Masami Ohrui

Relations of plasma high-sensitivity C-reactive protein to traditional cardiovascular risk factors

Variations of circulating C-reactive protein (CRP) levels are supposed to reflect chronic inflammatory process of the cardiovascular system. In particular, it has been reported that high-sensitivity CRP (hsCRP) is a promising marker of coronary heart disease. In the present study, we assessed the relationship between hsCRP and classic cardiovascular risk factors, such as age, blood pressure, smoking habit and serum lipids. Plasma hsCRP was measured by ELISA in 908 subjects, aged 30-79 years, who entered our health-check program. Plasma hsCRP level was 0.54+/-0.02 mg/l in 566 subjects without any disease currently treated. The level was significantly higher in patients treated for hypertension (0.74+/-0.06 mg/l, P=0.002), diabetes mellitus (0.77+/-0.09 mg/l, P=0.016) or coronary artery disease (0.99+/-0.16 mg/l, P=0.008) than in subjects without diseases. In a simple regression analyses of the 566 subjects without diseases, plasma hsCRP positively correlated with male gender, smoking, body mass index, systolic blood pressure, white blood cell count, blood hemoglobin, fasting blood glucose, serum gamma-GTP, uric acid and triglycerides, and inversely correlated with serum albumin and HDL-cholesterol. In multiple regression analysis, white blood cell count (r=0.276, P<0.001), body mass index (r=0.246, P<0.001), age (r=0.122, P=0.001) and smoking (r=0.112, P=0.009) showed independent correlations with plasma hsCRP. It is suggested that variation of circulating hsCRP, even within normal range, is involved in the interrelation of cardiovascular risk factors, such as age, smoking, obesity, high blood pressure and dyslipidemia, which are supposed to promote atherosclerosis and ultimately provoke cardiovascular diseases, such as coronary artery disease.

Molecular forms of plasma and urinary adrenomedullin in normal, essential hypertension and chronic renal failure.

Objectives Human adrenomedullin precursor is converted to glycine-extended adrenomedullin (AM-Gly), an intermediate inactive form of adrenomedullin. Subsequently, AM-Gly is converted to active form of mature adrenomedullin (AM-m). The aim of the present study was to investigate (i) whether sex or age influences plasma and urinary AM-m and AM-Gly levels in normal subjects; (ii) the daytime variability of plasma AM-m and AM-Gly levels in normal subjects; (iii) AM-m and AM-Gly levels and its ratio in plasma and urine in normal subjects, individuals with essential hypertension (HT), and chronic renal failure (CRF); and (iv) the ratio of AM-m and AM-total (T) in plasma of various veins and aorta. Methods We measured plasma levels and urinary excretions of AM-m, AM-Gly and AM-T (AM-m + AM-Gly) by recently developed immunoradiometric assay in normal subjects (n = 81), HT (n = 28) and CRF (n = 30). We also determined the molecular forms of plasma adrenomedullin taken from various sites during angiography in patients with suspected renovascular hypertension (n = 9). Results There were no differences in plasma and urinary excretions of two molecular forms of adrenomedullin among sexes or ages in normal subjects. There was no daytime variation of plasma two molecular forms of adrenomedullin in normal subjects. Plasma AM-m, AM-Gly and AM-T levels were increased in patients with HT and CRF compared with normal subjects, whereas urinary AM-m, AM-Gly and AM-T excretions were decreased in patients with HT and CRF compared with normal subjects. Urinary AM-m : AM-T ratios were significantly higher than plasma AM-m : AM-T ratios. Plasma AM-m and AM-T levels taken from various veins were similar, and they were significantly higher than those of aorta, although there were no differences in plasma AM-Gly levels between aorta and veins. Conclusions These results suggest that in normal subjects, and individuals with HT and CRF: (i) plasma and urinary excretions of AM-m and AM-Gly are not affected by age or sex; (ii) AM-m in parallel with AM-Gly is increased; (iii) urine contains a higher percentage of active adrenomedullin than plasma; and (iv) plasma AM-m may be partly metabolized in the lung.

Relationship between birth weight and cardiovascular risk factors in Japanese young adults.

A number of studies have recently shown a significant inverse relationship between birth weight and incidences of chronic and metabolic disorders such as hypertension and type 2 diabetes, though the findings are not consistent. So far, few investigations have been performed to determine whether this relationship exists in Japanese young adults. We investigated the influence of birth weight on cardiovascular risk factors such as blood pressure and several metabolic variables in Japanese young adults. The data of 299 medical students of Dokkyo University School of Medicine (207 men, 92 women; mean age ± SD: 23 ± 2 years) who underwent a medical check-up in 1998 were analyzed. Information on pregnancies and measurements at birth were obtained from The Maternal and Child Health Handbook, which is provided to every pregnant woman by the Ministry of Health and Welfare of Japan. Blood pressure was measured twice in the sitting position using an automated device based on the cuff-oscillometric method. The systolic and diastolic blood pressure in young adulthood was positively correlated with current body weight and body mass index (BMI) in both genders. Although birth weight was not significantly correlated with blood pressure in the young adults examined in the present study, male birth weight was inversely correlated with serum total cholesterol and triglyceride concentrations in young adulthood, independently of current BMI. These results partly support the hypothesis for the first time that low birth weight may be one of the risk factors for subsequent cardiovascular disease in Japanese men.

Microsatellite DNA Polymorphism of Human Adrenomedullin Gene in Normotensive Subjects and Patients With Essential Hypertension

Adrenomedullin (AM) is a hypotensive peptide widely produced in the cardiovascular organs and tissues. We have cloned and sequenced the genomic DNA encoding the human AM gene and have determined that the gene is located in the short arm of chromosome 11. The 3′-end of the gene is flanked by the microsatellite marker of cytosine adenine (CA) repeats. In this study, we investigated the association between DNA variations in AM gene and the predisposition to hypertension. Genomic DNA was obtained from 272 healthy normotensive subjects (NT) age 57±5 years and 266 patients with essential hypertension (EH) age 53±11 years. The DNA was subject to PCR using a fluorescence-labeled primer, and the number of CA repeats were determined by poly-acrylamide gel electrophoresis. The averaged blood pressure was 117±13/73±9 mm Hg in NT and 170±23/104±12 mm Hg in EH. In Japanese, there existed 4 types of alleles with different CA-repeat numbers: 11, 13, 14, and 19. The frequencies of these alleles were significantly different between NT and EH (&khgr;2=9.43, P =0.024). Namely, 13.5% of EH carried the 19-repeat allele, whereas the frequency was 6.2% in NT (&khgr;2=7.62, P =0.007). In NT, plasma AM concentrations were not significantly different between the genotypes. In conclusion, microsatellite DNA polymorphism of AM gene may be associated with the genetic predisposition to EH, although the gene expression is not likely to be affected by the genotypes.

Urinary excretion of liver fatty acid-binding protein in health-check participants

BackgroundMessenger RNA of liver fatty acid-binding protein (L-FABP) is expressed in proximal tubules of the kidney, and a certain amount is excreted into urine. We analyzed factors relating to the urinary L-FABP excretion in health-check participants.MethodsWe measured L-FABP in the first morning urine by ELISA in 715 men and 193 women 30–79 years of age who entered a 2-day hospitalized health checkup program. In addition to the routine physical examination and laboratory tests, plasma high-sensitivity C-reactive protein (HSCRP) was assayed.ResultsIn 150 healthy subjects, urinary L-FABP averaged 3.6 ± 0.2 µg/g creatinine, whereas the values were significantly increased in patients with hypertension (5.2 ± 0.4, P = 0.010), diabetes mellitus (5.5 ± 0.5, P < 0.001), and chronic hepatitis (5.8 ± 1.0, P = 0.022). Urinary L-FABP excretion was significantly greater in women than in men when the value was related to creatinine. In regression analysis in men, urinary L-FABP was positively correlated with fasting plasma glucose (r = 0.103, P = 0.033) and plasma HSCRP (r = 0.135, P = 0.006).ConclusionsIt is suggested that renal production and urinary excretion of L-FABP are increased in situations in which arteriosclerosis is promoted, such as hypertension, diabetes mellitus, and cardiovascular inflammation.

Relation between the angiotensin-converting enzyme insertion/deletion polymorphism and blood pressure in Japanese male subjects.

Inconsistent results have been reported regarding the association of the angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism and hypertension. Recent studies of population-based samples of three different areas in Japan presented conflicting results regarding this association. We, thus, investigated the relation between the ACE I/D polymorphism and blood pressure (BP), or the frequency of hypertension, respectively, in 706 Japanese male subjects who participated in the health check-up programme of our hospital. The ACE I/D polymorphism was determined by the polymerase chain reaction technique. Of 706 subjects, 203 were found to have hypertension and the other 503 were found to be normotensive. In all subjects, the frequencies of the DD, ID, and II genotypes were 0.123, 0.432, and 0.445, respectively, and the allelic frequency of the D allele was 0.339. In the younger subjects aged <50 years (n=264), neither systolic nor diastolic BP differed significantly among the genotypes. Conversely, in the older subjects aged⩾50 years (n=442), the systolic BP was significantly higher by 5.9 mmHg in the subjects with the ID genotype than those with the II genotype (P<0.01), and the diastolic BP was significantly higher in the subjects with the DD and ID genotypes by 5.1 and 3.3 mmHg, respectively than those with the II genotype (P<0.05 for each), although age, BMI, percentage of smoking habits, drinking habits, or the use of antihypertensive drugs did not differ significantly among the genotypes. In addition, in the older subjects, the hypertensive subjects showed significantly higher frequencies of the DD and ID genotypes and the D allele than the normotensive subjects. These results demonstrated that there was no significant association of the ACE I/D polymorphism with BP or a prevalence of hypertension in younger Japanese men aged <50 years but there was in older Japanese men aged ⩾50 years.

Lower Birth Weight Is Associated with Higher Resting Heart Rate during Boyhood

There is substantial evidence that low birth weight is associated with the development of cardiovascular disease in adult life. Moreover, resting heart rate is a prognostic factor of cardiovascular morbidity and mortality. However, there are scarce data regarding the association between birth weight and resting heart rate in later life. Therefore, we investigated the association of anthropometric data at birth and hemodynamic indices including resting heart rate in Japanese boys. The data of 1,107 male students of a junior high school in Tokyo, Japan, who underwent a medical check-up in the year of admission to the school (12 or 13 years old) were used. Information on anthropometric data at birth based on “The Maternal and Child Health Handbook” was obtained from 573 students. From a standard 12-channel resting electrocardiogram, 8 cardiac cycles were used to estimate heart rate. Resting heart rate correlated positively with body mass index at the same age (r=0.100, p=0.017) and correlated negatively with birth weight (r=−0.102, p=0.015), height at birth (r=−0.125, p=0.003), and head circumference at birth (r=−0.095, p=0.025). The negative correlation of anthropometric data at birth with heart rate at the age of 12 or 13 was independent of body mass index at the same age. The mean value of resting heart rate at the age of 12 or 13 adjusted for body mass index at the same age was significantly higher in the lower tertile of birth weight than in the higher tertile of birth weight (81.7 vs. 78.5 beats/min, p=0.028). In conclusion, lower birth weight is associated with higher resting heart rate during boyhood, suggesting that elevated heart rate may be one mechanism linking small size at birth with the development of cardiovascular disease in future life.

Birth weight and cardiovascular risk factors in Japanese young adults.

A number of studies have recently shown a significant inverse relationship between birth weight and incidences of chronic and metabolic disorders such as hypertension and type 2 diabetes, though the findings are not consistent. So far, few investigations have been performed to determine whether this relationship exists in Japanese young adults. We investigated the influence of birth weight on cardiovascular risk factors such as blood pressure and several metabolic variables in Japanese young adults. The data of 299 medical students of Dokkyo University School of Medicine (207 men, 92 women; mean age +/- SD: 23 +/- 2 years) who underwent a medical check-up in 1998 were analyzed. Information on pregnancies and measurements at birth were obtained from The Maternal and Child Health Handbook, which is provided to every pregnant woman by the Ministry of Health and Welfare of Japan. Blood pressure was measured twice in the sitting position using an automated device based on the cuff-oscillometric method. The systolic and diastolic blood pressure in young adulthood was positively correlated with current body weight and body mass index (BMI) in both genders. Although birth weight was not significantly correlated with blood pressure in the young adults examined in the present study, male birth weight was inversely correlated with serum total cholesterol and triglyceride concentrations in young adulthood, independently of current BMI. These results partly support the hypothesis for the first time that low birth weight may be one of the risk factors for subsequent cardiovascular disease in Japanese men.

Abstracts of selected papers presented at the 73rd general meeting of the Japanese Society of Gastroenterology Tokyo, Japan, April 7–9, 1987

S OF SELECTED PAPERS PRESENTED AT THE 73RD GENERAL MEETING OF THE JAPANESE SOCIETY OF GASTROENTEROLOGY Tokyo, Japan, April 7-9, 1987 Chairman : Shinroku ASHIZAWA, M. D.