Macrovascular and microvascular dysfunction in the metabolic syndrome

Abstract

The metabolic syndrome (MetS) is associated with increased risk of type-2 diabetes and cardiovascular disease (CVD). We hypothesized that both small and large arteries may be impaired in subjects with the MetS, even in the absence of known CVD or diabetes. We compared both skin capillary density (CD) and pulse-wave velocity (PWV) in 36 cases with the MetS with those from 108 age-and gender-matched controls from the SU.VIM.AX-2 cohort. Compared with controls, MetS subjects demonstrated increased PWV (12.2 ± 2.8 vs. 10.7 ± 1.9 m s À1 , P¼0.005) and lower functional CD (83.1 ± 15.7 vs. 89.4 ± 14.2 capillaries per mm 2 , P¼0.03). Functional CD was inversely related to fasting glucose, triglycerides (TGs) and HOMA-IR (all Po0.05). On the other hand, no association was found between CD and BP or with PWV. In multivariate models, the odds ratios (95% confidence interval) for one standard deviation change, for having an impaired PWV (X12 m s À1 , n¼44), were: 1.65 (1.11-2.45) for systolic BP and 1.93 (1.25-2.99) for TG only. For impaired CD (p80 capillaries per mm 2 ), the odds ratios (95% confidence interval) were 1.45 (1.00-2.08) for TG and 1.65 (1.13-2.43) for fasting glucose, only. In conclusion, MetS subjects exhibited evidence of macro-and microcirculatory dysfunction, even in the absence of diabetes and CVD. The common mechanism linking MetS components to CVD risk through small-and large-artery dysfunctions may be mediated through metabolic factors related to insulin resistance, not to increased BP.

Arterial Function in Cardio-Metabolic Diseases: From the Microcirculation to the Large Conduits

“…A reduction in functional capillary density in older adults with MetS but preservation of anatomical capillary density and capillary recruitment has been shown. 43 Whereas, in young MetS a deficit in anatomical capillary density was evident suggesting that cutaneous capillaries at rest were already maximally recruited, with little to no functional capillary reserve and a loss in autoregulatory capacity. 44 This discrepancy could be due to the smaller percentage of obese subjects, and relatively normal insulin-sensitivity in the older MetS group.…”

“…44 This discrepancy could be due to the smaller percentage of obese subjects, and relatively normal insulin-sensitivity in the older MetS group. 43 Indeed, a blunted capillary recruitment was registered predominantly in obese MetS patients with concomitant insulin resistance, and significant associations between functional capillary density and capillary recruitment with insulin resistance and visceral adiposity have been noted. 43,44 In the OZR, a reduced blood flow and increased maximum resistance state along with a reduction in the compliance of the arterioles from the peripheral vasculature are noted.…”

“…43 Indeed, a blunted capillary recruitment was registered predominantly in obese MetS patients with concomitant insulin resistance, and significant associations between functional capillary density and capillary recruitment with insulin resistance and visceral adiposity have been noted. 43,44 In the OZR, a reduced blood flow and increased maximum resistance state along with a reduction in the compliance of the arterioles from the peripheral vasculature are noted. 32 There is also an attenuated release and blunted responsiveness to endothelium-derived relaxing factors (i.e., prostacyclin and nitric oxide) in the OZR.…”

Associations Between Dietary Patterns and Skin Microcirculation in Healthy Subjects

“…2 The phenomenon of increased intercapillary distance, that is, of reduced capillary density, is called capillary rarefaction. 3 On the basis of studies that investigated mostly the human cutaneous capillaries, capillary rarefaction has been described in hypertension, [4][5][6][7][8][9] in subjects with metabolic syndrome, 10 and in overweight individuals, [11][12][13] even in the absence of insulin resistance or elevated blood pressure (BP). Of note, in healthy nonobese individuals, an inverse association between insulin resistance 14 and BP levels, 14,15 on one hand, with capillary recruitment, on the other hand, has been described, suggesting the presence of a possible pathophysiological continuum between them, even in normalcy.…”

Likelihood of obstructive coronary disease in metabolic syndrome patients with abnormal stress echocardiography

“…Furthermore, the observed association between the number of MetSx components and the prevalence of angiographically significant coronary disease did not prevail after the exclusion of IFG. All of these findings point to the central role for hyperglycemia in disease progression in individuals with MetSx [29]. It also suggests that patients with "Metabolic syndrome trait" have different propensities towards having more advanced CAD, depending on the different components making up the diagnosis of MetSx [30].…”