Letters to the Editor

Cardiology Review® Online, July 2007, Volume 24, Issue 7

I read the article by Scognamiglio and Fraccaro1 about coronary artery disease in asymptomatic diabetic patients with interest. I was amazed that there were no significant differences in coronary artery disease (CAD) determined by angiography in patients with multiple risk factors versus those with few risk factors. As a family physician interested in preventive cardiology in patients both with and without diabetes, I have to report that my experience has been different. (I speak mostly in regards to symptomatic CAD, particularly in terms of average age of onset of atherothrombotic disease (ATD), which includes peripheral vascular, cerebrovascular, and coronary vascular atherothrombosis). In terms of clinical ATD, few patients in my practice with diabetes (1% [1/96] of male and 9% [8/88] of female) exhibit any clinical evidence of ATD (including positive angiograms) in the absence of cigarette-smoking, dyslipidemia, and/or hypertension. The age of ATD onset for diabetic patients without the aforementioned risk factors is 60 for the sole male and an average of 75 for the females.2 Perhaps the discrepancy between my experience and those of the authors arises from the definition of dyslipidemia. I define dyslipidemia using what I term the cholesterol retention fraction (CRF), calculated as (low-density lipoprotein [LDL]— high-density lipoprotein [HDL])/LDL. The CRF is abnormal at > 0.70, or since HDL is unable to compensate for unlimited LDL, at any LDL level of ≥ 170 mg/dL (4.4 mmol/L). I have termed the combination of these 2 values the cholesterol threshold (CThr).3 Using CThr as the definition of dyslipidemia, 66% (63/96) of male and 51% (45/88) of female ATD patients with diabetes in my practice have dyslipidemia. By defining hypertension as systolic blood pressure (SBP) > 140 mm Hg, then 70% (67/96) of male and 76% (67/88) of female patients (both with ATD and diabetes) have hypertension. Finally, including current and past cigarette smokers to represent cigarette-related ATD, then 80% (77/96) male and 43% (38/88) female patients (again both with ATD and diabetes) have cigarette smoking (current or past) as a risk factor.2 The Figure presents a risk predictive tool integrating CRF, SBP, and cigarette smoking.3 Of all ATD patients in my practice, 85% have CRF-SBP plots above the threshold line. Of the 15% of ATD patients with CRF-SBP plots below the threshold line, most (9% of total ATD patients) of these patients are current or former cigarette smokers. That leaves only 6% of all ATD patients in my practice that could not have been predicted by CRF-SBP plot above the threshold line and/or cigarette smoking status— and such patients are quite old at age of ATD onset (78 years in males and 75 years in females). This amounts to virtual immunity to ATD. This 6% figure holds true even when the graphs are done separately for hypoglycemic, impaired glucose tolerance, and diabetic patients. Regarding patients with diabetes and ATD whose CRF-SBP plots lie below the threshold line and who never smoked cigarettes, the average age of ATD onset was 60 years for males (3 patients, 1 of whom had chronic hepatitis and treated hypertension, and 1 of whom was exposed to passive smoking, leaving only 1 71-year old who had treated hypertension but was not otherwise compromised) and 72 years for females (1 of whom had radiation therapy for Hodgkin's Disease and 2 of whom were exposed to passive cigarette smoking, leaving only 5 females not otherwise compromised, who had an average age of ATD onset of 76 years). The uncompromised male died at 84 years old and the uncompromised females had an average age of death of 83 years. My point in writing is that patients with diabetes whose CRF-SBP plots lie below the threshold line and who have never smoked cigarettes are at little risk of early onset ATD. I would be interested to hear the authors' response.

Figure. Atherothrombotic disease risk predictive tool. Cholesterol retention fraction is

defined as ([low-density lipoprotein — high density lipoprotein]/low-density lipoprotein).

William E. Feeman, Jr, MD

Bowling Green, Ohio

1. Scognamiglio R, Fraccaro C. Coronary artery disease in asymptomatic diabetic patients. Cardiol Rev. 2007;24(5):21-24.

2. Feeman WE Jr. How to decrease the cardiovascular death rate in diabetic patients with cardiovascular disease. Poster presented at the 2003 Annual Scientific Assembly of the American Academy of Family Physicians; October 1-5, 2003; New Orleans, La.

3. Feeman WE Jr. Prediction of the population at risk of atherothrombotic disease. Exp and Clin Cardiol. 2004;9:(4):235-241.


In Reply

Although Dr Feeman is surprised at our findings of no significant difference in coronary artery disease (CAD) determined by angiography in asymptomatic patients with multiple risk factors versus those with few risk factors, his letter describes his experiences with mostly symptomatic patients. We reiterate that our study enrolled only asymptomatic patients with diabetes, hence this is an warranted and confusing comparison. In this clinical setting, we demonstrated that among patients with myocardial perfusion defects there were no significant differences in the prevalence of CAD independent of risk factor profile. The letter contains a second, confusing opinion. In fact, the low prevalence of clinical atherothrombotic disease (ATD) including peripheral vascular, cerebrovascular, and coronary vascular atherothrombosis reported by Feeman is not in line with the real world. It's sufficient to cite the autopsy study by Goraya et al1 showing that, among diabetic decedents without clinical CAD, almost three-fourths had high-grade atherosclerosis and more than one-half had multivessel coronary disease. Finally, about the definition of dyslipidemia, it is mandatory to follow American Diabetes Association guidelines.2 This letter is quite important because several reported observations in it are not supported by controlled studies and these observations inform the current diagnostic and therapeutic approach to ischemic heart disease in diabetic patients. The diagnostic approach proposed in our study3 allowed us to identify an early phase of CAD in asymptomatic patients with diabetes, and the favorable anatomy of coronary vessels (with the high prevalence of 1-vessel disease) has the potential to improve results of revascularization procedures and to reduce the rate of cardiac events in asymptomatic patients with diabetes.

Roldano Scognamiglio, MDChiara Fraccaro, MD

University of Padua Medical School

Padua, Italy

1. Goraya TY, Leibson CL, Palumbo JP, et al. Coronary atherosclerosis in diabetes mellitus. A population-based autopsy study. J Am Coll Cardiol. 2002;40(5):946-953.

2. American Diabetes Association. Standards of medical care in diabetes (position statement). Diabetes Care. 2005;28(suppl 1):S4-S36.

3. Scognamiglio R, Negut C, Ramondo A, et al. Detection of coronary artery disease in asymptomatic patients with type 2 diabetes mellitus. J Am Coll Cardiol. 2006;47(1):65-71.