs. -4.3±11.7% in the placebo group, P=0.01). Platelet adhesion decreased from 4.9±1.1% to 3.8±0.8% (P=0.04) in the dark chocolate group, but remained unchanged in the control group. These results suggest that flavonoid-rich dark chocolate is effective in inducing coronary vasodilatation and improving coronary vasomotion and sheer-stress dependent platelet adhesion. Thus, they suggest a potential benefit on atherothrombosis. The observed improvements are significant and call for further study of flavonoid-rich dark chocolate.

An editorial [2] was published in the same issue of Circulation entitled “Is it the Dark in the Chocolate?” The authors warn that the term “dark chocolate” is misleading, and that despite evidence pointing to dark chocolate’s cardioprotective properties, the color and percent of cocoa have nothing to do with the flavonoid content of the chocolate. Many manufacturers use processing techniques that destroy flavonoids, and before it can be considered cardioprotective to consume “dark chocolate,” consumers must be given the flavonoid content of the chocolate on the label of the product.

[1] Flammer AJ, Hermann F, Sudano I, et al. Dark chocolate improves coronary vasomotion and reduces platelet reactivity. Circulation 2007;116:2376-82

[2] Hollenberg NK, Fisher NDL. Is it the Dark in the Chocolate? Circulation 2007;116:2360-62

Note: You may need subscriptions to access content from links on this page. You are responsible for obtaining these subscriptions.

* To view the online text from the book, please navigate to SpringerLink or use the DVD to access electronic content. SpringerLink is a subscription service. For further information, click here.

Job Strain and Risk of Acute Recurrent CHD Events

Further information: Medical Treatment of Stable Angina from Cardiovascular Medicine, 3rd Edn*

To learn more about the association of job strain on the risk of recurrent coronary heart disease (CHD) after a first myocardial infarction (MI), the investigators in this study [1] conducted a prospective cohort study in 972 men and women aged 35–59 years who returned to work after a first MI.

Patients were recruited between November 1995 and October 1997 and eligibility was determined by having had a first acute MI, having held a paid job in the 12 months before their MI, and having planned to return to work for at least 10 hours per week within 18 months after their MI. Job strain was defined as a work environment where psychological demands were high, but individuals had little opportunity to make decisions, work creatively, or develop their abilities. Patients were interviewed at baseline, approximately 6 weeks after returning to work, and at 2 and 6 years after returning to work. Several classes of characteristics were assessed as potential cofounders in multivariate models, and there were a number of factors considered within each of the following classes: sociodemographic factors, CHD risk factors, lifestyle factors, clinical prognostic factors, and other work environment factors. The outcome of the study was documented in 206 patients.

In the unadjusted analysis, chronic job strain was associated with recurrent CHD in the second period after 2.2 years of follow-up (hazard ratio [HR], 2.20; 95% confidence interval [CI], 1.32–3.66; respective event rates for patients exposed and unexposed to chronic job strain, 6.18 and 2.81 per 100 person-years). Chronic job strain remained an independent predictor of recurrent CHD in a multivariate model adjusted for 26 potentially confounding factors (HR, 2.00; 95% CI, 1.08–3.72).

The study found that chronic job strain significantly increased the risk of recurrent CHD among middle-aged patients who returned to work after a first MI, suggesting that preventative interventions aimed at reducing job strain might have a significant impact on recurrent CHD events. Further studies are required to establish optimal interventions, but this current information should be made available to practicing cardiac physicians and to occupational health service providers to enable them to help reduce job strain for workers returning to work after an MI.

[1] Aboa-Éboulé C, Brisson C; Maunsell E, et al. Job strain and risk of acute recurrent coronary heart disease events. JAMA 2007;298:1652-60

Note: You may need subscriptions to access content from links on this page. You are responsible for obtaining these subscriptions.

* To view the online text from the book, please navigate to SpringerLink or use the DVD to access electronic content. SpringerLink is a subscription service. For further information, click here.

Prasugrel Versus Clopidogrel in Patients with ACS

Further information: Medical Treatment of Unstable Angina, Acute Non-ST-Elevation Myocardial Infarction, and Coronary Artery Spasm from Cardiovascular Medicine, 3rd Edn*

In the TRITON-TIMI 38 trial, 13,608 patients with acute coronary syndromes (ACS) who were slated for percutaneous coronary intervention (PCI) were randomized to receive either prasugrel (60 mg loading dose and 10 mg daily maintenance dose) or clopidogrel (300 mg loading dose and 75 mg daily maintenance dose) for 6–15 months [1]. Prasugrel, like clopidogrel, is an inhibitor of adenosine diphosphate (ASP)-induced platelet aggregation.

Primary endpoint was death from cardiovascular causes, nonfatal myocardial infarction (MI), or nonfatal stroke, and the primary endpoint occurred in 9.9% of patients treated with prasugrel, but in 12.1% of patients receiving clopidogrel (P<0.0001). Secondary endpoints included major bleeding and stent thrombosis.

Significant reductions were found in the prasugrel group in the rates of MI, urgent target-vessel revascularization, and in stent thrombosis. Twice the rate of the events was found in the clopidogrel over the prasugrel group. However, in the prasugrel group, there was an increased risk of major bleeding, including fatal bleeding, in patients with a prior stroke or transient ischemic attack, and patients older than 75 years or age or who weighed less than 69 kg had more bleeding.

The data support the hypothesis that the use of the platelet inhibitor prasugrel is more effective at preventing ischemic events than is the inhibition conferred by a standard regimen of clopidogrel. However, the beneficial effect is accompanied by an increase in the rate of major bleeding. An important determination in the evaluation of the drug is whether those at higher risk for bleeding can be clearly identified before a decision is made on which drug to use.

[1] Wiviott SD, Braunwald E, McCabe CH, et al. Prasugrel versus clopidogrel in patients with acute coronary syndromes. N Engl J Med 2007;357:2001-15

Note: You may need subscriptions to access content from links on this page. You are responsible for obtaining these subscriptions.

* To view the online text from the book, please navigate to SpringerLink or use the DVD to access electronic content. SpringerLink is a subscription service. For further information, click here.

GDF-15 for Risk Stratification and Selection of an Invasive Treatment Strategy in Non-ST-Elevation ACS

Further information: Medical Treatment of Unstable Angina, Acute Non-ST-Elevation Myocardial Infarction, and Coronary Artery Spasm from Cardiovascular Medicine, 3rd Edn*

The Framingham and Fast Revascularization During Instability in Coronary Artery Disease (FRISC) II trial was the first randomized study to convincingly demonstrate that an early invasive strategy in patients (vs noninvasive strategy) was associated with improved outcomes. However, because results regarding low-risk patients that were revealed in subsequent trials did not confirm the results of the FRISC data, there has been an ongoing debate regarding the preferred treatment strategy for patients with acute coronary syndromes (ACS) without ST-segment elevation (NSTEMI). The primary end point of FRISC-II was a composite of death or myocardial infarction (MI) at 6 months.

The present study [1] used the 2-year follow-up data of the FRISC-II database to allow comparisons with previous reports of biomarkers as tools for risk stratification and therapeutic decision making. In the present study, the authors hypothesized that the circulating level of growth differentiation factor 15 (GDF-15) may improve risk stratification. GDF-15 is a member of the transforming growth factor beta cytokine superfamily and is induced in the myocardium after ischemia and reperfusion injury.
In this study, GDF-15 and other biomarkers were measured on admission in 2079 patients.

In 770 patients (37.0%), GDF-15 was moderately elevated (1200–1800 ng/l (37%); in 493 patients (23.7%) GDF-15 was highly elevated at >1800 ng/l. Elevated levels of GDF-15 independently predicted the risk of the composite end point of death or recurrent myocardial infarction in the conservative group (P=0.016), but not in the invasive group. The occurrence of the composite end point was reduced by the invasive strategy at GDF-15 levels >1800 ng/l (hazard ratio, 0.49; 95% confidence interval (CI), 0.33–0.73; P=0.001), between 1200 and 1800 ng/l (hazard ratio, 0.68; 91% CI, 0.46–1.00; P=0.048), but not <1200 ng/l (hazard ratio 1.06; 95% CI, 0.68–1.65; P=0.81). Patients with ST-segment depression or a troponin T level >0.01 µg/l with a GDF-15 level <1200 ng/l did not benefit from invasive strategy.

Although the present study shows that using levels of GDF-15 as a diagnostic tool for risk stratification to allow one to identify those patients with NSTEMI who will benefit from an invasive strategy, the authors suggest that only a prospective randomized trial would be able to validate the findings.

[1] Wollert KC, Kempf T, Lagerqvist B et al. Growth differentiation factor 15 for risk stratification and selection of an invasive treatment strategy in non-st-elevation acute coronary syndrome. Circulation 2007;116:1540-48

Note: You may need subscriptions to access content from links on this page. You are responsible for obtaining these subscriptions.

* To view the online text from the book, please navigate to SpringerLink or use the DVD to access electronic content. SpringerLink is a subscription service. For further information, click here.

Metabolic Syndrome Increases Operative Mortality in Patients Undergoing Coronary Artery Bypass Grafting Surgery

Further information: Percutaneous Coronary Intervention from Cardiovascular Medicine, 3rd Edn*

The Metabolic Syndrome (MS) largely results from the accumulation of abdominal fat and is characterized by insulin resistance, hypertriglyceridemia, low high-density lipoprotein (HDL) cholesterol, and a pro-inflammatory and pro-thrombotic state. Although components of the MS, such as diabetes and obesity, have been suspected as being factors in the mortality of patients undergoing coronary artery bypass graft surgery (CABG), this study [1] is the first to report that MS is a strong and independent risk factor in the mortality of patients after CABG.

Between 2000 and 2004, 5304 patients who underwent CABG in Canada were analyzed. Of that number, 2411 (46%) of those patients met the National Cholesterol Education Program-Adult Treatment Panel III criteria for MS.

Reported mortality after CABG was 2.4 % in patients with MS and 0.9% in patients without MS (P<0.0001). The MS was a strong independent predictor of operative mortality (relative risk [RR] 3.04; 95% confidence interval [CI] 1.73–5.32, P=0.0001). After adjusting for other risk factors, the risk of mortality was increased 2.69-fold (95% CI 1.43–5.06; P=0.002) in patients with MS and diabetes and 2.36-fold (95% CI 1.26–4.41; P=0.007) in patients with MS and no diabetes. There was no significant increase in patients with diabetes, but no MS.

Based on the evaluation of the results of this study, additional studies are warranted. It is necessary to understand the mechanisms responsible for the relationship between the MS and mortality after CABG, and because components of the MS are both preventable and treatable, it is important to recognize the components that should be targeted therapeutically in patients with CAD who are planning CABG.

[1] Echahidi N, Pibarot P, Després J-P, et al. Metabolic syndrome increases operative mortality in patients undergoing coronary artery bypass grafting surgery. J Am Coll Cardiol 2007;50:843-51

Note: You may need subscriptions to access content from links on this page. You are responsible for obtaining these subscriptions.

* To view the online text from the book, please navigate to SpringerLink or use the DVD to access electronic content. SpringerLink is a subscription service. For further information, click here.

Outcomes of Stent Thrombosis and Restenosis During Extended Follow-Up of BMS Patients

Further information: Percutaneous Coronary Intervention from Cardiovascular Medicine, 3rd Edn*

In percutaneous coronary intervention, two types of stents can be used to supplement balloon angioplasty. One stent is a bare-metal stent (BMS) and the other is a drug-eluting stent (DES). The major shortcoming of BMS has been that approximately 20% of native vessel and 30% of saphenous vein graft patients developed angiographic restenosis from neointimal hyperplasia. At least half of these patients required revascularization. The DES was developed to suppress neointimal hyperplasia and nearly replaced the use of BMS. However, even though restenosis became infrequent, another problem emerged with DES in the form of stent thrombosis, and that can result in myocardial infarction (MI) or death. Thus, there has been resurgence in the use of BMS. Although the incidence of early BMS thrombosis has been extensively studied, the incidence of BMS thrombosis during long-term follow-up has not.

The authors of this paper [1] performed an analysis of a large cohort of patients treated with BMS and dual antiplatelet therapy between 1994 and 2000. The cumulative incidence of stent thrombosis was 0.5% at 30 days (95% confidence interval [CI], 0.3–0.7%), 0.8% at one year (95% CI, 0.6–1.1%), and 2.0% at 10 years (95% CI, 1.5–2.5%). Risk of late (30 days to 1 year) and very late (>1 year) BMS thrombosis was increased among patients considered off label for drug-eluting stent use (P=0.024). When saphenous vein graft interventions were excluded, however, risk after off-label use was not significantly increased (P=0.23). Other correlates included vein graft intervention, prior MI, peripheral vascular disease, and ulcerated lesion (P=0.001). Mortality increased after late and very late BMS thrombosis during the first 30 days [hazard ratio (HR), 22 (95% CI, 3.1–159) and 40 (95% CI, 15–107), respectively]. The 10-year incidence of clinical restenosis was 18.1 % (95% CI, 16.5–19.7%), presenting with MI in 2.1% (95% CI, 1.6–2.6%). Restenosis presenting with MI was associated with increased mortality compared with no restenosis (HR. 2.37; P<0.001) and with restenosis with a non-MI presentation (HR, 2.42; P=0.001). The risk of BMS thrombosis during long-term follow-up is significant and is increased in patients treated for an off-label DES indication. The incidence of MI caused by BMS restenosis (2.1% at 10 years) is similar to the combined incidence of early, late, and very late stent thrombosis (2.0% at 10 years). Therefore, the tendency to increase use of BMS in place of DES may not solve the safety issues that occurred during long-term follow-up of DES patients. The decision should be made according to the relative risks of restenosis and thrombosis on the basis of lesion-specific and patient-specific variables.

[1] Doyle B, Rihal CS, O’Sullivan CJ, et al. Outcomes of stent thrombosis and restenosis during extended follow-up of patients with bare-metal coronary stents. Circulation 2007;116:2391-98

Note: You may need subscriptions to access content from links on this page. You are responsible for obtaining these subscriptions.

* To view the online text from the book, please navigate to SpringerLink or use the DVD to access electronic content. SpringerLink is a subscription service. For further information, click here.

High-Dosed Melphalan Versus Melphalan plus Dexamethasone for AL Amyloidosis

Further information: Restrictive Cardiomyopathy from Cardiovascular Medicine, 3rd Edn*

This study [1] was a randomized trial comparing high-dose IV melphalan plus autologous hematopoietic stem-cell transplantation (AHSCT) with standard-dose melphalan plus high-dose dexamethasone (M/D) in patients with immunoglobulin-light chain (AL) Amyloidosis. Fifty patients aged 18 to 70 years who had biopsy-proven systemic AL Amyloidosis were enrolled in each of two groups. However, 13 patients who were assigned to the AHSCT group did not undergo AHSCT because of early death, inadequate stem-cell harvest, or patient refusal. Nine of 37 patients (24%) who underwent AHSCT died within 100 days. In the M/D group, two early deaths and five late deaths occurred before day 130. M/D patients received a median of 12 cycles (range, 0-25) of therapy. Hematologic and organ-function responses were similar in the two groups. In intent-to-treat analysis, medial overall survival was 56.9 months in the M/D arm and 22.2 months in the AHSCT arm (P=0.04). In a per-protocol analysis that was performed in patients who survived for 6 months or longer and who received their assigned treatment (28 AHSCT and 37 M/D patients), no significant advantage was observed for either therapy. Therefore, the authors concluded that there was no superior outcome with high-dose melphalan plus AHSCT treatment than with standard-dose melphalan plus dexamethasone.

[1] Jaccard A, Moreau P, Leblond V, et al. High-dose melphalan versus melphalan plus dexamethasone for AL amyloidosis. N Engl J Med 2007;357:1083-93

Note: You may need subscriptions to access content from links on this page. You are responsible for obtaining these subscriptions.

* To view the online text from the book, please navigate to SpringerLink or use the DVD to access electronic content. SpringerLink is a subscription service. For further information, click here.

Cardiomyopathy and Exercise Intolerance in Muscle Glycogen Storage Disease 0

Further information: Other Cardiomyopathies from Cardiovascular Medicine, 3rd Edn*

This paper [1] is a brief report of three siblings who each had muscle and heart glycogen deficiency caused by a homozygous stop mutation in the muscle glycogen synthase gene. The storage of glycogen is necessary for glucose homeostasis and energy supply during activity and sustained muscle work.

For this study, clinically relevant investigations were performed, and they included cardiac evaluation and exercise tests, neurological examinations, glucose tolerance tests, morphologic and biochemical analyses, molecular genetics, and protein analyses. Parents of the three siblings were healthy, consanguineous parents of Syrian origin. There was no muscle disease, cardiac disease, or diabetes mellitus in 22 investigated family members, and no occurrence of sudden death in the family. Sibling 1 developed normally until age 4, and at that time, he had an episode of tonic-clonic seizures. EKG, ultrasound, and a 3-day electrocardiographic recording showed no abnormalities. Computed tomography and magnetic resonance imaging of the brain showed no abnormalities, but electroencephalography showed partial complex epilepsy. He tired easily and had difficulty keeping up with physical activities of his peers. At 10.5 years, he died suddenly. Sibling 1 was evaluated 2 years after the death of his brother. He had been unable to keep up with the physical activity of his peers and had muscle symptoms similar to Patient 1. Cardiac and neurological examinations indicated cardiac and skeletal muscle disease. Patient was treated with bisoprolol for cardiac protection. Sibling 3 had no symptoms and a normal psychomotor development. However, a cardiac examination indicated cardiac involvement, and after a skeletal-muscle biopsy was performed, she was started on cardio protective medication. At 8 years of age, sibling 4 had no symptoms.

The authors suggest that the profound skeletal- and cardiac-muscle glycogen deficiency caused by mutations in the muscle glycogen synthase gene be termed “Muscle Glycogen Storage Disease 0″. The study describes an inborn error of metabolism with zero muscle glycogen storage that could be easily identified by a routine histochemical investigation of muscle tissue in children and adolescents with obvious muscle symptoms, and also in those who have myocardial disease or epilepsy.  Muscle tissue examination should also be included in the forensic investigation of sudden death from cardiovascular causes or epilepsy.

[1] Kollberg G, Tulinius M, Gilljam T, et al. Cardiomyopathy and exercise intolerance in muscle glycogen storage disease 0. N Engl J Med 2007;357:1507-14

Note: You may need subscriptions to access content from links on this page. You are responsible for obtaining these subscriptions.

* To view the online text from the book, please navigate to SpringerLink or use the DVD to access electronic content. SpringerLink is a subscription service. For further information, click here.