We know high cholesterol causes heart attacks, but does it also cause heart failure?

It is well known that high levels of cholesterol in the blood can lead to heart attacks and strokes by triggering the buildup of plaque in the arteries, which can then break off and lodge in the heart or elsewhere. New research has shown that cholesterol can also cause heart failure, which is characterized by the inability of that organ to pump enough blood to supply oxygen throughout the body.

Heart failure affects 5.7 million Americans, with medical costs this year totaling $37.2 billion. About three-quarters of all cases are caused by high blood pressure. It is marked by shortness of breath, swelling in the lower extremities resulting from fluid buildup, fatigue and difficulties in carrying out everyday tasks, confusion and memory loss, and heart palpitations.

The most common treatment for heart failure is a drug that lowers blood pressure. But trials of the family of cholesterol-lowering drugs called statins in the prevention of heart attacks indicated that they also reduced the incidence of heart failure. Some researchers, however, thought this reduction was simply a benefit from the reduction in heart attacks in those receiving the drugs. Most previous studies have been inconclusive because patients in them already had heart disease, which clouded any conclusions that might be drawn.

To investigate, a team led by Dr. Daniel Levy of the National Heart, Lung and Blood Institute went back to the massive Framingham Heart Study, a decades-long study of the residents of the eponymous Massachusetts community. They identified 6,860 participants, none of whom had heart disease when they were enrolled. The group had an average age of 44 at the beginning of the study, and 54% were women. They were followed for an average of 26 years.

The team reported today in Circulation: Journal of the American Heart Association that 680 of the participants had developed heart failure. That group included:

-- 12.8% of those with low levels of high-density lipoprotein (HDL), the so-called good cholesterol, but only 6.1% of those with desirable levels of HDL;

-- 13.8% of those with high levels of low-desnity lipoprotein, the so-called bad cholesterol, compared with only 7.9% of those with desirable levels of LDL.

When the team adjusted for age, sex, body weight, smoking, blood pressure, diabetes and other factors, they concluded that those with high levels of undesirable LDL had a 29% greater risk of suffering heart failure, while those with high levels of desirable HDL had a 40% decreased risk of heart failure. Even when they took heart attacks into account, the results showed a statistically significant risk of heart failure associated with high levels of cholesterol.

Because the study was not a clinical trial, Levy said, it should not alter how physicians prescribe cholesterol-lowering drugs. Beyond drugs, he added, the best ways to improve cholesterol levels  include physical activity, stopping smoking, limiting alcohol consumption and eating a diet high in monounsaturated fats such as olive oil.

— Thomas H. Maugh II

Consumers didn't have the information they needed on this lemon: Vioxx

Thirty studies involving more than 20,000 people demonstrated an increased risk of heart attacks and strokes linked to the drug Vioxx, which was taken off the market in 2004 after generating billions of dollars annually in sales. However, this information was not easily accessible to the public, and the Food and Drug Administration's reservations about the drug were lost in a blizzard of direct-to-consumer marketing, according to a study and commentary published today in the Archives of Internal Medicine.

The analysis showed that safety concerns about Vioxx, a nonsteroidal anti-inflammatory manufactured by Merck & Co., arose at least four years before the drug was withdrawn. Under new FDA rules, however, manufacturers are now required to disclose the results of post-market safety studies.

"Substantial amounts of clinical trial data that have rarely been fully used to understand drug efficacy or safety will now be available and can be used by independent investigators to complement and corroborate surveillance done by the FDA and the manufacturers," the authors wrote in the paper.

The issue is crystallized further in a commentary by Dr. Lisa M. Schwartz and colleagues of the Veterans Affairs Outcomes Group. They point out that the FDA, as the repository of post-marketing surveillance studies, is a weak opponent to the media-savvy and heavily funded pharmaceutical industry.

"The Vioxx story really highlights the difference between marketing and informing," Schwartz wrote in the commentary. "If physicians and patients had had the facts, it would have taken an alchemist, not a marketing department, to turn this lemon into gold."

The new FDA rules requires public disclosure of study results on the ClinicalTrials.gov database within 12 to 24 months of completion. This should help prevent future Vioxx-type incidents, Schwartz wrote, but patients and doctors should be able to get this information, unfiltered, directly from the FDA. "For this to happen, the FDA needs to make what its reviews know more accessible. ... But it will take a lot of work to keep this information from being drowned in the sea of industry marketing. It's a pretty deep sea. Merck spent $500 million promoting Vioxx in 2003 alone."

-- Shari Roan

Photo credit: Daniel Hulshizer / Associated Press

Don't blame Starbucks: Cops may have poorer health due to night shifts

Midnight shift workers often find it hard to get enough quality sleep on a consistent basis. Police officers are not exempt, often working late shifts and overtime as part of their job.

A new study finds that their schedule may cause cops to develop metabolic syndrome, a cluster of symptoms including high blood pressure, insulin resistance and high trigylcerides that advance development of such conditions such as stroke, cardiovascular disease, and type 2 diabetes.

The research, published in the current issue of Archives of Environmental & Occupational Health, focused on 98 police offers who were part of the Buffalo Cardio-Metabolic Occupational Police Stress study, which began in 2003. The participants had their blood pressure checked, took a blood test and had their waist circumference measured. They also filled out a questionnaire focusing on lifestyle choices such as sleep habits, physical activity, and smoking and alcohol use.

Researchers discovered that in general, those on afternoon and midnight shifts were younger than those working during the day, and predominately male. Overall, 30% of the police officers on the night shift had metabolic syndrome. In the general population, that number was 21%, taken from the National Health and Nutritional Examination Survey. The younger officers on the night shift (average 36.5 years) also had higher rates of metabolic syndrome than age-matched men and women in the general population, who came in at 24%.

Waist circumference was larger and HDL "good" cholesterol levels were lower among night shift cops compared to the general population and to officers working day and evening shifts. Officers working nights who got less than six hours of sleep had higher averages of metabolic syndrome factors than day shift workers.

"One potential explanation for this unusual finding is that midnight shift officers were most likely to be sleep deprived because of difficulties associated with day sleeping," said John Violanti, the study's lead author, in a news release. The research associate professor at the University of Buffalo's department of social and preventive medicine added, "Sleep debt has been shown to have a harmful impact on carbohydrate metabolism and endocrine function, which could contribute to metabolic disorders."

In the study, the authors wrote, "Information gained through this study may be useful to aid further investigation of not only police officer health, but also the health of those in other first-responder occupations."

--Jeannine Stein

Photo credit: Allen J. Schaben / Los Angeles Times

More evidence that Transcendental Meditation helps the heart

Transcendental Meditation has been around for many years and is perhaps the most scientifically tested of all forms of meditation. Two studies presented this week add to the evidence that this form of stress reduction benefits people with heart disease and those at high risk for it.

One study, presented on Monday at the American Heart Assn.'s annual meeting, found that heart disease patients who practice TM have almost 50% lower rates of heart attacks, stroke and deaths compared to similar patients who don't practice meditation. The study was funded with a $3.8-million grant from the federal government and was conducted at the Medical College of Wisconsin in collaboration with the Institute for Natural Medicine and Prevention at Maharishi University of Management in Fairfield, Iowa, a major center of TM research.

The study followed African American men and women over nine years. The participants were randomly assigned to practice the stress-reducing TM technique or attend traditional health education classes on heart disease prevention.

The results of TM were so striking, it was as if the participants who meditated were taking a new class of medications, the authors said.

"Previous research on Transcendental Meditation has shown reductions in blood pressure, psychological stress, and other risk factors for heart disease, irrespective of ethnicity," the lead author of the study, Dr. Robert Schneider, said in a news release. "But this is the first controlled clinical trial to show that long-term practice of this particular stress reduction program reduces the incidence of clinical cardiovascular events."

In the second study, published today in the American Journal of Hypertension, researchers found that TM was an effective tool to reduce blood pressure, anxiety, depression and anger among college students at risk for high blood pressure.

Scientists at American University in Washington, D.C., and Maharishi University randomly assigned 298 students to either learn TM techniques or remain on a waiting list for the class. After three months, the students practicing TM had reductions of 6.3 millimeters of mercury (mm Hg) in systolic blood pressure and 4.0 mm Hg in diastolic. The reductions translate to a 52% lower risk of developing hypertension in later years. The students also showed improvements in psychological distress and coping.

-- Shari Roan

Photo: The meditation room at UCI Medical Center. Credit: Bob Chamberlin  /  Los Angeles Times

Even ancient Egyptians suffered hardening of the arteries, CT scans show

CT scans of Egyptian mummies, some as much as 3,500 years old, shows evidence of atherosclerosis or hardening of the arteries, which is normally thought of as a disease caused by modern lifestyles, researchers said today. "Atherosclerosis is ubiquitous among modern-day humans and, despite differences in ancient and modern lifestyles, we found that it was rather common in ancient Egyptians of high socioeconomic status," said co-author Dr. Gregory Thomas, a cardiologist at UC Irvine. "The findings suggest that we may have to look beyond modern risk factors to fully understand the disease."

"Perhaps atherosclerosis is part of being human, as we are observing the footprint of the same disease process in people who lived thousands of years ago," added co-author Dr. Michael I. Miyamoto, a cardiologist at the UC San Diego School of Medicine."The possibility that humans throughout time might share the same predisposition to the development of certain afflictions was poignantly illustrated to us" by the study, presented at the American Heart Association meeting in Orlando.

The study was conceived by Thomas after he read the nameplate of Pharoah Merenptah in the Museum of Egyptian Antiquities in Cario. The nameplate says that, when he died at age 60 in 1203 BC, Merenptah was plagued by atherosclerosis, arthritis and dental decay. Because atherosclerosis is characterized by calcium in plaques, Thomas reasoned that some evidence of the disease might still be present even after so long. He organized a team of cardiologists and Egyptologists who scanned a series of 20 mummies in the Egyptian Museum during the week of Feb. 8, 2009. The scanning was performed on a Siemens machine permanently installed at the museum.

Among the 16 mummies who had identifiable arteries or hearts, nine had calcification clearly seen in the arteries or in the path where the arteries should have been. The disease was clearly age-related. Seven of the eight who were over the age of 45 when they died had calcification, compared to only two of eight that were younger than 45. Men and women were affected equally. The most ancient of the mummies afflicted with atherosclerosis was Lady Rai, who had been a nursemaid to Queen Ahmose Nefertiti. She died at the age of 30 to 40 around 1530 BC, about 300 years prior to the time of Moses and 200 years before King Tut. Other mummies examined died as recently as AD 364.

The findings should, perhaps not have been surprising. The high-status Egyptians ate a diet high in meat from cattle, ducks and geese, all fatty. Because mechanical refrigeration was not available, salt--another constributing factor in heart disease--was widely used for preservation. Maybe the question that should be asked is why they didn't have higher levels of disease.

-- Thomas H. Maugh II

Top: Mummy of Esankh (male, Third Intermediate Periodm 1079-712 BC) undergoing scanning.

Middle: Mummy of Djeher (male, Ptolemaic Era, 304-30 BC) entering scanner.

Bottom: Mummy of Esankh undergoing preparation for CT scanning.

Credit: Dr. Michael Miyamoto

U.S. cholesterol levels going down

The development of statins, a class of drugs that lower bad cholesterol, have made a big effect. A study published today found that the prevalence of American adults with high levels of LDL cholesterol (that's the bad kind) fell by about one-third from 1999 to 2006. Paradoxically, the study also found that a huge number of people still have excessively high levels of bad cholesterol, are not being treated for it or may even be unaware of their levels.
 
The study, published in the Journal of the American Medical Assn., examined LDL cholesterol levels among more than 7,000 men and women across four study cycles: 1999-2000, 2001-2002, 2003-2004 and 2005-2006. Rates of high LDL cholesterol decreased from 31.5% in 1999-2000 to 21.2% in 2005-2006.
 
Yet researchers from the federal government found that many people had elevated rates of bad cholesterol, particularly those at the highest risk for developing heart disease. Fewer than 70% of adults nationwide were screened for cholesterol levels in the 2005-2006 period. During that time period of the study, 64.5% of people received cholesterol screening, 39.6% were screened but were untreated or inadequately treated and 24.9% were not told the results of screening.
 
In two commentaries accompanying the study, experts noted that cholesterol screening guidelines have become too complex and should be simplified so that more people receive statins. Dr. J. Michael Gaziano and Dr. Thomas A. Gaziano noted in one editorial that the last set of cholesterol guidelines, published in 2002, was 280 pages long. The guidelines are not only complicated, they are far from perfect, sometimes leading doctors to prescribe statins to someone with elevated LDL cholesterol but who has an overall low risk of heart disease and not prescribing drugs to someone with normal LDL cholesterol but who has an overall high risk of developing heart disease.
 
Another approach to treating cholesterol, said the authors of the other commentary, is to prescribe generic statins to all adults based on age. This approach may be justified, they said, in light of the large number of people who could benefit from statins but are not getting the medication; because statins have been shown to be safe and because generic versions of the medications are inexpensive. 

However, that approach may overly simplistic, said Michael Gaziano and Thomas Gaziano. Arbitrary, fixed LDL thresholds for prescribing statins should be abandoned, they said.

"The guideline should begin with simple risk assessment with the goal of classifying patients into only two strata: those for whom lipid-lowering therapy should be considered and those for whom it is not warranted," they wrote. "The use of a simplified risk-based approach could increase the ease of implementation of treatment and increase the number of patients receiving beneficial lipid-lowering therapy."
 
-- Shari Roan
 
Photo credit: Bob Chamberlin / Los Angeles Times

Rapid, irregular heartbeats while exercising may not spell doom

The feeling can be scary: While exercising, the heart begins to beat quickly and irregularly for a short period of time. No wonder, then, that many people who experience it stop working out, afraid that they might have a heart attack.

Despite previous studies showing a link between that type of rapid heartbeat (called non-sustained ventricular tachycardia) and sudden death, a new report suggests that people without underlying heart disease may have little to fear.

Researchers examined data on 2,234 men and women ages 21 to 96 in the Baltimore Longitudinal Study of Aging who did at least one treadmill test that measured the heart's ability to pump. In that group, 3.6% developed non-sustained ventricular tachycardia with exercise that lasted, on average, about three to six heartbeats at about 175 beats per minute.

Death rates overall were higher in the group with tachychardia than the non-tachycardia group (29% versus 16%), and were higher among men and increased with age. However, after adjusting for gender, age, and people who early on developed heart disease risk factors, there was no significant increased risk between the groups of death overall, or death from heart disease, or having a heart attack.

"So long as a medical examination shows no underlying heart disease or other serious health condition, then people should continue to live a normal lifestyle, including a return to exercise after clearance from their physician," said the study's lead author, Dr. Joseph Marine, in a news release. "Our results suggest that brief, non-sustained ventricular arrhythmia during exercise testing should, generally, not cause undue alarm in patients or physicians," added Marine, an associate professor at the Johns Hopkins University School of Medicine.

The research was presented Monday at the American Heart Assn.'s annual Scientific Sessions conference in Orlando, Fla.

-- Jeannine Stein

Photo credit: Rick Meyer / Los Angeles Times

FDA says don't use Prilosec or Nexium with Plavix

The Food and Drug Administration warned today that patients taking the blood-thinning drug Plavix should avoid taking the acid reflux medications Prilosec and Nexium because they can interfere with Plavix's activity, reducing its efficacy by half. Plavix, which helps prevent the formation of clots, is usually prescribed after bypass surgery or angioplasty, especially when a stent is implanted to keep arteries open, and is the world's second-best-selling drug (behind the cholesterol-lowering drug Lipitor), with global sales of $8.6 billion per year.

Researchers have been warning about the potential interaction for some time now, but the overall strength of the interaction has not been clear. In January, Sanofi and Bristol-Myers, which distribute Plavix, updated the medication's label to caution against using it with the drugs. A Sanofi spokesman said today that the label would be updated to say that the two heartburn drugs should be avoided altogether.

The FDA said patients who take Plavix and need to reduce acid reflux should take drugs from a different family, such as Mylanta or Zantac. Other drugs that should be avoided for the same reason include Tagamet, Diflucan, Nizoral, Intelence, Felbatol, Prozac, Luvox and Ticlid. The agency said there is not enough data yet to determine if other drugs in the same family as Nexium and Prilosec -- which is sold over the counter by the generic name esomeprazole -- such as Protonix, also present a risk. "There is not enough data to tell us how these drugs interact with" Plavix, Mary Ross Southworth, the FDA's deputy director for safety of cardiovascular products, said at a news conference.

Both Prilosec and Protonix, however, were shown to be dangerous in a study released Monday at the American Heart Assn. meeting in Orlando, Fla. Researchers at Mount Sinai Medical Center in New York studied 8,311 patients who had balloon angioplasty -- in which a catheter is inserted into the coronary artery and a balloon inflated to crush plaque that could otherwise break off and form clots -- and who received a drug-releasing stent to keep the artery open. The researchers found that 17% of the patients were taking either Prilosec or Protonix. During the five years of follow-up, those taking Prilosec or a generic form had a 72% higher risk of death than those not taking any heartburn drugs, while those taking Protonix had a 54% higher risk. Surprisingly, they found no increased risk with Nexium, which has the same active ingredient as Prilosec.

Other studies, however, have given mixed results, with some finding no interaction between the two drugs. The FDA said the new warning came on the heels of a 150-patient study submitted to the agency by Sanofi over the summer that showed the risks.

-- Thomas H. Maugh II

Phorto: Plavix, which is often prescribed after bypass surgery, such as this procedure being performed at Bakersfield Heart Hospital, and heartburn drugs Prilosec and Nexium do not mix, the FDA said today. Credit: Ricardo DeAratanha / Los Angeles Times

New heart-assist device significantly improves survival in heart failure patients

 Mechanical pumps originally designed to supplement the pumping action of a failing heart and keep the patient alive until a transplant could be found have taken a major step toward becoming a permanent treatment, a development that could expand their use to tens of thousands of patients in the United States alone. The key to the improvement is the development of a new smaller, quieter, more reliable pump that is less likely to break down and need to be replaced -- an outcome that requires the patient to undergo a second major surgery.

The pumps are called left ventricular assist devices or LVADs. They are not meant to replace the entire heart, only to assist in the pumping action of the left ventricle, which pushes blood out through the aorta to the body. Researchers originally thought that LVADs had to mimic the action of the heart, pushing out blood in a series of pulses that were timed to coincide with pulses from the heart itself. That required complex machinery to produce the pulses and sophisticated electronics to synchronize them with the heart. Such devices had a high propensity to fail.

But more recently, researchers have concluded that a simple, continuously operating pump can work just as well, if not better. Such pumps typically have only one moving part -- the impeller -- and don't need to be synchronized with the heart, so their reliability is much greater. They are also much smaller, typically only about one-seventh the size of older models.

New results presented today at the Orlando, Fla, meeting of the American Heart Assn. show that one such device, manufactured by Thoratec Corp. of Pleasonton and called the HeartMate II, doubled the two-year survival of heart failure patients compared with the older pulsing pump. The device is currently approved by the Food and Drug Administration only as a bridge to a transplant.

"We had a sense that these smaller devices were going to have better long-term outcomes, and this trial proves it," said Dr. Alfred A. Bove, president of the American College of Cardiology, who was not involved in the research. "These devices have come a long way in five years. I expect that technology will continue to move things forward and they will be even better five years from now."

The need is great. An estimated 150,000 Americans have advanced heart failure that could be treated with a heart transplant, but there are only about 2,100 donors available in a given year. The big issue in the future may be not the availability of the devices but their cost and the strain that they will put on the healthcare system. The Thoratec pump costs about $80,000 and the surgery to implant it an additional $45,000. With thousands of patients needing the device, costs could mount quickly.

In the new trial, headed by researchers from Duke University Medical Center and the University of Louisville, researchers at 38 centers in the United States enrolled 200 heart failure patients between the ages of 26 and 81. All had failed medical therapy for their condition and were considered too sick to be candidates for a transplant. About two-thirds of the patients received the HeartMate II, and the rest received an older version that pumps in pulses.

The team reported in Orlando and in a report published online in the New England Journal of Medicine that  patients receiving the new pump lived longer and had a higher quality of life than those receiving the older one. One year after the original surgery, 68% of those with the new pump were still alive, compared with 55% of those who received the older pump. But at two years, the results were much more dramatic: 58% of those who received the HeartMate II were still alive, compared with only 24% of those receiving the old pump. Similar patients receiving only medical therapy typically survive for only about six months, and fewer than 10% survive two years.

"The survival differences are compelling and provide a rationale to begin exploring use of continuous-flow LVADs earlier in the heart-failure continuum," said Dr. Joseph G. Rogers of Duke, a co-author. One reason for the better survival rate is the reliability of the new device. About one-third of the older pumps failed during the experiment and had to be replaced, compared with only 10% of the new ones.

In addition to survival, the devices also improved quality of life. "Patients with continuous-flow LVADs could walk twice as far, on average, as those with a pulsatile-flow device," said Dr. Mark Slaughter of Louisville, a co-author. "Patients with continuous-flow devices went from being unable to walk any distance at all without being short of breath to being able to walk the length of three football fields, on average. This is hugely significant for these patients."

The Thoratec device is not the only one attempting to capture this market. A similar device developed by Heartware International Inc. of Australia has been shown to keep as many as 80% of patients alive for two years in smaller clinical trials.

The bottom line of the studies: An editorial by Dr. James C. Fang of University Hospitals Case Medical Center in Cleveland in the New England Journal accompanying the new report said, "The first priority would be to make sure patients and physicians are aware that ventricular assist therapy is available, effective and safe for well-selected patients. Second, we should not delay referral until surgical morbidity and mortality become prohibitive. ... The optimal time for referral is most likley before the development of major complications from heart failure."

The new study was funded by Thoratec.

-- Thomas H. Maugh II

Photo: The HeartMate II is operated by a controller that fits on the belt. Credit: Thoratec Corp.

Screen a heart, save a life

The tragedy of a young athlete dying is sometimes compounded by the discovery that he or she had an undiagnosed heart condition. And while those deaths due to heart rhythm disturbances are rare in young people (about 3,000 a year), some health experts believe heart screenings are the way to prevent those deaths.

A new study found benefits in screenings, particularly an echocardiogram, or an ultrasound of the heart that provides more details than an x-ray; and an electrocardiogram, or EKG, which evaluates the heart's electrical activity. Researchers collected health histories and did screenings on 134 male and female Maryland high school athletes at the state track and field championships in 2008. They specifically looked for cardiac abnormalities such as hypertrophic cardiomyopathy, or thickening of the heart muscle that makes it more difficult for the heart to pump blood.

The screenings included taking the athletes' blood pressure and listening for abnormal heart rhythms or murmurs, in addition to the echocardiogram and EKG.

Researchers found no life-threatening heart defects among the study participants. However, abnormalities were discovered in 36 athletes, including high blood pressure, elevated blood pressure, and low blood pressure. Of those irregularities, 22 were found via EKG alone, nine by echocardiogram alone, and five were discovered via both tests.

In a news release, study co-author Dr. Theodore Abraham of the Johns Hopkins University School of Medicine said, "If you are going to screen, it has to be comprehensive. An EKG does show you a lot, but it doesn't tell you the whole story. The advantage of a comprehensive screening is that it is holistic, rather than being pinpoint."

The study was presented yesterday at the American Heart Assn.'s annual Scientific Sessions conference in Orlando, Fla.

--Jeannine Stein

Photo credit: Gina Ferazzi / Los Angeles Times