The Diminishing Returns of Reducing Medical Risk

In the United States, the issues that patients ask about during routine medical check-ups have been changing. Reports of physical symptoms like chest pain, shortness of breath and racing heartbeats have been giving way to concerns about numerical abstractions without any physical manifestations: results from a lab test, a few high blood pressure measurements or a blood sugar report showing mildly elevated values. It is normal for even a healthy person to have values slightly outside the normal range, but a growing number of patients have been showing me their meticulously documented “abnormalities” and anxiety over these has become commonplace.

Many patients now take risk factors for heart disease as seriously as medical staff do—perhaps even a little more seriously—but the actual health improvements gained from this attitude are questionable. Medical science recommendations for risk reduction have become increasingly subject to the law of diminishing returns. Attitudes towards the most prominent risk factors for heart disease provide a good example of the way in which our efforts at risk reduction have begun to go a little too far.

Blood Pressure

There was once a lively debate on which was more likely to cause fatality: high or low blood pressure (BP). While it is now well understood that low BP tends to produce better outcomes than high, doctors were concerned about the dangers of lower than average BP for many years, until their fears were disproven by evidence gathered by the life insurance industry. Since then, worries about high BP have led to tighter and tighter recommendations as to the upper threshold needed to reduce the likelihood of things like heart attacks and strokes.

Unfortunately, as with many risk factors, the efficacy of BP treatments follows a U-shaped curve—meaning that, while initial efforts to lower BP can be effective, additional treatments can cause more harm than good. It is difficult to design trials of BP treatments since patients vary widely in their age, the number of medications they take and their baseline level of risk. Slightly hypertensive patients may benefit from the new drug protocols—or they might simply end up taking yet another pill, which offers them only minimal benefits.

The wide variety of different expert recommendations on how to manage BP confuse the issue even more. Here in the US, the last Joint National Commission update (JNC8) produced significant controversy: it left it unclear as to what a “controlled” BP should look like, since scientific trials in this area vary so much, as do expert interpretations of their findings. In fact, as Dr Steven Hatch has summarized, “the process of producing JNC8 was so fraught with contentiousness that the entire method by which national guidelines are generated is unlikely to continue.”

Medical guidelines in different countries often deviate from each other in subtle yet perplexing ways. For example, the US, European and Canadian guidelines all recommend slightly different ideal BP values. Patients who are considered mildly hypertensive in the US are viewed as healthy in Europe. When we lower the threshold for treatment, we automatically create millions of new hypertensive patients overnight, and the benefit this affords to any given patient will vary considerably.

Blood Sugar

Diabetes is associated with just about everything we doctors don’t like. Excessive sugar in the bloodstream irritates bodily tissues and can lead to blocked arteries from plaque build-up. Since diabetics are around twice as likely to get heart disease than nondiabetics of the same age, it is not surprising that health institutions have spent vast amounts of time and money combatting the disease.

This association with heart disease unfortunately transformed diabetes from a mere risk factor to be addressed into an equivalent of coronary artery disease (CAD) at the beginning of the twenty-first century. This was a controversial decision, largely based on small, unreliable studies that were sometimes composed of only one sex and failed to adequately control for confounding factors. Many diabetic patients have now been aggressively treated with high-dose statins for two decades, often taking a daily aspirin to boot—as if they had already suffered a heart attack.

The rhetoric about diabetes may sometimes be exaggerated—but it’s nothing in comparison to the hyperbole that surrounded the invention of prediabetes as a diagnosis. Prediabetes implies that you don’t yet have high enough circulating sugars to be considered a diabetic but are merely at risk of becoming one. A person diagnosed with prediabetes, then, is at risk of developing a risk factor.

Richard Kahn, the previous chief scientific and medical officer of the American Diabetes Association (ADA) has revealed that the diagnosis of prediabetes was created to raise awareness of diabetes despite uncertainty as to how much of a risk prediabetes actually poses for patients. Public health institutions spent billions on preventative programmes and research—money wasted according to Kahn, given the often neutral results. As Kahn points out, medical therapy for prediabetes has, at best, modest benefits and carries inherent risks of its own.

While diabetes poses a variable risk for the development of heart disease, a diagnosis of prediabetes may do nothing but raise an American patient’s insurance premiums. Unsurprisingly, Kahn now sees the ADA’s awareness-raising efforts as “a big mistake.”

The case of prediabetes shows that medical providers should hesitate to institute aggressive new treatments to combat something relatively trivial.

Fat

Like the early debates about blood pressure, the lipid hypothesis—which posits that elevated blood cholesterol is directly linked to the development of heart artery plaque (coronary artery disease) was fraught with controversy. Daniel Steinberg has detailed how difficult it was to get the medical community to accept the hypothesis initially, given the then general impatience with the notion of preventative practices. Our profession now takes cholesterol quite seriously and is making increasingly energetic efforts to all but eradicate low-density lipoproteins (LDL), and a significant proportion of the population have been prescribed statins to prevent or treat coronary artery disease. For some patients, these drugs have been lifesavers, but the threshold for treatment has gone from unreasonably high to all but non-existent.

This has had several knock-on effects. First, the realisation that blood cholesterol is a risk factor led to the inference that dietary cholesterol should also be aggressively reduced. This prompted public health officials to issue misleading dietary guidelines that inadvertently led to the consumption of unhealthier foods. But the heart healthy dietary recommendations still preach the evils of fat, creating a bias in the nutrition science milieu. Gordan Guyatt, one of the fathers of evidence-based medicine, learned this first hand when he published an extensive study on red meat consumption and its tenuous association with various diseases. Guyatt’s critics responded by saying that these findings would only “confuse the general public” and asked for the paper to be retracted.

The medical profession’s unwavering dedication to cholesterol reduction has also inadvertently boosted the careers of various online contrarians who argue that statins (one of the better treatments for high cholesterol) are not just over-prescribed, but completely useless and even harmful: that they are a form of “duct tape” that weakens the immune system or are “poison” to your body’s cells. Some even assert that high cholesterol is an “invented disease,” concocted by the US government and the medical establishment to sell statins. While there are various strands of truth among these claims, the anti-statin coalition seem to have no interest in a balanced discussion. Unfortunately, medical experts have responded equally poorly by dismissing those concerned about statins as akin to anti-vaxxers and accusing them of fearmongering. This is not exactly a helpful way of addressing the real concerns the public may have about these medications.

Medical scientists like Maryanne Demasi have raised legitimate questions about the evidence in favour of statin treatments, but most medical societies have responded by simply doubling down on aggressive anti-cholesterol treatments. Some are now also recommending the reduction of triglyceride cholesterol, despite the fact that it is more weakly associated with cardiovascular disease than LDL and that the perception of risk is mainly attributable to a single industry-funded trial, which has been used to create a  meta-analysis. This has not stopped the CDC from approving expensive new therapies to treat slightly high triglyceride levels, which could just as easily be managed through lifestyle changes.

The discovery that blood cholesterol is a risk factor in heart disease was a triumph for medical science, but, over time, overstatement of the risk involved has produced confusing dietary recommendations and a polarized narrative as to how best to approach the treatment of individual patients.

Conclusions

The campaign to eliminate risk shows no signs of slowing down. Geza Halasz and Massimo Piepoli have  recently argued that heart disease “prevention should start … before birth … because events that occur early in life have a great impact on the cardiovascular risk profile of an adult.”

Risk reduction does not get much more extreme than this.

As H. Gilbert Welch has written: “Chronic disease epidemiology has hit the flat of the curve.” The ongoing debates as to how aggressively blood pressure, cholesterol and sugar should be controlled can feel like arguments over lines in the sand. Many physicians now classify more than one fifth of medical care as unnecessary, and there are a growing number of initiatives aimed at combatting over-treatment.  But the good news is that the fact that doctors are now focused on increasingly tenuous associations and smaller degrees of effectiveness is itself a mark of just how competent modern healthcare is at treating severe disease. Whatever unwanted side effects result from the risk-reduction industry, that fact alone is surely worth celebrating.