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Cardiol- PAD

Primary Care Corner with Geoffrey Modest MD: Dark Chocolate helps with peripheral arterial disease (PAD)

29 Sep, 14 | by EBM

A recent article on the impressive role of dark chocolate in improving walking for patients with PAD (see DOI: 10.1161/JAHA.114.001072). I can’t resist it: so many bad things going on around the world and here is a chance to trumpet a universal (or nearly so) positive. So, in this remarkably important study (albeit small, with only 20 patients, mean age 69, 85% with hypertension, 30% diabetes, 90% dyslipidemia, 80% former smokers, 60% on ACE-I, 100% on statins, 95% on anti-platelet drugs), they measured maximal walking distance (MWD) and maximal walking time (MWT) in those randomly given 40 g of dark chocolate (>85% cocoa) vs. 40 g of mild chocolate (<=35% cocoa) in single-blind cross-over design study, checking the MWD and MWT at baseline and 2 hours after chocolate ingestion. And…

Chocolate_-_stonesoup–dark chocolate increased MWD by 11% (p<0.001) and MWT by 15% (p<0.001). MWD increased from 110.7m to 122.2m, MWT  from 124.8 to 142.2 seconds. also flow-mediated dilation doubled (p=0.003)
–dark chocolate also increased serum NOx​ by 57% (p<0.001) and decreased serum isoprostanes by 23% (p=0.01), and sNOX2-dp by 37% (p<0.001)
–no change in above after milk chocolate

There are some data suggesting that oxidative stress as well as endothelial dysfunction, reduced glucose-oxidation, accumulation of toxic metabolites, impaired nitric oxide generation (above study measured the metabolic endproducts of serum nitrite and nitrate, or NOx) play a role in intermittent claudication. Cocoa is rich in polyphenols, which induce arterial dilation (by lowering activation of NOX2, catalytic substrate of NADPH oxidase, which acts as a vasoconstrictor — above study measured the sNOX2-dp, the serum NOX2-derived protein). This study suggests that dark chocolate down-regulates NOX2-mediated oxidative stress (perhaps mediated by the polyphenols). Other data note increased arterial dilation in smokers with dark chocolate.

Of note, these very positive changes were after only 40 g of dark chocolate. Just imagine the effects of a much higher dose? Continuous infusion? This study does not undermine the most important PAD therapies: stopping smoking and exercise; it just raises the possibility of combo therapies — eating dark chocolate instead of smoking, or eating dark chocolate while walking.


Primary Care Corner with Geoffrey Modest MD: Conundrum–Ankle-Brachial index not recommended but Periph arterial disease important and under-diagnosed

10 Sep, 13 | by EBM

US Preventive Services Taskforce just published their guidelines for peripheral arterial disease screening with ankle-brachial index (ABI) — see link: they do not find sufficient evidence to recommend routine screening, though point out:


–PAD common, with recent NHANES survey showing that 5.9% of US population >40 years old have ABI <0.9, most of whom are asymptomatic

–PAD is a marker for coronary heart disease (approx 2-fold increased risk – see  JAMA. 2008;300(2):197-208, which found twice the 10-year mortality in those with PAD), and is independent of traditional risk factors. adding PAD to the framingham risk score would result in reclassification of patient risk as follows: for men, who get more PAD at an earlier age, 19% were reclassified, mostly by a normal ABI resulting in high risk decreasing to intermediate risk; in women, there was a 36% reclassification rate, mostly from low to intermediate or high risk based on low ABI) — but there are no data that this reclassification and potentially changed treatment would affect clinical outcomes. one study in JAMA (2010; 303(9):841-8) did not show that aspirin was effective in general population with low ABI. USPSTF comments that there are no studies addressing lipid-lowering in patients without known diabetes or CAD (one point of the guidelines is whether the testing would alter therapy; diabetics and patients with CAD should already be on lipid-lowering meds and probably aspirin anyway). [there actually are a couple of studies – one small study of patients with severe PAD who did have a survival benefit with statins and another larger study of patients also found a mortality benefit, but this study had patients with many different underlying medical problems (44% with CAD) and didn’t perform subgroup analysis. so, there are some data suggesting statins do confer cardioprotection in those with PAD.]


coincidentally, the european cardiology conference this month reported the results of the REACH trial (reduction of atherothrombosis for continued health) registry in patients with symptomatic PAD. full report not available for evaluation,  but i am bringing it up given the above guidelines.  basically:

–5861 patients with established symptomatic PAD assessing 4-year data.

–primary outcome (localized) — worsening claudication or new episode of critical limb ischemia, revascularization or amputation.  secondary outcome (systemic) — cardiovascular death, nonfatal MI and nonfatal stroke.

–3643 on statin and 2218 not. (note: this is not an intervention trial)

–adverse limb outcomes:  occurred in 22% of those on statin and 26.2% not on statin (unadjusted rates), with 14.7 vs 18.2% with worsening claudication or critical limb ischemia; 18.2% vs 21.7% with revascularization; 3.8% vs 5.6% with amputation

–adverse systemic outcomes: 19.6 vs 20.3% with total cardiovasc outcomes; 17.3 vs 19.7% all-cause mortality; 11.4 vs 12.4% cardiovascular mortality; 5 vs 4.6% nonfatal MI; 6 vs 6.8% nonfatal stroke.  — unclear how statistically significant this is. [though these numbers don’t show much improvement with statins, unlike the 25-30% risk reduction in the CAD trials]


so, what makes sense here???  it is true from several studies that PAD is associated with CAD. one would think this to be true whether the PAD were symptomatic or not. adding PAD to the framingham risk score seems to reclassify a lot of people. and statins do seem to improve walking distances and decrease need for limb revascularization. (also, see article showing that ramipril increases walking distances in dropbox, or JAMA. 2013;309(5):453-460).  i would suggest the following:


–would not screen for PAD in asymptomatic patients, given the above-noted lack of good data.

–statins should be part of treatment for symptomatic PAD (one reason i brought this study up is the pretty surprising finding that >1/3 of the patients in this registry with symptomatic PAD were not on statins), esp if LDL is >100.



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