Bisphenol A: An Environmental Risk Factor for Cardiovascular Disease?

In a cross-sectional analysis, high urine concentrations of a commonly used industrial chemical were associated with diabetes and coronary events.

Bisphenol A (BPA) is added to the plastic used in products such as baby bottles and to the epoxy that lines food cans. Most individuals in industrialized countries are thought to have BPA in their bodies. In humans, BPA may bind to estrogen receptors, and concern has arisen as to whether it might adversely affect health.

In this study from the U.S. National Health and Nutrition Examination Survey 2003–2004, investigators measured total concentration of BPA in urine samples collected from 1455 adult participants and determined whether urine BPA concentrations were associated with self-reported histories of physician-diagnosed arthritis, cancer, cardiovascular disease (angina, coronary heart disease, or heart attack), diabetes, liver disease, respiratory disease (asthma, bronchitis, or emphysema), stroke, or thyroid disease. The odds ratio for a diagnosis of cardiovascular disease or diabetes was 1.39 for each 1 standard-deviation increase in urine BPA concentration (P<0.001>

Comment

Despite recent assertions by the FDA of the safety of bisphenol A, criticism is mounting about its use in consumer products because of its potential neurologic and reproductive health effects. By linking BPA concentrations to increased risks for diabetes and heart disease, these new data raise questions about the current assumptions and assessments the FDA has made. These findings should stimulate additional studies into the potential health effects of BPA.

— JoAnne M. Foody, MD

Cryopreserved Sperm from Men with Malignancies Can Produce Pregnancies

Preserving sperm before cancer therapy can enhance the likelihood of later fatherhood.

As survival rates after cancer rise, more emphasis has been placed on preserving fertility despite probable chemotherapy- and radiation-induced sterility in both men and women. Does cryopreservation of sperm before treatment allow men who survive cancer to father children later? To address this issue, researchers evaluated data from all 118 couples who underwent in vitro fertilization (IVF) procedures with pretreatment cryopreserved sperm during a 12-year period at a single center in New York City.

Before cancer treatment, about 43% of men had at least one abnormal parameter in their semen analyses, and about 20% had very-low total sperm counts (<5>

Comment

Data on the health of the children born to this cohort are still limited, but no evidence has accrued to date for excess genetic abnormalities. Although we must remain cautious, these findings emphasize the need to discuss future fatherhood with young men who have malignancies and to encourage cryopreservation of sperm before cancer treatments.

— Robert W. Rebar, MD

Noninvasive Risk Stratification for Sudden Cardiac Death

For now, LVEF is still the most useful basis for decisions about preventive intervention.

Sponsoring Organizations: American Heart Association, American College of Cardiology, Heart Rhythm Society

Background and Purpose: Accurate identification of individuals who are likely to die of cardiac arrhythmias would allow selective use of implantable cardioverter-defibrillators and other therapies to prevent sudden cardiac death (SCD). A vast amount of research energy has been spent in attempts to find noninvasive tests that can separate individuals into high-risk and low-risk groups. This scientific statement summarizes the findings of those studies.

Key Points:
1. Noninvasive tests evaluated to date measure:

• Slowed conduction (QRS duration, signal-averaged electrocardiogram)
  
• Variations in ventricular repolarization (QT interval, QT dispersion, T-wave alternans)
  
• Disparities in autonomic tone (heart rate variability, heart rate turbulence, heart rate recovery
  after exercise, baroreceptor sensitivity)
• Degree of myocardial damage (LV ejection fraction, 6-minute walk)
  
• Ventricular ectopy (long-term ambulatory monitoring)
  

2. In patients with ischemic or nonischemic cardiomyopathies, LVEF remains the best and possibly the only clinical test currently available to identify high-risk populations.

3. Patients with LVEF 35% are at the highest risk for SCD and, in the absence of comorbidities that severely shorten life expectancy, should undergo ICD implantation.

4. Most patients with LVEF 35% will not suffer SCD. However, at present, no noninvasive test has been proven to adequately identify low-risk patients with LVEF 35% who can be treated without an ICD.

5. Most SCDs occur in individuals with LVEF >35%. However, at present, no noninvasive test has been proven to adequately identify high-risk patients with a preserved LVEF who can be treated with an ICD.

6. In patients with hypertrophic cardiomyopathy, risk factors for SCD include history of resuscitated SCD or unexplained syncope, nonsustained ventricular tachycardia, hypotensive response to exercise, family history of SCD, and massively thick septum. None of the other noninvasive tests studied has been shown to add incremental value to these clinical features for risk stratification in these patients.

Comment:

Despite decades of sometimes quite promising research, LVEF measurement is the only clinically useful test to distinguish patients who need an ICD from those who do not. Although many of the other noninvasive tests studied show promise, at present none is sufficiently sensitive or specific to drive clinical decisions regarding ICD implantation. Such a tool would be most welcome, and we hope one or a combination of the tests described in this report will prove to be a more effective strategy in the coming years.

— Mark S. Link, MD

Images taken from:

http://www.ahealthyme.com/Imagebank/adam/1429.jpg

http://nurse-ratcheds.blogspot.com

Diet’s Effect on Diabetes Risk: Is It the Fat? Or the Carbs?

In older women, lowering fat intake alone did not affect diabetes risk; in black women, sugar-sweetened drinks were associated with excess diabetes risk.

In the quest for modifiable diabetes risk factors, dietary alteration is a prime target. But should we simply counsel overweight patients to lower their BMIs, or should we also target specific dietary components, such as fats or sugar-sweetened drinks? In two studies, investigators addressed these questions.

In the Women’s Health Initiative Dietary Modification Trial, 48,835 healthy postmenopausal women (age range, 50–79) were randomized to a usual-diet comparison group or to an individualized dietary intervention that specified 20% of energy from fat. The intervention group received self-monitoring instructions and group sessions; the comparison group was given reading material about dietary guidelines. Dietary intake was monitored with a standardized food frequency questionnaire (FFQ) at baseline and at regular intervals; incident cases of treated diabetes were self-reported. Complete data were available for 45,887 women (mean follow-up, 8 years). Diabetes incidence did not differ significantly between the intervention and comparison groups (1303 cases [7.1%] vs. 2039 cases [7.4%]). A trend toward lower diabetes incidence in the intervention group likely was attributable to weight loss rather than to the low-fat diet alone.

The authors of the Black Women’s Health Study investigated the relation of sugar-sweetened beverage consumption to self-reported incident diabetes among women in this ethnic group (who are twice as likely to develop diabetes as are white women). Almost 44,000 women were followed for 10 years and completed standardized FFQs at regular intervals. Participants (age range at baseline, 21–69) reported their intake of "regular" (non-diet) soft drinks, orange or grapefruit juice, and "other fruit juices, fortified fruit drinks, or Kool-Aid." Overall, 2713 women developed diabetes. In analyses adjusted for age, family history, and BMI, daily consumption of 2 soft drinks compared with <1>P=0.002). The highest level of sweetened fruit-drink intake, 2 drinks daily, also was associated with higher diabetes risk (IRR, 1.31; P=0.001) compared with <1>

Comment:

Although these studies both shed some light on the effects of fats and certain refined carbohydrates on the likelihood of developing diabetes in high-risk groups, they probably won’t alter our nutrition advice — most of which, an editorialist observes, is not evidence-based. Until we have more information, our best approach to diabetes prevention is to counsel overweight and obese patients about reducing total calorie intake and exercising more (or at all) and, when possible, to refer them to resources such as nutritionists, diabetes educators, the American Diabetes Association and the American Dietetic Association for additional support.

— Diane E. Judge, APN/CNP

Duration of Anticoagulant Therapy for Unprovoked Venous Thrombosis

Researchers identify a subgroup of women who might not need indefinite anticoagulation.

Risk for recurrent venous thrombosis (VT) varies: Patients with single major reversible VT risk factors (e.g., recent surgery) have risk for recurrent VT of 3%, whereas those with unprovoked VT have 10% risk for recurrence. In this multinational prospective study in 600 patients with first episodes of unprovoked VT or pulmonary embolism, researchers attempted to identify factors that predicted low recurrence risk. All patients had received 5 to 7 months of anticoagulation before enrollment. During a mean follow-up of 18 months, the annualized rate of recurrent VT was higher among men than women (13.7% vs. 8.9%). Men with post-thrombotic symptoms (leg hyperpigmentation, edema, or redness) had 24.0% annual risk for recurrence; no subgroup of men could be identified in whom risk for recurrence was while they received warfarin; body-mass index, 30 kg/m2; or age 65. Women with two or more factors had annual risk of 14.1%.

Comment:

The American College of Chest Physicians guideline suggests that patients with first unprovoked venous thromboses be considered for indefinite anticoagulation; however, the guideline recommends a minimum of 6 to 12 months of anticoagulation. In this study, researchers attempted to define a subgroup of patients for whom about 6 months of anticoagulation therapy after unprovoked venous thrombosis would be sufficient. No such group could be identified for men; however, women with [Photo]1 standard risk factor had low risk for recurrence. If the results of this study are replicated, shorter anticoagulation courses should be considered for such women.

— Jamaluddin Moloo, MD, MPH

Obesity and Chronic Kidney Disease

The association between obesity and chronic kidney disease seems to be mediated by hypertension and diabetes in many — but not all — cases.

Several years ago, U.S. researchers published a biopsy-based case series that involved 71 patients with obesity-related glomerulopathy (ORG), which is characterized by glomerular enlargement, frequent (but not universal) presence of focal segmental sclerosis, and substantial proteinuria. An increasingly recognized association between obesity and kidney disease is the subject of three new reports. A case series from China involved 90 obese patients who had renal biopsy findings consistent with ORG; no patients had diabetic or hypertensive nephropathy. Mean 24-hour urine protein excretion was 1.5 g. Mean serum creatinine level was 0.9 mg/dL, and about half the patients had elevated creatinine clearance, suggesting that hyperfiltration is an early finding in ORG patients. Framingham Heart Study researchers followed 2676 adults (baseline obesity prevalence, 12%). During an average follow-up of 19 years, obesity at baseline was associated significantly with subsequent development of stage 3 chronic kidney disease (odds ratio, 1.7). However, after adjustment for diabetes and hypertension, the association became statistically insignificant (OR, 1.1).

In another study, researchers analyzed data from two other large U.S. epidemiologic studies in which more than 13,000 adults were followed for an average of 9 years. In multivariable analyses, waist-to-hip ratio, but not body-mass index, was associated with development of chronic kidney disease. This association was somewhat attenuated, but remained significant, after adjustment for diabetes and hypertension.

Comment:

Taken together, these studies suggest that the association between obesity and kidney disease is complex. In most cases, the association likely is mediated by coexisting diabetes and hypertension. But in others, obesity could cause glomerular injury directly by mechanisms that are not fully understood. Because waist-to-hip ratio — an indicator of visceral obesity — was a better predictor than BMI, metabolic abnormalities particularly associated with visceral obesity presumably predispose to chronic kidney disease.

-Allan S. Brett, MD

Paying for Performance Can Improve Quality of Care

Financial incentives can improve care but can also have unintended consequences.

Aligning financial incentives with good clinical practice has the potential to improve quality of care. Researchers systematically reviewed the literature to find controlled studies that assessed the effect of explicit financial incentives on quantitative measures of health care quality.
Of nine studies of provider-group incentives, two found small improvements in quality measures and five found partial effects (e.g., an improvement in cervical cancer screening, but not in mammography). One study of a payment-system incentive found an increase in nursing home admissions for patients who needed that level of care (the intended effect). However, in that study and one other study of a payment-system incentive, there were unintended negative effects of incentives, such as avoidance of severely ill patients, or a tendency to claim that patients were severely ill and then to report short recovery periods. In six studies of physician-level incentives, five found positive or partial effects. But in two studies (one of a physician incentive to provide vaccinations and one of a provider-group incentive to provide smoking cessation advice), there were improvements in documentation but not in actual provision of these services.

Comment:

Because of the small number and limited scope of the studies identified, the authors suggest that generalize ability of the findings is limited. Nonetheless, financial incentives apparently can have positive effects on quality of care. But carefully designed incentives and further study are clearly needed to achieve these improvements while avoiding unintended negative effects.

-Richard Saitz, MD, MPH, FACP, FASAM

Does Flu Vaccination Lower Risk for Pneumonia in Elders?

In contrast to results of previous studies, flu vaccine did not lower risk in this study. Previous observational studies have shown that influenza vaccination lowers risk for pneumonia in older patients.

In a population-based case-control study, conducted during the preinfluenza and influenza seasons of 2000, 2001, and 2002, Seattle investigators studied managed-care records for 1173 older patients (age range, 65–94) with community-acquired pneumonia (CAP) and for 2346 age- and sex-matched controls without CAP. Both groups were equally likely to have been vaccinated (roughly 60% before the CAP index date and 77% by the end of each influenza season). In unadjusted analyses, vaccinated patients had a 40% lower risk for CAP than unvaccinated patients in the preinfluenza period — when no biologically plausible explanation exists for vaccine benefit — but the difference disappeared when analyses were adjusted for a wide range of chronic diseases and functional impairment. No difference in risk for CAP was observed between vaccinated and unvaccinated groups during the influenza season, whether analyses were adjusted or not, and no difference was observed in risk for CAP that required hospital admission during peak influenza season.

Comment:

According to this provocative study, influenza vaccination offered no benefit in broad measures of risk for community-acquired pneumonia. Editorialists noted that this study has several strengths that have been missing in many other studies: It was conducted during seasons when the antigenic match between influenza strains and vaccine was good; CAP was ascertained with chart audit rather than by evaluating administrative data; the analysis was controlled for a wide range of chronic disease and functional status measures; and both inpatient and outpatient cases were identified.

-Thomas Schwenk, M.D.