Vascular Effects of Caffeine
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1 Vascular Effects of Caffeine John P. Higgins MD, MBA, MPHIL, FACC, FACP, FAHA, FACSM, FASNC, FSGC Director of Exercise Physiology Memorial Hermann Sports Medicine Institute Chief of Cardiology, Lyndon B. Johnson General Hospital Associate Professor of Medicine, Cardiology Division, The University of Texas, Houston TX
2 About Myself
3 Outline Endothelial Cell Function (ECF) Caffeine at rest improves ECF Caffeine blocks Adenosine Receptors Caffeine + exercise decreases ECF Energy Drink at rest decreases ECF Research at UTHealth Conclusions
4 Endothelial Cell Function (ECF)
5 ECs : Endothelial Cell (EC) Form the inner lining of blood vessels Have basal & inducible metabolic/synthetic functions Carry out multiple important tasks Sumpio BE et al. Int J Biochem Cell Biol Dec;34(12):
6 Normal ECF Normal ECF is important to regulate vascular resistance (vessel tone & variation). Dynamic continuum: Vascular tone Thrombosis Barrier Sumpio BE et al. Int J Biochem Cell Biol Dec;34(12):
7 Normal ECF Vasodilating Thromboresistant Anti-adhesive (NO, PgI2, Endothelium-derived hyperpolarizing factor, Bradykinin) Abnormal ECF Vasoconstricting Procoagulant Pro-adhesive (Renin, Angiotensin, ET-1) Echeverri D et al. Int J Vasc Med. 2010;2010:
8 Abnormal ECF Short Term: During stress and with certain exposures, the impaired ability to dilate the coronary arteries could Result in supply-demand imbalance/coronary spasm Potentially leading to myocardial ischemia or cardiac arrhythmia. Long Term: Atherosclerosis - CVD, PAD, CAD
9 ECF Improvement in ECF is a desirable goal: Exercise Smoking cessation Antioxidants (vit C, flavonoids-dark chocolate) Cholesterol lowering (Statins) Omega-3 fatty acids Glycemic control in DM L-arginine (->NO) ACEI/ARB Lee R et al. Curr Vasc Pharmacol ; 10(1): Widlansky ME et al. J Am Coll Cardiol. 2003; 42(7):
10 Caffeine at Rest Improves ECF
11 Caffeine & ECF Caffeine increases intracellular calcium Expression of the endothelial nitric oxide synthase (enos) enzyme Stimulates EC production of nitric oxide (NO) NO diffuses to the vascular smooth muscle VSMC vasodilation Echeverri D et al. Int J Vasc Med. 2010;2010:
12 Artery Relaxation Echeverri D et al. Int J Vasc Med. 2010;2010:
13 Caffeine at Rest n (male) Mean Age (ys) Caffeine (mg) Test & Measuring Tool Results 40 (33) 53+/ mg (test 60 min later) Flow-mediated dilatation of the brachial artery. % flow-mediated dilation = (maximum diameter - baseline diameter)/baseline diameter x 100. Resting flow-mediated dilation increased 10% after caffeine ingestion (P <.001). 10 (10) 27+/ mg (test 60 min later) Forearm blood flow responses to acetylcholine (an endothelium dependent vasodilator) and sodium nitroprusside (endotheliumindependent vasodilator). Forearm blood flow was measured by using a strain-gauge plethysmograph. Resting forearm blood flow was not affected by caffeine. Resting forearm blood flow response to acetylcholine was increased 25% (P <.05). Higgins JP, Babu KM. Am J Med Aug;126(8):730.e1-8.
14 Caffeine Blocks Adenosine Receptors
15 Adenosine Caffeine competitively blocks all adenosine receptors. Echeverri D et al. Int J Vasc Med. 2010;2010:
16 Adenosine Caffeine blocks adenosine receptors Increases plasma adenosine levels Stimulates circulation chemoreceptors Increases sympathetic tone, catecholamines, PVR, & renin secretion Results e.g. increased SBP 7mm, DBP 3mm noted 60 mins after 300 mg caffeine. Echeverri D et al. Int J Vasc Med. 2010;2010:
17 Caffeine + Exercise Decreases ECF
18 Caffeine + Exercise Regarding ECF, especially interested in myocardial blood flow, so measure : PET (myocardial perfusion) Flow Mediated Dilation (FMD) - Accurate method for measuring brachial artery ECF - Accepted surrogate for coronary artery ECF Echeverri D et al. Int J Vasc Med. 2010;2010:
19 Caffeine + Exercise n (male) Mean Age (ys) Caffeine (mg) 15 (5) 58+/ mg (tested 50 min later) Test & Measuring Tool Myocardial perfusion reserve using PET. Ratio of myocardial blood flow during bicycle stress divided by myocardial blood flow at rest. Results Exercise-induced myocardial blood flow response decreased 14% after caffeine ingestion (P <.05). 18 (11) 27+/ mg (tested 50 min later) Myocardial perfusion reserve using PET. Ratio of myocardial blood flow during bicycle stress divided by myocardial blood flow at rest. Exercise-induced myocardial blood flow response decreased 22% after caffeine ingestion (P <.01). Higgins JP, Babu KM. Am J Med Aug;126(8):730.e1-8.
20 Caffeine + Exercise n (male) Mean Age (ys) Caffeine (mg) 10 (3) 30+/ mg (6 mg/kg) Test & Measuring Tool Forearm blood flow was made at baseline; performed 55 minutes bicycle ergometer and at 20-min intervals during dynamic leg exercise. Forearm blood flow was measured by using the indirect plethysmographic venous occlusion technique. Results At rest, caffeine had no effect on forearm blood flow. During dynamic exercise, caffeine attenuated the increase in forearm blood flow by 53%, P <.05. Higgins JP, Babu KM. Am J Med Aug;126(8):730.e1-8.
21 Energy Drinks at Rest Decreases ECF
22 Energy Drinks + ECF at Rest 50 healthy volunteers 34 male, 22+/-2 years ECF: - Adenosine diphosphate-induced platelet aggregation - Reactive Hyperemia Index (RHI) on peripheral arterial tonometry Tested before & 1 hour after 250 ml (1 can) of a sugar-free Energy Drinks. Worthley MI et al. Am J Med. 2010;123:
23 ECF : Platelet Function Increase in platelet aggregation following EB: -0.3% [control] vs. 13.7% [EB] * P<0.007 Worthley MI et al. Am J Med. 2010;123:
24 ECF : RHI RHI decreased following EB: 0.07 RHI [control] vs [EB] * P<0.05 Worthley MI et al. Am J Med. 2010;123:
25 Blood Pressure Mean arterial pressure increased following Energy Beverage consumption * P<0.05 Worthley MI et al. Am J Med. 2010;123:
26 Research at UTHealth
27 SHADE-ONE Study of Heart effects from Adults Drinking Energy beverages: ON Endothelial function Pilot Study: Me!
28 Energy Drink at Rest : ECF REST 0.42 cm 0.45 cm 90 min after drinking 24 oz Monster Energy Drink 0.43 cm 0.44 cm Higgins JP. Int J Cardiol 2013 Jul 19.
29 Energy Drink at Rest : ECF Higgins JP. Int J Cardiol 2013 Jul 19.
30 Conclusions
31 Conclusions Healthy individuals Aged years Consume ~ mgs caffeine Improved ECF Vasodilation at rest
32 Conclusions (cont.) Caffeine blocks adenosine receptors Reduces ability of adenosine to vasodilate Coronary and other blood vessels Reduced supply when demand increased Ischemia?
33 Conclusions (cont.) Healthy individuals Aged years Consume ~ mgs caffeine Perform aerobic exercise 1 hr later Indirect tests Reduction in ECF Reduction in myocardial blood flow
34 Conclusions (cont.) Healthy individuals Aged years Consumed Energy Drinks Reduced ECF at rest
35 Conclusions (cont.) Additional research needed: Effects/mechanisms of Caffeine & Energy Drinks on ECF Assess the safety of high-dose caffeine & Energy Drinks in - Younger - Caffeine naïve - Exercise 1-2 hours later
36 Q & A
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