What is the relationship between inflammatory and cardiovascular diseases?

Editor's note

Cardiovascular disease (CVD) is a major health problem affecting 500 million adults worldwide and has become the leading cause of death in the world. It has been shown that the immune-inflammatory response is involved in the occurrence and development of CVD [1]. It is necessary to pay attention to the clinical value of inflammation-related biomarkers in the early diagnosis, disease monitoring, efficacy evaluation, and prognosis judgment of CVD [2]. At the 73rd Annual Meeting of the American College of Cardiology (ACC.24) in 2024, two of the studies will explore their relationship with CVD from the perspectives of chronic inflammation-related diseases (ChrIRD) and immune-mediated inflammatory diseases (IMIDs), respectively, which will undoubtedly be a highlight of the conference. It is organized below for the benefit of readers.

To observe the association of ChrIRD with CVD in multi-ethnic arteriosclerosis studies[3]

（03 - CHRONIC INFLAMMATORY-RELATED DISEASE AND CARDIOVASCULAR DISEASE IN THE MULTI-ETHNIC STUDY OF ATHEROSCLEROSIS）

background

Although many of the risk factors for CVD are well understood, their relationship with inflammation needs to be further studied. ChrIRD encompasses a variety of life-threatening non-CVD and non-cancerous pathological changes, in which oxidative stress or infection is the underlying cause of inflammation. The investigators explored the interaction between CVD and ChrIRD in a longitudinal cohort of the Multiethnic Atherosclerosis Study (MESA). This cohort did not have significant CVD at baseline.

way

Participants were followed for 16 years. CVD events are determined by medical records, and ChrIRD is determined based on ICD codes for all deaths and hospitalizations. The investigators identified risk factors for CVD, ChrIRD, and total mortality through time-dependent proportional hazards regression analysis, with covariates including baseline age, ethnicity, sex, heart rate, body mass index, smoking, blood pressure and its medications, lipids and its medications, diabetes mellitus, high-sensitivity C-reactive protein, interleukin-6 (IL-6), D-dimer, GlycA, and chronic kidney disease, and time-dependent CVD and ChrIRD.

outcome

A total of 6434 participants were included, with a mean age of 62±10 years, 47% male, 39% white, 27% black, 22% Hispanic, and 12% Chinese. At 16 years of follow-up, the cumulative incidence of CVD was 18% and that of ChrIRD was 24%. The most common ChrIRD was a condition caused by local tissue damage (46.1%), followed by infectious diseases (40.7%), as well as diffuse tissue damage (7.9%) and autoimmune/rheumatic diseases (4.6%). Both CVD and ChrIRD were fatal compared with people without either disorder (CVD or ChrIRD) (40% mortality in participants with either diagnosis), and up to 66% in participants with both CVD and ChrIRD. After adjusting for traditional risk factors, IL-6 (P<0.002), D-dimer, and GlycA (P<0.05) were predictive of future CVD and ChrIRD. CVD significantly increased the risk of future ChrIRD [HR 1.98 (1.73 to 2.28)], and ChrIRD significantly increased the risk of future CVD [HR 1.85 (1.63 to 2.09)].

conclusion

Both CVD and ChrIRD are common and fatal. Studies have shown that these diseases have a potential phenotype of dysregulation of inflammation and are independent risk factors for each other.

To assess the association of IMIDs and Lp(a) with cardiovascular outcomes in individuals with or without baseline ASCVD [4]

（05 - THE ASSOCIATION OF IMMUNE-MEDIATED INFLAMMATORY DISEASE AND LIPOPROTEIN(A) WITH MAJOR ADVERSE CARDIOVASCULAR EVENTS AMONG INDIVIDUALS WITH AND WITHOUT BASELINE ATHEROSCLEROTICCARDIOVASCULAR DISEASE: THE MASS GENERAL BRIGHAM LP(A) REGISTRY）

background

Patients with IMIDs are at higher risk of CVD. Lp(a) is associated with atherosclerosis, thrombosis, and pro-inflammatory effects. The aim of this study was to assess the association between Lp(a) and IMIDs and adverse cardiovascular outcomes in patients with or without a history of atherosclerotic cardiovascular disease (ASCVD).

way

This study performed a retrospective study of a cohort of patients who measured Lp(a) levels at two medical centers in Boston, Massachusetts, USA. IMIDs are identified by ICD codes before Lp(a) is detected. According to the previous literature, the enrolled patients were divided into four Lp(a) percentile groups. Cox proportional assessments were used to assess the association of IMID and Lp(a) with CV death or myocardial infarction (MI).

outcome

A total of 16 419 patients were included in this study, of whom 445 (2.7%) had IMIDs. Patients with IMID were significantly older [64 (54~75) years vs. 60 (49~72) years], more women (57% vs. 40%), and higher rates of hypertension (68% vs. 58%), hyperlipidemia (72% vs. 65%), and diabetes mellitus (27% vs. 23%). Both IMID and Lp(a) were independently associated with CV mortality and MI. After adjusting for Lp(a) and CV risk factors, IMID was significantly associated with CV mortality and MI in patients without ASCVD [HR 1.62 (95%CI: 1.1~2.37, P=0.01)] and ASCVD [HR 1.27 (95%CI: 1.03~1.58, P=0.028)]. Similarly, Lp(a) was significantly associated with CV mortality and MI (Figure 5).

Figure 5. The relationship between the four Lp(a) percentile groups and the mortality rate of MI and CV in patients with ASCVD and those without ASCVD (A and B, respectively) and the relationship between IMID and MI and CV mortality in patients with ASCVD and those without ASCVD (C and D, respectively)

conclusion

Even after taking into account ASCVD and Lp(a) levels, IMIDs were independently associated with adverse cardiovascular events.

Bibliography:

1. Zhao Wenliu, Wei Zhihao, Song Zongshuang, et al. Research Progress on the Relationship between Immune Inflammation Indicators and Cardiovascular Diseases[J]. Modern Health Care,2023,23(14):1041-1044.

2. Wang Junjun, Wei Weishi, Wu Jia. Focus on the role of inflammation-related biomarkers in cardiovascular disease risk assessment[J]. Journal of Clinical Laboratory Medicine,2020,38(2):85-89.

3.1020-03 - CHRONIC INFLAMMATORY-RELATED DISEASE AND CARDIOVASCULAR DISEASE IN THE MULTI-ETHNIC STUDY OF ATHEROSCLEROSIS. 2024 ACC.

4.1020-05 - THE ASSOCIATION OF IMMUNE-MEDIATED INFLAMMATORY DISEASE AND LIPOPROTEIN(A) WITH MAJOR ADVERSE CARDIOVASCULAR EVENTS AMONG INDIVIDUALS WITH AND WITHOUT BASELINE ATHEROSCLEROTICCARDIOVASCULAR DISEASE: THE MASS GENERAL BRIGHAM LP(A) REGISTRY.