Recently I was asked by a member of an audience during a webinar “How much should we investigate an asymptomatic diabetic patient for occult vascular disease?”. I said jokingly that it depends upon your clinical inertia or zeal. However, seriously this issue needs a considered thought. I regularly see such patients who have undergone stress echocardiography or evaluation of carotid-intimal thickness or even CT coronary angiography and then consult me when an abnormality is reported. Extreme variability in diagnostic work-up really surprises me. On one hand , there are patients who are long standing diabetics but never had a 12-lead surface electrocardiogram ( even though we know that these patients are prone to silent myocardial infarction or may have prognostically important information in ECG );on the other hand stress testing is performed in such a routine manner by many enthusiasts. You could argue that we can go by the guidelines and perform relevant tests if there are atypical symptoms, abnormal ECG, some kind of claudication , vascular bruit or calcium scoring as a risk enhancer in a diabetic with normolipidemia. All these indications are stretchable and hence have class II recommendations in all guidelines which means the testing may be desired but not mandatory. The same applies to cardiac biomarkers even though data suggest that there is prognostic information hidden in these biomarkers.
Let us dissect the problem. What is the purpose of non-invasive or invasive cardiac evaluation in asymptomatic patients ?. We want to find out if the patient has underlying coronary, carotid or peripheral vascular disease. We also want to find out if the patient has heart failure. Excuse me, is not heart failure a clinical syndrome of effort intolerance?. So, how can an asymptomatic patient have heart failure?. Okay, you want to find out if the patient has asymptomatic systolic or diastolic dysfunction. That appears logical because it will risk stratify my patient. What are the chances of having systolic dysfunction in an asymptomatic patient with normal ECG and chest skiagram?. Very small. So what about diastolic dysfunction?. Alright, you have a point that by performing echocardiogram, you will know about diastolic dysfunction. Now I have performed an Echo-Doppler study which shows grade 1 or indeterminate diastolic dysfunction. So, I shall label this patient having pre-clinical diabetic cardiomyopathy which is a high risk phenotype. That is correct. How will I treat this patient?. Now I have hit a road-block. There is no study which says that by administering a specific lusitropic drug, I can change the future course of this patient. See, I am in a zero-sum game. Majority of such patients have hypertension and anti-hypertensive drugs will improve diastolic function by unloading the left ventricle and the left atrium. Would not you treat hypertension anyway. You may suggest, I will use anti-renin -angiotensin drugs if diastolic dysfunction is present. Is there data in its favor? Unfortunately , no study has shown any advantage of this class of agents unless albuminuria is present. Your last straw couldbe that I will use SGLT2 inhibitors if there is pre-clinical cardiomyopathy. Do we have any study supporting this contention ? . unfortunately , none. If there is some evidence, it is tenuous at best.
Now let us come to the issue of unearthing subclinical vascular disease. A number of physicians are keen to detect subclinical vascular disease in patients with diabetes mellitus and go to length to do so. What happened to the hypothesis that diabetes itself is equivalent to vascular disease ?. However, let us assume that you find a positive stress test in such a patient. What is the next step? Would you perform invasive angiography and possible revascularization for obstructive disease ?. Is there evidence that such a strategy helps these patients ?. Even in symptomatic patients , COURAGE and ISCHEMIA trials have shown no incremental benefit of revascularization over medical management. You can also advance the argument that after detection of vascular disease, aggressive treatment would be initiated. Aggressive treatment includes statins, aspirin, beta-blockers and angiotensin-converting enzyme inhibitors. Most diabetic patients , in any way, are on moderate or high intensive statin therapy. Aspirin only works if there has been a previous vascular event and hence there is class IIb recommendation ( no study has been performed to show its efficacy in asymptomatic vascular disease). ASCEND trial in large number of middle-aged and elderly diabetics showed no net benefit of aspirin for primary prevention. Majority of patients are prescribed anti-renin-angiotensin-aldosterone axis drugs either for control of hypertension or to slow down albuminuria progression. Hence the argument of aggressive medical therapy in patients with asymptomatic vascular disease is fallacious and facetious.
Then, there is diagnostic and therapeutic inertia. Simple urine test for proteinuria may not be done. Vaccination against pneumonia or flu may not be advised. There is gross under-utilization of statin therapy. Of course, control of dysglycemia remains dismal in two-thirds of the patients. Why not take small cost-effective steps rather than waste resources on unproven hypothesis of uncovering asymptomatic or subclinical vascular disease. Consider this view when you treat your next patient with diabetes.
1.Boden WE, O’Rourke RA, Teo KK, et al. Optimal medical therapy with or without PCI for stable coronary disease. N Engl J Med 2007;356:1503-1516
2. Maron DJ , Hochman JS, Reynolds HR et al.Initial Invasive or Conservative Strategy for Stable Coronary Disease. New Engl J Med 2020;382:1395-1407
3. The ASCEND trial collaborative Group. Effects of Aspirin for Primary Prevention in Persons with Diabetes Mellitus. New Eng J Med 2018;379:1529-1539