X-Message-Number: 31391
Date: Thu, 19 Feb 2009 20:29:16 -0800 (PST)
From: 
Subject: FMD may be the ONLY risk factor for atherosclerosis

  [For years, atherosclerosis progression in individuals with no risk
factors such as age, high blood pressure and cholesterol has been a
puzzle. In what appears to be a major advance in the understanding of
this process it has now been shown that of the traditional risk factors,
NONE has amy direct effect on progression. Progression has been found to
be mediated emtirely by a non-traditional risk factor called flow-mediated
dilatation (FMD). Pending confirmation by other studies, the implication
is that if endothelial function is maintained, atherosclerosis may never
develop. Atherosclerosis would thus cease to play any part in the
mortality of endothelial competent humans.
  Want to do? Consuming red (or black) grapes every day is probably one
ticket to a longer and more disease free lifespan.]

Circulation. 2009 Feb 9. [Epub ahead of print]
Endothelial Function Predicts Progression of Carotid Intima-Media Thickness.

  Halcox JP, Donald AE, Ellins E, Witte DR, Shipley MJ, Brunner EJ, Marmot MG, 
  Deanfield JE. Department of Cardiology, Cardiff University.

  BACKGROUND: -Endothelial dysfunction develops early and has been shown to 
  predict the development of clinical complications of atherosclerosis. However,
  the relationship between early endothelial dysfunction and the progression of
  arterial disease in the general population is unknown. We investigated 
  endothelial dysfunction, risk factors, and progression of carotid intima-media
  thickness (cIMT) in late-middle-aged individuals at low to intermediate 
  cardiovascular risk in a prospective study between 1997 and 2005. Methods and 
  Results-Brachial artery flow-mediated dilatation and cIMT were measured in 213
  nonsmoking British civil servants recruited from a prospective cohort 
  (Whitehall II study). Participants (age, 45 to 66 years) were free of clinical
  cardiovascular disease and diabetes mellitus. Risk factors and Framingham 
  Risk Score were determined at baseline. cIMT was repeated 6.2+/-0.4 years 
  later. At baseline, age, blood pressure, low-density lipoprotein cholesterol, 
  and Framingham Risk Score correlated with cIMT. However, only flow-mediated 
  dilatation, not risk factors or Framingham Risk Score, was associated with 
  average annual progression of cIMT. This relationship remained significant 
  after adjustment for risk factors whether entered as separate variables or as 
  Framingham Risk Score. Further adjustment for waist circumference, 
  triglycerides, and employment grade had no significant effect. 
  Conclusions-Systemic endothelial function was associated with progression of 
  preclinical carotid arterial disease over a 6-year period and was more closely
  related to cIMT changes than conventional risk factors. Thus, the 
  relationship between endothelial dysfunction and adverse outcome is likely to 
  be due not only to destabilization of established disease in high-risk 
  populations but also to its impact on the evolution of the atherosclerotic 
  substrate. Flow-mediated dilatation testing provides an integrated vascular 
  measure that may aid the prediction of structural disease evolution and 
  represents a potential short- to intermediate-term outcome measure for 
  evaluation of preventive treatment strategies.
PMID: 19204308

Eur J Cardiovasc Prev Rehabil. 2005 Dec;12(6):596-600.

Polyphenolic compounds from red grapes acutely improve endothelial function in 
patients with coronary heart disease.

  Lekakis J, Rallidis LS, Andreadou I, Vamvakou G, Kazantzoglou G, Magiatis P, 
  Skaltsounis AL, Kremastinos DT. Second Department of Cardiology, University 
  General Hospital, Attikon, Greece.

  BACKGROUND: It has been shown that acute intake of red wine improves 
  endothelial-dependent vasodilatation. It is not clear, however, which 
  constituents of red wine are responsible for this effect. We examined whether 
  acute intake of a red grape polyphenol extract has a positive effect on 
  brachial artery flow-mediated dilatation. METHODS: We recruited 30 male 
  patients with coronary heart disease. They were randomly assigned either to a 
  red grape polyphenol extract (600 mg) dissolved in 20 ml of water (n = 15) or 
  20 ml of water (placebo) (n = 15). The extract of grapes contained 4.32 mg 
  epicatechin, 2.72 mg catechin, 2.07 mg gallic acid, 0.9 mg trans-resveratrol, 
  0.47 mg rutin, 0.42 mg epsilon-viniferin, 0.28 mg, p-coumaric acid, 0.14 mg 
  ferulic acid and 0.04 mg quercetin per gram. Flow-mediated dilatation of the 
  brachial artery was evaluated after reactive hyperemia induced by cuff 
  obstruction of the forearm, using high-resolution ultasonography. 
  Particularly, flow-mediated dilatation was measured after fasting and 30, 60 
  and 120 min after the intake of the grape extract or placebo. RESULTS: Intake 
  of the red grape polyphenol extract caused an increase in flow-mediated 
  dilatation, peaking at 60 min, which was significantly higher than the 
  baseline values (4.52+/-1.34 versus 2.6+/-1.5%; P < 0.001) and the 
  corresponding values at 60 min after the intake of placebo (4.52+/-1.34 versus
  2.64+/-1.8%, P < 0.001). There was no change in FMD values after the intake 
  of placebo throughout the whole duration of the study. CONCLUSION: 
  Polyphenolic compounds from red grapes acutely improve endothelial function in
  patients with coronary heart disease. These results could probably, at least 
  partly, explain the favorable effects of red wine on the cardiovascular 
  system.
PMID: 16319551

Circulation. 1999 Sep 7;100(10):1050-5.

Purple grape juice improves endothelial function and reduces the susceptibility 
of LDL cholesterol to oxidation in patients with coronary artery disease.

  Stein JH, Keevil JG, Wiebe DA, Aeschlimann S, Folts JD. University of 
  Wisconsin Medical School, Madison, WI 53792-3982, USA.

  BACKGROUND: In vitro, the flavonoid components of red wine and purple grape 
  juice are powerful antioxidants that induce endothelium-dependent vasodilation
  of vascular rings derived from rat aortas and human coronary arteries. 
  Although improved endothelial function and inhibition of LDL oxidation may be 
  potential mechanisms by which red wine and flavonoids reduce cardiovascular 
  risk, the in vivo effects of grape products on endothelial function and LDL 
  oxidation have not been investigated. This study assessed the effects of 
  ingesting purple grape juice on endothelial function and LDL susceptibility to
  oxidation in patients with coronary artery disease (CAD). METHODS AND 
  RESULTS: Fifteen adults with angiographically documented CAD ingested 
  7.7+/-1.2 mL. kg(-1). d(-1) of purple grape juice for 14 days. Flow-mediated 
  vasodilation (FMD) was measured using high-resolution brachial artery 
  ultrasonography. Susceptibility of LDL particles to oxidation was determined 
  from the rate of conjugated diene formation after exposure to copper chloride.
  At baseline, FMD was impaired (2.2+/-2. 9%). After ingestion of grape juice, 
  FMD increased to 6.4+/-4.7% (P=0.003). In a linear regression model that 
  included age, artery diameter, lipid values, and use of lipid-lowering and 
  antioxidant therapies, the effect of grape juice on FMD remained significant 
  (mean change 4.2+/-4.4%, P<0.001). After ingestion of grape juice, lag time 
  increased by 34.5% (P=0.015). CONCLUSIONS: Short-term ingestion of purple 
  grape juice improves FMD and reduces LDL susceptibility to oxidation in CAD 
  patients. Improved endothelium-dependent vasodilation and prevention of LDL 
  oxidation are potential mechanisms by which flavonoids in purple grape 
  products may prevent cardiovascular events, independent of alcohol content.
PMID: 10477529

Braz J Med Biol Res. 2005 Sep;38(9):1339-47. Epub 2005 Aug 26.

The action of red wine and purple grape juice on vascular reactivity is 
independent of plasma lipids in hypercholesterolemic patients.

  Coimbra SR, Lage SH, Brandizzi L, Yoshida V, da Luz PL. Instituto do Coracao, 
  Hospital das Clinicas, Faculdade de Medicina, Universidade de Sao Paulo, Sao 
  Paulo, SP, Brazil.

  Although red wine (RW) reduces cardiovascular risk, the mechanisms underlying 
  the effect have not been identified. Correction of endothelial dysfunction by 
  RW flavonoids could be one mechanism. We measured brachial artery reactivity 
  by high-resolution ultrasonography, plasma lipids, glucose, adhesion molecules
  (ICAM-1 and VCAM), and platelet function in 16 hypercholesterolemic 
  individuals (8 men and 8 women; mean age 51.6 +/- 8.1 years) without other 
  risk factors. Twenty-four normal subjects were used as controls for vascular 
  reactivity. Subjects randomly received RW, 250 ml/day, or purple grape juice 
  (GJ), 500 ml/day, for 14 days with an equal wash-out period. At baseline, all 
  16 subjects were hypercholesterolemic (mean LDL = 181.0 +/- 28.7 mg/dl) but 
  HDL, triglycerides, glucose, adhesion molecules, and platelet function were 
  within normal limits. Brachial artery flow-mediated dilation was significantly
  decreased compared to controls (9.0 +/- 7.1 vs 12.1 +/- 4.5%; P < 0.05) and 
  increased with both GJ (10.1 +/- 7.1 before vs 16.9 +/- 6.7% after: P < 0.05) 
  and RW (10.1 +/- 6.4 before vs 15.6 +/- 4.6% after; P < 0.05). RW, but not GJ,
  also significantly increased endothelium-independent vasodilation (17.0 +/- 
  8.6 before vs 23.0 +/- 12.0% after; P < 0.01). GJ reduced ICAM-1 but not VCAM 
  and RW had no effect on either molecule. No significant alterations were 
  observed in plasma lipids, glucose or platelet aggregability with RW or GJ. 
  Both RW and GJ similarly improved flow-mediated dilation, but RW also enhanced
  endothelium-independent vasodilation in hypercholesterolemic patients despite
  the increased plasma cholesterol. Thus, we conclude that GJ may protect 
  against coronary artery disease without the additional negative effects of 
  alcohol despite the gender.
PMID: 16138217

Rate This Message: http://www.cryonet.org/cgi-bin/rate.cgi?msg=31391