Nonobstructive Coronary Artery Disease Associated With Increased Risk of Heart Attack, Death

In a study that included nearly 38,000 patients, those diagnosed with nonobstructive coronary artery disease (CAD) had a significantly increased risk of heart attack or death one year after diagnosis, according to a study in the November 5 issue of JAMA.

Nonobstructive coronary artery disease (CAD) is atherosclerotic plaque that would not be expected to obstruct blood flow or result in anginal symptoms (such as chest pain). Although such lesions are relatively common, occurring in 10 percent to 25 percent of patients undergoing coronary angiography, their presence has been characterized as “insignificant” or “no significant CAD" in the medical literature. However, this perception of nonobstructive CAD may be incorrect, because prior studies have noted that the majority of plaque ruptures and resultant myocardial infarctions (MIs; heart attacks) arise from nonobstructive plaques. Despite the prevalence of nonobstructive CAD identified by coronary angiography, little is known about its risk of adverse outcomes, according to background information in the article.

Thomas M. Maddox, M.D., M.Sc., of the VA Eastern Colorado Health Care System, Denver, and colleagues compared heart attack and mortality rates among patients with nonobstructive CAD, obstructive CAD, and no apparent CAD. The patients included in the study were all U.S. veterans who underwent elective coronary angiography for CAD between October 2007 and September 2012 in the Veterans Affairs health care system. Patients with prior CAD events were excluded. CAD extent was defined by degree of vessel narrowing and distribution (1, 2, or 3 vessel).

During the study period, 37,674 patients underwent elective coronary angiography for indications related to CAD; of those, 22.3 percent had nonobstructive CAD and 55.4 percent had obstructive CAD. Within 1 year, 845 patients died and 385 were rehospitalized for MI. The researchers found that the 1-year MI risk progressively increased by the extent of CAD, rather than abruptly increasing between nonobstructive and obstructive CAD. Patients with nonobstructive CAD had an associated risk of MI that was 2-to 4.5-fold greater than among those with no apparent CAD. Similar observations were seen with 1-year mortality and the combined outcome of 1-year MI and death.

“These findings highlight a need to recognize that nonobstructive CAD is associated with significantly increased risk for MI, consistent with prior biologic studies indicating that a majority of MIs are related to nonobstructive stenosis [narrowing of an artery]. Correspondingly, these results reveal the limitations of a dichotomous [divided into two parts] characterization of angiographic CAD into ‘obstructive’ and ‘nonobstructive’ to predict MI and highlight the importance of preventive strategies such as pharmacotherapy treatments and lifestyle modifications to mitigate these risks,” the authors write.

(doi:10.1001/jama.2014.14681)

Testosterone Therapy May Increase Risk of Heart Attack, Stroke and Other Cardiovascular Events

CHICAGO -- Among a group of men who underwent coronary angiography and had a low serum testosterone level, the use of testosterone therapy was associated with increased risk of death, heart attack, or ischemic stroke, according to a study in the November 6 issue of JAMA.

“Rates of testosterone therapy prescription have increased markedly in the United States over the past decade. Annual prescriptions for testosterone increased by more than 5-fold from 2000 to 2011, reaching 5.3 million prescriptions and a market of $1.6 billion in 2011. Professional society guidelines recommend testosterone therapy for patients with symptomatic testosterone deficiency. In addition to improving sexual function and bone mineral density and increasing free-fat mass and strength, treatment with testosterone has been shown to improve lipid profiles and insulin resistance and increase the time to ST depression [a finding on an electrocardiogram suggesting benefit] during stress testing,” according to background information in the article. However, a recent randomized clinical trial of testosterone therapy in men with a high prevalence of cardiovascular diseases was stopped prematurely due to adverse cardiovascular events raising concerns about testosterone therapy safety.

Rebecca Vigen, M.D., M.S.C.S., of the University of Texas at Southwestern Medical Center, Dallas and colleagues evaluated the association between the use of testosterone therapy and all-cause mortality, myocardial infarction (MI; heart attack), and stroke among male veterans and whether this association was modified by underlying coronary artery disease (CAD). The study included 8,709 men with low testosterone levels (<300 ng/dL) who underwent coronary angiography in the Veterans Affairs (VA) system between 2005 and 2011. There was a high level of co-existing illnesses among this group, including prior history of heart attack, diabetes, or CAD. Of the 8,709 patients, 1,223 (14.0 percent) initiated testosterone therapy after a median (midpoint) of 531 days following angiography. The average follow-up was approximately 2 years, 3.5 months. The primary measured outcome for the study was a composite of all-cause mortality, heart attack, and ischemic stroke.

The researchers found that the proportion of patients experiencing events 3 years after coronary angiography was 19.9 percent in the no testosterone therapy group (average age, 64 years) and 25.7 percent in the testosterone therapy group (average age, 61 years), for an absolute risk difference of 5.8 percent. Even accounting for other factors that could explain the differences, use of testosterone therapy was associated with adverse outcomes and was consistent among patients with and without CAD. The increased risk of adverse outcomes associated with testosterone therapy use was not related to differences in risk factor control or rates of secondary prevention medication use because patients in both groups had similar blood pressure, low-density lipoprotein levels, and use of secondary prevention medications.

“These findings raise concerns about the potential safety of testosterone therapy,” the authors write. “Future studies including randomized controlled trials are needed to properly characterize the potential risks of testosterone therapy in men with comorbidities.”
“Perhaps the most important question is the generalizability of the results of this study to the broader population of men taking testosterone: men of this age group who are taking testosterone for ‘low T syndrome’ or for antiaging purposes and younger men taking it for physical enhancement,” writes Anne R. Cappola, M.D., Sc.M., of the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, in an accompanying editorial.

“Are the benefits—real or perceived—for these groups of men worth any increase in risk? These populations represent a sizable group of testosterone users, and there is only anecdotal evidence that testosterone is safe for these men.”

“In light of the high volume of prescriptions and aggressive marketing by testosterone manufacturers, prescribers and patients should be wary. There is mounting evidence of a signal of cardiovascular risk, to which the study by Vigen et al contributes. This signal warrants both cautious testosterone prescribing and additional investigation.”
(doi:10.l001/jama.2013.280387)

Carnitine (L-carnitine) works as an antioxidant to fight free radicals

Overview

Carnitine helps the body turn fat into energy. The body makes it in the liver and kidneys and stores it in the skeletal muscles, heart, brain, and sperm.

Carnitine is found in avocados

Usually, the body makes all the carnitine it needs. However, when the body doesn't make enough or can't transport it into tissues, a supplement may be necessary.  Conditions, such as angina or intermittent claudication, can cause low levels of carnitine in the body, as can some medications.

Carnitine  acts as an antioxidant so may be effective in dealing with many conditions. Antioxidants fight harmful particles in the body known as free radicals, which damage cells and tamper with DNA.

Carnitine seems safe (but may not help much) with fatigue and improving athletic performance. For more serious conditions, a doctor should be consulted before using carnitine.

Health Conditions 

• Angina -- Some evidence shows that carnitine can be used along with conventional treatment for stable angina. Several clinical trials show that L-carnitine and propionyl-L-carnitine can help reduce symptoms of angina and improve the ability of people with angina to exercise without chest pain. Do not self-treat chest pain with carnitine, however.
• Heart attack -- A few studies have found that carnitine may help when used with conventional medicines after a heart attack, but not all studies agree. Some small studies suggest that people who take L-carnitine supplements soon after a heart attack may be less likely to have another heart attack, die of heart disease, have chest pain and abnormal heart rhythms, or develop heart failure. However, other studies have shown no benefit. Treatment with oral carnitine may also improve muscle weakness. Carnitine should be used along with conventional medication under your health care provider supervision.
• Heart failure -- A few small studies have suggested that carnitine (usually propionyl-L-carnitine) can help reduce symptoms of heart failure and improve exercise capacity in people with heart failure. However, more studies are needed to know for sure.
• Peripheral Vascular Disease -- Decreased blood flow to the legs from atherosclerosis or hardening of the arteries (where plaque builds up in the arteries) often causes an aching or cramping pain in the legs while walking or exercising. This pain is called intermittent claudication, and the reduced blood flow to the legs is called peripheral vascular disease (PVD). Several studies show that carnitine can help reduce symptoms and increase the distance that people with intermittent claudication can walk. Most studies have used propionyl-L-carnitine. 
• Diabetic Neuropathy -- Diabetic neuropathy happens when high blood sugar levels damage nerves in the body, especially the arms, legs, and feet, causing pain and numbness. Some small preliminary studies suggest acetyl-L-carnitine may help reduce pain and increase feeling in affected nerves. It is also possible that carnitine can help nerves regenerate. More research is needed.
• Exercise Performance -- Although carnitine is often taken to boost exercise performance, there is no evidence it works.
• Weight Loss -- No scientific evidence exists to show that L-carnitine works for weight loss. Some studies do show that oral carnitine reduces fat mass, increases muscle mass, and reduces fatigue, which may contribute to weight loss in some people.
• Alzheimer's Disease and Memory Impairment -- The evidence is mixed as to whether carnitine is useful in treating Alzheimer's disease. Several early studies showed that acetyl-L-carnitine might help slow down the progression of Alzheimer's disease, relieve depression related to senility and other forms of dementia, and improve memory in the elderly. But larger and better-designed studies found it didn’t help at all. People should take carnitine for Alzheimer's and other forms of dementia only under the supervision of their health care provider.
• Kidney Disease and Dialysis -- Because the kidneys make carnitine, kidney disease could lead to low levels of carnitine in the body. Your health care provider may prescribe carnitine for kidney disease, don't take it without medical supervision.
• Male Infertility -- Low sperm counts have been linked to low carnitine levels in men. Several studies suggest that L-carnitine supplements may increase sperm count and mobility.
• Erectile Dysfunction -- Preliminary studies suggest propionyl-L-carnitine may help improve male sexual function. One study found that carnitine improved the effectiveness of sidenafil (Viagra) in men with diabetes who had not previously responded to Viagra. In another study, a combination of propionyl-L-carnitine and acetyl-L-carnitine improved the effectiveness of Viagra in men who had erectile dysfunction after prostate surgery. More studies are needed.
• Peyronie's Disease -- One study compared acetyl-L-carnitine to the medication tamoxifen in 48 men with this condition. Acetyl-L-carnitine worked better than tamoxifen at reducing pain during sex and reducing the curve of the penis. Acetyl-L-carnitine also had fewer side effects than tamoxifen. More research is needed.
• Hyperthyroidism -- Some research suggests that L-carnitine may help prevent or reduce symptoms of an overactive thyroid, such as insomnia, nervousness, heart palpitations, and tremors. In one study, a small group of people with hyperthyroidism saw these symptoms improve, and their body temperature become normal, when taking carnitine. Researchers think carnitine may work by blocking the action of thyroid hormone, which could be dangerous for people with low thyroid levels. Don’t take carnitine for hyperthyroidism without your doctor’s supervision.

Dietary Sources
Red meat (particularly lamb) and dairy products are the main food sources of carnitine. It can also be found in fish, poultry, tempeh, wheat, asparagus, avocados, and peanut butter.

Available Forms
Carnitine is available as a supplement in a variety of forms.

• L-carnitine: the most widely available and least expensive
• Acetyl-L-carnitine: Often used in studies for Alzheimer's disease and other brain disorders
• Propionyl-L-carnitine: Often used in studies for heart disease and peripheral vascular disease

Avoid D-carnitine supplements. They interfere with the natural form of L-carnitine and may produce unwanted side effects. In some cases, L-carnitine may be taken by prescription or given intravenously by a health care provider.


Source: Carnitine (L-carnitine) | University of Maryland Medical Center http://umm.edu/health/medical/altmed/supplement/carnitine-lcarnitine#ixzz2j2Hel9ep
University of Maryland Medical Center
Follow: @UMMC on Twitter | MedCenter on Facebook

Repairing the heart with stem cells

Repairing the heart with stem cells, from the March 2013 Harvard Women's Health Watch

BOSTON—Stem cells have the potential to grow into a variety of cell types, including heart cells. Could they possibly be used to repair and regenerate heart tissue damaged by a heart attack? To answer that question, the March 2013 Harvard Women's Health Watch asked a leading stem cell expert to weigh in on this experimental treatment.

A recent study from Cedars-Sinai Heart Institute in Los Angeles suggests that stem cells may, indeed, heal damaged hearts. The researchers treated 17 heart attack survivors with an infusion of stem cells taken from their own hearts. A year later, the amount of scar tissue had shrunk by about 50%.

These results sound dramatic, but are they an indication that we're getting close to perfecting stem cell therapy? "This is a field where, depending on which investigator you ask, you can get incredibly different answers," says Dr. Richard Lee, professor of medicine at Harvard Medical School and a leading expert on stem cell therapy.

"The field is young. Some studies show only modest or no improvement in heart function, but others have shown dramatically improved function," he says. "We're waiting to see if other doctors can also achieve really good results in other patients."

Studies are producing contradictory results partly because researchers use different methods to harvest and use stem cells. Some are taken from the bone marrow of donors, others from the recipient's own heart. It's not clear which approach works the best.

"Some investigators think this is just a few years away," says Dr. Lee. "And then there are others who feel that there is much more work to be done."

Right now, stem cell therapy is available only to people who participate in a research trial. Anyone who has had a heart attack or who is living with heart failure and wants to take part in a stem cell study can visit www.clinicaltrials.gov and search for trials in their area (for example, search "stem cells," "heart," "Los Angeles").

Read the full-length article: "Repairing the heart with stem cells"

Also in the March 2013 issue of the Harvard Women's Health Watch:

• Update on hormone therapy
• Needling away chronic pain
• Preventive mastectomy—is it worth the risks?

Harvard Women's Health Watch is available from Harvard Health Publications, the publishing division of Harvard Medical School, for $20 per year. Subscribe at www.health.harvard.edu/womens or by calling 877-649-9457 (toll-free).