ABC | Volume 111, Nº3, September 2018

Original Article Marino et al Adiponectin and IVUS-VH Coronary Plaque Characteristics Arq Bras Cardiol. 2018; 111(3):345-353 Table 4 – Association of adiponectin with major adverse cardiac events, secondary endpoints and death Univariable p Adjusted for age and gender† p HR* (95% CI) HR* (95% CI) Total (n = 570) MACE (n = 56) 1.28 (0.81 – 2.02) 0.29 1.19 (0.71 – 1.99) 0.52 Acute MACE (n = 32) 1.77 (0.96 – 3.23) 0.069 1.36 (0.68 – 2.72) 0.38 Death (n = 19) 3.36 (1.49 – 7.59) 0.004 2.52 (1.02 – 6.23) 0.045 ACS (n = 309) MACE (n = 26) 1.29 (0.66 – 2.50) 0.46 1.02 (0.48 – 2.19) 0.95 Acute MACE (n = 20) 1.75 (0.81 – 3.72) 0.14 1.40 (0.59 – 3.29) 0.44 Death (n = 14) 2.44 (0.98 – 6.06) 0.055 1.87 (0.67 – 5.19) 0.23 SAP (n = 261) MACE (n = 30) 1.30 (0.69 – 2.46) 0.42 1.43 (0.69 – 2.98) 0.34 Acute MACE (n = 12) 1.75 (0.61 – 4.94) 0.29 1.33 (0.41 – 4.28) 0.64 Death (n = 5) 8.15 (1.49 – 44.68) 0.016 8.48 (0.92 – 78.03) 0.058 HR: hazard ratio; CI: confidence interval of 95%; MACE: major adverse cardiac events; ACS: acute coronary syndrome; SAP: stable angina pectoris; Acute MACE: composite of death or acute coronary syndrome (secondary endpoints). †Additionally adjusted for indication for coronary angiography in the total cohort. * Hazard ratio per unit increase in ln-transformed biomarker concentration we found between SAP and ACS. While in SAP patients, atherosclerosis appears to be a slowly progressing disorder, in ACS patients, coronary plaque rupture may be present, and the latter is accompanied by the production of tissue factor and other homeostatic factors that increase the risk of thrombosis. 3 Plasma adiponectin levels have been inversely correlated with markers of platelet activation. 26,27 This might have possibly influenced the association between adiponectin and clinical outcome in these patients. Adipose tissue produces both pro- and anti-inflammatory adipocytokines, 10 and adiponectin has shown in vitro and in vivo anti-inflammatory effects. 28 However, little is known about the clinical significance of adiponectin for coronary plaque stability in vivo . Only a few studies have been performed on this topic, all of which at the University of Kobe, Japan. Sample size of these studies was modest. In a randomized trial of 54 patients with type 2 diabetes and stable angina, treated with pioglitazone, adiponectin was found to be associated with a reduction of necrotic core components as assessed by VH-IVUS. 29 A case control study of 63 ACS and 43 non‑ACS patients showed that serum adiponectin was inversely associated with necrotic core evaluated by VH-IVUS in both culprit and non-culprit lesions in patients with ACS, but not in those with stable angina. 30 In 50 men with stable CAD, low plasma adiponectin was associated with presence of TCFA. 31 Altogether, these studies point toward an inverse association of adiponectin with plaque vulnerability. In contrast, in our study, we found a positive association of adiponectin with VH-IVUS TCFA in SAP patients. This finding is in line with the association of adiponectin with death, as well as the association of VH-IVUS TCFA with adverse outcome which we demonstrated earlier. 12 However, the exact mechanism behind the positive association between adiponectin and VH-IVUS-derived TCFA lesions warrants further investigation. With regard to the discrepancy between our study and the Japanese ones, differences in study population and sample size could have played a part. Ethnic differences in adiponectin levels are of particular interest in this context. The Mediators of Atherosclerosis in South Asians Living in America (MASALA) study and the Multi-Ethnic Study of Atherosclerosis (MESA) have shown that adiponectin levels are lowest in persons from South Asian or Chinese descent compared to other ethnic groups. 32 Moreover, polymorphisms in the adiponectin gene have been found to be associated with adiponectin levels. 33 Some of these polymorphisms have also shown associations with insulin resistance, metabolic syndrome and the onset of CAD. 32-34 Finally, while we found a positive association of adiponectin with VH-IVUS TCFA, we could not demonstrate such an association with necrotic core fraction. This seeming discrepancy may be explained by the fact that these measures reflect somewhat different aspects of atherosclerosis. Size of necrotic core fraction alone may not be able to fully capture the properties of rupture-prone plaques; the definition of VH-IVUS TCFA on its part incorporates additional plaque properties, such as confluence of the necrotic core and direct contact of the necrotic core with the lumen. Some limitations of this study need to be acknowledged. The spatial resolution of VH-IVUS (200 µm) is insufficient to exactly replicate histopathological definitions of a thin fibrous cap (<65 µm). 13 Therefore, VH-IVUS tends to over‑estimate the number of TCFA lesions. Nevertheless, the presence of VH‑IVUS-detected TCFA lesions carries prognostic information 12 and is therefore clinically relevant. Furthermore, VH-IVUS imaging was performed in a prespecified single target segment of a single non-culprit coronary artery. 35 This approach was chosen because previous studies have demonstrated that such segments reflect larger coronary disease burden and are associated with subsequent cardiac events. 12,36 Finally, adiponectin was associated with mortality, but the number of deaths in our dataset was small. Conclusion In conclusion, in the full cohort, adiponectin levels were associated with death but not with VH-IVUS measures of atherosclerosis. In SAP patients, adiponectin levels were 350