We are all now abnormal and all shall have a pill

No, it’s not your imagination. They really said that.

As news media reported (verbatim from the press release), a new study published in the American Heart Journal found that nearly two-thirds of patients admitted to hospitals for heart attacks and cardiovascular events had low LDL-cholesterol levels, indicating they were not at high risk for heart problems. Yet — in another extraordinary example of ad-hoc reasoning — the authors concluded that since most heart attacks are occurring in people with low cholesterol levels, that this provided support for lowering the LDL-cholesterol goals even further.

They never applied Occam’s razor and considered the simpler, more obvious explanation: that cholesterol is a flawed risk factor and doesn’t predict who will go on to have a heart attack! Even the headline writers seemed to get that “cholesterol levels may not measure cardiac risk.”

Remember when? If this sounds familiar, it’s akin to the reasoning used by the American Heart Association in its latest Guidelines for Cardiovascular Disease Prevention in Women when it decided that all women were at “high risk” for heart disease — because nearly all heart attacks occur in women without risk factors. Rather than admit that the risk factors themselves are poor measures for predicting heart disease, the guidelines called for treating the risk factors in nearly all women.

As covered in-depth here, none of the clinical trials the AHA used to support its new guidelines for women made their case at all. Multiple cardiologists examining the evidence, as well as several major studies published since the AHA guidelines, concluded cholesterol and, except for age, the traditional risk factors are next to worthless for predicting risks for heart disease, from Framingham scores to metabolic syndrome. Nor did the heart-healthy diets and lifestyle interventions in the AHA guidelines prove effective for the primary prevention of heart attacks or in reducing premature deaths.

Even the Cochrane Review of 39 clinical trials conducted in multiple countries over the course of three decades concluded that “heart-healthy” programs of diet and lifestyle changes “had little or no impact on the risk of heart attacks or death.”

This fact, continues to be replicated and confirmed in major randomized controlled clinical trials.

This new study in the news was conducted by Gregg C. Fonarow, M.D., chair of the Get with the Guidelines Steering Committee, and colleagues. This program is supported by the American Heart Association in part through an unrestricted education grant from the Merck Schering Plough Partnership. [*Author disclosures below.] The authors used the electronic medical records in the AHA’s Get with the Guidelines CAD program of 541 participating hospitals.

Between January 1, 2000 and April 30, 2006, a total of 231,896 patients had been hospitalized with cardiovascular disease. Their average age was 65 years. Just over half of these patients (59%) had had lipid levels drawn within the first 24 hours of admission. After excluding patients with heart failure, the authors used these 136,905 patients for their analysis. Fewer than half of those patients (45.6%) had a history of cardiovascular disease or diabetes, making these hospitalizations their first for heart problems.

The authors reported that half of the people hospitalized for heart disease, had LDL-cholesterol levels below 100 mg/dl, and 17.6% had LDL-cholesterol levels less than 70 mg/dl. The LDL-cholesterol levels among the patients were distributed, as most health indices are, in a bell-shape:

Is this indicative of any cholesterol level being of higher risk? Or, does LDL-cholesterol not appear to predict those with heart attacks and cardiovascular events? Clearly, the latter, but to these authors, normal is now abnormal.

Among these hospitalized heart patients, their average LDL-cholesterol levels were 104.9 ± 39.8, according to the authors. “People with LDL-cholesterol levels in the 100 to 130 range may feel they are at low risk,” Dr. Fonarow said to media, however: “In this study, there was nothing normal about having an LDL reading of 100.”

Instead, they suggested that normal levels should be redefined at even lower levels, concluding: “These findings may provide further support for recent guideline revisions with even lower LDL goals.”

They explained that the current National Cholesterol Education Program guidelines, first written in 2001, were updated in 2004 by lowering “optimal therapeutic goals” for LDL levels to <70 mg/dl for high risk adults. In its update of the guidelines, the NHLBI also called for weight loss and more physical activity to prevent heart attacks and other cardiovascular events, said Dr. Fonarow. "As much as 80 percent of the risk factors are under individual control and are modifiable." By modifying your lifestyle, he stated, you can reduce risk.

While the evidence clearly disproves these lifestyle claims, as we’ve seen, were the average LDL-cholesterol levels of 104.9 mg/dl among these patients actually associated with higher risks for cardiac events, as the authors asserted? To answer that, we can look at how these patients’ levels compare to those among the general population, most not suffering heart problems.

Doctors with the National Center for Health Statistics at the Centers for Disease Control and Prevention recently published the lipoprotein cholesterol levels of the U.S. population, as measured in representative samplings across the country in the National Health and Nutrition Examination Surveys (NHANES). The trends from 1960 to 2002 found no significant changes in serum triglyceride levels or HDL-cholesterol levels for more than forty years, and a small decrease in average LDL-cholesterol levels from 129 mg/dl to 123 mg/dl.

In other words, the people who end up hospitalized for heart problems have average LDL-cholesterol levels that are lower than the general population (104 versus 123 mg/dl). This clearly would not support a claim that lower LDL levels reduce cardiovascular risks — just the opposite.

Nor did lower LDL-cholesterol levels among the cardiac patients represent people more likely to already have heart problems and be being treated with cholesterol-lowering statins. Only 21.1% of the hospitalized patients had been on lipid-lowering statins (14.2% of those without a history of heart disease and 29.4% of those with a medical history of cardiovascular disease or diabetes). These are similar to the percentages among all adults of similar age in the general population, according to NHANES 1999-2002 data, which found 24.3% of men and 21.6% of women were taking cholesterol-lowering drugs.

Dr. Fonarow and colleagues, in fact, reported that the patients on statins had only modestly lower LDL-cholesterol levels (10 mg/dl), yet among those who had been taking statins, those who ended up hospitalized for heart problems had the lowest LDL-cholesterol levels — two-thirds had levels under 100 mg/dl and one-quarter under 70 mg/dl.

The news quoted Dr. Manesh Patel, an assistant professor of medicine at Duke University in Durham, North Carolina, as calling the study “excellent” and saying: “It’s quite possible that the cholesterol guidelines will be changed. Ongoing studies have led to getting the LDL level to 100 and then to 70.” The reporters failed to reveal that Duke Clinical Research Institute served as the data analysis center and analyzed the data for this study.

Medical research or marketing?

It is impossible to not recognize that lowering LDL-cholesterol thresholds mandating medical intervention — i.e. cholesterol-lowering statin drugs — mean more people to be prescribed with statins.

Coincidentally, another study made the news this week reportedly finding that 8 out of 10 men over age 50 should be on cholesterol-lowering statins and 6 out of every 10 women. This study’s conclusions would raise the total number of Americans for whom statins will be recommended by more than 11 million to 44.7 million adults, according to USA Today. Given the average cost of the popular statin, Crestor, for example, this would add $10 BILLION to the country’s medical bill. And drug company profits.

The source for this news story turned out to be based on that JUPITER clinical trial.

Remember when? Remember that huge controversy last November when the large JUPITER trial of the statin rosuvastatin (Crestor) had been stopped halfway through, invalidating any credible analysis of the benefits or effectiveness of the statin, and making safety and longer-term risks impossible for the medical community to evaluate? While this denounced move had been excused by claims of having already demonstrated dramatic, huge, spectacular and unprecedented benefits, when the data was finally released, it was found that actual (absolute) difference in mortality between the statin and control groups after nearly 2 years was only 0.25%, that troubling indications of adverse events were surfacing, and unprecedented percentages of study participants had stopped taking their study pills.

This added to a string of clinical trials and reviews suggesting that the benefits of lowering cholesterol were being overstated, and held potentially harmful effects for certain segments of the population, such as women, children and elderly.

In fact, JUPITER was viewed among many cardiologists as ending the cholesterol hypothesis. Dr. James Stein, M.D., from the University of Wisconsin Medical School in Madison told Heartwire, for example, that JUPITER demonstrated that current therapeutic LDL-cholesterol levels are arbitrary, but more importantly, a poor indicator of cardiovascular risk. “Many patients with heart attacks have normal LDL-cholesterol values,” he said.

This new study in the news was published in the journal Circulation Cardiovascular Quality and Outcomes. It was authored by Erica S. Spatz, M.D., and Robert Wood Johnson Clinical Scholar colleagues at Yale University School of Medicine. Dr. Spatz research was supported by RWJF. [Disclosure: As readers may remember, Johnson & Johnson pharmaceuticals purchased the world-wide marketing rights to the statin lovastatin (Mevacor) and the over-the-counter Zocor and had unsuccessfully petitioned the FDA to sell statins without a prescription.]

Essentially, these authors used the JUPITER trial to support recommendations for greater statin use — not only based on stricter LDL-cholesterol cut-offs, but even people without heart disease and “at goal LDL values” with “elevated” high-sensitivity C-reactive protein values were now said to benefit from statins. Using NHANES data to estimate total population numbers, they calculated Framingham scores to categorize risks and to identify the LDL-cholesterol levels that would now indicate statin treatment. For the current NCEP/ATPIII guidelines, they said: “We decided to use the lower treatment threshold as current clinical practice is moving toward the achievement of lower LDL values with medication therapy, more specifically with statin medications.

They determined that over half (57.9%) of the population of adults (all men age 50+ and women 60+) — an estimated 33.5 million people — should be on statins based on their risk assessment and current NCEP/ATPIII guidelines. Of this group, 42% were currently taking a statin. The remaining 58% were judged to be “undertreated” and labeled as being in the high-risk group.

Of the remaining people, their new “strict” JUPITER criteria added another 8.07 million people, with an additional 3.07 million meeting “extended” JUPITER criteria. Thus, they said, 80% of all mature adults now have an indication for statin therapy.

If the Get with the Guidelines authors get their way, the LDL-cholesterol treatment targets would be lowered still more. Never mind the evidence. It would appear they won’t stop until every American is taking statins every day for life.

© 2009 Sandy Szwarc

* Get With The Guidelines study author disclosures:

Gregg C. Fonarow, MD (chair) — research from Pfizer and GlaxoSmithKline; consultant and honorarium from Abbott, AstraZeneca, GlaxoSmithKline, Merck, Pfizer, and Schering Plough

Christopher P. Cannon, MD — grants: Accumetrics, AstraZeneca, Bristol-Myers Squibb, GlaxoSmithKline, Merck, Sanofi-Aventis, Schering Plough

Prakash C. Deedwania, MD — consultant to AstraZeneca and Pfizer

David Dai, PhD — employee of Duke Clinical Research Institute

Amit Sachdeva, MD; Kenneth A. LaBresh, MD; Sidney C. Smith, Jr., MD; Adrian Hernandez, MD (none)