[RESEARCH] Vascular events in healthy older women receiving calcium supplementation: randomised controlled trial
Objective To determine the effect of calcium supplementation on myocardial infarction, stroke, and sudden death in healthy postmenopausal women.
Design Randomised, placebo controlled trial.
Setting Academic medical centre in an urban setting in New Zealand.
Participants 1471 postmenopausal women (mean age 74): 732 were randomised to calcium supplementation and 739 to placebo.
Main outcome measures Adverse cardiovascular events over five years: death, sudden death, myocardial infarction, angina, other chest pain, stroke, transient ischaemic attack, and a composite end point of myocardial infarction, stroke, or sudden death.
Results Myocardial infarction was more commonly reported in the calcium group than in the placebo group (45 events in 31 women v 19 events in 14 women, P=0.01). The composite end point of myocardial infarction, stroke, or sudden death was also more common in the calcium group (101 events in 69 women v 54 events in 42 women, P=0.008). After adjudication myocardial infarction remained more common in the calcium group (24 events in 21 women v 10 events in 10 women, relative risk 2.12, 95% confidence interval 1.01 to 4.47). For the composite end point 61 events were verified in 51 women in the calcium group and 36 events in 35 women in the placebo group (relative risk 1.47, 0.97 to 2.23). When unreported events were added from the national database of hospital admissions in New Zealand the relative risk of myocardial infarction was 1.49 (0.86 to 2.57) and that of the composite end point was 1.21 (0.84 to 1.74). The respective rate ratios were 1.67 (95% confidence intervals 0.98 to 2.87) and 1.43 (1.01 to 2.04); event rates: placebo 16.3/1000 person years, calcium 23.3/1000 person years. For stroke (including unreported events) the relative risk was 1.37 (0.83 to 2.28) and the rate ratio was 1.45 (0.88 to 2.49).
Conclusion Calcium supplementation in healthy postmenopausal women is associated with upward trends in cardiovascular event rates. This potentially detrimental effect should be balanced against the likely benefits of calcium on bone.
Trial registration Australian Clinical Trials Registry ACTRN 012605000242628.
[RESEARCH] Effects of different regimens to lower blood pressure on major cardiovascular events in older and younger adults: meta-analysis of randomised trials
Objective To quantify the relative risk reductions achieved with different regimens to lower blood pressure in younger and older adults.
Design Meta-analyses and meta-regression analyses used to compare the effects on the primary outcome between two age groups (<65 v ≥65 years). Evidence for an interaction between age and the effects of treatment sought by fitting age as a continuous variable and estimating overall effects across trials.
Main outcome measures Primary outcome: total major cardiovascular events.
Results 31 trials, with 190 606 participants, were included. The meta-analyses showed no clear difference between age groups in the effects of lowering blood pressure or any difference between the effects of the drug classes on major cardiovascular events (all P≥0.24). Neither was there any significant interaction between age and treatment when age was fitted as a continuous variable (all P>0.09). The meta-regressions also showed no difference in effects between the two age groups for the outcome of major cardiovascular events (<65 v ≥65; P=0.38).
Conclusions Reduction of blood pressure produces benefits in younger (<65 years) and older (≥65 years) adults, with no strong evidence that protection against major vascular events afforded by different drug classes varies substantially with age.
[RESEARCH] Cumulative funnel plots for the early detection of interoperator variation: retrospective database analysis of observed versus predicted results of percutaneous coronary intervention
Objective To use funnel plots and cumulative funnel plots to compare in-hospital outcome data for operators undertaking percutaneous coronary interventions with predicted results derived from a validated risk score to allow for early detection of variation in performance.
Design Analysis of prospectively collected data.
Setting Tertiary centre NHS hospital in the north east of England.
Participants Five cardiologists carrying out percutaneous coronary interventions between January 2003 and December 2006.
Main outcome measures In-hospital major adverse cardiovascular and cerebrovascular events (in-hospital death, Q wave myocardial infarction, emergency coronary artery bypass graft surgery, and cerebrovascular accident) analysed against the logistic north west quality improvement programme predicted risk, for each operator. Results are displayed as funnel plots summarising overall performance for each operator and cumulative funnel plots for an individual operator’s performance on a case series basis.
Results The funnel plots for 5198 patients undergoing percutaneous coronary interventions showed an average observed rate for major adverse cardiovascular and cerebrovascular events of 1.96% overall. This was below the predicted risk of 2.06% by the logistic north west quality improvement programme risk score. Rates of in-hospital major adverse cardiovascular and cerebrovascular events for all operators were within the 3 upper control limit of 2.75% and 2 upper warning limit of 2.49%.
Conclusion The overall in-hospital major adverse cardiovascular and cerebrovascular events rates were under the predicted event rate. In-hospital rates after percutaneous coronary intervention procedure can be monitored successfully using funnel and cumulative funnel plots with 3 control limits to display and publish each operator’s outcomes. The upper warning limit (2 control limit) could be used for internal monitoring. The main advantage of these charts is their transparency, as they show observed and predicted events separately. By this approach individual operators can monitor their own performance, using the predicted risk for their patients but in a way that is compatible with benchmarking to colleagues, encapsulated by the funnel plot. This methodology is applicable regardless of variations in individual operator case volume and case mix.
[RESEARCH] Duplex ultrasonography, magnetic resonance angiography, and computed tomography angiography for diagnosis and assessment of symptomatic, lower limb peripheral arterial disease: systematic review
Objectives To determine the diagnostic accuracy of duplex ultrasonography, magnetic resonance angiography, and computed tomography angiography, alone or in combination, for the assessment of lower limb peripheral arterial disease; to evaluate the impact of these assessment methods on management of patients and outcomes; and to evaluate the evidence regarding attitudes of patients to these technologies and summarise available data on adverse events.
Design Systematic review.
Methods Searches of 11 electronic databases (to April 2005), six journals, and reference lists of included papers for relevant studies. Two reviewers independently selected studies, extracted data, and assessed quality. Diagnostic accuracy studies were assessed for quality with the QUADAS checklist.
Results 107 studies met the inclusion criteria; 58 studies provided data on diagnostic accuracy, one on outcomes in patients, four on attitudes of patients, and 44 on adverse events. Quality assessment highlighted limitations in the methods and quality of reporting. Most of the included studies reported results by arterial segment, rather than by limb or by patient, which does not account for the clustering of segments within patients, so specificities may be overstated. For the detection of stenosis of 50% or more in a lower limb vessel, contrast enhanced magnetic resonance angiography had the highest diagnostic accuracy with a median sensitivity of 95% (range 92-99.5%) and median specificity of 97% (64-99%). The results were 91% (89-99%) and 91% (83-97%) for computed tomography angiography and 88% (80-98%) and 96% (89-99%) for duplex ultrasonography. A controlled trial reported no significant differences in outcomes in patients after treatment plans based on duplex ultrasonography alone or conventional contrast angiography alone, though in 22% of patients supplementary contrast angiography was needed to form a treatment plan. The limited evidence available suggested that patients preferred magnetic resonance angiography (with or without contrast) to contrast angiography, with half expressing no preference between magnetic resonance angiography or duplex ultrasonography (among patients with no contraindications for magnetic resonance angiography, such as claustrophobia). Where data on adverse events were available, magnetic resonance angiography was associated with the highest proportion of adverse events, but these were mild. The most severe adverse events, although rare, were mainly associated with contrast angiography.
Conclusions Contrast enhanced magnetic resonance angiography seems to be more specific than computed tomography angiography (that is, better at ruling out stenosis over 50%) and more sensitive than duplex ultrasonography (that is, better at ruling in stenosis over 50%) and was generally preferred by patients over contrast angiography. Computed tomography angiography was also preferred by patients over contrast angiography; no data on patients' preference between duplex ultrasonography and contrast angiography were available. Where available, contrast enhanced magnetic resonance angiography might be a viable alternative to contrast angiography.
May 31 is 'World No Tobacco Day'
Filed under: Events
The WHO has declared tomorrow (May 31st) World No Tobacco Day, and the theme for this year is "smoke free environments." Smoking bans in public places are spreading rapidly across the country, and even more and more private homes are asking people to step outside before they light up -- there's even talk of banning smoking in certain outdoor environments like parks and other public property!This is all great news about moving in the right direction, so consider some long-term changes starting tomorrow like quitting smoking for good or maybe making your home smoke-free. And if that doesn't work even just quitting for the day is something!
[RESEARCH] Effects of statins in patients with chronic kidney disease: meta-analysis and meta-regression of randomised controlled trials
Objective To analyse the benefits and harms of statins in patients with chronic kidney disease (pre-dialysis, dialysis, and transplant populations).
Design Meta-analysis.
Data sources Cochrane Central Register of Controlled Trials, Medline, Embase, and Renal Health Library (July 2006).
Study selection Randomised and quasi-randomised controlled trials of statins compared with placebo or other statins in chronic kidney disease.
Data extraction and analysis Two reviewers independently assessed trials for inclusion, extracted data, and assessed trial quality. Differences were resolved by consensus. Treatment effects were summarised as relative risks or weighted mean differences with 95% confidence intervals by using a random effects model.
Results Fifty trials (30 144 patients) were included. Compared with placebo, statins significantly reduced total cholesterol (42 studies, 6390 patients; weighted mean difference –42.28 mg/dl (1.10 mmol/l), 95% confidence interval –47.25 to –37.32), low density lipoprotein cholesterol (39 studies, 6216 patients; –43.12 mg/dl (1.12 mmol/l), –47.85 to –38.40), and proteinuria (g/24 hours) (6 trials, 311 patients; –0.73 g/24 hour, –0.95 to –0.52) but did not improve glomerular filtration rate (11 studies, 548 patients; 1.48 ml/min (0.02 ml/s), –2.32 to 5.28). Fatal cardiovascular events (43 studies, 23 266 patients; relative risk 0.81, 0.73 to 0.90) and non-fatal cardiovascular events (8 studies, 22 863 patients; 0.78, 0.73 to 0.84) were reduced with statins, but statins had no significant effect on all cause mortality (44 studies, 23 665 patients; 0.92, 0.82 to 1.03). Meta-regression analysis showed that treatment effects did not vary significantly with stage of chronic kidney disease. The side effect profile of statins was similar to that of placebo. Most of the available studies were small and of suboptimal quality; mortality data were provided by a few large trials only.
Conclusion Statins significantly reduce lipid concentrations and cardiovascular end points in patients with chronic kidney disease, irrespective of stage of disease, but no benefit on all cause mortality or the role of statins in primary prevention has been established. Reno-protective effects of statins are uncertain because of relatively sparse data and possible outcomes reporting bias.
Young golfer doesn't let heart defect end dreams, it's the LPGA for her
Filed under: Events, Children Heart Health
I am always inspired when I hear of a young person overcoming the restrictions that a congenital heart defect can place on them. As a mother of a child with a heart defect, I often experience those niggling questions of, "Will my child truly lead a normal life? Will this unfortunate bit of misdirected body tissue stop him from pursuing his dreams?"Young MacKinzie Kline, just 15 years old, has not allowed her defect to mar her dreams. Last week she participated in an LPGA golf tour event in Charleston, North Carolina. Kline received permission to ride in a golf cart during the competition, a huge decision for the event organizers, because she has difficulty breathing and walking long distances.
Kline is an inspiration for both children and parents of children who have congenital heart defects. It is always such a joy to read of somebody overcoming hurdles and setting higher goals for the rest of us.
[RESEARCH] Main morbidities recorded in the women's international study of long duration oestrogen after menopause (WISDOM): a randomised controlled trial of hormone replacement therapy in postmenopausal women
Objective To assess the long term risks and benefits of hormone replacement therapy (combined hormone therapy versus placebo, and oestrogen alone versus combined hormone therapy).
Design Multicentre, randomised, placebo controlled, double blind trial.
Setting General practices in UK (384), Australia (91), and New Zealand (24).
Participants Postmenopausal women aged 50-69 years at randomisation. At early closure of the trial, 56 583 had been screened, 8980 entered run-in, and 5692 (26% of target of 22 300) started treatment.
Interventions Oestrogen only therapy (conjugated equine oestrogens 0.625 mg orally daily) or combined hormone therapy (conjugated equine oestrogens plus medroxyprogesterone acetate 2.5/5.0 mg orally daily). Ten years of treatment planned.
Main outcome measures Primary outcomes: major cardiovascular disease, osteoporotic fractures, and breast cancer. Secondary outcomes: other cancers, death from all causes, venous thromboembolism, cerebrovascular disease, dementia, and quality of life.
Results The trial was prematurely closed during recruitment, after a median follow-up of 11.9 months (interquartile range 7.1-19.6, total 6498 women years) in those enrolled, after the publication of early results from the women's health initiative study. The mean age of randomised women was 62.8 (SD 4.8) years. When combined hormone therapy (n=2196) was compared with placebo (n=2189), there was a significant increase in the number of major cardiovascular events (7 v 0, P=0.016) and venous thromboembolisms (22 v 3, hazard ratio 7.36 (95% CI 2.20 to 24.60)). There were no statistically significant differences in numbers of breast or other cancers (22 v 25, hazard ratio 0.88 (0.49 to 1.56)), cerebrovascular events (14 v 19, 0.73 (0.37 to 1.46)), fractures (40 v 58, 0.69 (0.46 to 1.03)), and overall deaths (8 v 5, 1.60 (0.52 to 4.89)). Comparison of combined hormone therapy (n=815) versus oestrogen therapy (n=826) outcomes revealed no significant differences.
Conclusions Hormone replacement therapy increases cardiovascular and thromboembolic risk when started many years after the menopause. The results are consistent with the findings of the women's health initiative study and secondary prevention studies. Research is needed to assess the long term risks and benefits of starting hormone replacement therapy near the menopause, when the effect may be different.
Trial registration Current Controlled Trials ISRCTN 63718836
Super Bowl heart attack
Filed under: Events
The rain, the game, the parties -- and of course, the commercials. That's what yesterday's Super Bowl was all about. In a departure from last year's collection of "guy-getting-kicked-in-the-groin" advertisements, this year boasted a more diverse assemblage of Madison Avenue brainstorms. And, mixed right in with the fifteen or so ads for Budweiser, the three or four for Doritos, and the one or two for Chevy, was one for the American Heart Association high blood pressure website: www.beatyourrisk.com
Supported by King Pharmeceuticals, who have committed to a three-year sponsorship agreement with the AHA, the commercial followed a giant heart (who was actually a many dressed in a giant heart costume, similar to the way the Fruit of the Loom men are dressed as apples and grapes) who was being targeted by potential threats; Diabetes, High Cholesterol, High Blood Pressure, etc. Each of these thuggish characters chased the heart around town and down dark alleys, until they finally caught him and beat the tar out of him. In sum, the heart was attacked.
My first reaction to the commercial was, Um. Yeah, that's it -- Um. I used that quasi-word/time stalling device to formulate my opinion. Then, about a minute later, I decided that I did enjoy the commercial. I felt that it passed along the information in a way that has a more lasting effect than, say, issuing yet another public report on research. The message was to be aware of risk factors that can lead to heart attack, and to do what you can to keep your heart as safe as it can be. As remedial as that explainatin probably sounds, that was sort of the point with the commercial -- keep it simple. Keep it easy to remember, which means in doing so, it is also difficult to forget. The finer points, the minutia, and the data aren't exactly the best way to get people's attention. A giant heart being attacked by Diabetes, Weight Problem, and High Blood Pressure? Um -- yeah, I'd say that got my attention.
Reversing Autoimmunity Q & A
Filed under: Type 1, Childhood, Research, Events
Like a dog chasing its own tail (but nowhere near as funny), type 1 diabetes is caused by a self-imposed attack on insulin producing cells. Here's your chance to chat live and learn about the latest discoveries to interfere with the automimmune confusion. Chat live with the head of the Immunogenetics Program at the Diabetes Research Institute, Alberto Pugliese, M.D.
The DRI program is specifically focused on understanding how genetic and immunological factors play a role in the development of type 1 diabetes and how certain genetic and immunological factors may actually afford protection from diabetes. The program is uncovering ways to interfere with the immune cells that attack the insulin producing cells in the pancreas resulting in diabetes.
In plain English, join Dr. Pugliese to enlighten yourself and ask any questions you may have regarding this impressive research. The chat begins at 9pm EST and those who miss it can catch the excitement in the transcript, to be posted shortly thereafter. I hope to see fellow IDDMs on the chat roster.