Call it the wages of sin, the price so many Americans pay for their love affair with high-fat foods. Sure, there's a genetic component to dangerously high cholesterol levels, but it's love of butter, ice cream and well-marbled meat that puts so many at increased risk of clogged arteries that can lead to heart attacks and strokes. Statins were breakthrough drugs to lower blood cholesterol, but now federal health officials are reminding us that all drugs carry health risks along with their benefits.
By the Numbers
High total cholesterol is defined as 240 mg/dL(milligrams per deciliter) and those at such levels carry twice the risk of heart disease as individuals with lower levels. A healthy level of total cholesterol is considered to be less than 200 mg/dL. Numbers in between are considered borderline high, a gray area in which patients increasingly have been encouraged to use pharmaceuticals to lower their levels.
Since the late 1980s, a class of drugs known as statins has been a lifesaver for millions who couldn't, with dietary changes alone, lower their levels of low-density lipoprotein (LDL), also known as the "bad cholesterol." Statins originally were approved for those who already had suffered a heart attack after initial studies showed the medication could help prevent a repeat heart attack.
Since then, some eight, single-ingredient statins and three combination products have come to market, some around long enough to have spawned generic equivalents. Today, one in four Americans older than 45 takes a statin. As people age, odds increase they will take one of the drugs; some 36 percent of women ages 65 to 74 take a statin and a full 50 percent of men in that age bracket take one of these prescription drugs aimed at lowering their cholesterol.
Those prescriptions may well be one of the reasons the number of Americans with high cholesterol has dipped. Average cholesterol levels have reduced in recent decades from 222 mg/dL in the early 1960s to about 200 today -- significantly lower, but still considered borderline high risk. The CDC estimates that one in six Americans has high cholesterol, though some 20 percent have never had their blood tested and don't know their numbers.
New Warnings
When the FDA first approves a drug, it's for a specific use. Statins initially were targeted to prevent second heart attacks. But once on the market, companies work hard to expand the number of patients taking a drug, and now statins are used widely for primary prevention of heart attacks or strokes. Often, it's only after a drug has been on the market for years and large numbers of people take it that unexpected side effects surface. That's what seems to have happened with statins. So after more than two decades of use by millions of people worldwide, the Food and Drug Administration has issued new warnings on the pharmaceuticals' labels. Because of concern over increasing reports of memory loss as well as evidence of increases in blood sugar levels -- a precursor to type 2 diabetes -- the FDA has revised its labeling on cholesterol-lowering drugs including Lipitor, Lescol, Mevacor, Altoprev, Livalo, Pravachol, Crestor and Zocor.
Memory Loss
The FDA reviewed its database called the Adverse Events Reporting System and examined a review of studies on statins' effect on memory. Investigators found a very low risk among men and women, age 50 and older, of memory loss or changes in thinking skills. Sometimes the loss was noted within days of starting the drugs; sometimes it was noticed years after statin exposure. In any case, the problem disappeared when statin use was discontinued.
The reports are all the more surprising since there have been studies looking at the relationship between dementia and statins. Many of those studies have been inconclusive, but several have suggested the opposite: that statins actually lower the risk of dementia.
Blood Sugar and Diabetes Risk
The new FDA label also warns patients that taking a statin may increase their odds of developing type 2 diabetes. Again, the FDA looked at its database of adverse events and also at analyses of several large studies and found, among people who used statins, an increased risk of higher blood sugar levels (known as prediabetes) as well as a small increased risk of developing type 2 diabetes.
Controversial Drugs
Statins have had a bumpy history. They have been hailed as miracle drugs and equally vilified as drugs that are overprescribed and insufficiently understood.
The pharmaceutical industry has sponsored dozens of studies on statins, each attempting to establish a benefit in the prevention of diseases far removed from cardiovascular conditions: Alzheimer's disease, rheumatoid arthritis and some cancers including those affecting the prostate and breast. The studies largely have proved inconclusive.
What has really driven the growth of statin use has been the belief that statins could help prevent not just a second heart attack but also reduce the risk of a first heart attack in healthy people with high cholesterol. Called primary prevention, it has resulted in prescriptions for millions of people who feel just fine but whose LDL number is high.
Recently, treatment decisions have gone even further. Based on a large-scale trial called JUPITER (Justification for the Use of Statins in Primary Prevention), the study found that healthy people with normal levels of cholesterol, but elevated levels of a protein called C-reactive protein (a cardiovascular risk factor that is independent of cholesterol) could benefit from statin treatment.
No sooner was the JUPITER study released, heavily backed by pharmaceutical industry makers of statins, when skeptics began questioning its conclusions. Among the questioners were experts who wrote an article in 2010 in which they offered this concluding advice to fellow physicians: "...do not forget diet, exercise, weight loss, and risk factor control (life-style modification trumps pharmacologic intervention for primary prevention, but if patients do not modify their lifestyle, statins can be used judiciously."
So over the years, indications for the drugs have cast an ever-widening net: from people with high LDL who had already suffered a heart attack; to otherwise healthy people with high LDL; to people with normal cholesterol levels who might otherwise be at risk for heart disease. At a recent, national meeting of cardiologists, new research, was presented supporting an effort to reduce cholesterol in the younger population.
A Brief History of Statins
The scientific quest to understand the plaque that builds up in arteries and is responsible for the sometimes fatal blocked blood flow to the heart and brain began more than half a century ago. That's when researchers were shocked to learn from autopsy studies that 75 percent of soldiers killed in Korea -- whose average age was 22 -- already were showing signs of coronary plaque build up.
Scientists also were studying laboratory animals, feeding them concoctions of what was a typical American diet: steak, mashed potatoes and gravy pureed with banana as a flavor enticement for their subjects, rhesus monkeys. When the primates ate the goop, it took no time at all for them to go from having healthy arteries to having severe atherosclerosis or arteries blocked by plaque. Then, in the 1970s, scientists proved that by changing the diet back to bananas and greens, the damage to the arteries of the lab monkeys could be reversed.
Such animal studies, along with autopsy studies of soldiers, were the basis for a search for a pharmaceutical way of lowering cholesterol in the blood. And in the 1980s, thanks to the Nobel Prize-winning work of Drs. Michael Brown and Joe Goldstein, science began to understand how cholesterol works within the body. With that understanding, it was only a matter of time before the first statins appeared on the market, becoming what the industry calls a blockbuster drug.
People were dying because of clogged arteries, and there's no doubt that the discovery of statins has saved countless lives.
But these new FDA warnings offer a cold dose of reality: before we start indiscriminately dumping statins into the water supply as an easy way to reduce cardiovascular disease, we must individually -- patient by patient -- examine the tradeoffs.
If you're on a statin, talk to your physician about these new warnings. If you're talking the herbal red yeast rice, which has statin-like qualities, you also should discuss your situation with your physician. Be alert to side effects involving memory and plan with your doctor to watch your blood sugar levels while taking statins. It's long been known, too, that statins can cause muscle pain and inflammation -- and signs of these also should be discussed with your physician. Some of the statins also can interact with other drugs including antibiotics, HIV drugs, some heart drugs and the ingestion of large amounts of grapefruit juice (more than one quart a day).
The evidence is clear that statins reduce the risk of a second heart attack for patients who have already suffered one. And for otherwise healthy patients with cardiovascular risk factors such as hypertension, diabetes, elevated C-reactive protein, or a strong family history of heart attacks occurring at an early age who have tried and failed to control high cholesterol through lifestyle changes, statins may be an appropriate choice.
But the best preventive steps, before cholesterol levels climb dangerously high, are those old standbys: Don't smoke, exercise regularly, eat a Mediterranean-style diet rich in fruits and vegetables and drink alcohol only in moderation.