This new WNBA meme is too good NOT to use for bringing awareness to Cardiovascular Disease screening and prevention! And most people are comfortable using CACs as “The Colonoscopy of the Heart Without the Nasty Pregame Show” as a screening diagnostic in asymptomatic people. (The people out there who hate on CACs are probably cut from the same cloth as the players who try to undermine Caitlin Clark’s greatness and then attempt to smash her throat). Additionally, if someone in midlife has a CAC of zero, most folks are comfortable with the strategy of repeating a CAC in 3-7 years depending on risk factors given that incident CAC and CAC progression have been associated with increased risk of major adverse cardiovascular events (MACE) in data sets like THIS ONE. (The people out there who hate on re-CAC-ulating in people with CAC of zero also are more likely to hate puppies, sunsets, and Journey’s Don’t Stop Believin’).
But an interesting and under-explored topic is that of CAC PROGRESSION, and two recent studies add to what we have previously observed on the subject. Historically, repeating CACs once therapy has been initiated and/or baseline CAC is greater than 0 has been frowned upon. Statins increase the calcific content of existing coronary plaque, which is thought to confer a more benign phenotype. But perhaps there may be certain situations where repeating CACs could enhance risk stratification, even in those with CAC>0 and those on statins…behold!
The FIRST STUDY was conducted in Taiwan and showed that rapid annual progression on CAC was associated with increased risk of MACE. Participants that progressed between 20 and 50 Agatston units (AU) per year had a 72% increased risk of having a cardiovascular event, whereas those with progression of over 50 units per year had a nearly threefold risk of MACE (a hazard rate of 2.86). Interestingly, this increased risk of MACE applied to those both on statin therapy and not on statin therapy; even though they were on statins, the participants with progression over 50 units annually had a SIXFOLD INCREASED RISK OF MACE (hazard rate 6.08). Rapid progressors not on statins had a greater than twofold risk of MACE (hazard rate 2.27). The strongest predictors of CAC progression were baseline CAC (once you’ve been broken into, serial break-ins are more likely) and elevated fasting glucose (sounds a lot like Pillar 1 of the Metabolic Home Security System).
The SECOND STUDY was from the CLARIFY registry, which included 4166 patients from 2014 to 2023 with at least 2 CACs. Mild annual CAC progression was defined as 10-50 AU, moderate was 51-150 units, and severe >150 AU. And, once again, CAC progression was associated with an approximate twofold risk of MACE across the board (hazard rate 1.96) with greater MACE risk in the more rapid progressors. This association was consistent even among smokers, diabetics…and STATIN USERS. In fact, 84% of the “severe progressors” were on statins, although the group on statins still had a baseline LDL cholesterol of 116 mg/dL (a pretty dangerous Lipid Neighborhood for someone with a baseline CAC>0). And accordingly, this group had the highest rate of MACE…so much for the archaic “Set It and Forget It” approach of perceived invincibility conferred by simply being on a statin.
Interestingly, the subset of individuals who progressed from CAC zero to CAC>0 did not have an increased risk of MACE in this second study, although the follow-up period wasn’t particularly long. Additionally, those with baseline CAC>0 who DID NOT PROGRESS in CAC also did not have an increased risk of MACE here. Halting CAC progression seems to be good, and there are many potential interventions that can stabilize and regress plaque that vary in appropriateness depending on the individual context.
So should we repeat CACs in those with baseline CAC>0 and/or those on lipid-lowering therapy? It’s a definite maybe…but only if it’s going to change the intervention😊
