Diagnosing The Course of Cardiovascular Disease in the US

You may have heard the old adage, "The art of medicine consists of amusing the patient while nature cures the disease.” To some degree, that quip from Voltaire in 1773 still rings true today. Modern medicine is very good at treating acute illnesses with amazing, lifesaving technology, but not so good at altering the course of chronic degenerative diseases. Once diagnosed with a chronic illness, the course is predictably downhill, punctuated by periods of relative reprieves and remissions.

The United States’ reduction in cardiovascular disease since the 1960s, though, has been a shining exception to that rule. As one of the few preventive health measure practices the country can claim to be the best in the world, cardiovascular disease reduction in the US stands out in a healthcare system which Walter Cronkite once famously noted is “neither healthy, caring, nor a system.”

The influence of atherosclerosis on coronary artery disease has been well-established as far back as ancient Greece, when the former word originated from a combination of the words “groats” and “hardening.” Though coronary artery and carotid artery disease wasn’t frequently diagnosed until about 50 years ago, investigators soon tracked its peak incidence: approximately one-third of Americans, mostly men, were dying from the condition.

It was deemed an epidemic of crisis proportions, leading to a huge amount of research and resources allocated to combating it. While it was initially believed to be a disease of just wealthy countries—due to lavish lifestyles—investigators soon found the burden of cardiovascular disease is mostly in underdeveloped countries.

In the 1940s, University of Minnesota investigator Ancel Keys, PhD, MS, postulated that the apparent epidemic of heart attacks in middle-aged American men was related their lifestyle. He observed a higher rate in more affluent men, who smoked and ate high fat meals. He began a study in 1947 looking at professional men from Minnesota, which in 1961 confirmed the results of larger studies that enumerated various risk factors and their role in causing cardiac disease. These included elevated blood pressure, high blood cholesterol levels, and cigarette smoking. Keys went on to recruit researchers in several countries with varied cultures to look at the effect of different diets, and different cultural characteristics and the incidence of cardiac disease.

The so-called 7 Country Study established the lipid hypothesis, which stated that LDL cholesterol caused atherosclerosis, and saturated fat increased LDL cholesterol; therefore, saturated fat was a major driver for developing heart disease. In 1948, the Framingham heart study identified several risk factors for coronary artery disease which included hypertension, age, family history, male sex, smoking, fat intake, obesity and cholesterol as risk factors. That study continues to this day, evaluating the offspring of the original study participants and includes 3 generations of families.

The results of these and other major studies established the basis of our current approach to prevention of heart disease. Drugs were developed to successfully treat hypertension, lipids and diabetes. Interestingly enough, effective blood pressure medications were not available until after World War II. President Roosevelt, who suffered from hypertension, was known to have blood pressures as high as 300/130 and was advised to reduce his smoking from 3 packs a day to 2, take phenobarbital (which he did), and avoid stress. His hypertension eventually led to vascular dementia, and ultimately, cerebral hemorrhage.

From the mid-1960s until the end of the 1980s, there was a remarkable decline in cardiovascular mortality of approximately 50%. Why? Better diagnostic tests, better drugs, better surgery, reduced smoking, decreased fat intake, the advent of Medicare and Medicaid, more public awareness? Take your pick. No one knows for sure, because too many things changed. Several expert panels were convened to look at what was responsible for this great, and largely American, success story.

Something interesting happened in the late 1980s: our sophisticated tracking tools began to notice that the great decline in cardiac disease began to level off and plateau. Surveillance programs provided the first warnings. When Millicent Higgins and Thomas Thom presented data from the United States at the 1988 National Heart, Lung, and Blood Institute (NHLBI) workshop on international comparisons, they showed that the rate of decline had dropped from 4% in the late 1970s, to 3% in the 1980s—a concerning trend accompanied by a rise in obesity.

The national rate of decline slowed again, from 3% to 2.7% in the 1990s. Adverse trends in risk factors dimmed prospects for continuing decline. Some risk models predicted an eventual rise in cardiovascular mortality, and indeed, the US Centers for Disease Control and Prevention reported in 2016 that heart disease deaths actually increased by 3% from 2011-2014.

But an issue greater than that returning increase may be that cardiac disease is still responsible for about 50% of the population’s annual death rate. Why people still dying from diseases brought on by preventable causes?

Scientists have recently questioned our approach to diet, and the recommendation to reduce saturated fat intake and drastically increase carbohydrate intake. Salim Yusuf, MD, the president of the World Cardiology Foundation, published a recent epidemiologic trial involving 150,000 patients in 20 countries showing that carbohydrate intake, rather than saturated fat, was the main driver of atherosclerosis.

Others have questioned our traditional diagnostic methods. The Cleveland Clinic reports that 50% of people who get heart attacks and stroke have “normal cholesterol.” Our diagnostic tools may be not be precise enough. We learned that lipoprotein analysis was far more precise at predicting risk, but still not as precise as we would like. There is a cohort of patients in the Framingham trial who had extremely high LDL cholesterol yet lived into their 90s. This suggests that cholesterol levels are not very good at predicting risk.

Coronary calcium scores and traditional stress testing are just not good enough to assess risk at an early stage. By the time a traditional stress test is positive, there is significant occlusion of coronary arteries.

Our medicines may not be the wonder drugs they are touted to be; some blood pressure-lowering therapies can increase cardiac disease risk. Pharmaceutical companies once believed that raising HDL levels with medications would result in a changing of tides; several decades and billions of dollars later, they now understand such drugs increase cardiac risk. For decades, it’s been known that some diabetes treatments actually increase cardiac risk at such a substantial rate the US Food and Drug Administration (FDA) requires any new diabetes drug to prove its cardiac safety prior to approval.

Despite a reduction in smoking rates to the lowest ever recorded, dramatic reductions in the intake of saturated fat, and better surgical techniques, cardiovascular mortality remains high. Even if there isn’t a significant increase in incidence, the question remains: why are half of all at-risk patients being missed?

In future articles, we will discuss advanced diagnostic testing—which currently exists, and is being used by cutting-edge cardiologists. We will focus on the major drivers for atherosclerosis: inflammation, insulin resistance, endothelial dysfunction, genetic predisposition, and lipoproteins. And we will address the need to establish early diagnoses and pursue improved patient outcomes: treatments and diagnostic tools that don’t lead to actionable changes are merely expensive toys.

Simon Murray, MD, is an internist based in Princeton, NJ. The piece reflects his views, not necessarily those of the publication.Healthcare professionals and researchers interested in responding to this piece or contributing to MD Magazine® can reach the editorial staff here.