Relevance of traditional cardiovascular risk factors for the development of cardiac allograft vasculopathy– a meta-analysis

Background Cardiac allograft vasculopathy (CAV) is a major long-term complication after heart transplantation (HT), affecting up to 50% of recipients within 10 years and significantly impairing survival rates. Intravascular ultrasound (IVUS) enables early detection of subclinical CAV and allows identification of patients at increased risk for disease progression and adverse outcomes. The pathophysiology of CAV is widely assumed to be a combination of transplant-specific risk factors as well as traditional cardiovascular risk factors. However, the contribution of traditional cardiovascular risk factors remains controversial in the current literature due to small sample sizes in observational studies and a lack of stringent screening for cardiovascular risk factors. Purpose To investigate the role of traditional cardiovascular risk factors in the development of early-stage CAV. Methods This systematic meta-analysis was conducted in accordance with the Cochrane and PRISMA recommendations. PubMed and Scopus were searched for observational studies of adult HT recipients with IVUS-assessed CAV and reported cardiovascular risk factors. CAV was defined as a maximal intimal thickness of ≥0.5 mm. Effect measures and statistical models were selected according to the outcome type and degree of heterogeneity using RevMan software. Results Ten studies published between 1994 and 2021 were included (n=714 patients). Seven studies performed early IVUS after 1-2 months to exclude donor-associated vasculopathy with follow-up after 1 year, while three studies only performed follow-up IVUS at a mean time of 49 months after HT. Recipient age (mean difference (MD): 2.64 years, 95%CI: 1.00-4.29 years, p=0.002) and donor age (MD: 7.41 years, 95%CI 4.24-10.58 years, p<0.001) were significant predictors of CAV. Arterial hypertension (relative risk (RR): 1.09, 95%CI: 0.91-1.32, p=0.34) and low-density lipoprotein levels (MD: 15.78 mg/dL, 95%CI: -7.09-38.64 mg/dL, p = 0.18) were not statistically significant. Higher body mass index (MD: 2.74 kg/m2, 95%CI: 0.42-5.06 kg/m2, p<0.001), diabetes mellitus (RR: 1.87, 95%CI: 1.32-2.63, p<0.001), and higher triglyceride levels (MD: 50.25 mg/dL, 95%CI: 34.24-66.26 mg/dL, p<0.001) were significantly associated with CAV. Conclusion This meta-analysis demonstrated that traditional metabolic risk factors, such as obesity, diabetes, and hypertriglyceridemia, are relevant contributors to the development of early-stage CAV. These findings highlight potential modifiable targets for structured cardiovascular risk management in HT recipients.