Peripheral Arterial Disease
Conditions
Keywords
Peripheral arterial disease, Oxidative stress, Cocoa, polyphenols, NADPH oxidase
Brief summary
Peripheral arterial disease (PAD) is a clinical setting characterized by an exceptionally high risk for cardiovascular events. Oxidative stress seems to play a role in impairing flow-mediated dilation (FMD) and contributing to atherosclerosis in patients with PAD. Cocoa seems to exert artery dilatation via oxidative stress inhibition. OBJECTIVES: To investigate whether in PAD patients, dark chocolate elicits artery dilatation via down-regulation of NOX2, the catalytic core of NADPH oxidase.
Detailed description
Atherosclerosis represents the major cause of worldwide death; it is a complex phenomenon that encompasses the intricate interplay of classic cardiovascular risk factors, oxidative stress and inflammation. Peripheral artery disease (PAD) is a clinical setting that well represents the model of widespread atherosclerosis. PAD affects 20% of patients over the age of 75. Furthermore, PAD patients are at an exceptionally high risk for cardiovascular events and the majority will eventually die of a cardiac or cerebrovascular etiology. Polyphenol could represent a novel therapeutic strategy to counteract atherosclerosis. During the last decades, a growing interest in polyphenols resulted from prospective and epidemiological studies that showed the beneficial effects of these substances on human health. In particular, polyphenols exert their beneficial effect by inhibition of NADPH oxidase (NOX2), an enzyme directly involved in atherosclerosis; thus, the activation of this enzyme leads to an enhanced production of oxidative stress and inflammatory processes. The objective of this study is to evaluate the effect of polyphenols on oxidative stress and inflammation and on surrogate markers of atherosclerosis in PAD patients. Polyphenols, inhibiting NOX2-mediated oxidative stress and immune-mediated process, could represent a novel therapy to reduce the high risk of cardiovascular events in PAD.
Interventions
DIETARY_SUPPLEMENTdark chocolate with crossover to milk chocolate
40 g/d of dark chocolate for 4 weeks followed by wash-out (1 week) and by 40 g/d of milk chocolate for 4 weeks
DIETARY_SUPPLEMENTmilk chocolate with crossover to dark chocolate
40 g/d of milk chocolate for 4 weeks followed by wash-out (1 week) and by 40 g/d of dark chocolate for 4 weeks.
Sponsors
University of Roma La Sapienza
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
20 Years to 90 Years
Healthy volunteers
No
Inclusion criteria
Every PAD patient to be enrolled in the study had: 1. claudication (defined as leg pain on walking, disappearing within 10 minutes of standing, of presumed atherosclerotic origin) and 2. ankle/brachial index (ABI), that was assessed as ankle/arm systolic blood pressure ratio by Doppler ultrasonography \<0.90 on the worst leg at rest. Patients had to be in stable conditions without abrupt changes of ABI (\>20%) in the last month before the enrolment.
Exclusion criteria
Subjects were excluded from the study if they had liver insufficiency, serious renal disorders (serum creatinine\>2.8 mg/dL), acute stroke, acute myocardial infarction, deep venous thrombosis or if they were current smokers or were taking antioxidants.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| endothelial function assessed by flow mediated dilation (FMD) | 2 hours after (dark or milk) chocolate ingestion |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Oxidative stress markers | 2 hours after (dark or milk) chocolate ingestion | Oxidative stress markers: sNOX2dp, Isoprostanes, NOx |
| Maximal walking distance | 2 hours after (dark or milk) chocolate ingestion | — |
| Ankle Brachial Index (ABI) | 2 hours after (dark or milk) chocolate ingestion | — |
Countries
Italy
Outcome results
None listed