Influence of dietary intervention on microvascular endothelial function in coronary patients and atherothrombotic risk of recurrence

Endothelial dysfunction is a key player in both the onset and development of atherosclerosis. No study has examined whether healthy dietary patterns can improve microvascular endothelial function in patients with coronary heart disease (CHD) in the long-term and whether this relationship can affect patient’s risk of CHD recurrence. In the CORDIOPREV study, a randomized, double-blind, controlled trial, dietary intervention with either the Mediterranean diet or a low-fat diet was implemented in 1,002 CHD patients. A laser-doppler flowmetry was performed at baseline and after 6 years of follow up in 664 patients, evaluating the effects of this dietary intervention on microvascular basal flow and reactive hyperaemia area, as well as on the risk of CHD recurrence, based on the TRS2P risk score. Basal flow (97.78 ± 2.79 vs. 179.31 ± 5.06 arbitrary perfusion units, 83.38% increase, p < 0.001) and reactive hyperaemia area (4233.3 ± 127.73 vs. 9695.9 ± 205.23 arbitrary perfusion units per time, 129.04% increase, p < 0.001) improved after the dietary intervention in the cohort, without finding differences due to the diet (p > 0.05 for the diet-effect). When patients were stratified to low, moderate or high-risk of recurrence, basal flow was similarly increased in all three groups. However, reactive hyperaemia area was improved to a greater extent in patients at the low-risk group compared with those at moderate or high-risk. No differences were observed between diets. Healthy dietary patterns can improve microvascular endothelial function and this improvement persists in the long-term. Patients with a low-risk of CHD recurrence show a greater improvement in reactive vasodilation to ischemia than patients in the moderate or high-risk groups.

Abstract MP16: Perivascular Adipose Tissue Inflammation Impairs Microvascular Endothelial Function In People Living With HIV

Introduction and hypothesis: We had reported that people living with HIV (PLWH) have microvascular endothelial dysfunction and increased ROS. We now tested the hypothesis that perivascular adipose tissue (PVAT) could enhance oxidative stress and inflammation and impair the function of subcutaneous microarterioles (SMAs) in PLWH. Methods: SMAs were obtained from young, virally-suppressed HIV-infected subjects (n=11) or matched controls (n=11). Subjects were without associated CVD risk factors. Microvascular reactivity and PVAT function were accessed by myograph from isolated subcutaneous vessels with or without PVAT of skin biopsy. Results: The HIV-infected group had significantly (P<0.05) increased adipose MDA, TNFα, IL-1α, leptin and reduced adiponectin. The PVAT-denuded SMAs from the HIV group had significantly (P<0.05) impaired acetylcholine-induced endothelium-dependent relaxation factor (EDRF, 26±4 vs 38±3%) and NO activity (0.35±0.03 vs 0.58± 0.07 Δfluoresence unit) and significantly (P<0.05) increased contraction to U-46,619 (200±8 vs 141±7%) and endothelin 1 (ET1, 167±12 vs 118±17%) and ROS generation (0.32 ± 0.06 vs 0.1 ± 0.03 (E/DHE fluoresce unit). PVAT enhanced EDRF (50±4 vs 38±3 %) and NO (0.84 ±0.1 vs 0.58±0.07 Δfluoresence unit ) only in controls (P<0.05). The reduction of U46,619 anti-contractivity by PVAT is decreased in HIV (48±7 vs 85±9%, P<0.05). Conclusion: HIV-infected individuals have intrinsic vascular defects from ROS augmented by extrinsic vascular defects from adipose inflammation that impairs the beneficial microvascular PVAT signaling. Therefore, targets for potential prevention of cardiovascular morbidity in PLWH should include the elimination of ROS and inflammation in both microvessels themselves and the surrounding extravascular PVAT.

Is There Association between Altered Adrenergic System Activity and Microvascular Endothelial Dysfunction Induced by a 7-Day High Salt Intake in Young Healthy Individuals

This study aimed to test the effect of a 7-day high-salt (HS) diet on autonomic nervous system (ANS) activity in young healthy individuals and modulation of ANS on microvascular endothelial function impairment. 47 young healthy individuals took 7-day low-salt (LS) diet (3.5 g salt/day) followed by 7-day high-salt (HS) diet (~14.7 g salt/day). ANS activity was assessed by 24-h urine catecholamine excretion and 5-min heart rate variability (HRV). Skin post-occlusive reactive hyperemia (PORH) and acetylcholine-induced dilation (AChID) were assessed by laser Doppler flowmetry (LDF). Separately, mental stress test (MST) at LS and HS condition was conducted, followed by immediate measurement of plasma metanephrines’ level, 5-min HRV and LDF microvascular reactivity. Noradrenaline, metanephrine and normetanephrine level, low-frequency (LF) HRV and PORH and AChID significantly decreased following HS compared to LS. MST at HS condition tended to increase HRV LF/HF ratio. Spectral analysis of PORH signal, and AChID measurement showed that MST did not significantly affect impaired endothelium-dependent vasodilation due to HS loading. In this case, 7-day HS diet suppressed sympathetic nervous system (SNS) activity, and attenuated microvascular reactivity in salt-resistant normotensive individuals. Suppression of SNS during HS loading represents a physiological response, rather than direct pathophysiological mechanism by which HS diet affects microvascular endothelial function in young healthy individuals.

Quantification of Retinal Vessel Myogenic Constriction in Response to Blood Pressure Peaks: Implications for Flicker Light-Induced Dilatation

Background/AimsFlicker-light induced retinal vessel dilatation (FID), a marker of microvascular endothelial function, has been shown to be blunted in sedentary cardiovascular risk patients (SR) as well as healthy physically active individuals (HA). This study aimed to quantify the retinal myogenic response to blood pressure (BP) peaks and its effects on consecutive FID for differentiation of microvascular health.MethodsTen HA and eleven SR with a previously established restriction of arteriolar FID (aFID) (&lt;2.2%) were invited in order to assess BP-induced myogenic constriction following a standardized handgrip task and a consecutive FID. BP was measured beat-to-beat.ResultsThe complete dataset of nine HA (3 female, mean age 65 years) and nine SR (5 female, mean age 61 years) individuals was analyzed. The central retinal arteriolar diameter equivalent (CRAE) was 183 ± 11 μm for HA and 176 ± 20 μm for SR. Initial baseline aFID was 1.6 ± 0.4% in HA and 1.6 ± 0.7% in SR. Systolic (p = 0.334) and diastolic (p = 0.245) BP increase following the handgrip task was in the range of 20–30% and comparable in both groups. BP increase was followed by a significantly higher arteriolar (−2.9 ± 1.3% vs. −1.3 ± 0.6%, p &lt; 0.01) myogenic constriction in HA compared to SR. Moreover, in the consecutive assessment of FID directly after the BP-induced vessel constriction, aFID (4.1 ± 2.0% vs. 1.6 ± 0.9%, p &lt; 0.01) was higher in HA compared to SR.ConclusionInitial baseline aFID was blunted in HA and SR. Retinal myogenic constriction was impaired in SR compared to HA. The consecutive aFID after BP-induced myogenic constriction recovered in HA but remained blunted in SR. Additional assessment of retinal myogenic constriction needs to be considered to improve CV risk stratification and reduce false-positive findings of endothelial dysfunction in otherwise healthy active individuals.Clinical Trial RegistrationClinicalTrials.gov: NCT03986892 (https://clinicaltrials.gov/ct2/show/NCT03986892).

Relationship between serum testosterone concentration and microvascular endothelial function in Japanese men

Background: Both endothelial dysfunction and low circulating androgen levels predict cardiovascular disease in men. Endothelial function evaluation is commonly performed by measuring flow-mediated vasodilatation of the brachial artery. However, studies have suggested that compared with evaluation of large arteries, microvascular function evaluation of peripheral arteries is a better predictor of increased cardiovascular disease risks. Although circulating levels of androgens, such as testosterone and dehydroepiandrosterone sulfate (DHEA-S), positively correlate with cardiovascular function, the association between circulating androgen levels and microvascular function is unknown. In this study, we investigated whether serum androgen levels correlate with microvascular endothelial function in men. Methods: The study included 105 Japanese men (age 59 ± 1 years) in whom we measured serum testosterone and DHEA-S levels. The reactive hyperemia index (RHI) determined by the Endo-PAT system (finger plethysmography) was used to evaluate microvascular endothelial function. Results: Serum testosterone levels were significantly correlated with the RHI (r = 0.32, P < 0.01). The association between serum testosterone levels and the RHI remained significant even after adjustment for confounders, including age and body mass index (β = 0.31, P < 0.01). Notably, serum DHEA-S levels were not associated with the RHI (r = 0.01, n.s.). Conclusion: This study showed that serum testosterone levels were positively correlated with microvascular endothelial function in men. These results suggest that endogenous testosterone level is one of the determinants of microvascular endothelial function and may become a biomarker reflecting lifestyle modifications-induced improvement in cardiovascular function in men.

Comparison of biomarkers of endothelial dysfunction and microvascular endothelial function in patients with primary aldosteronism and essential hypertension

Introduction: Studies have shown that primary aldosteronism (PA) has a higher risk of cardiovascular events than essential hypertension (EH). Endothelial dysfunction is an independent predictor of cardiovascular events. Whether PA and EH differ in the endothelial dysfunction is uncertain. Our study was designed to investigate the levels of biomarkers of endothelial dysfunction (Asymmetric dimethylarginine, ADMA; E-selectin, and Plasminogen activator inhibitor-1, PAI-1) and assess the microvascular endothelial function in patients with PA and EH, respectively. Methods: The biomarkers of endothelial dysfunction were measured by enzyme-linked immunosorbent assay (ELISA). Microvascular endothelial function was evaluated by Pulse amplitude tonometry (PAT). Results: Thirty-one subjects with EH and 36 subjects with PA including 22 with aldosterone-producing adenoma (APA) and 14 with idiopathic hyperaldosteronism (IHA) were enrolled in our study. The ADMA levels among the three groups were different (APA 47.83 (27.50, 87.74) ng/ml vs EH 25.08 (22.44, 39.79) ng/ml vs IHA 26.00 (22.23, 33.75) ng/ml; p = 0.04), however, when the APA group was compared with EH and IHA group, there was no statistical significance (47.83 (27.50, 87.74) ng/ml vs 25.08 (22.44, 39.79) ng/ml for EH, p = 0.11; 47.83 (27.50, 87.74) ng/ml vs IHA 26.00 (33.75) ng/ml, p = 0.07). The results of ADMA levels are presented as Median (p25, p75). Whereas, levels of PAI-1 and E-selectin, microvascular endothelial function were not significantly different between PA and EH subjects. Conclusions: Our study shows no significant differences between PA and EH in terms of biomarkers of endothelial dysfunction and microvascular endothelial function. The microvascular endothelial function of PA and EH patients is comparable.