Impact of free thyroxine levels and other clinical factors on bare metal stent restenosis

ABSTRACT Objective Thyroid hormones have both direct and indirect effects on thermogenesis such as modulating vascular smooth muscle cell proliferation. However, the influence of more subtle changes in thyroid hormones on coronary atherosclerosis remains a matter of speculation. Smooth muscle cells play a crucial role in the pathogenesis of in-stent restenosis (ISR). However, the relationship between free thyroxine (fT4) and ISR has not been studied. In the present study, we aimed to assess the role of preprocedural serum fT4 level on the development of ISR in patients undergoing coronary bare metal stent (BMS) implantation. Materials and methods We enrolled and analyzed clinical, biochemical, and angiographic data from 705 consecutive patients without a history of primary thyroid disease [mean age 60.3 ± 9.3 years, 505 (72%) male]; all patients had undergone BMS implantation and further control coronary angiography owing to stable or unstable angina pectoris. Patients were divided into 3 tertiles based on preprocedural serum fT4 levels. Results ISR was observed in 53 (23%) patients in the lowest tertile, 82 (35%) patients in the second tertile, and 107 (46%) patients in the highest fT4 tertile (p < 0.001). Using multiple logistic regression analysis, five characteristics emerged as independent predictors of ISR: diabetes mellitus, smoking, HDL-cholesterol, stent length, and preprocedural serum fT4 level. In receiver operating characteristics curve analysis, fT4 level > 1.23 mg/dL had 70% sensitivity and 73% specificity (AUC: 0.75, p < 0.001) in predicting ISR. Conclusion Higher preprocedural serum fT4 is a powerful and independent predictor of BMS restenosis in patients with stable and unstable angina pectoris.

Effect of oral sirolimus therapy on inflammatory biomarkers following coronary stenting

We studied the effect of oral sirolimus, administered to prevent and treat in-stent restenosis (ISR), on the variation of serum levels of inflammatory markers following coronary stenting with bare metal stents. The mean age of the patients was 56 ± 13 years, 65 percent were males and all had clinically manifested ischemia. Serum levels of high sensitivity C-reactive protein (hs-CRP) concentration were determined by chemiluminescence and serum levels of all other biomarkers by ELISA. One group of patients at high risk for ISR received a loading oral dose of 15 mg sirolimus and 5 mg daily thereafter for 28 days after stenting (SIR-G). A control group (CONT-G) was submitted to stenting without sirolimus therapy. The increase in hs-CRP concentration was highest at 24 h after stenting in both groups. A significant difference between SIR-G and CONT-G was observed at 4 weeks (-1.50 ± 5.0 vs -0.19 ± 0.4, P = 0.008) and lost significance 1 month after sirolimus discontinuation (-1.73 ± 4.3 vs -0.01 ± 0.7, P = 0.0975). A continuous fall in MMP-9 concentration was observed in SIR-G, with the greatest reduction at 4 weeks (-352.9 ± 455 vs +395.2 ± 377, P = 0.0004), while a positive variation was noted 4 weeks after sirolimus discontinuation (227 ± 708 vs 406.2 ± 472.1, P = 0.0958). SIR-G exhibited a higher increase in P-selectin after sirolimus discontinuation at week 8 (46.1 ± 67.9 vs 5.8 ± 23.7, P = 0.0025). These findings suggest that the anti-restenotic actions of systemic sirolimus include anti-proliferative effects and modulation of the inflammatory response with inhibition of adhesion molecule expression.

An Elevated Value of C-Reactive Protein is the Only Predictive Factor of Restenosis after Percutaneous Coronary Intervention

BACKGROUND: The current techniques for percutaneous coronary interventions (PCI) remain limited by restenosis. Recent studies have provided evidence of inflammation playing a role in the pathogenesis of cardiovascular disease. METHODS: Whether inflammatory markers are predictors of subsequent restenosis were prospectively tested in 272 consecutive patients with angiographically proven coronary artery disease. Patients having undergone PCI at Chonnam National University Hospital, between Sept. 1999 and Mar. 2001, were divided into two groups according to the occurrence of restenosis on a follow-up coronary angiogram: Group I were patients with restenosis (n=99, 59.5 +/- 10.8 years, M: F=77: 22) and Group II were those without restenosis (n=173, 58.8 +/- 10.2 years, M: F=131: 42). The IgG seropositivity, cytomegalovirus (CMV) titers, C. pneumoniae, H. pylori and levels of C-reactive protein (CRP) were compared between the two groups. RESULTS: There were no statistical differences in the seropositivity of the CMV IgG C. pneumoniae IgG and H. pylori IgG between the two groups (Groups I vs. II: 100 vs. 100%, 24.7 vs. 25.7% and 62.2 vs. 63.7%, respectively). Of the angiographic parameters, a low Thrombolysis In Myocardial Infarction (TIMI) flow (TIMI 0 or I) was more common in Group I than Group II (p=0.038). The patients with an elevated CRP (> 0.5 mg/dL) were more common in Group I than Group II (57.6 vs. 36.4%, p=0.001), with the CRP values being higher in Group I than Group II (3.3 +/- 5.8 vs. 1.3 +/- 2.6 mg/dL, p=0.001). According to a multiple logistic regression analysis, the CRP was the only predictor of restenosis, with an odds ratio of 2.1169 (95% C.I. 1.2062-3.7154, p=0.009). CONCLUSION: The CRP value is the most important predictor of restenosis after PCI.

Homocysteine and restenosis after percutaneous coronary intervention.

Numerous clinical studies in Western and Asian countries suggest that individuals with elevated blood levels of homocysteine have an increased risk of atherosclerosis, myocardial infarction, cerebral infarction, and deep vein thrombosis. Homocysteine is also known to induce both atherogenic and thrombogenic mediators in cultured vascular cells so that homocysteine may influence the damage of endothelial cells, promote smooth muscle cell growth, induce atherogenic mediators and thrombus formation after coronary angioplasty. The association between homocysteine and restenosis after percutaneous coronary intervention (PCI) has been discussed. In this study, the relationship between plasma homocysteine levels and restenosis after PCI to investigate whether plasma homocysteine levels may be a predictor of restenosis after PCI was examined. One hundred consecutive patients who underwent successful PCI were enrolled and plasma homocysteine level was measured in all patients prior to PCI. Plasma for homocysteine level was obtained in 99 of 100 patients who had angioplasty. The mean plasma homocysteine concentration in the enrolled patients was 13.61 +/- 6.04 micromol/L. The minimum and maximum of plasma homocysteine were 4.40 micromol/L and 50.00 micromol/L, respectively. In healthy subjects, the normal reference range of homocysteine level is 5-15 micromol/L However, recent data suggest that some patients may be at increased cardiovascular and cerebrovascular risk at levels as low as 12 micromol/L. For this reason, both cut off points of homocysteine level > or = 15 micromol/L or > or = 12 micromol/L to identify the high homocysteine level group were used. Of 99 patients, high homocysteine level (> or = 15 micromol/L) was established in 9 patients with restenosis versus 20 patients without restenosis. If the cut off point of homocysteine level > or = 12 micromol/L was used, high homocysteine level was established in 14 patients with restenosis versus 39 patients without restenosis. From both cut off points of homocysteine level, there was no correlation between plasma homocysteine level and the restenosis group. (p>0.05).

Serum lipoprotein (a) level and restenosis after percutaneous coronary intervention.

Restenosis is regarded as the result of a combination of various pathological events. The mechanisms are complex and not completely understood. In this study, the authors focused on the lipoprotein (a) (Lp (a)). It is one of the novel risk factors in atherosclerotic vascular disease. Numerous clinical studies suggest that individuals with elevated blood levels of Lp (a) have been shown to be associated with atherosclerotic vascular disease. However, whether a high serum concentration of Lp (a) affects restenosis after PCI remains controversial. In this study, the relationship between serum Lp (a) levels and restenosis after PCI was examined to investigate whether serum Lp (a) levels may be a predictor of restenosis after PCI. Of the 100 patients studied, 31 patients (31%) were classified as the restenosis group and 69 patients (69%) the non-restenosis group. Both groups did not significantly differ in serum concentration of total cholesterol, triglyceride, HDL-C, and LDL-C. The mean serum Lp (a) concentration in patients with restenosis was 41.50 +/- 34.99 mg/dL compared with a mean serum Lp (a) concentration of 29.87 +/- 25.47 mg/dL in those without restenosis. There was no statistical significance of Lp (a) level between the restenosis and non-restenosis groups (p=0.06). In healthy subjects, the normal reference range of serum Lp (a) concentration is below 30 mg/dL. From this reference, if a cut off point of serum Lp (a) concentration equal to 30 mg/dL or above to identify high Lp (a) level group was used. High serum Lp (a) level was established in 15 patients with restenosis versus 21 patients without restenosis. From this cut off point of serum Lp (a) level, the authors did not find a correlation between serum Lp (a) level and the restenosis group. (p=0.08).