(2002) 16, 837 841 & 2002 Nature Publishing Group All rights reserved 0950-9240/02 $25.00 www.nature.com/jhh ORIGINAL ARTICLE Low fractional diastolic pressure in the ascending aorta increased the risk of coronary heart disease Y Nakayama 1, T Hayashi 1, K Yoshimaru 1, K Tsumura 2 and H Ueda 1 1 Department of Cardiology, Ishikiriseiki Hospital, Osaka, Japan; 2 Center for General Medicine, Osaka City University Medical School, Osaka, Japan Although the fractional pulse pressure in the ascending aorta is related to the occurrence of coronary heart disease (CHD) and restenosis after percutaneous transluminal coronary angioplasty, the relative values of diastolic pressure in the ascending aorta at the onset of CHD have not been reported. The purpose of this study was to evaluate whether the relative values of diastolic pressure are associated with the risk of CHD. For this study, we enrolled 406 patients with chest pain, normal contractions, no local asynergy, and no history of myocardial infarction. We measured the ascending aortic pressure using a fluid-filled system. To quantify the relative diastolic pressure, we normalised the diastolic pressures to the mean pressure and referred to this value as the fractional diastolic pressure (FDP). We investigated the association between the FDP and the risk of CHD. Low FDP in the ascending aorta was associated with an increased risk of CHD. The multipleadjusted odds ratio of CHD was 1.68 (95% CI, 0.67 4.22) in FDP for the middle tertile of the level. The multipleadjusted odds ratio of CHD was 2.20 (1.16 4.75) in FDP for the lowest tertile compared with the highest tertile. FDP was associated with the risk of CHD. (2002) 16, 837 841. doi:10.1038/sj.jhh.1001489 Keywords: mechanics; aortic pressure; coronary disease Introduction We reported that the pulsatility index in the proximal arteries is an attractive tool to diagnose pulmonary hypertension and ischaemic heart disease, and to predict the occurrence of restenosis after percutaneus transluminal angioplasty. 1 3 The analysis is useful to prevent cardiac events, and also to treat patients with heart disease. An ascending aortic pressure waveform would provide a lot of useful information for patients with cardiac diseases. With a lot of information, in addition to the pulsatility index, it is easy to diagnose cardiac heart disease and predict the occurrence of coronary heart disease (CHD). Therefore, we focused on the relative values of systolic and diastolic pressures in ascending aortic pressure. Since arteriosclerosis decreases the compliance of the systemic arteries and increases the characteristic impedance, it causes the systolic pressure to be high relative to the mean pressure, and the diastolic pressure to be low relative to the mean pressure. 4,5 Correspondence: Dr Y Nakayama, Department of Cardiology, Ishikiriseiki Hospital, 18-28, Yayoi, Higashiosaka, Osaka, Japan. To quantify the relative systolic and diastolic pressures, we normalised the systolic and diastolic pressures to the mean pressure, and referred to these values as the fractional systolic pressure (FSP) and the fractional diastolic pressure (FDP). Since arteriosclerosis decreases compliance in the ascending aortic artery and increases the characteristic impedance, we hypothesised that patients with CHD might have higher FSP and lower FDP in the ascending aorta than subjects without CHD. We investigated the effects of FSP and FDP in the ascending aorta in relation to the risk of CHD. This revealed that FDP was closely associated with an increased risk of CHD in the ascending aorta. Methods Study subjects The study group consisted of 406 consecutive patients who were admitted to Ishikiri Seiki Hospital, Osaka, Japan, because of a CHD diagnosis by means of cardiac catheterisation. They were eligible for entry into the study when they had normal contractions, no local asynergy shown by left
838 ventriculography, and no history of myocardial infarction to repair cardiac function approximately. We enrolled 1367 patients ranging in age from 34 to 83 years between January 1990 and February 2001 in whom cardiac catheterisations were done for the first time. Of these, 425 were excluded from this study because of acute coronary syndrome, 386 because of arrhythmia and abnormal ST-segment changes, and 150 because of chronic renal failure and severe valvular disease. The protocol was in accordance with the Institutional Guidelines for Human Research, and each individual provided a written statement of informed consent for the diagnostic and therapeutic procedures required for the examination, which stated that the results of the examination could be used for the study. Measurement of haemodynamic variables Haemodynamic measurements were made with the patient in the supine position. Aortic pressure was measured using a fluid-filled system (5F pig-tail catheter) at the ascending aorta. A hard copy was made of the pressure tracing using a chart recorder (Nihon Koden, Surgical Monitoring System, Tokyo, Japan) at a paper speed of 100 mm/s. We compared tracings of systolic, diastolic, mean and pulse pressures in patients with and without CHD. The relative systolic and relative diastolic pressures were characterised as the ratio of systolic and diastolic pressures to mean pressure, that is, FSP and FDP. Measurement of angiographic variables Cardiac catheterisation was performed according to a standard technique. Optimal views of the target lesions from all technically suitable angiograms were analysed using hand-held electronic digital calipers (Mitutoyo Corporation, Tokyo, Japan), 6 and measurements were made of the maximal narrowing of the target lesion, as well as a noninvolved segment. Angiographic measurements were calibrated using the guiding catheter as the reference dimension. The absolute values for the minimal lumen diameter (MLD) and the reference lumen diameter (RLD) were measured at end-diastole. CHD was defined as MLD stenosis 450% on the angiogram, and non-chd was defined as MLD stenosis p50% on the angiogram. Statistical analysis Values were expressed as the mean 7 1 s.d. Categoric variables were compared using the w 2 test. Differences in the mean values between the two groups were compared using an unpaired t-test. A P-value of less than 0.05 was considered statistically significant. Multiple logistic regression analysis was used to evaluate the simultaneous effects of FSP, FDP, age, body mass index, smoking habits (current smokers or nonsmokers), type II diabetes (yes or no), hypercholesterolaemia (yes or no), Ca blockers (yes or no), b blockers (yes or no), ACE inhibitors (yes or no), nitrates (yes or no), parental history of CHD and gender. The linear trends in the risks were evaluated by entering indicators for each categorical level of exposure using the median value for each category. We calculated the 95% confidence interval (CI) for each odds ratio (OR) and all P-values were twotailed. Statistical analyses were performed using the SPSS 10.0 software package. Results Baseline clinical characteristics The baseline clinical characteristics of the study group are summarised in Table 1. Although the distribution of gender and parental history of CHD, body mass index, medication with Ca blockers, b blockers, ACE inhibitors or nitrates and smoking status were similar in the two groups, the mean age, presence of hypertension or hypercholesterolaemia and type II diabetes were higher in patients with CHD than those without CHD. There were no significant differences in the heart rate or ejection fraction between the two groups. Although the mean pressure in the ascending aorta was not different, systolic pressure, pulse pressure, PPf and FSP were higher in those with CHD than those without CHD. Diastolic pressure and FDP were lower in patients with CHD than those without CHD. Multivariate analysis of the risk of CHD To examine the association between the indexes of pressure and the risk of CHD, all patients were classified into tertiles of pressure levels. The analysis of systolic and diastolic pressures in the ascending aorta is summarised in Table 2. The analyses of FSP and FDP in the ascending aorta are summarised in Table 3. Although aortic FSP was not related to an increase in the risk of CHD, FDP was associated with an increase in the risk of CHD. Crude prevalence rates of stenosis were 28.1% for the lowest, 43.0% for the middle, and 51.1% for the highest tertile of aortic FSP levels. The crude ORs of CHD were 1.92 (95% CI, 1.16 3.19) for the middle tertile of the aortic FSP level and 2.67 (95% CI, 1.61 4.42) for the highest tertile compared to the lowest tertile. After multiple adjustment, the ORs of CHD were 1.63 (95% CI, 0.69 3.85) for the middle tertile of the aortic FSP level and 2.34 (95% CI, 0.94 5.18) for the highest tertile compared to the lowest tertile. Crude prevalence rates of stenosis were 57.3% for the lowest, 47.1% for the middle, and 21.5% for the
Table 1 Baseline characteristics of the study patients (n=406) 839 Variables CHD ( ) CHD (+) P-value Male/number 140/241 (58.1) 107/165 (64.8) 0.180 Age (years) 60.3 7 11.0 64.2 7 9.7 o0.001 Body mass index (kg/m 2 ) 23.3 7 3.3 23.7 7 3.3 0.355 Hypertension 99/241 (41.0) 87/165 (52.7) 0.026 Type II diabetes (%) 53/241 (22.0) 71/165 (43.0) o0.001 Hypercholesterolaemia (%) 117/241 (48.5) 100/165 (60.6) 0.020 Current smoker (%) 112/241 (46.5) 68/165 (41.2) 0.310 Ca blocker (%) 133/241 (55.2) 87/165 (55.3) 0.685 b Blocker (%) 49/241 (20.3) 38/165 (23.0) 0.539 ACE inhibitor (%) 119/241 (49.3) 83/165 (50.3) 0.920 Nitrates (%) 132/241 (54.8) 86/165 (52.1) 0.614 Parental history of CHD (%) 43/191 (19.4) 29/102 (19.6) 0.527 Heart rate (bpm) 69.3 7 14.0 67.1 7 11.5 0.900 Ejection fraction (%) 75.0 7 7.2 73.5 7 7.1 0.550 Ascending aorta Systolic pressure (mmhg) 142.6 7 25.6 150.2 7 25.7 0.003 Diastolic pressure (mmhg) 73.7 7 10.5 71.3 7 11.1 0.033 Mean pressure (mmhg) 97.8 7 13.9 99.7 7 14.6 0.189 Pulse pressure (mmhg) 68.9 7 21.2 78.9 7 21.3 o0.001 PPf 0.70 7 0.17 0.79 7 0.17 o0.001 FSP 1.45 7 0.12 1.51 7 0.12 o0.001 FDP 0.76 7 0.06 0.72 7 0.06 o0.001 CHD: coronary heart disease. Table 2 ORs of CHD according to the aortic systolic and diastolic pressures N Cases % OR (95% CI) Crude Multiple adjusted a Systolic pressure Tertile 1 (90 130) 135 43 31.9 1.00 1.00 Tertile 2 (131 155) 133 59 44.4 1.71 (1.04 2.81) 1.02 (0.49 2.12) Tertile 3 (156 228) 137 63 46.0 1.82 (1.11 2.98) 1.11 (0.51 2.42) P for trend 0.022 0.821 Continuous, per 10 mmhg 1.12 (1.04 1.22) 1.02 (0.97 1.12) Diastolic pressure Tertile 1 (39 67) 127 59 46.5 1.07 (0.66 1.74) 1.21 (0.61 2.39) Tertile 2 (68 76) 144 56 38.9 1.46 (0.90 2.39) 1.63 (0.78 3.39) Tertile 3 (77 113) 134 56 41.8 1.00 1.00 P for trend 0.146 0.231 Continuous, per 5 mmhg 1.11 (1.00 1.22) 1.12(0.91 1.31) a Adjusted for age, body mass index, smoking habits, type II diabetes, hypercholesterolaemia, Ca blockers, b blockers, ACE inhibitors, nitrates, parental history of CHD and gender. highest tertile of aortic FDP levels. The crude ORs of CHD were 3.29 (95% CI, 1.91 5.53) for the middle tertile of the aortic FDP level and 4.25 (95% CI, 2.49 7.23) for the lowest tertile compared to the highest tertile. After multiple adjustment, the ORs of CHD were 1.68 (95% CI, 0.67 4.22) for the middle tertile of the aortic FDP level and 2.20 (95% CI, 1.16 to 4.75) for the lowest tertile compared to the highest tertile. To further quantify the effect of FDP on CHD, we modelled FDP as a continuous variable. The results suggested that the multiple-adjusted OR of CHD was increased by 38% when FDP was decreased by 0.1 (relative risk, 1.38 (95% CI, 1.09 1.71)). Discussion Low FDP in the ascending aorta clearly increased the risk of CHD. Even after adjustment for age, body mass index, smoking habits, type II diabetes, hypercholesterolaemia, Ca blockers, b blockers, ACE inhibitors, nitrates and parental history of CHD, the association was significant. Clinical implications of fractional systolic and diastolic pressures Although major risks include smoking, 7 hypertension, 8 high serum cholesterol, 9 low levels of
840 Table 3 ORs of CHD according to the aortic fractional systolic and fractional diastolic pressures n Cases % OR (95% CI) Crude Multiple adjusted a FSP Tertile 1 (1.11 1.42) 135 38 28.1 1.00 1.00 Tertile 2 (1.43 1.52) 135 58 43.0 1.92 (1.16 3.19) 1.63 (0.69 3.85) Tertile 3 (1.53 1.89) 135 69 51.1 2.67 (1.61 4.42) 2.34 (0.94 5.18) P for trend 0.001 0.087 Continuous, per 0.1 1.47 (1.23 1.77) 1.18 (0.95 1.37) FDP Tertile 1 (0.55 0.72) 134 72 53.7 4.25 (2.49 7.23) 2.20 (1.16 4.75) Tertile 2 (0.73 0.77) 136 64 47.1 3.29 (1.91 5.53) 1.68 (0.67 4.22) Tertile 3 (0.78 0.86) 135 29 21.5 1.00 1.00 P for trend 0.001 0.015 Continuous, per 0.1 1.68 (1.41 2.04) 1.38 (1.09 1.71) a Adjusted for age, body mass index, smoking habits, type II diabetes, hypercholesterolaemia, Ca blockers, b blockers, ACE inhibitors, nitrates, parental history of CHD and gender. high-density lipoprotein cholesterol, 10 diabetes mellitus and ageing, 11 the risk factors for CHD remain a challenge in clinical settings. Although some patients with CHD have high absolute systolic pressures, they have low relative systolic pressure (FSP) to mean pressure in their ascending aortic pressure. In contrast, many patients have both high absolute and high relative systolic pressures (FSP). Although some patients with CHD have low absolute diastolic pressures, they have high relative diastolic pressure to mean pressure (FDP) in the ascending aortic pressure. In contrast, many patients have both low absolute and low relative pressures (FDP). Therefore, absolute systolic and diastolic pressures in the ascending aortic pressure occasionally do not represent the aortic imput impedance correctly. These analyses of fractional systolic and diastolic pressures, in addition to fractional pulse pressure, 1 3,12,13 in the ascending aorta directly reflect the aortic imput impedance for the fixed condition of cardiac function. Therefore, this analysis is particularly important when choosing antihypertensive and antianginal drugs as these drugs can alter the aortic imput impedance. Limitations There are several study limitations. First, we analysed a limited number of patients. To generalise the results of this study, studies involving a large number of patients are essential. Second, we used a fluid-filled system to record the ascending aortic pressure and brachial arterial pressure. The use of a high-fidelity pressure transducer would increase the accuracy of the recorded pressure waveform. Third, we did not use computerised angiographic analysis. We used hand-held electronic digital caliper measurement to determine the percentage of diameter reduction as an index of stenotic severity. Although coronary angiography is precise, electronic digital caliper measurements can estimate the reduction in diameter in a rapid, low-cost way with acceptable accuracy. References 1 Nakayama Y et al. Characteristics of pulmonary artery pressure waveform for differentially diagnosing chronic pulmonary thromboembolism and primary pulmonary hypertension. J Am Coll Cardiol 1997; 29: 1311 1316. 2 Nakayama Y et al. Noninvasive differential diagnosis between chronic pulmonary thromboembolism and primary pulmonary hypertension by means of Doppler ultrasound measurement. J Am Coll Cardiol 1998; 31: 1367 1371. 3 Nakayama Y et al. Pulsatility of ascending aortic pressure waveform is a powerful predictor of restenosis after percutaneous transluminal coronary angioplasty. Circulation 2000; 101: 470 472. 4 Sunagawa K, Maughan WL, Sagawa K. Stroke volume effect of changing arterial input impedance over selected frequency ranges. Am J Physiol 1985; 248: H477 H486. 5 Urschel CW et al. Effect of decreased aortic compliance on performance of the left ventricle. Am J Physiol 1968; 214: 298 304. 6 Uehata A et al. Accuracy of electronic digital calipers compared with quantitative angiography in measuring coronary arterial diameter. Circulation 1993; 88: 1724 1729. 7 Doyle JT. Cigarette smoking and coronary heart disease: combined experience of the Albany and Framingham studies. N Engl J Med 1988; 266: 796 801. 8 Kannel WB. Smoking and hypertension as predictors of cardiovascular risk in population study. J Hypertens 1990; 8: 53 58. 9 Shah PK, Pasternak R. The role of lipids in restenosis following angioplasty. Curr Opin Lipidemiol 1993; 4: 310 313.
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