Volume 258 Issue March 2017
By Simona Negrini and Arnold von Eckardstein (Editor–in-Chief).
Both quantitative and qualitative differences in body fat are generally considered as important determinants of cardiovascular disease (CVD) risk, either directly or indirectly, by associated risk factors such as dyslipidemia, hyperglycemia, hypertension, low grade inflammation and prothrombotic state. In this issue of Atherosclerosis, several articles describe the associations of overweight and obesity, body fat mass, ectopic fat accumulation in the liver, or lipogenic treatment with corticoids with the incidence of cardiovascular events or preclinical measures of atherosclerotic CVD. Overall, the reported data provide further evidence that the atherogenic effects of both increased and ectopic body fat are modified by ethnicity, sex, age, and comorbidities.
Mirzaei et al. aimed to investigate the development of cardiovascular disease (CVD) in different obesity phenotypes over a median follow-up of 12 years.
7842 participants (44.8% men; aged ≥ 30 years), previously enrolled in the Tehran Lipid and Glucose Study (TLGS), were selected for the analysis. Participants were divided into six phenotypes based on body mass index and metabolic status. Metabolic health was estimated based on two definitions: 1) having ≤1 component of metabolic syndrome using the Joint Interim Statement (JIS) criteria, and 2) having homeostasis model assessment-insulin resistance (HOMA-IR) <2.6 mole×μU/L2. Multivariate adjusted hazard ratios (HRs) were calculated for cardiovascular events.
712 new CVD events occurred over a 12-year follow-up. CV risk increased in all metabolically unhealthy phenotypes. Multivariable adjusted HRs for CVD events in metabolically healthy overweight (MHOW) and metabolically healthy obese (MHO) participants were 1.22 and 1.74, respectively. CV risk increased in all obesity phenotypes based on insulin resistance, except in the insulin resistance-normal weight group. However, this increased risk disappeared after further adjustment for metabolic risk factors.
In conclusion, CV risk did not increase in metabolically healthy overweight or obese individuals. However, all metabolically unhealthy phenotypes were associated with increased CVD incidences. Further studies with longer follow-up are needed to confirm the benign nature of the MHOW/MHO phenotypes.
Remigio-Baker et al. investigated the associations of non-alcoholic fatty liver disease (NAFLD) and abdominal aortic calcification (AAC) volume and density, and assessed whether this relationship varies according to race/ethnicity and/or sex.
1004 adults from the Multi-Ethnic Study of Atherosclerosis were selected to study the relationship between NAFLD and the following measures of AAC: presence, change in volume score and morphology, and interaction by race/ethnicity and sex.
Among Blacks, subjects with NAFLD had greater prevalence of AAC compared to Whites, regardless of sex. Comparing Chinese and Blacks with Whites, a concurrent interaction by race/ethnicity and sex was found in the association between NAFLD and the prevalence of increasing AAC. Among women, this relationship was inverse in Chinese, and positive in Whites and this was reversed when the male counterpart was evaluated. Black men also had a positive association, which differed from the inverse relationship among White men, and was greater compared to Black women. In addition, NAFLD was unrelated to the AAC morphology.
These results show that NAFLD is related to the presence of AAC, however, limited to Blacks. The association of NAFLD with increasing AAC was significantly modified by interactions of race/ethnicity (Chinese and Blacks vs. Whites) with sex. Taken together, these findings suggest disparities in the pathophysiologic pathways in which atherosclerosis develops.
Excess weight is a widespread condition related to increased risk of coronary heart disease (CHD). Sarcopenia is a catabolic pathway common to the aging process and associated with CHD. In the elderly, both changes occur concurrently and the relative contribution on CHD risk remains unclear. Campos et al. aimed to investigate whether sarcopenia, excess weight, or both are associated with subclinical atherosclerosis and/or endothelial dysfunction in very elderly individuals.
The authors performed a cross-sectional study of cohort enrolled individuals, aged 80 years or older (n = 208), who had never manifested cardiovascular diseases. Blood tests, medical and nutritional evaluations, cardiac computed tomography, flow-mediated dilation (FMD) and physical performance tests were obtained at the study admission. Odds ratio (OR) was calculated by multivariate regression models using coronary calcium score (CCS) categories and FMD as dependent variables. Adjustment for potential confounders was performed.
Muscle mass, but not fat mass, was inversely associated with CCS categories. The lowering of gait speed was negatively related to CCS>100 while skeletal muscle index was directly associated with FMD. Total caloric intake was correlated positively with fat mass but not CCS.
These results reveal that sarcopenia is associated with subclinical atherosclerosis and endothelial dysfunction. Surprisingly, the excess of fat mass seems not to be related to atherosclerotic burden in very elderly individuals.
Glucocorticoids could impair vascular function directly or indirectly by reducing insulin sensitivity. Peterson et al. aimed to determine the direct and indirect effects of acute and chronic low-dose prednisolone on arterial stiffness and endothelial function.
Twelve subjects with inflammatory arthritis, who had not taken oral glucocorticoids for ≥6 months, and 12 subjects with inflammatory arthritis, taking chronic (>6 months) low-dose prednisolone, were studied. To assess the acute effects of prednisolone, arterial stiffness (pulse wave velocity (PWV)) and endothelial function (reactive hyperaemia index (RHI)) were measured in patients not on glucocorticoids, before and after 7–10 days of prednisolone administration. Baseline data obtained were compared with those of patients on long-term prednisolone, to determine the chronic effects of this corticosteroid. Hepatic insulin sensitivity was estimated from percentage suppression of endogenous glucose production and peripheral insulin sensitivity as glucose infusion rate (M/I) during a hyperinsulinaemic-euglycaemic clamp.
The authors found no significant changes in PWV with acute or chronic prednisolone. In multiple regression analysis, PWV was negatively associated with M/I during hyperinsulinemic-euglycemic clamp, but not with suppression of endogenous glucose production or glucocorticoid use. Chronic, but not acute prednisolone use resulted in a higher RHI.
The results suggest that arterial stiffness is not affected by low-dose prednisolone per se, but it is negatively associated with peripheral insulin sensitivity. Patients with rheumatoid arthritis taking long-term prednisolone had better endothelial function.