Cardiovascular literature reading 20,110,126

January 26, 2011
1, Early Cigarette Smoking Associated with Breast Cancer smoking women with early breast cancer moderate increase. 2002 Nurses Health Study that smoking, the risk of breast cancer in women increased slightly. The Conclusion: Smoking> 25 / d,> 35 years, started smoking at age <18 years of age, compared with never smokers, the risk increased 1.25 times. Period before and started smoking before the first birth, more dangerous. Started smoking after menopause the risk is slightly increased. Exposed to secondhand smoke, and no increased risk.
Young female patients who smoke may benefit from knowing that early smoking is associated with a modest increase in breast cancer risk, according to an Archives of Internal Medicine study.
Researchers analyzing updated data from the Nurses Health Study report that they have confirmed their 2002 finding of a slight elevation in breast cancer risk associated with smoking. During some 3 million person-years of follow-up between 1976 and 2006, women who smoked more than 25 cigarettes per day for more than 35 years and began smoking before age 18 had a hazard ratio for invasive breast cancer of 1.25, compared with never-smokers.
The effect was stronger when smoking began before the woman first birth and before menopause. Postmenopausal smoking was associated with a slightly decreased risk. There was no apparent increased risk from exposure to secondhand smoke. [Archives of Internal Medicine article]
2, Behavioral Therapy Prevents Recurrences of Cardiovascular Events in Trial
behavioral therapy to prevent recurrence of cardiovascular events. Reduce the pressure to reduce recurrent cardiovascular events in patients with CHD. 350 CHD patients were randomly divided into conventional therapy and conventional therapy group cognitive-behavioral therapy group. Behavior therapy group, psychologist or nurse for more than one year a total of 202 hours of group discussions, the main treatment is to reduce daily stress, time urgency and hostility. After eight years of follow-up. Intervention group for the first time and then reduce cardiovascular events 41%, MI recurrence by 45%. All-cause mortality in both groups were not significantly different.
authors speculate that cognitive-behavioral therapy may reduce the patient behavior and emotional responses, so reducing the cardiovascular burden of psycho-physiological system. They roughly estimated 10 per treatment to prevent one case of cardiovascular events.
Cognitive-behavioral therapy, with a focus on stress management, is associated with fewer recurrent cardiovascular events in patients with coronary heart disease, according to an Archives of Internal Medicine study.

Some 350 adults who had recently had a coronary heart disease event were randomized to either usual care alone or usual care plus cognitive-behavioral therapy. Psychologists and nurses led 20 2-hour group sessions over 1 year. The therapy emphasized ways to reduce daily stress, time urgency, and hostility.
Over 8 years follow-up, the intervention group experienced 41% fewer first recurrent cardiovascular events and 45% fewer recurrent myocardial infarctions, compared with the control group. All -cause mortality did not differ significantly between groups.
The authors speculate that the CBT group may have reduced their behavioral and emotional reactivity, “which would lead to less psychophysiologic burden on the cardiovascular system.” They estimate that roughly 10 people would need to be treated in order to prevent one cardiovascular event. [Archives of Internal Medicine article]
3, Can We Identify Unstable Coronary Plaques Before They Rupture?
in unstable coronary plaque rupture before the recognition it?
IVUS revealed some predict the characteristics of plaque rupture, but clinical application is still a long way to go.
According to the regression of the study, many of MI and ACS criminals are those non-flow limiting lesions of plaque rupture, resulting in rapidly progressive thrombosis, blood vessel blockage.
this prospective, multicenter, corporate-funded research selected 697 cases (mean age 58 years; 24% female; 17% with DM) due to the success of ACS patients undergoing PCI. In order to identify disease-specific factors that predict recurrence of events, the researchers also all the major epicardial coronary artery on the proximal 6-8 cm of gray-scale and frequency IVUS, with a median follow-up of 3.4 years.
IVUS-related complication rate was 1.6%, including 10 cases of arterial dissection and 1 case of perforation, resulting in three cases of non-fatal MIs (0.4%). 3-year follow-up, the estimated cumulative MACEs rate is 20%, including recurrent angina hospitalization (18%), MI (3%), cardiac death (2%). Half of which is due to the primary lesion criminals, half is due to lesions caused by non-indigenous offenders.
in lesions caused by non-indigenous offenders in the case of subsequent MACE, the average baseline angiography stenosis was 32%, follow-up was 65%. Independent predictors of events that characterized the baseline IVUS plaque burden> 70% (hazard ratio, 5.03), thin fibrous cap (HR, 3.35), and minimum lumen area <4.0 mm2 (HR, 3.21). With the three characteristics of MACE events occurred 18% of lesions, rather than a sub-3 characteristics of the lesions, MACE occurred in <1%.
Intravascular ultrasound uncovers some predictive plaque characteristics, but clinical application of the findings is still a long way off.
According to retrospective studies, many (if not most) lesions responsible for acute myocardial infarction (MI) and other acute coronary syndromes (ACS) are non flow-limiting plaques that rupture, causing rapid progression, thrombosis, and vessel obstruction. This prospective, multicenter, industry-sponsored study included 697 patients (mean age, 58; 24% women; 17% with diabetes) who underwent successful percutaneous coronary intervention for ACS. To identify lesion-specific factors predictive of recurrent events, investigators performed both gray-scale and radiofrequency intravascular ultrasound (IVUS) of the proximal 6 8 cm of all major epicardial coronary arteries. Median follow-up was 3.4 years.
IVUS-related complications occurred in 1.6% of patients and included 10 dissections and 1 perforation, causing 3 nonfatal MIs (0.4%). At 3 years, the estimated cumulative rate of major adverse cardiovascular events (MACEs) was 20%, including rehospitalization for recurrent angina (18%), MI (3%), and cardiac death (2%). Of the events, about half were attributed to the original culprit lesion and half to nonculprit lesions.
In the nonculprit lesions judged responsible for subsequent MACE, mean angiographic stenosis was 32% at baseline and 65% at follow-up. Baseline IVUS characteristics that independently predicted events were plaque burden> 70% (hazard ratio, 5.03), thin-cap fibroatheroma (HR, 3.35), and minimal luminal area of ??<4.0 mm2 (HR, 3.21). A MACE occurred in 18% of lesions that had all three of these characteristics and in <1% of lesions with none of them.
Comment: These investigators are the first to use ultrasound to prospectively examine nonobstructive lesion characteristics predictive of subsequent adverse cardiac events. They found that lesions with a large plaque burden, small luminal area, and thin cap are associated with the highest risk for causing later events. Although these findings are mechanistically interesting, their specificity is low, IVUS conferred procedural risk, and the appropriate therapeutic approach to these lesions is uncertain. Therefore, the strategy is presently unsuitable for clinical application. [Howard C. Herrmann, MD. Journal Watch Cardiology January 19, 2011]
4, Candesartan vs. Losartan for Heart Failure < br />
candesartan vs losartan HF. Class effect of ARB questioned. ARB with different affinity AT1 different effect on blood pressure are also different.
taking losartan with HF compared with those who serve the young people candesartan, HF is not too heavy, less treatment to achieve the target dose. 1-year survival rate: 90% of candesartan, losartan 83%. 5-year survival, respectively, 61% vs 44%. More variable, bias correction analysis, losartan higher risk of death, vs candesartan (HR1.43, 95% CI :1.23-1 .65; P <0.001)
a class of drugs internal, between the drugs and medicines have risks and benefits are important differences, many examples, but if there is no evidence to the contrary, guidelines generally believed that the single trial found the drug is a class effect.
this case, if the choice is a toss-ARB, candesartan preference.
Disturbing findings from a registry study call into question the class effects of angiotensin-receptor blockers.
Although angiotensin II receptor blockers (ARBs) are widely used to treat heart failure ( HF), different agents have not been directly compared. However, ARBs vary in their affinity for the AT1 receptor and in their effects on blood pressure. These investigators used data from theSwedish Heart Failure Registry to assess the comparative effectiveness of candesartan and losartan, the ARBs most often prescribed in the cohort, with respect to all-cause mortality.
Of 30,254 registered patients with HF, 2639 received candesartan, and 2500 received losartan. Compared with losartan recipients, candesartan recipients were younger, had less-severe heart failure, and were less likely to reach the target dose of the medication. One-year survival was 90% in candesartan recipients and 83% in losartan recipients; 5-year survival was 61% and 44%, respectively. In multivariable, propensity-adjusted analysis, losartan conferred a significantly higher risk for death compared with candesartan (hazard ratio, 1.43; 95% confidence interval, 1.23 1.65; P <0.001).
Comment: Despite many examples of important differences in risks and benefits within drug classes, guideline authors generally assume that individual drug trial findings are class effects in the absence of evidence to the contrary. The present findings raise the troubling prospect that the results of a trial of one ARB cannot be generalized to another ARB. But how to apply them in practice? The authors suggest that their findings are not strong enough to affect clinical decision-making. The evidence is indeed more exploratory than definitive, but it merits concern. We need additional direct comparisons. In the meantime, if the choice of ARB in our patients with HF is a toss-up, we should have a preference for candesartan. [Harlan M. Krumholz, MD, SM. Journal Watch Cardiology January 19, 2011]
Citation (s):
Eklind-Cervenka M et al. Association of candesartan vs losartan with all-cause mortality in patients with heart failure. JAMA 2011 Jan 12; 305:175.
5, THE ORIGINAL COURAGE TRIAL
COURAGE study: 2287 cases of myocardial ischemia and significant coronary artery disease specifically in patients randomly assigned to optimal medical therapy (OMT) group or the PCI OMT group. The median follow-up time was 4.6 years. The primary end point – death or nonfatal MI two similar, PCI group slightly higher than the OMT group (19.0% vs. 18.5%; P = 0.62). On death, nonfatal MI, or ACS hospitalization, or quality of life (follow-up report) is concerned, PCI group there is no advantage.
As reported in 2007 in the New England Journal of Medicine, 2287 patients with objective evidence of myocardial ischemia and significant epicardial coronary artery disease were randomized to receive either optimal medical therapy (OMT) alone or percutaneous coronary intervention (PCI) plus OMT. During a median follow-up of 4.6 years, incidence of the primary endpoint – death or nonfatal myocardial infarction (MI) – was statistically similar in the two groups, but slightly higher with PCI than with OMT alone (19.0 % vs. 18.5%; P = 0.62). PCI also showed no advantage in the individual endpoints of death, nonfatal MI, or hospitalization for acute coronary syndrome, or (as reported subsequently) in quality of life.
THE NUCLEAR SUBSTUDY
In 2008, the COURAGE nuclear substudy (the first substudy from the trial) was published in Circulation. It involved 314 patients who underwent rest / stress myocardial perfusion single-photon-emission computed tomography (MPS), both before treatment and 6 to 18 months after randomization. The primary endpoint was defined as 5% reduction in myocardial ischemia at follow-up. The investigators reported that the PCI group had a significantly greater mean reduction in ischemic myocardium than the OMT-alone group (2.7% vs. 0.5%) and a significantly higher percentage of patients who achieved the 5% reduction endpoint (33% vs. 19%). The 5% reduction in ischemic burden was not significantly associated with better outcome in a multivariable analysis, and as the authors acknowledge, their study “was not powered to examine differences in clinical outcomes according to change in ischemic burden.” In the conclusion of their abstract, the authors say that “adding PCI to OMT resulted in greater reduction in ischemia compared with OMT alone. “They further state,” Our findings suggest a treatment target of 5% ischemia reduction with OMT with or without coronary revascularization. “
THE LEAP IN LOGIC
The authors conclusion is quite provocative. The full trial showed that patients with ischemia did equally well with an initial strategy of PCI or OMT. In the substudy, the authors assert that, given their results, clinicians should seek a target of 5% ischemia reduction, implying that these patients should undergo MPS, that therapeutic strategies should be guided over time by the MPS results, and that PCI is better than OMT alone in reducing ischemia. How did the authors make this leap? Their reasoning appears to be as follows:
The PCI strategy was better than OMT in reducing ischemic burden by 5% in the unadjusted but not the multivariable analysis. On the basis of the unadjusted result, the authors conclude that reducing ischemic burden by 5% should be a treatment goal and, by their assertion that PCI is better than OMT in reducing ischemic burden (although they do not even do an appropriate multivariable analysis for that question), that PCI plus OMT would be better than OMT alone .
UNTANGLING THE LOGIC
The substudy was not designed to test whether targeting treatment to a certain threshold of ischemia reduction benefits patients; the findings simply suggest (but do not prove) that the PCI strategy was more effective than OMT alone in reducing ischemic burden. Given that the subjects in this substudy represented a convenience sample of patients, this suggestion is weak: The groups that were compared were not obtained by randomization (a nuance that is acknowledged but easy to miss), and the authors do not control for baseline differences in the groups. However, even if PCI reduced ischemic burden, PCI did not significantly reduce the risk for clinical events or substantially affect symptoms in the overall trial. Moreover, in the substudy, the relative reduction of ischemic burden did not reduce the risk for events according to the multivariable analysis, which is important because patients who had a reduction may have been different at baseline from those who did not. Moreover, if ischemic-burden reduction had really mattered, the trial should have shown evidence of clinical differences between the two treatment groups.Another issue is that ischemic burden is a surrogate for clinical outcomes that affect patients. Surrogate endpoints can be useful when we do not have clinical outcomes to examine; however, clinical outcomes were reported in COURAGE. Perhaps the most important finding in this substudy is the failure of ischemic burden as a surrogate endpoint. If COURAGE had defined ischemic-burden reduction as the primary endpoint, and PCI were truly associated with a greater reduction in ischemic burden, then the PCI advocates would have declared victory. However, the findings identified no difference between the groups in the major clinical endpoints that were measured, and such a surrogate endpoint would have been useless in predicting the outcome of the trial. This finding suggests to me that treating to a target reduction in ischemic burden is not a useful surrogate.Furthermore, for the investigators to track ischemic burden over time, the participants had to be around for the follow-up study. They are, then, patients who survived at least 6 months and, in some cases, up to 18 months. No information is provided about who in this substudy was lost to follow-up or did not return for a follow-up MPS study, or whether the time to the follow-up MPS was similar in both intervention groups – or in the group classified by the amount of ischemia reduction. That information is essential to evaluating the results.A BETTER LINE OF INQUIRY What nuclear substudy might have been most useful to a clinician? Personally , I would have wanted to know whether PCI was better than OMT alone in patients with a large ischemic burden at baseline. Such an analysis would have investigated an interaction: whether the difference between the PCI and OMT-alone groups varied according to baseline ischemic burden . A reasonable hypothesis would have been that the PCI strategy was superior in patients who initially had the most ischemia according to MPS. Unfortunately, the investigators did not do that analysis.Do you think this COURAGE substudy complements the original trial? How do you assess the authors suggestion to target a certain reduction in ischemic burden for patients like those in this trial? How would you have written the conclusion to the abstract? Please join the discussion underway on CardioExchange. [Harlan M. Krumholz, MD, SM. Journal Watch Cardiology January 19, 2011]