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Clinically silent obstructive coronary atherosclerosis was linked to substantially elevated heart attack risk in middle-aged persons without known cardiovascular disease, a Danish population-based study showed.

Over a median 3.5 years of follow-up, myocardial infarction (MI) risk was 9.19-fold higher with obstructive subclinical coronary atherosclerosis and 7.65-fold elevated with extensive subclinical coronary atherosclerosis after adjustment for other factors.

The highest absolute risk was seen with the combination of obstructive, extensive disease, at around 0.8%, Klaus Fuglsang Kofoed, MD, PhD, DMSc, of Copenhagen University Hospital-Rigshospitalet and the University of Copenhagen, and colleagues reported in .

Notably, asymptomatic, subclinical coronary atherosclerosis was identified in 61% of men and 36% of women in the Copenhagen General Population Study (CGPS) of 9,533 participants ages 40 and older without known ischemic heart disease.

Because these noninvasive coronary CT angiography (CTA) findings were not passed along to patients or their physicians, the findings filled a critical gap -- providing a contemporary natural history for coronary artery disease in the absence of intervention, which was uncommon in the cohort (7% took prophylactic aspirin and 11% were prescribed statins).

"This exceptional and important study now provides a benchmark," wrote Michael McDermott, MBChB, and David E. Newby, DM, PhD, both of the University of Edinburgh in Scotland, in an .

"It also provides invaluable data about event rates and prevalence of asymptomatic coronary artery disease that will inform public health prevention strategies and ongoing clinical trials of targeting preventative therapies in persons screened for occult coronary artery disease," McDermott and Newby added.

Indeed, almost all the pieces are now in place to recommend screening, Kofoed's group suggested.

The essential question remains, though, they pointed out: "Does preventive treatment guided by coronary CTA reduce the risk for heart attacks or death and avoid harm to persons not in need of treatment as compared with current primary cardiovascular prevention practice?

"To answer this question, we have initiated a randomized controlled trial -- the ... trial -- in which 6,000 asymptomatic persons at risk for ischemic heart disease will be randomly assigned to primary preventive treatment guided by coronary CTA or current primary prevention practice," the researchers noted. The (Computed Tomography Coronary Angiography for the Prevention of Myocardial Infarction) is being done in parallel.

Meanwhile, opportunistic screening in patients getting cardiac CT and/or electrocardiogram-gated chest CT for other clinical indications, like procedural planning before atrial fibrillation ablation, left atrial appendage closure, or invasive treatment of heart valve disease, could offer potentially clinically relevant, incremental risk assessment, the group suggested. "[P]atients with obstructive and/or extensive subclinical coronary atherosclerosis could benefit from referral to intensified cardiovascular primary prevention therapy."

In their current population-based study, there was a low event rate over the median 3.5 years of follow-up (range 0.1 to 8.9 years), with 71 MIs (0.7%) and a total of 260 patients with the secondary composite endpoint of either death or MI (2.7%). Four patients died after an MI.

"This low event rate is what would be anticipated in an asymptomatic general population," the editorialists noted.

The most common type of subclinical coronary atherosclerosis was nonobstructive (36%), with single vessel obstructive disease in just 8% and multivessel disease or left main stenosis rare at 2%. The extent of this atherosclerosis was most frequently non-extensive (36%).

Obstruction appeared to be most important for MI risk, being present in two-thirds of those who had MI.

But for the composite of mortality and MI risk, the risk was similarly elevated with extensive subclinical disease regardless of the degree of obstruction (adjusted RR 2.70 with ≥50% luminal stenosis, 95% CI 1.72-4.25, and 3.15 with <50% stenosis, 95% CI 2.05-4.83).

"This contrasts with symptomatic populations where nonobstructive disease accounts for most future myocardial infarctions, presumably from plaque rupture," the editorialists noted. "This suggests that in asymptomatic patients, obstructive disease may be more closely linked to myocardial infarction perhaps because the provocation of more severe ischemia is left unchecked in the absence of limiting symptoms. This needs further exploration in future studies."

The researchers noted no interaction of any cardiovascular risk factors with subclinical coronary atherosclerosis to modify risk of either the MI or composite MI and mortality endpoints.

One key limitation of the study was the largely white, Nordic European participants, which might constrict generalizability in other populations. "Furthermore, persons undergoing coronary CTA in the CGPS tended to have less cardiovascular risk factors, higher education level, and higher income class," the researchers wrote. Only 5% of the study population were low income, and that group tended to have higher risk plaques.

Also, coronary CTA was assessed visually, not quantitatively, the team added. Nor was there information on MI anatomical location or specific causes of death.

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