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Cardiology Casebook

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THE IMPORTANCE OF
VITAMIN C IN THE INCIDENCE
OF ATRIAL FIBRILLATION
By Kathryn Buchanan Keller, RN, PhD, and Louis Lemberg, MD

77-year-old man with symptomatic coro-

A
c. vitamin C may play a role in prevent-
nary atherosclerotic heart disease was ing postoperative AF
admitted for elective coronary revascu- d. atrial remodeling may be caused by
larization. He had a history of chronic oxidative stress
obstructive pulmonary disease due to
cigarette smoking and essential hypertension. He was ANSWERS
managed on diuretics and a salt-poor, low-cholesterol 1. b. vitamin C deficiency increases mortality
diet. An echocardiogram revealed left ventricular c. vitamin C deficiency is common in dia-
hypokinesis and atrial enlargement. Wide and notched betics
P waves in standard leads II and III of the electrocar- e. in the past, vitamin C was synthesized
diogram were considered to be related to his chronic by humans
obstructive pulmonary disease, which put him at risk Vitamin C (ascorbic acid) is an essential element
for postoperative atrial fibrillation (AF). A cardiac in the adult population. It is a cofactor in enzymatic
consultant advised adding vitamin C (ascorbic acid) functions necessary for metabolic reactions, such as
to his management. biosynthesis of collagen, amino acids, and norepi-
nephrine. Vitamin C is a powerful antioxidant that
QUESTIONS protects cellular constituents (proteins, lipids, and
1. Which of the following statements regarding DNA) and protects against oxidative stress produced
vitamin C is/are correct? by peroxide and free radicals.1 Vitamin C is found
a. vitamin C deficiency is rare in developed in fruits and vegetables and synthesized by most
countries living creatures. Humans and the higher primates
b. vitamin C deficiency increases mortality lost this function millions of years ago and are now
c. vitamin C deficiency is common in dia- dependent on exogenous sources of this essential
betics nutrient. Although scurvy, a disease of severe vitamin
d. vitamin C can be toxic in high doses C deficiency, is rarely seen in developed nations,
e. in the past, vitamin C was synthesized prevalence of vitamin C deficiency has been found
by humans in the adult population of the United States. Low
vitamin C serum concentrations were found in 25%
2. Which of the following are correct? of noncigarette smoking adult men 60 to 74 years
a. atrial fibrillation is an expected, benign of age.2 The incidence in the younger population
postoperative complication has been less striking, but not insignificant.3
b. -blockers are effective in preventing Vitamin C requirements increase during
postoperative AF trauma or injury, reflecting an increase in vitamin

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C utilization and metabolism. Diabetics and cigarette only a -blocker.7 The group that received both vita-
smokers have lower serum levels of vitamin C.3,4 min C and a -blocker had a 4% incidence of AF
Symptoms of severe vitamin C deficiency (which compared with 25% in the control group. Additional
may precede overt scurvy) include fatigue, weakness, studies have reported similar findings. In a study8
myalgia, irritability, skin rash, and swelling of the (2005) on the role of vitamin C in the prevention
lower extremities. Some of these symptoms are vague of early recurrence of AF following cardioversion,
but physiologically relevant and may be overlooked AF recurred in 4.5% of patients pretreated with vita-
or misdiagnosed.3 min C, compared with 36.3% in the control group.
Vitamin C is not highly toxic and interacts with The control group treated with vitamin C had a sig-
a number of medications such as aspirin, nonster- nificant reduction in serum inflammatory indices,
oidal antiinflammatory drugs, acetaminophen, loop such as white blood cell count, fibrinogen level,
diuretics, -blockers, tetracycline, and cyclosporine; and level of C-reactive protein.8
consequently, vitamin C levels should be monitored. Many factors have been implicated in the etiology
Warfarin therapy was thought to be problematic of postoperative AF, including acute intraoperative
when administered with vitamin C; however, subse- atrial enlargement, ischemia, surgical trauma, peri-
quent findings did not support the earlier case reports. carditis, chronic obstructive pulmonary disease,
Warfarin can be administered with vitamin C at doses hypertension, hypomagnesemia, inadequate cool-
not exceeding 1000 mg daily, but requires monitor- ing of the atria, and withdrawal of preoperative -
ing of the prothrombin time/international normal- blockers.5,6,9 Inflammation after cardiac surgery is a
ized ratio. Additionally, vitamin C reduces the significant factor in the genesis of AF. Surgical trauma
development of nitrate tolerance.4 and the ischemic and reperfusion injury that ensues
promote the accumulation of proinflammatory
2. c. vitamin C may play a role in preventing cytokines responsible for oxidative stress that in
postoperative AF turn are caused by oxygen radical signaling.1 Surgi-
d. atrial remodeling may be caused by cal trauma also causes a depletion of plasma
oxidative stress antioxidants. The inflammatory process affects the
Atrial fibrillation, a common arrhythmia follow- electrophysiological properties of atrial myocytes.
ing cardiac surgery, has an incidence of 20% to 30% Experimental evidence correlates oxidative stress
that is even greater following valvular heart proce- with atrial electrical remodeling.10,11 The strong
dures. Atrial fibrillation, which in the past was con- antioxidant properties of ascorbic acid are thought
sidered to be a transient and benign arrhythmia, is to attenuate the impact of oxidative damage, blunt
actually a significant cause of postoperative morbid- the inflammatory response and atrial remodeling,
ity and mortality. Postoperative patients in whom and thereby lessen the chances for postoperative AF.
AF develops have an increased incidence of strokes Finally, the multiple factors that may be implicated
and perioperative myocardial infarction, are prone in the incidence of postoperative AF can be attenu-
to development of congestive heart failure and res- ated by the preoperative and postoperative adminis-
piratory failure, and thus are at an increased risk of tration of vitamin C (ascorbic acid).
mortality.5,6 Postoperative AF is a major cause of mor-
bidity and mortality in cardiac surgery and increases ACKNOWLEDGMENT
the length of stay in the intensive care unit, as well Supported in part by a grant from the Applebaum Foun-
dation, in loving memory of Joseph Applebaum.
as total hospitalization, by approximately 3 days.5 In-
hospital mortality and long-term mortality (5 years)
REFERENCES
are also increased.6 1. Wilson JM. A day without orange juice is like an invitation
The pharmacological agents used in the preven- to atrial fibrillation. Texas Heart Inst J. 2007;34(3):265-267.
2. Dickinson VA, Block GB, Russek-Cohen E. Supplement use,
tion of postoperative AF brought modest results. other dietary and demographic variables, and serum vita-
These include -blockers, sotalolol, and amiodarone. min C in NHANES II. J Am Coll Nutr. 1994;13(1):22-32.
3. Johnston CS, Thompson LL. Vitamin C status of an outpa-
The role of vitamin C was studied in 100 randomized tient population. J Am Coll Nutr. 1998;17(4):366-370.
patients undergoing coronary bypass surgery; half 4. Vitamin C (ascorbic acid). University of Maryland Medical
Center Web site. http://www.umm.edu/altmed/articles
received ascorbic acid and a -blocker preoperatively /vitamin-c-000339.htm. Accessed March 7, 2008.
and postoperatively, and the other half received 5. Almassi GH, Schowalter T, Nicolosi AC, et al. Atrial fibrillation
after cardiac surgery. A major morbid event? Ann Surg. 1997;
226(4):501-513.
About the Authors 6. Villareal RP, Hariharan R, Liu BC, et al. Postoperative atrial
fibrillation and mortality after coronary artery bypass sur-
Kathryn Buchanan Keller is an associate professor at the
gery. J Am Coll Cardiol. 2004;43(5):742-748.
Florida Atlantic University Christine E. Lynn College of 7. Eslami M, Badkoubeh RS, Mousavi M, et al. Oral ascorbic
Nursing, Boca Raton, Florida. Louis Lemberg is professor acid in combination with beta-blockers. Texas Heart Inst J.
of clinical cardiology in the Division of Cardiology, Depart- 34(3):268-274.
ment of Medicine, University of Miami Miller School of 8. Korantzopoulos P, Kolettis TM, Kountouris E, et al. Oral vita-
Medicine, Miami, Florida. min C administration reduces early recurrence rates after

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electrical cardioversion of persistent atrial fibrillation and
attenuates associated inflammation. Int J Cardiol. 2005;
102(2):321-326.
9. Chung MK. Cardiac surgery: Postoperative arrhythmias.
Crit Care Med. 2000;28(10 Suppl):N136-N144.
10. Carnes CA, Chung MK, Nakayama T, et al. Ascorbate attenu-
ates atrial pacing-induced peroxynitrite formation and electri-
cal remodeling and decreases the incidence of postoperative
atrial fibrillation. Circulation Res. 2001;89(6):e32-e38.
11. Korantzopoulos P, Kolettis T, Siogas K, Goudevenos J. Atrial
fibrillation and electrical remodeling: the potential role of
inflammation and oxidative stress. Med Sci Monit.
2003;9(9):RA225-RA229.

Reprint requests: Louis Lemberg, MD, University of


Miami Miller School of Medicine, Division of Cardiology
(D-39), PO Box 016960, Miami, FL 33101.

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The Importance of Vitamin C in the Incidence of Atrial Fibrillation
Kathryn Buchanan Keller and Louis Lemberg
Am J Crit Care 2008;17:270-272
2008 American Association of Critical-Care Nurses
Published online http://www.ajcconline.org

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