A new study added heart failure with preserved ejection fraction (HFpEF) to the growing list of cardiovascular conditions linked to clonal hematopoiesis of indeterminate potential (CHIP), which already includes atherosclerotic cardiovascular disease (ASCVD).
But what exactly is CHIP, and what is its potential value in CVD risk and management?
CHIP is an age-related condition marked by clonal expansion of blood stem cells with leukemia-associated mutations in individuals without evidence of hematologic malignancy. CHIP is estimated to affect about 10% of people aged 70 years and older.
First described as a risk factor for hematologic, particularly myeloid, malignant neoplasms, CHIP has recently emerged as a novel CVD risk factor.
CHIP gives rise to proinflammatory immune cells, which can exacerbate ASCVD and may induce or accelerate HF.
“The association between CHIP and HFpEF may be particularly relevant, given that the prevalence of HFpEF is rising due to the progressive aging of the population,” José J. Fuster, PhD, coordinator for the program on novel mechanisms of atherosclerosis, Spanish National Center for Cardiovascular Research, Madrid, Spain, told theheart.org | Medscape Cardiology.
Yet previous studies examining CHIP and HF have either focused on overall HF without distinguishing HF subtypes of preserved vs reduced ejection fraction, or have examined its prognostic significance in the setting of established HF, rather than the development of future HF.
To help fill the gap, Boston-based researchers recently evaluated associations of CHIP and the two most common gene-specific CHIP subtypes (TET2 and DNMT3A CHIP) with incident HFpEF and HF with reduced ejection fraction (HFrEF).
In two racially diverse cohorts with a total of 8090 adults, TET2 CHIP was independently associated with > twofold higher risk of incident HFpEF. By contrast, there were no significant associations of CHIP with incident HFrEF.
“Our study’s fundings suggest that previously described associations between CHIP and future development of heart failure may be driven primarily by HFpEF,” Michael Honigberg, MD, with the Cardiovascular Research Center and Center for Genomic Medicine, Massachusetts General Hospital, Boston, told theheart.org | Medscape Cardiology.
In addition, the “clearest signal for an association with HF was observed for TET2 CHIP, the second-most common subtype of CHIP in the population. This finding aligns with a recently published study that reported relative enrichment of TET2 CHIP in a small human HFpEF cohort,” Honigberg said.
Fuster said the connection between CHIP and aging “enhances the potential clinical relevance of this study, as CHIP is frequent in elderly individuals and, therefore, may contribute to the pathophysiology of HFpEF in a high proportion of patients.”
He cautioned, however, that the findings need to be validated in other studies.
“In addition, there is a growing recognition that the effects of CHIP are heterogeneous, as mutations in different genes have different effects on cardiovascular and act through different mechanisms. Additional studies will be needed to dissect gene-specific effects in HFpEF. It will also be important to explore whether CHIP influences the clinical progression of the disease,” Fuster said.
Honigberg said the findings may aid in the development of new targeted-treatment strategies for at least the subset of patients with HFpEF.
Based on multiple lines of evidence, the mechanism linking TET2 CHIP to CVD appears to be heightened inflammation, he explained.
For example, in a substudy of the CANTOS trial, patients with atherosclerosis and TET2 CHIP who received canakinumab appeared to derive “outsized benefit” in preventing CV events compared with the overall trial population, Honigberg said.
“HFpEF is a particularly challenging disease with limited effective therapies. Our findings support the premise that targeted anti-inflammatory therapies may prevent and/or treat HFpEF driven by TET2 CHIP. Of course, this hypothesis will require testing in prospective randomized trials,” Honigberg said.
“The field of CHIP has developed rapidly, and it is an exciting area of research,” Fuster added. “However, I personally believe that much work lies ahead before it is ready for prime time in the clinical setting.
“Although the link between CHIP and CVD is solid, we still lack evidence-based interventions to mitigate the elevated CVD risk associated with these mutations. In the absence of effective interventions, the added value of screening for CHIP as a risk factor may be limited,” Fuster noted.
“For instance, in the setting of HFpEF, we don’t really know whether CHIP mutation carriers may respond favorably to contemporary HF medications or may require new personalized approaches. Additional research and, eventually, clinical trials, are needed,” he added.
Honigberg has disclosed relationships with Genentech, Miga Health, CRISPR Therapeutics and Comanche Biopharma. Fuster has no relevant disclosures.
Source link : https://www.medscape.com/viewarticle/chip-tied-hfpef-and-ascvd-whats-link-2024a10002br?src=rss
Publish date : 2024-02-02 10:04:00
Copyright for syndicated content belongs to the linked Source.