Study Design: A systematic review and meta-analysis. Objectives: The results from previous meta-analyses are limited by the small number of included studies. Moreover, the risk factors of heterotopic ossification (HO) have not been well studied. Therefore, this study aims to estimate the prevalence of HO after cervical total disc replacement (CTDR) at different follow-up time points and explore potential risk factors for HO. Methods: We searched databases to identify eligible studies that reported the rate of HO after CTDR. The pooled prevalence of HO, according to different grades of HO, length of follow-up and types of prosthesis, and 95% confidence intervals (CIs) were calculated. Multivariable meta-regression analyses were performed to identify factors that may contribute to the heterogeneity between estimates. Results: Of the 94 studies included, 82 studies reported an overall rate of HO, encompassing a total of 5861 cervical spinal levels that underwent CTDR. The overall pooled prevalence of HO was 32.5% (95% CI 26.7% to 38.4%). Single-level CTDR was associated with a higher overall rate of HO. When the rate of HO was stratified by McAfee/Mehren classification, the pooled prevalence of range of motion (ROM)–limiting HO was 11.0% (95% CI 9.2% to 12.8%). Latest publication, single-level CTDR, longer follow-up period, and studies published outside were associated with a higher rate of ROM-limiting HO. Conclusions: We provide a comprehensive overview of the prevalence of different grades of HO. This meta-analysis also identifies and rules out some risk factors for HO after CTDR.

Metabolic disorders are associated with an increased risk of cardiovascular disease (CVD), and are commonly characterized by a low plasma level of high-density lipoprotein cholesterol (HDL-C). Although cholesterol lowering medications reduce CVD risk in these patients, they often remain at increased risk of CVD. Therapeutic strategies that raise HDL-C levels and improve HDL function are a potential treatment option for reducing residual CVD risk in these individuals. Over the past decade, understanding of the metabolism and cardioprotective functions of HDLs has improved, with preclinical and clinical studies both indicating that the ability of HDLs to mediate reverse cholesterol transport, inhibit inflammation and reduce oxidation is impaired in metabolic disorders. These cardioprotective effects of HDLs are supported by the outcomes of epidemiological, cell and animal studies, but have not been confirmed in several recent clinical outcome trials of HDL-raising agents. Recent studies suggest that HDL function may be clinically more important than plasma levels of HDL-C. However, at least some of the cardioprotective functions of HDLs are lost in acute coronary syndrome and stable coronary artery disease patients. HDL dysfunction is also associated with metabolic abnormalities. This review is concerned with the impact of metabolic abnormalities, including dyslipidemia, obesity and Type 2 diabetes, on the metabolism and cardioprotective functions of HDLs.

Background: Higher plasma fibroblast growth factor 21 (FGF21) levels predict incident cardiovascular events in type 2 diabetes patients. However, whether FGF21 levels predict cardiovascular events in statin-treated patients in the general population is unknown. We investigated whether FGF21 levels predict major cardiovascular event (MCVE) in the Treating to New Targets (TNT) trial participants. Methods: After 8-week run-in on atorvastatin 10 mg/day, 10,001 patients with stable coronary disease in the TNT trial were randomized to 10 mg or 80 mg/day of atorvastatin for a median of 4.9 years. We analyzed data from 1996 patients with plasma FGF21 levels measured at randomization. Among them, 1835 patients had FGF21 measured one-year post-randomization. Results: Higher ln-transformed FGF21 levels at randomization were associated with higher risk of incident MCVE (adjusted hazards ratio per SD increase = 1.18, P = 0.019). At 1-year post-randomization, FGF21 levels were lower in patients randomized to receive 80 mg versus 10 mg atorvastatin (186.9 versus 207.5 pg/mL respectively, P = 0.006). Higher ln-transformed FGF21 levels at 1-year post-randomization were also associated with higher subsequent risk of MCVEs (adjusted hazards ratio per SD increase = 1.24, P = 0.009). However, changes in FGF21 levels over 1-year were not related to subsequent MCVE risk. FGF21 levels had significant incremental value in net reclassification improvement in MCVE risk prediction. Conclusions: Higher plasma FGF21 levels are associated with higher CVD risk in statin-treated high-risk patients. Higher dose atorvastatin is associated with a reduction in FGF21 levels. FGF21 provides incremental value in CVD risk prediction in statin-treated patients.

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