Macapanton, Raihana D.

DNA Variants Explain Over Ten Percent of Inherited Genetic Risk for Heart Disease
Nov. 8, 2012 About 10.6% of the inherited genetic risk for developing coronary artery disease (CAD) can be explained by specific DNA variations, according to research reported November 8 at the American Society of Human Genetics 2012 meeting. The research, conducted by scientists in the CARDIoGRAMplusC4D consortium, pinpointed 20 previously unidentified mutations during a two-stage meta-analysis of 63,746 patients with CAD, which causes more deaths worldwide than any other disease. These genetic variants generally were infrequently found in the DNA of the 130,681 individuals without heart disease who were in the control group. The new mutations have boosted to 47 the total number of DNA variants that have thus far been linked to an increased risk for developing CAD, said Panos Deloukas, Ph.D., who co-led the study and heads the Genetics of Complex Traits in Humans research group at the Wellcome Trust Sanger Institute, Cambridge, UK. Scientists had previously estimated that 30 to 60% of the variation in CAD might be attributable to genetic risk factors, according to a study published in 2005. The research reported at ASHG 2012 expands the number of specific genes that are likely involved. "We no longer assume that coronary heart disease is triggered by just a handful of genes, each with a strong effect on a person's risk for the disease," said Dr. Deloukas. "Our research supports the current assumption that heart disease risk is determined by a large group of genes, each with a modest effect on risk." Identifying the genetic mutations that set the stage for CAD enables researchers to investigate the underlying mechanisms of the disease, which may lead to therapeutic targeting through drugs, he said. Many of the newly identified variations are in genes that operate in biological pathways involved in the body's metabolism of lipids or fats as well as in inflammation. The build-up of fatty cholesterol-rich plaque in blood vessels, a classic feature of CAD, not only can impair blood circulation but also can unleash the clots that obstruct blood flow to the heart and thereby cause heart attacks. "Exactly how inflammation plays a role in heart attack remains a topic of ongoing research," said Dr. Deloukas, adding that the consortium's findings underscore the roles of high cholesterol levels and inflammation in CAD.

http://www.sciencedaily.com/releases/2012/11/121108141014.htm

Macapanton, Raihana D.

Beta-Blocker Use May Not Prevent Heart Attack, Death and Stroke, New Study Reveals Oct. 2, 2012 Among patients with either coronary artery disease (CAD) risk factors only, known prior heart attack, or known CAD without heart attack, the use of betablockers was not associated with a lower risk of a composite of cardiovascular events that included cardiovascular death, nonfatal heart attack or nonfatal stroke, according to a study in the October 3 issue of JAMA. "Treatment with beta-blockers remains the standard of care for patients with coronary artery disease, especially when they have had a myocardial infarction [MI; heart attack]. The evidence is derived from relatively old post-MI studies, most of which antedate modern reperfusion or medical therapy, and from heart failure trials, but has been widely extrapolated to patients with CAD and even to patients at high risk for but without established CAD. It is not known if these extrapolations are justified. Moreover, the long-term efficacy of these agents in patients treated with contemporary medical therapies is not known, even in patients with prior MI," according to background information in the article. Sripal Bangalore, M.D., M.H.A., of the NYU School of Medicine, New York, and colleagues conducted a study to evaluate the association between beta-blocker use and long-term cardiovascular outcomes. The observational study included data from patients in the Reduction of Atherothrombosis for Continued Health (REACH) registry. From this registry, 44,708 patients met the study inclusion criteria of whom 14,043 patients (31 percent) had prior MI, 12,012 patients (27 percent) had documented CAD but without MI, and 18,653 patients (42 percent) had CAD risk factors only. The last follow-up data collection was April 2009. The primary outcome for this study was a composite of cardiovascular death, nonfatal MI, or nonfatal stroke. The secondary outcome was the primary outcome plus hospitalization for atherothrombotic events or a revascularization procedure. The overall median (midpoint) follow-up was 44 months. Among the 44,708 patients in the study, 21,860 were included in the propensity scorematched analysis.The researchers found that in the prior MI group, the event rates were not significantly different among those with beta-blocker use (489 [16.93 percent]) vs. those without beta-blocker use (532 [18.60 percent]) for the primary outcome, or the secondary outcome (30.96 percent vs. 33.12 percent, respectively). In the CAD without MI cohort, the event rates were not different in those with beta-blocker use (391 [12.94 percent]) vs. those without p-blocker use (405 [13.55 percent]) for the primary outcome, for cardiovascular death, for stroke, and for MI. The event rates were higher in those with beta-blocker use (1,101 [30.59 percent] vs. those without beta-blocker use (1,002 [27.84 percent]) for the secondary outcome and for hospitalization in the propensity score-matched model. In the risk factors alone group, the event rates were higher in those with beta-blocker use (467 [14.22 percent] vs. those without beta-blocker use (403 [12.11 percent]) for the primary outcome, for the secondary outcome (870 [22.01 percent] vs. 797 [20.17 percent], respectively) but not for MI or stroke. In the propensity score-matched model, there were similar event rates for cardiovascular death and for hospitalization. The researchers also found that among patients with recent MI (one year or less), betablocker use was associated with a lower incidence of the secondary outcome. "Among patients enrolled in the international REACH registry, beta-blocker use was not associated with a lower event rate of cardiovascular events at 44-month follow-up, even among patients with prior history of MI. Further research is warranted to identify subgroups that benefit from beta-blocker therapy and the optimal duration of betablocker therapy," the authors conclude. http://www.sciencedaily.com/releases/2012/10/121002161753.htm

Hisola, Alvina Lamb H.

Diabetic Foot Ulcers Linked With Higher Risk of Death, Heart Attack and Stroke
Oct. 10, 2012 People with diabetes who develop foot ulcers are at more risk of dying prematurely than those without the complication, finds a new large-scale study. The researchers say the findings highlight the potential need for improved detection and management of those with diabetes and foot ulcers. The study, which is the largest analysis of diabetes into the link between foot ulcers and the condition, is published in this month's (November) edition of the journal Diabetologia. There are 3.7million people diagnosed with diabetes in the UK and an estimated 850,000 people who have the condition but do not know it. Diabetes can damage a person's blood vessels and nerves, especially if their blood sugar is poorly controlled. Poor circulation and nerve damage in the feet makes people vulnerable to unnoticed cuts or other injuries and progress into poorly healing ulcers, or sores. In severe cases, this can lead to foot or leg amputation. In a study of 17,830 patients with diabetes -- 3,095 diagnosed with foot ulceration and 14,735 without -- researchers from St George's, University of London investigated how diabetic foot ulcers affected a person's risk of dying earlier. They found that those with a history of foot ulceration had a higher death rate than those without. There were an extra 58 deaths per 1,000 people each year with diabetic foot ulcers. The investigators analysed patient records from eight studies, conducted in Europe, America, Australasia and South-East Asia, published between 2006 and 2011. The length of time the health of participants was followed for varied between an average of two and 10 years for each of the studies. People with foot ulcers and diabetes showed more cardiovascular risk factors, such as high blood pressure, and were more likely to die from cardiovascular causes. Approximately half of the additional mortalities were due to cardiovascular disease, such as heart attack or stroke. The cause of non-cardiovascular deaths was not studied as part of this investigation but the researchers say this is potentially linked to infections and complications of foot ulceration, such as blood poisoning. Robert Hinchliffe from St George's, University of London, who co-led the study, said: "Our research, which is the largest and therefore most reliable study to date, shows that people with diabetes who have foot ulcers are at considerably higher risk of an earlier death compared to those patients without. We suspect that this may be due in part to the effect of infections among those with foot ulcers and the greater co-existence of cardiovascular disease and foot ulcers with diabetes although the reasons are not entirely clear." The researchers say these results underline the importance of a two-pronged approach for people with diabetes: enhanced foot ulceration screening as early detection and treatment may help reduce some of the complications; and more intensive control of blood pressure and cholesterol among those diagnosed with foot ulcers as they are at higher cardiovascular risk. Currently, experts already recommend that people with diabetes undertake a number of precautions to prevent foot ulcers including blood sugar control, wearing socks to prevent cuts, self-checking for abrasions and getting a complete foot examination at least once a year. Existing guidelines to prevent cardiovascular disease include healthy diet choices, regular exercise, a medical check-up at least once a year and, often, medically prescribed drug treatment. Professor Kausik Ray, who also co-led the study, said: "Our results warrant further investigation as to whether even greater control of risk factors such as blood pressure, blood glucose and early preventative screening can further reduce mortality among those with foot ulcers. There is likely an unmet potential to reduce deaths in this group." http://www.sciencedaily.com/releases/2012/10/121010084208.htm

Hisola, Alvina Lamb H.

Study Identifies Women at Risk for Urinary Tract Infections After Pelvic-Floor Surgery
Oct. 8, 2012 Women who have a positive urine culture test on the day of surgery for a pelvic-floor disorder are more likely to have a urinary tract infection (UTI) in the first six weeks after the procedure. These findings were presented this past week by researchers from Loyola University Chicago Stritch School of Medicine at the American Urogynecologic Society's 33rd Annual Scientific Meeting in Chicago. "Urinary tract infections are extremely common in women following pelvic-floor surgery," said Cynthia Fok, MD, fellow, Division of Female Pelvic Medicine and Reconstructive Surgery, Loyola University Chicago Stritch School of Medicine. "This research will help us to identify and treat patients who are at risk for urinary tract infections to reduce the incidence of this complication following surgery." One in five patients who undergo surgery for a pelvic-floor disorder develops a UTI following the procedure. With this in mind, researchers evaluated the proportion of patients with a positive day-of-surgery urine culture and the consequences of a positive culture. Urine samples were collected through a catheter in the operating room before a patient was given antibiotics prior to surgery. A culture was considered positive if more than 1,000 colonies per milliliter of bacteria were found in the sample. Nearly one-tenth of patients had positive day-of-surgery cultures. Women with a positive culture had an increased risk (29.6 percent versus 5.6 percent) of developing a UTI within six weeks after surgery despite antibiotic use prior to surgery. "Further research will be necessary to determine how we better manage these patients preoperatively to prevent complications following surgery," Dr. Fok said.

http://www.sciencedaily.com/releases/2012/10/121008144254.htm