Search

We recently reported that thigh muscle sarcopenia measured by computed tomography is related to arterial stiffness, pressure wave reflection, and central pulse pressure (PP). However, it remains to be determined whether more straightforward and simple techniques such as hand grip strength and the bio-impedance method are also useful for the clinical evaluation of sarcopenia.A total of 1593 middle-aged to older patients participated in this cross-sectional study. Brachial-to-ankle pulse wave velocity (baPWV) was measured as an index of arterial stiffness. Second PP (PP2) at the second peak of radial SBP was used to estimate central PP. Radial augmentation index was calculated as PP2/PP. Thigh muscle cross-sectional area and abdominal visceral fat area were quantified by computed tomography. Patients were classified as sarcopenic if their hand grip strength or skeletal muscle mass (measured by bioelectrical impedance) was more than 1 SD lower than the mean of those in a reference group aged below 50 years, or in the lowest 20% of the studied population. Visceral obesity was defined as visceral fat area greater than 100 cm.Antidyslipidemia drug and antidiabetic drug were significantly associated with lower hand grip strength. Both sarcopenic indices were significantly and independently associated with baPWV, radial augmentation index, and PP2. Sarcopenia defined by either criterion was significantly associated with higher baPWV, radial augmentation index, and PP2. Visceral obesity was significantly associated only with baPWV.These findings indicate the clinical usefulness of noninvasive methods for assessment of sarcopenia, which is a risk factor for cardiovascular disease.

In the 'Millennium Genome Project', we identified ATP2B1 as a gene responsible for hypertension through single-nucleotide polymorphism analysis. The ATP2B1 gene encodes the plasma membrane calcium ATPase isoform 1, which contributes to the maintenance of intracellular calcium homeostasis by removing calcium ions.Since ATP2B1 knockout mice are reported to be embryo-lethal, we generated systemic heterozygous ATP2B1 null (ATP2B1(+/-)) mice, and evaluated the implication of ATP2B1 in blood pressure.ATP2B1(+/-) mice revealed significantly higher SBP as measured by a radiotelemetric method. Phenylephrine-induced vasoconstriction was significantly increased in vascular rings from ATP2B1(+/-) mice, and the difference in this contraction disappeared in the presence of a nitric oxide synthase (NOS) inhibitor. Vasorelaxation to acetylcholine was significantly attenuated in vascular rings from ATP2B1(+/-) mice. In addition, cultured endothelial cells of ATP2B1(+/-) mice showed that the phosphorylation (Ser-1177) level of endothelial NOS protein was significantly lower, and nitric oxide production in endothelial cells and aorta was lower compared with those in control mice. In contrast, neural NOS expression in vascular smooth muscle cells from ATP2B1(+/-) mice and control mice were not significantly different.These results suggest that decreased ATP2B1 gene expression is associated with impaired endothelial NOS activity and nitric oxide production, and the ATP2B1 gene plays a crucial role in the regulation of blood pressure.

[Objective]: Increasing blood pressure (BP) variability is reported to be a cardiovascular risk factor. However, the clinical implications of postprandial hypotension (PHYPO), a commonly observed BP variability in elderly persons, are poorly understood. Here, we investigated the possible associations between postprandial BP decline and asymptomatic cerebral damage in community residents. [Methods]: Study participants consisted of 1308 general community residents (65 ± 9 years old). Postprandial BP change was calculated from SBP measured just before and 30 min after lunch. PHYPO was defined as a decline in SBP of more than 20 mmHg. The presence of asymptomatic cerebrovascular damage was evaluated by brain MRI. [Results]: Prevalence of lacunar infarction was significantly higher in participants with PHYPO (P = 0.004). A postprandial decline in SBP was linearly increased with the number of lacunar lesions (none, n = 1200, −3.4± 11.3 mmHg; one lesion, n = 82, −5.2 ± 11.8; two lesions, n = 18, −6.9 ± 11.5; three lesions, n = 7, −13.4 ± 11.3; and four lesions, n = 1, −27; P = 0.012). Although participants with PHYPO were older (P

OBJECTIVE Loss of the nocturnal blood pressure (BP) drop is a risk factor for cardiovascular outcomes. However, clinical parameters that predispose to changes in nocturnal BP are currently uncertain. Given the possible involvement of salt sensitivity in nocturnal BP levels, we investigated a hypothesized association between plasma B-type natriuretic peptide (BNP) levels - a marker of body fluid retention - and nocturnal BP in a general population. METHODS Study participants were 1020 general individuals. Participants were divided into four groups (riser, nondipper, dipper, and extreme dipper) by their percentage changes in nocturnal SBP measured using an ambulatory BP monitor. RESULTS Plasma BNP levels were positively associated with circadian BP change (β = 0.162, P

Central aortic blood pressure (BP) has been postulated to correlate more closely with cardiovascular disease risk than brachial cuff BP. However, the effect of insulin sensitivity and resistance on central BP is not fully understood. Here, we evaluated the associations between insulin sensitivity/resistance and central BP using the oral glucose tolerance test.A total of 1034 Japanese participants were enrolled in this study. The absolute pressure of the late systolic peak (SBP2) of the brachial BP obtained by the radial waveform was considered to be the central systolic BP. Oral glucose tolerance test was performed by administering 75 g of glucose, and blood samples were obtained at 0, 60, 120 min after glucose loading.Mean SBP2 was found to be lower than mean brachial systolic BP (SBP) (119 ± 20, 126 ± 19 mmHg, P 0.001), and differences between SBP and SBP2 were significantly larger in patients with reduced insulin sensitivity (-8.2 ± 5.2, -7.2 ± 5.3, -7.1 ± 5.1, and -6.5 ± 4.9 mmHg, in the first, second, third and fourth quartiles, respectively; P = 0.002) and increased insulin resistance (-6.6 ± 5.1, -6.6 ± 4.8, -7.3 ± 4.8, -8.5 ± 5.6 mmHg, P 0.001). Multiple linear regression analysis identified reduced insulin sensitivity (β = 0.067, P = 0.033) and increased insulin resistance (β = -0.081, P = 0.009) as independent determinants of the difference between SBP and SBP2.Given that both insulin sensitivity and insulin resistance were found to be significant determinants of the difference between SBP and SBP2 in a healthy general population, we suggest measuring the SBP2 in individuals with impaired insulin action in order to accurately assess their risk of developing cardiovascular disease.

Background Essential hypertension is a complex disorder that results from the interaction of a number of susceptibility genes and environmental factors. The TNFRSF4 (tumor necrosis factor receptor superfamily, member 4) gene was one of the genes that showed altered renal expression in long-term salt loading in mice. Moreover, association of the TNFRSF4 and TNFSF4 (tumor necrosis factor (ligand) superfamily, member 4) genes with myocardial infarction was recently reported. Since essential hypertension is a well-known risk factor for myocardial infarction, we hypothesized that TNFRSF4 could be a susceptibility gene for essential hypertension. Methods We performed a case–control study of TNFRSF4 in two independent population. Results Extensive investigation of single nucleotide polymorphisms of the entire gene suggested that it resided in one linkage disequilibrium block, and four single nucleotide polymorphisms in the 5′ flanking region sufficiently represented major haplotypes. In the combined population, the frequency of the most frequent haplotype, C-C-A-A, was significantly lower (P = 8.07 × 10−5) and that of the second most frequent haplotype, C-T-G-A, was significantly higher (P = 6.07 × 10−4) in hypertensive subjects than in control subjects. This difference was observed only in female patients. The C-T-G-A haplotype showed a lower promoter activity than other haplotypes, suggesting a relationship with disease susceptibility. Conclusion Our results suggest that TNFRSF4 is a female-specific susceptible gene for essential hypertension.

OBJECTIVE Clinical implications of a high ankle-brachial index (ABI) remain controversial. The involvement of atherosclerotic vascular changes as well as a close positive association with body weight has been postulated. We evaluated possible associations between a high ABI and atherosclerotic and anthropometric parameters. METHODS Study participants were 407 community residents (68 +/- 8 years). Atherosclerosis was evaluated by arterial pulse wave velocity, carotid hypertrophy, and related plasma markers. Composition of the body trunk and lower extremity was evaluated by computed tomography. RESULTS The frequency of high ABI individuals (> or =1.3) was 6.6%, and that was higher in men (70.4 vs. 37.4%, P < 0.001). Characteristics included a significantly larger waist circumference (high ABI, 86 +/- 5; normal ABI, 82 +/- 9 cm, P = 0.033), lower high-density lipoprotein-cholesterol (60 +/- 16, 68 +/- 20 mg/dl, P = 0.042), and higher glucose (112 +/- 30, 104 +/- 20 mg/dl, P = 0.044), but not carotid hypertrophy (P = 0.315) and pulse wave velocity (P = 0.828). The high ABI individuals also had a significantly higher values for stature (162 +/- 8, 157 +/- 8 cm, P = 0.002), body weight (64 +/- 9, 56 +/- 10 kg, P < 0.001), and visceral fat area (132 +/- 60, 100 +/- 64 cm, P = 0.012). Femoral muscle area (133 +/- 23, 109 +/- 23 cm, P < 0.001) but not fat area (P = 0.301) was also larger in this group. Multiple regression analysis indicated that female sex (beta = -0.138, P = 0.019) and body weight (beta = 0.288, P < 0.001) were independent determinant for ABI. However, after adding femoral muscle cross sectional area to the model, the latter became the only determinant of ABI (beta = 0.341, P < 0.001). CONCLUSION Lower extremity composition is a strong determinant of ABI. A high ABI value might not be an adverse maker of atherosclerosis in the general population.

OBJECTIVE The genetic background of orthostatic hypotension, an important risk factor for future cardiovascular morbidity and mortality, was investigated. DESIGN AND METHODS The study subjects comprised 415 community-dwelling individuals, who were free from any cardiovascular complications, aged 50 years or older (mean age 70.5 +/- 9 years). Basal systolic blood pressure (SBP) was measured twice in supine posture after resting for more than 10 min. The orthostatic change in SBP was determined at 1 min and 3 min after standing up. The maximum change in SBP after standing was determined. Orthostatic hypotension was defined as a decline in SBP greater than 20 mmHg. The polymorphisms of genes encoding components of the renin-angiotensin system and sympathetic nervous system, which play pivotal roles in postural change in blood pressure regulation, were determined. RESULTS There were no significant associations between the maximum change in SBP, the prevalence of orthostatic hypotension and gene polymorphisms of angiotensin-converting enzyme I/D, angiotensinogen M235T and angiotensin II type 1 receptor A1166C. On the contrary, polymorphism of the Gs protein alpha-subunit (GNAS1) T131C was significantly associated with the maximum change in SBP after standing [1.9 +/- 16 versus -3.6 +/- 16 mmHg (TT + TC versus CC), P = 0.008]. The prevalence of orthostatic hypotension was significantly different among GNAS1 genotypes (chi squared = 10.12, P = 0.011) and G-protein beta 3 subunit (GNB3) genotypes (chi squared = 6.12, P = 0.020). Multiple logistic regression analysis showed that both GNAS1 CC genotype [odds ratio (OR) = 2.79, 95% confidence interval (CI) 1.35-5.79, P = 0.006] and GNB3 C allele (OR = 1.78, 95% CI 1.06-3.00, P = 0.030) were independent risks for orthostatic hypotension. CONCLUSIONS These findings indicate that genes encoding sympathetic nervous components could be involved in the predisposition for orthostatic hypotension.

Background Several studies have reported that the circulating concentration of hepatocyte growth factor (HGF) was increased in individuals with clinically overt atherosclerotic disease, including coronary heart disease and peripheral arterial disease. However, whether changes in the circulating concentration of HGF are associated with early atherosclerotic changes in apparently healthy individuals remains to be determined. Objective To investigate the relationship between the plasma concentration of HGF and carotid arterial remodeling. Methods Plasma concentrations of HGF were measured in 201 community-dwelling healthy residents free from any medications and signs and history of cardiovascular disease. Carotid intima-media thickness (IMT) and carotid internal diameter were determined by ultrasonography with a 7.5 MHz probe. The study participants were divided into four groups according to the presence or absence of carotid atherosclerosis (presence of plaque, IMT > or = 0.85 mm) and carotid arterial dilatation (diameter > or = 7.0 mm). Results Carotid arterial remodeling, atherosclerosis or dilatation, or combinations thereof, was associated with significantly greater concentrations of plasma HGF. Among risk factors, plasma HGF was significantly associated with advanced age (> or = 65 years), current smoking and diabetes mellitus, whereas sex, obesity, hypertension and hypercholesterolemia did not affect plasma concentrations of HGF. Multiple regression analysis showed that plasma HGF was independently associated with carotid arterial remodeling (atherosclerosis, dilatation, or both) in addition to age and systolic blood pressure. Conclusions These results indicate that the plasma concentration of HGF increases in relation to carotid arterial remodeling, independently of known risk factors for atherosclerosis. These findings further support a possible role of HGF in atherosclerosis.

The possible point-mutational activation of the ras oncogene, which probably contributes to the evolution of aldosterone-producing adenomas and ectopic reninoma, was evaluated. Chromosomal DNA was extracted from six aldosterone-producing adenomas and one renin-secreting liver carcinoma, using the standard method with phenol:chloroform:isoamyl alcohol. One microgram of sample DNA, forward and reverse primers, Taq I polymerase and deoxyribonucleotide triphosphates (dNTPs) were mixed and the ras gene was amplified by the polymerase chain reaction. Point mutations at ras-12 or ras-61 sites of amplified DNA were tested by dot-blotting, using H-, N- and K-ras oligonucleotide probes with mutations at codons 12 or 61. However, there were no point mutations at amino acid codons 12 or 61 of c-Hi-ras, c-Ki-ras and N-ras oncogenes in all aldosterone-producing adenomas and the one ectopic reninoma. These results indicate that point-mutational activation of ras oncogenes does not contribute, at least in this series, towards the evolution of aldosterone-producing adenomas and the reninoma.