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Stroke. 2002;33:2345-2346
doi: 10.1161/01.STR.0000033073.01689.B8
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*Coronary Artery Disease

(Stroke. 2002;33:2345.)
© 2002 American Heart Association, Inc.


Letters to the Editor

Cerebral Atherosclerosis and Coronary Calcification

Ken Ikeda, MD, PhD

Department of Neurology, PL Tokyo Health Care Center and, Fourth Department of Internal Medicine, Toho University Ohashi Hospital

Hitoshi Ohno, MD Masaki Tamura, MD

Department of Internal Medicine, PL Tokyo Health Care Center

Hidetoshi Kashihara, PhD; Kouzo Anan, PhD Ken-ichi Hosozawa, PhD

Department of Biostatistics, PL Tokyo Health Care Center

Masao Kinoshita, MD Yasuo Iwasaki, MD

Fourth Department of Internal Medicine, Toho University Ohashi Hospital, Tokyo, Japan

To the Editor:

We read with great interest the article by Vliegenthart et al1 concerning an association between stroke and coronary calcification. It is of interest whether coronary calcification is correlated with cerebral atherosclerosis. We also believe that coronary calcification could play a crucial role in the incidence of cerebral infarctions. We would like to show a possible relationship between coronary calcification and cerebral atherosclerosis and then we would like to compare their study and ours.

At the PL Tokyo Health Care Center, 31 646 Japanese subjects (19 901 men and 11 745 women) received physical checkups between April 1, 2001, and March 31, 2002. Among them, brain checkup and helical CT of the chest were done in 1100 subjects (865 men, 245 women). Mean age was 53.8 years (SD, 10.9 years), 54.0 years (SD, 10.8 years) in men and 53.1 years (SD, 11.2 years) in women. Brain MRI and magnetic resonance angiography (MRA) were produced by a 1.5-Tesla superconducting system (Stratis II, Hitachi Medical Co). Axial T1-weighted (repetition time/echo time=400/20 ms) and T2-weighted (repetition time/echo time=4750/120 ms) images were performed on MRI. The slice/gap thickness of the MRI was 6.0/0.5 mm, and the matrix size was 224x256. The number of acquisitions was 2. MRA was applied by 3-dimensional time-of-flight technique. The slice thickness was 0.6 mm, and the matrix size was 140x140. Helical CT was used with CT-W3000 (Hitachi Medical Co). The slice thickness was 5 to 10 mm, and the matrix size was 256x256. Scan areas included the root of aorta through the heat. The total number of slices was 40.

Lacuna was defined as T1-hypointense and T2-hyperintense areas (3 mm<diameter<15 mm). MRA score of atherosclerosis was classified from grade 1 to 4. In grade 1 (normal), blood flow signal intensities were displayed clearly in the A3 segment of the anterior cerebral artery, M3-4 segment of the middle cerebral artery, or P3-4 segment of the posterior cerebral artery. In grade 2 (mild atherosclerosis), blood flow signal intensities were seen equivocally in the distal portion of the A3 segment, M3 segment, or P3 segment. In grade 3 (moderate atherosclerosis), blood flow signal intensities were absent in the distal portion of the A3 segment, distal portion of the M3 segment, or distal portion of P3 segment. Finally, in grade 4 (severe atherosclerosis or obstruction), blood flow signal intensities were absent in the A1 segment of the proximal portion of A3 segment, M1 segment of the proximal portion of the M3 segment, or P1 segment of the proximal portion of P3 segment.

Total atherosclerotic score was calculated as 3 to 12 in the anterior, middle, and posterior cerebral arteries. One experienced neurologist and 2 diagnostic radiologists reviewed brain MRI and MRA. Three experienced diagnostic radiologists reviewed chest CT. Calcium score was determined according to the method of Agatston et al.2 Coronary calcification was diagnosed as calcium score >500 and a density of >130 Hounsfield units in the epicardial coronary arteries. One hundred forty-nine subjects (131 men, 18 women) had coronary calcification. The incidence of calcification was 12.5%, 14.2% in men and 6.5% in women. The mean age of the calcification group was 63.9 years (SD, 8.7 years), 63.1 years (SD, 8.6 years) in men and 70.3 years (SD, 6.6 years) in women. That of the noncalcification group was 52.3 years (SD, 10.4 years), 52.4 years (SD, 10.3 years) in men and 51.9 years (SD, 10.5 years) in women. The frequency of diabetes mellitus (fasting plasma glucose >126 mg/dL or current medication), hypertension (systolic pressure >140 mm Hg, diastolic pressure >90 mm Hg, or current medication), or hypercholesterolemia (total cholesterol >220 mg/dL or current medication) was significantly higher in the coronary calcification group compared with the noncalcification group. Current or history of smoking was also seen more frequently in subjects with coronary calcification. The number of lacunas did not differ between subjects with and without coronary calcification. The MRA score was associated with hypertension and diabetes mellitus. Severity of cerebral atherosclerosis and incidence of coronary calcification were increased by age in our adult subjects. The atherosclerotic score was significantly higher in subjects with coronary calcification than in those without calcification. In logistic regression analysis, there were no statistical associations between coronary calcification and the degree of cerebral atherosclerosis when adjusted for diabetes mellitus, hypertension, hypercholesterolemia, and smoking. An age-adjusted model showed a statistical tendency between coronary calcification and cerebral atherosclerosis in women (odds ratio, 3.7) but not in men (odds ratio, 1.3).

Vliegenthart et al1 report the association between coronary calcification and stroke history in Rotterdam older inhabitants. We evaluated the degree of cerebral atherosclerosis in individuals with coronary calcification on the basis of the retrospective data of helical CT, brain MRI, and MRA. Our data indicated that subjects with coronary calcification had higher cerebral atherosclerotic score and several cardiovascular risk factors. The calcification subjects were {approx}10 years older than the noncalcification subjects. We would like to know the mean age of subjects with calcium scores >500 in the study of Vliegenthart et al. In addition, what is the frequency of hypertension, diabetes mellitus, and hypercholesterolemia and the smoking history in those subjects? Vliegenthart et al suspect the possibility that most of stroke types may consist of lacunar infarctions in their study. Our data of brain checkups show that asymptomatic lacunar infarction occurs in 20% to 30% of healthy senile subjects. We would like to know neuroradiological data if they performed brain CT, MRI, or MRA in subjects with calcium scores >500. The percentage of calcium scores >500 was lower in our study (12.5%) than in the Rotterdam study (27.5%). Vliegenthart et al applied electron-beam CT scan. A severe degree of coronary calcification on conventional helical CT was detected in our subjects. Helical CT is known to be restricted for the quantitative measurement of coronary calcification compared with electron-beam CT.3 The age of subjects also differs between their study and ours. The mean age was 70.8 years (SD, 5.5 years) in the study of Vliegenthart et al1 and 53.8 years (SD, 10.9 years) in our subjects. A previous report suggests that calcium score increases with age in older adults.4

In our study, coronary calcification and cerebral atherosclerosis are associated with age and several cardiovascular risk factors. Age-adjusted logistic analysis discloses a statistical tendency between coronary calcification and cerebral atherosclerosis in our female subjects. Further long-term studies are needed to determine whether coronary calcification is an independent risk factor of stroke in the Japanese population.

References

1. Vliegenthart R, Hollander M, Breteler MMB, van der Kuip DAM, Hofman A, Oudkerk M, Witteman JCM. Stroke is associated with coronary calcification as detected by electron-beam CT: the Rotterdam Coronary Calcification Study. Stroke. 2002; 33: 462–465.[Abstract/Free Full Text]

2. Agatston AS, Janowitz WR, Hildner FJ, Zusmer NR, Viamonte M Jr, Detrano R. Quantification of coronary artery calcium using ultrafast computed tomography. J Am Coll Cardiol. 1990; 15: 827–832.[Abstract]

3. Becker CR, Jakobs TF, Aydemir S, Becker A, Knez A, Schoepf UJ, Bruening R, Haberl R, Reiser MF. Helical and single-slice conventional CT versus electron beam CT for the quantification of coronary artery calcification. AJR Am J Roentgenol. 2000; 174: 543–547.[Abstract/Free Full Text]

4. Newman AB, Naydeck BL, Sutton-Tyrrell K, Feldman A, Edmundowicz D, Kuller LH. Coronary artery calcification in older adults to age 99: prevalence and risk factors. Circulation. 2001; 104: 2679–2684.[Abstract/Free Full Text]

Rozemarijn Vliegenthart, MSc Jacqueline C.M. Witteman, PhD

Department of Epidemiology and Biostatistics, Erasmus University Medical School, Erasmus Medical Center, Rotterdam, the Netherlands

Response

Dr Ikeda reports a positive association between coronary calcification and cerebral atherosclerosis evaluated by MRI and MRA. The severity of cerebral atherosclerosis was related to the presence of a calcium score >500. These findings are in agreement with previously published data from our study1: We found a graded association between the amount of coronary calcification and the intima-media thickness of the common carotid artery, and an even stronger association with the presence of carotid plaques. The MRI data from Ikeda et al allow assessment of lacunar infarctions, whether symptomatic or asymptomatic. Unfortunately, MRI was not performed in our study, except for those patients who experienced a stroke and subsequently had diagnostic evaluation in hospital.2 However, the association between cerebral atherosclerosis and coronary atherosclerosis is interesting and deserves further evaluation.

References

1. Oei HHS, Vliegenthart R, Hak AE, Iglesias del Sol A, Hofman A, Oudkerk M, Witteman JCM. The association between coronary calcification assessed by electron beam computed tomography and measures of extracoronary atherosclerosis: the Rotterdam Coronary Calcification Study. J Am Coll Cardiol. 2002; 39: 1745–1751.[Abstract/Free Full Text]

2. Vliegenthart R, Hollander M, Breteler MMB, van der Kuip DAM, Hofman A, Oudkerk M, Witteman JCM. Stroke is associated with coronary calcification as detected by electron-beam CT: the Rotterdam Coronary Calcification Study. Stroke. 2002; 33: 462–465.[Abstract/Free Full Text]





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*Coronary Artery Disease