Rise of the Lysenkoist Cardiologists

A review of the recent chest pain guidelines reveals ideology overshadows science

Science has a long history of being subsumed to serve rabid ideologues. Soviet biologist Trofim Lysenko famously rejected the objective reality of Mendelian genetics because it clashed with the Marxist philosophy that the environment, not genetics, was the primary determinant of outcomes. The Soviet party was enamored by Lysenko because his “Science” said that soaking crops in freezing water would educate them to sprout at different times of the year, and even more startlingly, this “education” would be passed down to future generations of crops.

Lysenko’s theories played into the brave new Marxist world that desperately needed to reject Western “capitalist” science that acknowledged genetic determinism. It didn’t matter that Lysenko’s plans to grow oranges in the barren soviet hinterlands sounded insane to farmers, the communist state put Lysenko in charge of modernizing Soviet agriculture. Disagreement with Lysenko’s science was met by ostracism, jail and death. The subsequent and frankly insane adoption of Lysenkoist agriculture lead to millions starving to death in the Soviet Union and China.

America faces its own version of Lysenkoist ideologues that have no interest in an objective reality that doesn’t suit a political narrative - and the world of cardiology is unfortunately no exception.

This latest assault on reality comes from a group of cardiologists desperate to convince the world that coronary disease afflicts men and women equally.

This is false.

While coronary disease is an important contributor to morbidity in both men and women, the objective reality is that men suffer from malignant coronary disease at much higher rates than women. Knowledge of this fundamental pillar of biology should drive how cardiologists approach men and women being evaluated for the presence of significant coronary disease.

This means that at every age, the probability a man complaining of chest pain has significant underlying coronary disease as a cause of this chest pain is much higher than a woman complaining of chest pain. Quantifying this difference to help clinicians arrive at probabilistic estimates was most famously done by authors Diamond and Forrester in the New England Journal of Medicine in the 1970s.

Diamond and Forrester accomplished this by first establishing the prevalence of coronary artery disease based on how clinically likely patients with chest pain symptoms were found to have coronary disease based on a coronary angiogram. Not surprisingly, a dataset of coronary angiograms and chest pain syndromes showed that the more classic the chest pain syndrome was, the higher the likelihood that angiographic coronary disease was present. Typical angina was defined as a symptom complex that includes substernal chest pressure or pain that was made worse with exertion/emotional stress, and relieved by rest or nitroglycerin. Atypical angina is classified as having any two of the three symptoms, and non-anginal pain any one of the three symptoms. Impressively the presence of significant coronary disease is so prevalent in symptomatic patients in this dataset that 15% of patients with “non-anginal” chest pain were found to have significant coronary disease.

So given that angina classifications aren’t enough, Diamond & Forrester added in another unique dataset that pooled ~25,000 patients by age and gender who did not have known coronary disease and had autopsies performed. The results of this dataset by age and gender follow.

Marked differences can be seen in the prevalence of coronary artery stenosis at autopsy by age and gender. In 30-39 year old women the rate of coronary stenosis at autopsy was 5/1,545 (0.3%) while 60-69 year old men had a prevalence of 12%, almost 40 times higher.

Combining these two datasets allows an estimation of the prevalence of coronary disease by type of chest pain, age and gender.

The numbers are a testament to the vast biological differences that exists in the prevalence of significant coronary disease between men and women.

More recent studies of coronary calcium (another surrogate of coronary disease) show the same thing. In the MESA study, men had higher calcium scores than women and the amount and prevalence of calcium increased steadily with age. Almost two thirds of women (62%) had calcium scores of zero as opposed to 40% of men.

The CDC wonder database that tracks mortality data shows just how much more deadly heart disease is in men than women. The table below shows mortality from heart disease for men vs women in 2000. Men die of heart disease at more than two times the rate women die starting at the age of 35.

The data is overwhelming every way you can possibly look at it.

And yet the recent chest pain guidelines start with an interesting recommendation to “focus on the uniqueness of chest pain in women.”

The supporting text notes: “Traditional risk score tools and physician assessments often underestimate risk in women and misclassify them as having nonischemic chest pain.” The guidelines go onto quote the PROMISE trial and the BARI2D trial. The passage in its entirety for reference follows:

Women commonly presented with chest pain symptoms similar to men but also had a greater prevalence of other symptoms such as palpitations, jaw and neck pain, as well as back pain. Women also had more cardiovascular risk factors, including hypertension (66.6% versus 63.2%; P<0.001), hyperlipidemia (68.9% versus 66.3%; P=0.004), older age (62.4±7.9 years of age versus 59.0±8.4 years of age, P<0.001), cerebral or peripheral artery disease (6.2% versus 4.7%; P<0.001), family history of premature CAD (34.6% versus 29.3%; P<0.001), and sedentary lifestyle (53.5% versus 43.4%; P<0.001). Physician assessments often misclassify chest pain as nonanginal. The BARI 2D (Bypass Angioplasty Revascularization Investigation 2 Diabetes) trial reported that women with diabetes had a higher prevalence of angina than their male counterparts, with a lower functional capacity and a lower incidence of obstructive CAD

Nowhere in this paragraph will you find a word about the fact that outcomes for men (if reported) in every trial related to coronary disease show that men are actually at higher risk than women for the type of coronary artery disease that results in bad heart attacks and death. This particular passage references the fact women and men commonly complain of chest pain. The outcome data should make the good clinician less likely to work up women with advanced/potentially invasive cardiac imaging tests, and more likely to reassure women who have negative workups for the chest pain they are presenting with.

The guideline writers believe this to be bad medicine - they would regard it as a good thing to for the mass of women to get additional testing that leads to a diagnosis of “symptomatic” coronary artery disease.

There may be no better study to symbolize the dysfunction that has invaded cardiology than the VIRGO trial, a study examining the outcomes of young patients (18-55) presenting to the hospital with a heart attack. The study defines a relatively new term - MINOCA - which stands for Myocardial Infarction with Nonobstructive Coronary Arteries to describe the clinical scenario of patients presenting with a Chest pain syndrome that have evidence of cardiac injury, but turn out to have no blockages found that can be “seen”.

Coronary artery disease has traditionally been defined by the presence of disease that can be identified in the large epicardial arteries that course on top of the heart. While cardiologists have always recognized the presence of disease in the smaller arteries (microvascular disease), the presence of significant microvascular disease in the absence of epicardial disease is thought to be fairly rare.

The diagnosis typically requires classic clinical features, with no evidence of obstructive coronary disease, and typical findings of ischemia on functional studies. This happens. But its rare!

The push from certain quarters today is to suspect MINOCA on any patient with chest pain that turns out not to have epicardial coronary artery disease. Unsurprisingly, “MINOCA” turns out to be much more prevalent in women. But what should matter is outcomes not diagnoses. If women have more MINOCA, but the diagnosis doesn’t lead to a worse prognosis… who cares? It would be like diagnosing women with metastatic breast cancer, but finding that just as many women with metastatic breast cancer were alive in 5 years as women not diagnosed with breast cancer.

On the face of it, the Virgo study claims to find that MINOCA is just as bad as critical epicardial disease,

“Young patients with MINOCA were more likely women, had a heterogeneous mechanistic profile, and had clinical outcomes that were comparable to those of MI‐CAD patients.”

What is going on? Have we actually stumbled on a new, hitherto unrecognized phenomenon ?

“One‐ and 12‐month mortality with MINOCA and MI‐CAD was similar (1‐month: 1.1% and 1.7% [P=0.43]; 12‐month: 0.6% and 2.3% [P=0.68], respectively”

But there’s a whole lot of context missing.

1. In the modern era patients who survive a cardiac event to present to the hospital generally do well. The vast array of interventions that exist at hospitals now to take care of patients with acute cardiac conditions represent the amazing, almost miraculous progress made in cardiology over the past half century. Mortality still occurs, but the important point is that the vast majority of patients making it to the hospital will be alive in a year. Which is exactly what the numbers show.

2. MINOCA now encompasses Spontaneous Coronary Artery Dissection (SCAD), a rare condition that is known to manifest primarily in women and affects the epicardial coronary artery. The presentation for this condition is usually not subtle and presents with severe chest pain, electrocardiographic changes, and elevated cardiac biomarkers evident on blood tests. It’s not a conventional cause of heart attacks, but I don’t understand the decision to classify it under the MINOCA umbrella.

3. Despite padding the MINOCA numbers with SCAD, MINOCA is much rarer than conventional epicardial coronary disease. In the time period studied , ~2300 patients presented with epicardial coronary disease, while only ~300 patients presented with MINOCA. So no, there is no tsunami of MINOCA being missed.

4. In their haste to hyperventilate about MINOCA, the authors don’t highlight the high percentage of cardiac interventions that are needed in patients with conventional, common epicardial disease - 80% need a coronary stent and 10% need open heart surgery. To stay with the breast cancer example , this would be like pointing to equivalent outcomes between women with breast cancer and women with no diagnosis of cancer…. without mentioning the fact that women diagnosed with breast cancer had to undergo bilateral mastectomies and receive radiation and chemotherapy in order to achieve those great outcomes.

5. The amount of myocardial injury between MINOCA and epicardial coronary disease patients is starkly different. The numbers would be even more different if spontaneous coronary artery dissection that effects epicardial coronaries wasn’t included in MINOCA, but even so, the interquartile range of peak troponins ( a sensitive biomarker of amount of cardiac injury) is 1.6-29.7 for epicardial coronary disease, and 1.1 - 11.1 for MINOCA patients. IQR or Inter Quartile Range represents the range of the middle 50% of spread of troponins seen, and the damage seen here is three times more. More cardiac injury means more dead heart muscle, and a larger scar. Regardless of whether a difference in outcomes is going to be evident at a year, the patients presenting with heart attacks and epicardial coronary disease are objectively worse off.

To conclude, an objective summary of the data on gender and cardiac disease suggests that critical heart disease of the kind that may kill you is more prevalent in men, despite the best effort of today’s cardiac Lysenkoist’s working tirelessly to create an academic paper trail that says otherwise.

A clinician with any grasp on reality would work up men, on average, more aggressively for coronary disease than women. But these are words you won’t find in the chest pain guidelines of 2023.

Spin in science is supposed to be the provenance of banana republics where politicians decide what the science should say. The scientists that rise to the top in these systems provide answers the power structures want to hear. This would be how mediocre scientists like Lysenko rose to make policy for the Soviets. Unfortunately, the field of cardiology now has its own contemporary version of ideologues bending reality to serve a convenient narrative.

At best an approach that overdiagnoses women with coronary disease causes no additional harm. At worst, overdiagnosis results in lost time, lost money, un-needed medications, and un-needed invasive diagnostic procedures.

Not quite the makings of a winning strategy.

Patients be warned.

Anish Koka is a cardiologist. Follow him on twitter @anish_koka