DPP-4 Inhibitors May Not Be Linked to Increased Heart Attack Risk

The Wall Street Journal reported that research presented at the European Society of Cardiology Congress and published in the New England Journal of Medicine suggests that the diabetes medications known as DPP-4 inhibitors may not be linked to an increased heart attack risk. One study involved Onglyza (saxagliptin) and the other involved Nesina (alogliptin).

Extreme Exercise May Not Pose Danger to Heart

The Wall Street Journal reported that a study of Tour de France cyclists found that they had longer lives than the general population and were less likely to die from heart troubles. The findings are interpreted to mean that fears that extreme exercise might damage the heart appear to be not well founded.

Cystatin C Strengthens Link between Kidney Function and Risks for Death and Renal Failure

Using cystatin C alone or in combination with creatinine strengthened the association between the eGFR and risks of death and kidney failure in a NEJM meta-analysis of general-population studies (90,750 participants) and studies of CKD patients (2960 participants). In general-population cohorts, the prevalence of an eGFR of less than 60 mL/min/1.73 m² was higher with cystatin C–based eGFR than with creatinine-based eGFR (13.7% vs. 9.7%). Reclassification to a higher eGFR with cystatin C, as compared with creatinine, was associated with a reduced risk of kidney failure and death; reclassification to a lower eGFR was associated with an increased risk.

New Therapeutic Approach for Polycystic Kidney Disease?

Research suggests a possible therapeutic approach for autosomal dominant polycystic kidney disease (ADPKD) by placing normal polycystin-1 protein back into patients’ cells to correct a defect. A new JASN studyfound polycystin-1 protein may help shepherd polycystin-2 to a cell’s antenna, or cilium, and this process is defective in induced pluripotent stem cells derived from patients with ADPKD. The accompanying editorialstates that the study lays the groundwork for using induced pluripotent stem cells in PKD research.

Study: Faster heart attack care has not led to better in-hospital survival.

USA Today (9/4, Szabo, 5.82M) reports that research published in the New England Journal of Medicine indicates that while hospitals have “shaved 16 minutes off the time it takes to get heart attack patients into treatment from 2005-2006 to 2008-2009, reducing that time from 83 minutes to 67 minutes,” investigators “found that the percentage of heart attack patients who die while in the hospital, about 5%, hasn’t changed.” The researchers only looked at patients with ST-elevation myocardial infarctions.

        The Los Angeles Times (9/5, Brown, 3.4M) reports that approximately ten years ago, “the American College of Cardiology and the American Heart Assn. began instituting guidelines to help hospitals reduce their so-called door-to-balloon times to 90 minutes or less.” The ACC released “a statement Wednesday stressing that it stood by its guidelines and pointing out that ‘short-term mortality is not the only goal of door-to-balloon.’”

        Bloomberg News (9/5, Cortez, 1.41M) reports that in the statement, ACC President John Harold said, “We are also interested in recovery and quality of life after a heart attack.” Dr. Harold added, “Time is muscle, and the sooner treatment begins, the less muscle is damaged, which preserves functionality of the heart.”

        However, on its website, NBC News (9/5, Aleccia, 6.68M) reports that according to study leader Dr. Daniel Menees, “We’ve probably had an overemphasis on D2B time,.” Dr. Menees added “Clearly, it’s important to reevaluate it and reconsider.”

        Forbes (9/5, 5.76M) contributor Larry Husten writes that “in an accompanying editorial, Eric Bates and Alice Jacobs write that ‘the primary opportunity for reducing total ischemic time and time to treatment, and for improving outcomes, now lies in the prehospital STEMI system of care, where logistic challenges remain…. Although door-to-balloon time remains important, it’s time to turn our attention to the further development of systems that address the continuum of STEMI care, from symptom onset through return to the community.’” Also covering the story are HealthDay (9/5, Gordon, 2K) and MedPage Today (9/5, Smith, 185K).

Chronic Kidney Disease: Lifetime Risk Nears 60% in US

Janis C. Kelly

Aug 06, 2013

 

The National Kidney Foundation (NKF) has called for annual screening for chronic kidney disease (CKD) after a new study showed a lifetime risk of 59.1% for CKD stage 3a+ in the United States. However, not everyone agrees more screening is the answer, and some experts raise concerns about overdiagnosis.

Morgan E. Grams, MD, MHS, from the Department of Medicine, Johns Hopkins University School of Medicine, and the Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, and colleagues reported the long-term risk analysis for CKD stages 3 to 5 in an article published in the August issue of American Journal of Kidney Diseases.

"Our findings reinforce that CKD is a very common disease with significant disparities in risk by race. While disease onset can be late, appreciation of the high lifetime risk should motivate early detection and prevention," senior author Josef Coresh, MD, PhD, told Medscape Medical News. Dr. Coresh is professor of epidemiology at the Welch Center for Prevention, Epidemiology, and Clinical Research; director, Cardiovascular Epidemiology Training Program; and director, Comstock Center for Public Health Research and Prevention, Johns Hopkins University, Baltimore.

The researchers applied a Markov Monte Carlo model simulation to data from the National Vital Statistics Report, the National Health and Nutrition Examination Survey, the US Renal Data System, and the US Census Bureau, comprising prevalence data on 37,475 individuals and mortality risk data from more than 2 million individuals. The investigators used a simulated cohort of 10,000 individuals of the specified baseline age, race, and sex to estimate the residual lifetime risks for CKD stage 3a+ (estimated glomerular filtration rate [eGFR], <60 mL/minute/1.73 m²), CKD stage 3b+ (eGFR ,45 mL/minute/1.73 m²), CKD stage 4+ (eGFR,30 mL/minute/1.73 m²), and end-stage renal disease (ESRD; chronic kidney failure treated by dialysis or transplantation).

Overall, the lifetime risks were 59.1% for CDK3a+, 33.6% for CKD 3b+, 11.5% for CKD 4+, and 3.6% for ESRD. Women had higher CKD risk but lower ESRD risk, apparently because of their longer life expectancy. Black participants of both sexes had significantly higher CKD 4+ (lifetime risk for white men, 9.3%; white women, 11.4%; black men, 15.8%; and black women, 18.5%) and ESRD (lifetime risk for white men, 3.3%; white women, 2.2%; black men, 8.5%; and black women, 7.8%) risks than whites. As expected, CKD risk increased with age, and about half of the CKD 3a+ cases occurred after age 70 years.

Low Kidney Function in Elderly Is a Drug Safety Hazard

"Low eGFR in the elderly as a patient safety hazard is the most clinically relevant aspect of the high lifetime risk described by Grams et al. Medication management that considers eGFR levels in the elderly is the most actionable patient safety hazard, since the majority of drugs are cleared by the kidney," write Joseph A. Vassalotti, MD, and Beth Piraino, MD, in an accompanying editorial. Dr. Vassalotti is chief medical officer of the NKF and serves on the Clinical Faculty of Medicine in the Division of Nephrology at Mount Sinai Medical Center in New York City. Dr. Piraino is president of the NKF and professor of medicine and associate dean of admissions at the University of Pittsburgh School of Medicine in Pennsylvania. "Medications that require caution in prescribing to those with decreased GFR include antihypertensive agents, analgesics (nonsteroidal anti-inflammatory drugs and opioids), antimicrobials, hypoglycemics, dyslipidemia therapy (statins and fibrates), chemotherapeutic agents (cisplatin, melphalan, and methotrexate), anticoagulants (low-molecular-weight heparins, oral thrombin inhibitors, oral factor Xa inhibitors, and warfarin), and others," Dr. Vassalotti and Dr. Piraino write. Increased risk for acute kidney injury during cardiac surgery with contrast administration is also a concern.

CKD Risk Now Greater Than Risk for Diabetes, Coronary Heart Disease, Cancer

"The knowledge that the cumulative incidence of CKD has surpassed diabetes mellitus should stimulate even greater interest in CKD as a population health problem," writes Bryce A. Kiberd, MD, in asecond editorial. Dr. Kiberd is professor of medicine at Dalhousie University, staff physician at the Queen Elizabeth II Health Sciences Center, Halifax, Nova Scotia, Canada, and medical director of the Multi-Organ Transplant Program for Atlantic Canada.

According to Dr. Grams and colleagues, the predicted risk is 59% for CKD stage 3a+, 33% to 39% for diabetes, 32% to 49% for coronary heart disease (for a 40-year-old patient), and 38% to 45% for cancer. Dr. Kiberd wrote that although the utility of general population CKD screening is inconclusive, the data suggest that "screening in blacks should be reconsidered."

NKF Recommends Regular Urine Screening for Many Patients

The NKF responded to the new data by calling for annual urine screening for all Americans older than 60 years and for those with high blood pressure, diabetes, or family history of kidney failure requiring dialysis or transplantation. The NKF recommends that screenings be conducted as a part of an annual physical examination that should also include a blood test for kidney function.

However, other kidney experts expressed concern that this approach would lead to overdiagnosis. Expanding definitions of chronic kidney disease are "unnecessarily labelling many people as diseased," write Ray Moynihan, senior research fellow, Centre for Research in Evidence Based Practice, Bond University, Robina, Queensland, Australia, and colleagues (BMJ. Published online July 30, 2013).

"The current definitions may misclassify at least 30% of elderly people as having stage 3 disease, with those classified as stage 3A without albuminuria at highest risk of overdiagnosis," they add. Moreover, Moynihan and colleagues note that most people classified as having 3a CKD are older than 65 years, and many will have an eGFR within the normal range for their age.

"While accurate identification of those at risk for a disease that can have a material influence on the duration and quality of life and can be influenced by appropriate application of treatments proven to be safe and effective is highly laudable, what is missing from the NKF proposal is the expected benefit from 'true positive' risk identification (presumably from earlier interventions), the potential hazards of 'false positives,' and the inappropriate re-assurances of 'false negatives,' " coauthor Richard Glassock, MD, told Medscape Medical News. Dr. Glassock is emeritus professor of medicine at the University of California, Los Angeles, Geffen School of Medicine.

"Will such opportunistic screening lead ultimately to health benefits or to an epidemic of 'overdiagnosis,' an unnecessary anxiety, investigation, referrals, and expenses? Opportunistic screening for CKD is not like screening for cervical or colonic cancer, where benefits are known," said Dr. Glassock, who also noted that the US Preventive Services Task Forcerecommended against population-based CKD screening for exactly those reasons.

Dr. Coresh, though, stands by the recommendation for increased screening. "Rigorous analyses of large datasets have shown that CKD as currently defined is associated with risk across all age groups. The more abnormal markers the higher the risk, but even only mildly reduced kidney function without albuminuria is associated with risk. Kidney disease will benefit from more research, particularly clinical trials, but fortunately some treatments are known to work and some risks can be reduced."

Dr. Coresh has consulted for Amgen and Merck and has an investigator-initiated grant from Amgen. The other authors have disclosed no relevant financial relationships. Dr. Vassalotti serves on the Litholink Corporation CKD Advisory Board. Dr. Piraino and Dr. Kiberd have disclosed no relevant financial relationships. Moynihan and one coauthor have received support from a National Health and Medical Research Council STEP grant and are helping to organize a conference supported by BMJand Consumer Reports. Moynihan also has been advising on the BMJ "Too Much Medicine" series. Dr. Glassock provides consultation to a number of pharmaceutical companies, none directly involved in providing care for ESRD. He is a medical adviser to American Renal Associates and receives honorariums for engaging in educational activities for the American Society of Nephrology and UpToDate.

Am J Kidney Dis. 2013;62:217-222, 245-252.Article full text, Vassalotti and Piraino editorial full text, Kiberd editorial full text

CDC: One in four deaths from cardiovascular disease preventable.

CDC data suggesting that about one-quarter of cardiovascular deaths in the US are preventable received coverage in two of the most widely-circulated papers in the country, on at least ten major websites, and on one of last night’s national news broadcasts. Nearly all of the articles quote CDC Director Thomas R. Frieden. Much of the coverage focuses on the finding that many of the preventable deaths occur in individuals younger than age 65.

        The CBS Evening News reported, “The CDC estimates one in four deaths from heart attack and stroke can be prevented.”

        USA Today (9/4, Hellmich, 5.82M) reports currently, there are approximately 800,000 deaths annually in the US from cardiovascular disease. However, about 200,000 of these deaths “could be prevented if people made healthy changes including stopping smoking, maintaining a healthy weight, doing more physical activity, eating less salt and managing their high blood pressure, high cholesterol and diabetes, says” the CDC report.

        The Wall Street Journal (9/4, Mckay, Winslow, Subscription Publication, 5.33M) reports that Frieden said, “As a doctor, I find it really heartbreaking to know that the vast majority of people who are having a heart attack or stroke under the age of 65 in particular and dying from it didn’t have to have that happen.”

        Bloomberg News (9/4, Edney, 1.41M) reports that while “the rate of preventable deaths from heart disease and stroke fell 30 percent from 2001 to 2010,” there was little “improvement in those younger than 65, the CDC said.”

        Reuters (9/4, Steenhuysen) reports that Frieden pointed out that although “those who are age 65 to 74 still have the greatest rate of heart attack and stroke, more than half of the preventable deaths – about six in 10 – happen in people under the age of 65.”

        The US News & World Report (9/4, Bidwell, 595K) reports that the data indicated that “African-Americans are nearly twice as likely as whites to die from preventable heart disease and stroke,” which can be attributed to “an increased prevalence of other risk factors such as high blood pressure, diabetes, obesity and low fruit and vegetable consumption.”

        On its website, CBS News (9/4, Jaslow, 5.42M) reports that the data indicated that “counties with the highest avoidable death rates were located primarily in the South,” but “Frieden emphasized this isn’t just a problem facing black residents in these regions, and said a map of only white individuals would look virtually the same.”

        Also covering the story are the CNN (9/4, 11.58M) “The Chart” blog, the Los Angeles Times (9/4, Morin, 3.4M), the NPR (9/4, Hensley, 405K) “Shots” blog, the FOX News (9/4, Serrie, 6.72M) website, the Chicago Sun-Times (9/4, Thomas, 1.19M), MedPage Today (9/4, Phend, 185K), HealthDay (9/4, Reinberg, 2K),Medscape (9/4, Brooks, 187K), and CQ (9/4, Adams, Subscription Publication, 530).