As a doctor, many of my friends are also doctors, which means I often hear stories that stay with me. One of these stories happened when a colleague shared that he had a heart attack, despite having a coronary calcium score of zero and an entirely unremarkable angiogram.
In retrospect, he should not have been surprised. The fact that angiographic technologies miss a substantial fraction of coronary heart disease (CHD) has long been an open secret in cardiology. For decades, patients who presented with anginal chest pain but showed no significant obstruction on coronary angiography were often dismissed as hypochondriacs or suffering from “Syndrome X”, which was then thought to be a benign condition treated with cognitive therapy or antidepressants.1 The fact that many of those “hypochondriacs” or those with “panic disorder” went on to drop dead of a heart attack did not provoke much alarm in the field.2
Then, in 2017, cardiology underwent a major “sea change” with the introduction of the term "Ischemia with No Obstructive Coronary Arteries" (INOCA) by a National Heart, Lung, and Blood Institute (NHLBI) workshop. It was to designate those patients with objective evidence of myocardial ischemia in the absence of significant coronary artery stenosis.3 Since that seismic shift, there has been a steadily increasing body of evidence demonstrating that INOCA is a serious, often fatal part of the CHD spectrum.
In retrospect, the seriousness of INOCA presentations such as those experienced by my colleague should have been obvious. In 2012, Jespersen and colleagues published a study of 11,223 patients who underwent angiography for suspected stable CHD. Amazingly, 65% of the women and 32% of the men in the study had no significant obstruction. Despite “normal findings” these patients went on to experience between 50 to 85% more cardiac events than their matched controls.
Thankfully, now in 2025, major medical societies now recognize INOCA and have offered guidelines on how to diagnose it.4 These recommended methods, however, tend to be invasive, costly, and not widely available to the vast majority of the public.
Fortunately, PrecisionCHD™ was designed to both recognize INOCA presentations and provide personalized insights of disease drivers. At the most recent American Heart Association meeting, we presented data showing that the epigenetic indices in PrecisionCHD™ can sensitively and specifically detect INOCA.5 In addition, these indices provide a “molecular fingerprint” of the disease pathology in all CHD patients and provide specific treatment insights for those experiencing INOCA. It is ideal for assessing CHD in those from a rural setting or in healthcare systems such as the Veterans Administration Hospital system, which generally do not have the advanced infrastructure and typically have long waitlists to see providers.
Patients have the right to the best diagnostic evaluation, one that truly reflects their risk rather than the test that happens to be most readily available. Traditional approaches can be invasive, involve radiation or contrast dye, and still miss a substantial portion of early disease. Alternatively, there is an approach that can identify both obstructive and non-obstructive CHD and provide personalized insights to help guide treatment decisions.
For me, the evidence points to a clear choice, selecting a test that avoids unnecessary risk while offering comprehensive diagnostic accuracy.
Request an at-home test today.
1. Kaski, J.C., G. Aldama, and J. Cosin-Sales, Cardiac Syndrome X. American Journal of Cardiovascular Drugs, 2004. 4(3): p. 179-194.
2. Smoller, J.W., et al., Panic Attacks and Risk of Incident Cardiovascular Events Among Postmenopausal Women in the Women's Health Initiative Observational Study. Archives of General Psychiatry, 2007. 64(10): p. 1153-1160.
3. Bairey Merz, C.N., et al., Ischemia and No Obstructive Coronary Artery Disease (INOCA). Circulation, 2017. 135(11): p. 1075-1092.
4. Hansen, B., et al., Ischemia with No Obstructive Arteries (INOCA): A Review of the Prevalence, Diagnosis and Management. Current Problems in Cardiology, 2023. 48(1): p. 101420.
5. Philibert, R., et al., DNA Methylation Strongly Predicts Level of Coronary Artery Obstruction and Ischemia with No Obstructive Coronary Artery Spectrum Presentations in those with Acute Coronary Syndrome. Circulation, 2025. 152(Suppl_3): p. A4364789-A4364789.
