Featured from AHA Hypertension April: Chronic Supplementation With a Mitochondrial Antioxidant (MitoQ) Improves Vascular Function in Healthy Older Adults.

Hypertension. 2018 Apr 16. pii: HYPERTENSIONAHA.117.10787. doi: 10.1161/HYPERTENSIONAHA.117.10787. [Epub ahead of print]

Chronic Supplementation With a Mitochondrial Antioxidant (MitoQ) Improves

Vascular Function in Healthy Older Adults.

Rossman MJ1, Santos-Parker JR2, Steward CAC2, Bispham NZ2, Cuevas LM2, Rosenberg HL2, Woodward KA2, Chonchol M3, Gioscia-Ryan RA2, Murphy MP4, Seals DR2,3.

Author information

1
From the Department of Integrative Physiology, University of Colorado Boulder (M.J.R., J.R.S.-P., C.A.C.S., N.Z.B., L.M.C., H.L.R., K.A.W., R.A.G.-R., D.R.S.) matthew.rossman@colorado.edu.
2
From the Department of Integrative Physiology, University of Colorado Boulder (M.J.R., J.R.S.-P., C.A.C.S., N.Z.B., L.M.C., H.L.R., K.A.W., R.A.G.-R., D.R.S.).
3
Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora (M.C., D.R.S.).
4
MRC Mitochondrial Biology Unit, Cambridge, United Kingdom (M.P.M.).

Abstract

Excess reactive oxygen species production by mitochondria is a key mechanism of age-related vascular dysfunction. Our laboratory has shown that supplementation with the mitochondrial-targeted antioxidant MitoQ improves vascular endothelial function by reducing mitochondrial reactive oxygen species and ameliorates arterial stiffening in old mice, but the effects in humans are unknown. Here, we sought to translate our preclinical findings to humans and determine the safety and efficacy of MitoQ. Twenty healthy older adults (60-79 years) with impaired endothelial function (brachial artery flow-mediated dilation <6%) underwent 6 weeks of oral supplementation with MitoQ (20 mg/d) or placebo in a randomized, placebo-controlled, double-blind, crossover design study. MitoQ was well tolerated, and plasma MitoQ was higher after the treatment versus placebo period (P<0.05). Brachial artery flow-mediated dilation was 42% higher after MitoQ versus placebo (P<0.05); the improvement was associated with amelioration of mitochondrial reactive oxygen species-related suppression of endothelialfunction (assessed as the increase in flow-mediated dilation with acute, supratherapeutic MitoQ [160 mg] administration; n=9; P<0.05). Aortic stiffness (carotid-femoral pulse wave velocity) was lower after MitoQ versus placebo (P<0.05) in participants with elevated baseline levels (carotid-femoral pulse wave velocity >7.60 m/s; n=11). Plasma oxidized LDL (low-density lipoprotein), a marker of oxidative stress, also was lower after MitoQ versus placebo (P<0.05). Participant characteristics, endothelium-independent dilation (sublingual nitroglycerin), and circulating markers of inflammation were not different (all P>0.1). These findings in humans extend earlier preclinical observations and suggest that MitoQ and other therapeutic strategies targeting mitochondrial reactive oxygen species may hold promise for treating age-related vascular dysfunction.

CLINICAL TRIAL REGISTRATION:

clinicaltrials . gov. Unique identifier: NCT02597023.

KEYWORDS:

aging; arterial stiffness; endothelium; mitochondria; reactive oxygen species

Previous updates:

Presentations you might have missed at ACC 2018 last month:

Session 1213 – Microvascular Disease, Endothelial Dysfunction, Vasospasm and Other Clinical Conundrums

– Peripheral Endothelial Function Predicts 1-Year Adverse Clinical Outcome in Patients With Chest Pain Hospitalized in the Emergency Department (view)


– Coronary and Peripheral Vasomotor Responses to Mental Stress 
(view)

– Myocardial Bridge Muscle Index (MMI): A Marker of Disease Severity and Its Relationship With Endothelial Dysfunction … (view)


Five-year prospective study on cardiovascular events, in patients with

erectile dysfunction and hypotestosterone.

Iacona R1, Bonomo V, Di Piazza M, Sansone A, Usala M, Novo S, Pavone C.

Author information

1
Chair of Division of Cardiology, University Hospital “Paolo Giaccone”, Palermo. rosanna.iacona@virgilio.it.

Abstract

OBJECTIVE:

Testosterone levels play a role in cardiac and vascular pathology. In the present study we investigated the prognostic significance of this hormone for cardiovascular outcome, in a 5-year follow-up.

MATERIALS AND METHODS:

Our cohort included 802 adult subjects, from 40 to 80 years. Patients were excluded if they had a past history of peripheral or coronary artery disease, and revascularization. A blood sample was drawn to valuate testosterone level, and we considered normal testosterone levels 300 ng/dl. FMD (flow mediated dilatation) of the brachial artery was assessed by measuring the increase of the brachial artery diameter during reactive hyperemia after transient forearm ischemia. B-mode longitudinal images of the brachial artery were obtained at the level of the antecubital fossa. The FMD was defined as the percentage change in the brachial artery diameter 60 s after releasing the ischemic cuff. Erectile dysfunction (ERD) was assessed by the International Index of Erectile Function-5 (IIEF-5) score questionnaire. We considered composite end points including the following major adverse cardiovascular events (MACEs) Results: Subjects with lower serum testosterone levels (n = 332) had higher prevalence of traditional cardiovascular risk factors, such as hypertension (p = 0.009), diabetes (p = 0.03), dyslipidemia (p < 0.0001), obesity (p = 0.002), and endothelial function score (p < 0.0001). AMI, death after AMI, major stroke and all clinical events were more frequent (p < 0.001) in patients with testosterone levels < 300 ng/dl. Further, by multiple logistic regression analysis we found that only dyslipidemia (p = 0,001), obesity (p = 0,007), testosterone < 300 ng/dl (p < 0,0001) and ED (p < 0,0001) were independent predictors of future events.

CONCLUSIONS:

A therapeutic intervention on testosterone may not only have a positive effect on the cardiovascular system but also an important role in preventing new cardiovascular events.

KEYWORDS:

Cardiovascular events; Erectile dysfunction; Prevention

 Low testosterone and endothelial dysfunction.png

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The link between depression and atherosclerosis through the pathways of inflammation and endothelium dysfunction.

Chrysohoou C1, Kollia N2, Tousoulis D3.

Author information

1
First Cardiology Clinic, School of Medicine, University of Athens, Athens, Greece. Electronic address: chrysohoou@usa.net.
2
Department of Nutrition & Dietetics, School of Health Science and Education, Harokopio University, Athens, Greece.
3
First Cardiology Clinic, School of Medicine, University of Athens, Athens, Greece.

Abstract

A large body of evidence suggests that depression increases the risk of cardiovascular morbidity and mortality. The elevated risk associated with depression is not limited to clinical major depressive disorder but also extends to sub-syndromal depressive symptoms and constructs with overlapping characteristics, such as vital exhaustion. Multiple pathophysiological pathways are involved in the relationship between depressive symptoms and atherosclerosis and its clinical manifestations and progression. These underlying mechanisms are not yet fully understood and need further clarification. This review examines inflammation and endothelium dysfunction as potential biological factors involved in the relationship between depressive symptoms and atherosclerosis. It has been reported that systemic inflammation and psychological factors interact through complex pathophysiological and behavioral mechanisms and one question that has been raised concerns whether the inflammation drives depression or vice versa, or whether the association is merely coincidental. Although further investigation is needed, including well-designed prospective studies, to address this question thoroughly, it seems that there is a feedback relationship, although the biological pathways of each direction may be distinct.

KEYWORDS:

Cardiovascular disease; Depression; Mechanisms

 

Int J Cardiol. 2018 Jun 15;261:196-203. doi: 10.1016/j.ijcard.2018.02.041.

Endothelial dysfunction, abnormal vascular structure and lower urinary tract symptoms in men and women.

Matsui S1, Kajikawa M2, Maruhashi T1, Iwamoto Y1, Oda N1, Kishimoto S1, Hashimoto H1, Hidaka T1, Kihara Y1, Chayama K3, Hida E4, Goto C5, Aibara Y6, Nakashima A6, Yusoff FM6, Noma K7, Kuwahara Y8, Matsubara A9, Higashi Y10.

Author information

Abstract

BACKGROUND:

Lower urinary tract symptoms (LUTS) is not only common symptoms in elderly men and women but also risk of future cardiovascular events. The purpose of this study was to evaluate the relationships of vascular function and structure with LUTS in men and women.

METHODS:

We investigated flow-mediated vasodilation (FMD) and nitroglycerine-induced vasodilation (NID) as vascular function, brachial-ankle pulse wave velocity (baPWV) as vascular structure, and LUTS assessed by International Prostate Symptom Score (IPSS) in 287 men and 147 women.

RESULTS:

IPSS was significantly correlated with traditional cardiovascular risk factors, Framingham risk score, FMD, NID and baPWV. Moderate to severe LUTS was associated with the prevalence of coronary heart disease in men but not in women. In men, FMD and NID were significantly lower in the moderate to severe LUTS group than in the none to mild LUTS group (2.1 ± 2.0% vs. 4.0 ± 3.0% and 9.3 ± 6.1% vs. 12.8 ± 6.6%, P < 0.001, respectively). baPWV was significantly higher in the moderate to severe LUTS group than in the none to mild LUTS group (1722 ± 386 cm/s vs. 1509 ± 309 cm/s, P < 0.001). In multivariate analysis, FMD was independently associated with a decrease in the odds ratio of moderate to severe LUTS in men (OR: 0.83, 95% CI, 0.72-0.95; P = 0.008) but not in women. NID and baPWV were not independently associated with moderate to severe LUTS either in men or women.

CONCLUSIONS:

These findings suggest that endothelial dysfunction is associated with LUTS in men. LUTS in men may be useful for a predictor of cardiovascular events.

CLINICAL TRIAL REGISTRATION INFORMATION:

URL for Clinical Trial . Gov; Registration Number for Clinical Trial: UMIN000003409.

Endothelial dysfunction as a common soil of lower urinary tract symptoms and cardiovascular disease.

Yamagishi SI.

Int J Cardiol. 2018 Jun 15;261:209-210. doi: 10.1016/j.ijcard.2018.03.033.

J Nutr. 2018 Apr 1;148(4):581-586. doi: 10.1093/jn/nxy005.

Polyphenols Have No Impact on Endothelial Function in Patients with Obstructive Sleep Apnea: A Randomized Controlled Trial.

Trzepizur W1,2, Bironneau V2, Recoquillon S2, Priou P1,2, Meslier N1,2, Hamel JF3, Henni S4, Darsonval A5, Messaoudi K6, Martínez MC2, Andriantsitohaina R2, Gagnadoux F1,2.

Author information

1
Departments of Pneumology, Methodology and Biostatistics, Pharmacy, and Biochemistry and Genetics, Laboratory of Physiology and Vascular Explorations Vasculaires, CHU d’Angers, Angers, France.
2
Stress Oxydant et Pathologies Métaboliques (SOPAM), UNIV Angers, University of Bretagne Loire, Angers, France.
3
Departments of Methodology and Biostatistics, Pharmacy, and Biochemistry and Genetics, Laboratory of Physiology and Vascular Explorations Vasculaires, CHU d’Angers, Angers, France.
4
Departments of Laboratory of Physiology and Vascular Explorations Vasculaires, CHU d’Angers, Angers, France.
5
Departments of Pharmacy, and Biochemistry and Genetics, Laboratory of Physiology and Vascular Explorations Vasculaires, CHU d’Angers, Angers, France.
6
Departments of Biochemistry and Genetics, Laboratory of Physiology and Vascular Explorations Vasculaires, CHU d’Angers, Angers, France.

Abstract

BACKGROUND:

Endothelial dysfunction, a pathophysiologic determinant of atherogenesis, has been found to occur in obstructive sleep apnea syndrome (OSA) and is improved by continuous positive airway pressure (CPAP). However, the efficacy of CPAP therapy is limited by variable adherence. Alternative treatment strategies are needed. The impact of polyphenols on endothelial function has never been evaluated in OSA.

OBJECTIVE:

We evaluated the impact of 1-mo supplementation with grape juice polyphenols (GJPs) on the reactive hyperemia index (RHI), a validated measure of endothelial function in patients with severe OSA.

METHODS:

Forty participants [75% men, median (IQR) age: 61 y (34, 64 y), BMI (in kg/m2): 30.6 (20.9, 33.7)] with severe OSA [median apnea-hypopnea index 43/h (33/h, 56/h)] were randomly assigned to receive GJPs (300 mg/d; n = 20) or placebo (n = 20) for 1 mo. The primary outcome was the change in RHI between baseline and after 1 mo of GJPs or placebo. Secondary outcome measures included changes in blood pressure (BP), heart rate (HR), and polysomnographic indexes.

RESULTS:

No significant differences in RHI and BP outcomes were observed between the GJPs and placebo groups. A significant between-group difference was observed for HR changes [-1 bpm (-5, +5 bpm) in the GJPs group compared with +6 bpm (+3, +10 bpm) in the placebo group; P = 0.001]. A significant decrease in total sleep time was observed in the GJPs group compared with the placebo group [-10 min (-33, 6 min) compared with +15 min (-12, 40 min), respectively; P = 0.02], with no between-group differences in the distribution of sleep stages.

CONCLUSIONS:

In participants with severe OSA and no overt cardiovascular disease, 1-mo GJP supplementation had no effect on endothelial function.
This trial was registered in ClinicalTrials . gov NCT01977924.

Am J Physiol Heart Circ Physiol. 2018 Apr 13. doi: 10.1152/ajpheart.00734.2017. [Epub ahead of print]

Strategies for Optimal Cardiovascular Aging.

Seals DR1, Brunt VE2, Rossman MJ1.

Author information

1
Department of Integrative Physiology, University of Colorado Boulder, United States.
2
Department of Integrative Physiology, University of Colorado-Boulder, United States.

Abstract

This review summarizes the opening keynote presentation overview of the American Physiological Society conference on Cardiovascular Aging: New Frontiers and Old Friends held in Westminster, CO, in August 2017. Age is the primary risk factor for cardiovascular diseases (CVD). Without effective intervention, increased numbers of older adults in the future will translate to greater prevalence of CVD and related disorders. Advancing age increases the risk of CVD partly via direct effects on the heart and through increases in blood pressure; however, much of the risk is mediated by arterial dysfunction, including large elastic artery stiffening and both macro- and micro-vascular endothelialdysfunction. Although excessive superoxide-related oxidative stress and chronic low-grade inflammation are the major processes driving cardiovascular aging, the upstream mechanisms involved represent new frontiers of investigation and potential therapeutic targets. Lifestyle practices, including aerobic exercise, energy intake (caloric) restriction, and healthy diet composition are the most evidence-based strategies (old friends) for optimal cardiovascular aging, but adherence is poor in some groups. Healthy lifestyle “mimicking” approaches, including novel forms of physical training, intermittent fasting paradigms, exercise/healthy diet-inspired nutraceuticals (functional foods and natural supplements), as well as controlled environmental stress exposure (e.g., heat therapy), may hold promise, but are unproven. Mitigating the adverse effects of aging on cardiovascular function and health is a high biomedical priority.

KEYWORDS:

caloric restriction; energy-sensing; mitochondrial dysfunction; nitric oxide

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