Author + information
- aDivision of Cardiology, Kaiser Permanente Northern California, Oakland, California
- bDepartment of Medicine, University of California, San Francisco, San Francisco, California
- cDivision of Research, Kaiser Permanente Northern California, Oakland, California
- dCardiovascular Imaging Program, Cardiovascular Division, and Department of Radiology, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts
- ↵∗Reprint requests and correspondence:
Dr. Jamal S. Rana, Division of Cardiology, Kaiser Permanente Oakland Medical Center, 3600 Broadway, Oakland, California 94611.
“All animals are equal, but some are more equal than others.”
—George Orwell (1)
In 1998, Haffner et al. (2) reported that adults with diabetes had the same risk for future myocardial infarction (MI) as adults with previous MI who did not have diabetes. Consequently, in 2001, the Adult Treatment Panel III guidelines recommended that the presence of diabetes should be considered as a coronary heart disease (CHD) risk-equivalent (3). However, the notion that all patients with diabetes have a CHD risk-equivalent has been controversial (4). Recently, a study from Kaiser Permanente Northern California revisited the concept of risk equivalence by comparing the risk of subsequent CHD in a contemporary cohort (1,586,061 adults) over a 10-year period (5). As expected, patients with diabetes had a higher risk of CHD than nondiabetic patients; however, they had a significantly lower risk of CHD across all age and sex strata, compared with those with previous CHD (Figure 1). The risk of future CHD for patients with diabetes was similar to those with previous CHD only when diabetes was present for ≥10 years. The study concluded that not all patients with diabetes should be unconditionally assumed to be at the same risk as those with previous CHD.
Cardiac imaging techniques have helped elucidate the heterogeneity in the prevalence of coronary disease and outcomes among individuals with diabetes. Raggi et al. (6) showed that 30% of patients with diabetes had no coronary artery calcium (CAC) and demonstrated a survival similar to those without diabetes and no CAC. Analyses from MESA (Multi-Ethnic Study of Atherosclerosis) revealed that 38% of participants with diabetes had no CAC, and the absence of CAC was associated with a low annual rate (<1%) of CHD events (7).
The CONFIRM (Coronary CT Angiography Evaluation for Clinical Outcomes: An International Multicenter Registry) study enrolled consecutive adults, who underwent coronary computed tomography angiography (CTA) for suspected coronary artery disease (CAD). This study previously showed that compared with matched nondiabetic individuals, patients with diabetes had a higher prevalence, extent, and severity of CAD (8). In this issue of iJACC, Blanke et al. (9) extend the previous findings from the CONFIRM registry over a longer term follow-up of 5 years in patients with diabetes with no history of clinical CAD. They found that 24% of these patients had no CAD according to coronary CTA, experienced a low annual mortality rate (approximately 1%), and their risk of mortality was similar to propensity-matched nondiabetic subjects who had no CAD. Interestingly, the patients with diabetes with nonobstructive CAD experienced a mortality risk that was comparable to those who had single-vessel obstructive CAD. This finding could be due to the fact that the presence of diabetes is associated with greater extent of CAD and faster progression of plaque (10,11). The findings were different when examining major adverse cardiac events, in which there was more of a graded increase in risk, possibly reflecting the higher likelihood of angina and late revascularizations in those who were found to have obstructive CAD.
How can the results from these studies affect clinical practice? First, it is important for clinicians to recognize that once CAD is identified in a patient with diabetes, even if nonobstructive, that person is more likely to have diffuse plaque, faster plaque progression, and more events. Therefore, intensification of both lifestyle and pharmacologic preventive measures should be initiated. The more challenging question is whether there are subgroups in the diabetes population who should be screened for CAD or if a “treat-all” approach would be better.
The DIAD (Detection of Ischemia in Asymptomatic Diabetics) trial examined whether screening patients with diabetes for ischemia could improve clinical outcomes (12). However, over a mean follow-up of 5 years, there was no difference in the primary endpoint of cardiac death or nonfatal MI. There was a lower-than-expected cardiac event rate (0.6% annual rate), reflecting that patients in both groups benefited from excellent medical management. A similar finding was encountered in the FACTOR-64 study, which randomized asymptomatic patients with diabetes to undergo CTA or standard treatment (13). Annual event rates were low (<2%), and the primary outcomes did not differ significantly. Similar to the DIAD study, patients benefited from good medical management at baseline.
A recent study from MESA compared 13 different negative risk markers with respect to their ability to lower an individual’s risk and found that a calcium score of zero was the most powerful such test (14). A separate MESA study, evaluating the recent 2013 American College of Cardiology/American Heart Association cholesterol guidelines, showed that absence of CAC reclassified approximately one-half of candidates to low risk, suggesting that testing for CAC could be used to identify some individuals in whom treatment with statins could be deferred (15). A question that is raised is whether the very low risk of events observed with CAC of 0, across a 10- to 15-year horizon, is sufficient for decision-making, particularly for patients with diabetes who may have a higher lifetime risk.
If the purpose of screening is to identify those who have a sufficiently low risk, in which some therapies can be withheld, then low- to intermediate-risk cohorts may need to be evaluated, where 1 in 3 (MESA) or 1 in 4 (CONFIRM) patients screened with CAC or CTA, respectively, may have no evidence of CAD. Such downward reclassification will only be beneficial when incorporating the value that a patient (or physician) may place on avoiding therapies due to their expense or potential risk for side effects.
Perhaps one day, more individualized treatment algorithms, which incorporate both factors (i.e., all available therapies as well as more precise estimates for a person’s risk of disease), while also considering their values regarding the risk and preferences of various treatment options, will be available. In the meantime, although existing data are not sufficient to endorse any changes in treatment recommendations, in the current era in which we seek to expand precision medicine, the recognition that not all individuals with diabetes are equal may in and of itself be important.
↵∗ Editorials published in JACC: Cardiovascular Imaging reflect the views of the authors and do not necessarily represent the views of JACC: Cardiovascular Imaging or the American College of Cardiology.
Dr. Rana has received a research grant from Regeneron-Sanofi. Dr. Blankstein has reported that he has no relationships relevant to the contents of this paper to disclose.
- American College of Cardiology Foundation
- ↵Brainyquote. George Orwell quotes. Available at: http://www.brainyquote.com/search_results.html?q=All+animals+are+equal%2C+but+some+are+more+equal+than+others. Accessed June 30, 2016.
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