Serum ferritin is not a risk factor for coronary artery disease in men and women aged ≥62 years

and by the intracoronary rate in the remaining 6. Both protocols involved pacing patients at increasing rates until they had angina and ST depression. The results showed that both sublingual and intracoronary administration of nitrates could reduce the ischemic threshold, causing a concurrent decrease in aortic pressure and coronary flow at peak pacing. Individual analysis of the response to nitrates before pacing showed that sublingual isosorbide dir&rate could diminish flow soon after its administration, whereas its intracoronary administration caused a transient increase in flow in 4 of 6 patients, which was often associatedwith the development of chest pain and ST depression. Symptoms and increasedblood flow persistedfor a few minutes, and then disappearedspontaneously. The decreasein blood flow after systemicadministration of isosorbide dinitrate was parallel to changes in aortic pressure, and was probably due to the combination of decreasedcoronary perfusion pressure and myocardial oxygen demand.(jNormally, the effects of decreasedarterial blood pressureon coronary flow reserve are minimal or absent,becauseof compensatorydilation of downstream resistancevesselsdue to autoregulation. If autoregulation is impaired so that an appropriate compensatory dilation of resistance vessels can not occur, as in the present patients, then reduction of arterial pressuredue to administration of nitrates will cause coronary flow reserve to decrease.This may influence the level of anginal threshold at peak pacing and explain the paradoxical effects of these drugs. In this study, it was also shown that a relatively high local dose of isosorbide dir&rate administered by the intracoronary mute may cause a transient increase in flow at rest, which should result from coronary arteriolar vasodilation. Becausethe subendocardialareaswould have been fully vasodilated, further drug-induced vasodilation of small coronary arteries should only have occurred in the subepicardialareasof the muscle. This may have caused transmural myocardial blood flow steal. The pathogenesisof angina with normal appearing coronary arteries remains unkn~wn.~~~ The cause of the implied coronary microcirculation dysfunction does not have to be the same in all patients. The present study examined a subset of patients in whom chest pain was ischemic, as shown by the occurrenceof regional perfu-

sion defects during exercise.It has been speculatedthat a possible cause of impaired microvascular activity could be due to the endothelium-derived relaxing factor.9 This substancemay be nitric oxide or a closely related molecule.*oThe fact that isosorbide dir&rate was found to be ineffective in improving symptoms and STsegment changes during atrial pacing does not support the hypothesis that an impaired releaseof endotheliumderived relaxing factor may have a role in causing abnormal arteriolar constriction, at least in the present series of patients. In conclusion, this study was performed in a cohort of patients with angina pectoris and normal coronary angiograms showing a reduced coronary flow response to pacing and reversible thallium abnormalities during exercise.The results of this investigation show that isosorbide din&ate may further reduce coronary flow response to pacing, thus increasing the discrepancy between myocardial oxygen demand and supply. An inability of the autoregulatory mechanismsto adequately maintain coronary blood flow during decreasedaortic pressure is probably the reason for this unexpected effect. 1. Cannon RO, Leon RM, Rosing DR. Epstein SE. Angina causedby reduced vasodilator reserve of the. small coronary arteries. J Am CON Cardiol 1983;l: 1359-1373. 2. Brown GB, Bolsoo E, PetersenRB, PierceCD, Dodge HT. The mechanismof nitroglycerinaction:stenosisvasodilationasa majorcomponentof thedrugresponse. Circularion 1981;&1:1089-1096. 3. Ganz W, TamuraK. Marcus HS, Donoso R, Yoshida S. Swan HJC. Measurement of coronary sinusblood flow by continuousthermodilutionin man. Circuladon 1971;44:181-195. 4. Mathey DG, ChatterjeeK, Tyberg JV, Lekven J, BmndageB, Parmley WW. Coronary sinus mflux: a sourceof emx in measurementof themmdilutioncommy sims flow. Circulation 1978;57:778-786. 5. Badger RS, Brown BG, Gallery CA, Bolson EL, Dodge HT. Coronary artery dilatation and hemodyoamicresponseafter isosorbidedinitmte therapy in patients with coronary artery disease.Am J Car&l 1985:56:390-395. 6. Cohn PF, Maddox D, Hohnan LB, Ma&is JE, Adams JE, See JR. Effects of sublinguallyadministeredoitroglywin on regionalmyowdial blood flow in patients with coronary artery disease..I Am Co11Cardiol 1!977;39:672-678. 7. Maseri A, Crea F, Kaski JK, Crake T. Mechanismsof anginapectoris in syndrome X. J Am CONCardiol 1991;17:499-506. 8. CannonRO, EpsteinSE. “Microvascular angina” as a causeof chestpain with aogiogmphicallynormal coronary arteries.Am J Cardiol 1988;61:13311343. 9. V&s CJM, Bolt H, Hitter E, HermaoAG, SnoeckJF’.Impairedendotheliumdependentcholioergic coronary wsodilation in patients with angina and normal coromwyarteriogmms.J Am CONCardiol 1992;19:21-31. 10. palmer RMJ, Fenige AG, Moncada S. Nitric oxide releaseaccountsfor the biological activity of endotheliumderivedrelaxingfactor.Nature 1987;327:524526.

Serum Ferritin is Not a Risk Factor for Coronary Artery Disease in Men and Women Aged 262 Years Wilbert S. Aronow. MD in middle-aged EasternFinnish men. Therefore, we performed a study to correlate serum ferritin levels with the prevalence of CAD in elderly men and women. Serumferritin levels were obtained after a 14-hour showed that increasedserum ferritin levels were associated with an excessrisk of acute myocardial infarction overnight fast in I71 unselected elderly men and 406 unselectedelderly women in a long-term health carefaFrom Hebrew Hospital Home, 801 Co-op City Boulevard, Bronx, New cility. Blood was also obtained at the same time for York 10475;and the Departmentof Geriatrics and Adult Development, Mount Sinai School of Medicine, New York, New York. Manuscript hemoglobin and hematocrit determinations. The mean age of women with CALI was 82 + 8 years (range 62 received January 19, 1993; revised manuscript received and accepted to 100) and without CAD 81 f 8 years (range 62 to March 3, 1993.

ulli~at$~~hypothesizedthat iron overload is a major cause of the greater occurrence of coronary artery S disease (CAD) in men than in women. Salonen et al3

BRIEFREPORTS 347

TABLE I Percentagewith Increased Serum Ferritin Levels, and Mean Serum Ferritin Levels in Elderly Men and Women With and Without CoronaryArtery Disease (CAD) Men With CAD Men Without CAD Women With CAD Women Without CAD (n = 234) (n = 172) (n = 74) (n = 97) Increasedserum ferritin Mean serum ferritin

6 (8%) 149 2 118

6 (6%) 141 -c 124

12 (7%) 118 f 101

23 (10%) 1312 99

(nglml)

TABLE II Mean Hemoglobin and Hematocrit Levels in Elderly Men and Women with

Increasedand Normal Serum Ferritin Levels

Mean hemoglobin

Men with IncreasedSerum Ferritin (n = 12)

Men with Normal Serum Ferritin (n = 159)

Women with IncreasedSerum Ferritin (n = 35)

Women with Normal Serum Ferritin (n = 371)

12.5 2 1.6

12.9 2 1.5

12.3 5 1.5

12.6 k 1.4

37.8 2 4.7

38.8 f 4.2

37.1 f 4.5

38.0 + 4.0

WI)

Mean hematocrit (%)

97) (p = NS). The mean age of men with CAL? was 82 + 8 years (range 62 to 92) and without CAD 81 f 8 years (range 62 to 100) (p = NS). Patients were cons&red to have CAD if they had a documented clinical history of myocardial infarction or electrocardiographic evidence of Q-wave myocardial infarction (n = 241 patients), or typical angina pectoris without prior myocardial infarction (n = 5). Two of the 5 patients with angina pectoris without myocardial infarction also had prior coronary artery bypass graft surgery or percutaneous transluminal coronary angioplasty. Serum ferritin concentrations were measured by Smith Kline Clinical Laboratories, Inc., by a 2-site chemiluminometric immunoassay using a constant amount of 2 antiferritin antibodies.4 All measurements were made in duplicate. An increased serum ferritin level was >282 nglml in men and >219 nglml in women. Chi-square analysis and Student’s t test were used to analyze data. CAD was present in 74 of I71 elderly men (43%) and in I72 of 406 elderly women (42%) (p = NS). Table I shows the percentage with increased serum ferritin, and the mean serum ferritin levels in elderly men and women with and without CAD. The percentage of patients with increased serum ferritin levels, ana’ the mean serum ferritin levels were not significantly different between men with and without CAD nor between women with and without CAD. Table II shows the mean hemoglobin and hematocrit levels in men and women with increased ana’ normal serum ferritin levels. The mean hemoglobin and hematocrit levels were not sig-

348

THE AMERICANJOURNALOF CARDIOLOGY VOLUME72

nijicantly different between men with increased ana’ normal serum ferritin levels nor between women with increased and normal serum ferritin levels.

Salonen et al3 showed that an increased serum ferritin concentration was a risk factor for CAD in rniddleaged EasternFinnish men. The mean blood hemoglobin concentration was greater in the middle-aged Eastern Finnish men than in our elderly men. In the present elderly population, the prevalenceof CAD was similar in elderly men and women. The data showed that the prevalence of increased serum ferritin concentrations was similar in elderly men and women with and without CAD. The data also showed that the mean semm ferritin concentration was not signiticantly different between elderly men with and without CAD nor between elderly women with and without CAD. In addition, the data showed that the mean serum ferritin concentration was not signilicantly dilferent between men aged 62 to 75 years with and without CAD nor between women aged 62 to 75 years with and without CAD. Therefore, we found that serum ferritin was not a risk factor for CAD in our elderly men or women.

1. Sullivan JL. The iron paradigm of ischemic heart disease. Am Heart J 1989;

117:1177-1188. Sullivan JL. Inn and the sex difference in heart diseaserisk. L.unct?1981:l: 1293-1294.

2.

2. Salonen JT, Nyyssonen K, Korpela H, Tuomilehto J, Sqpanen R, Salonen R. High stored iron levels are associated with excess risk of myocardial infarction in

EasternFinnish men. Circulation

1992;86:803-811.

4. Franc0 CD. Fenitin. In: Kaplan LA, Peace AJ, eds. Methods in Clinical Chemistry, 2nd ed. St Louis: CV Mosby, 1987:124&1242.

AUGUST1,1993