Michiya Igase

Arterial stiffness is associated with low thigh muscle mass in middle-aged to elderly men.

OBJECTIVE Sarcopenia of legs is an important cause of physical dysfunctions, frailty and dependence. Many predisposing and underlying mechanisms of sarcopenia, including age, sedentary life style, oxidative stress, insulin resistance, and low testosterone levels, are also known to be related to atherosclerosis, which is another leading cause of morbidity and mortality in elderly subjects. In this study, we investigated our hypothesis that sarcopenia and atherosclerosis are associated with each other to facilitate mutual abnormalities. METHODS Study was performed in apparently healthy 496 middle-aged to elderly persons recruited consecutively among the visitors to the medical check-up program, Anti-Aging Doc, in a University hospital, from March 2006 to December 2007. Mid-thigh muscle cross-sectional area (CSA) was measured by computed tomography and corrected by body weight (CSA/BW). Carotid intima-media thickness (IMT) and brachial-ankle pulse wave velocity (baPWV) were measured. RESULTS Thigh muscle CSA/BW was significantly and negatively associated with carotid IMT and baPWV in men but not in women. After correction for other confounding parameters, baPWV was an independent risk for the presence of sarcopenia in men (odds ratio of 1 m/s increase of baPWV=1.14, 95% CI=1.01-1.30, p<0.05) in addition to age, body height, low physical activity, free testosterone level. Conversely, thigh muscle CSA/BW was an independent determinant of baPWV (beta=-0.15, p<0.01) in addition to age, blood pressure, triglyceride, and antihypertensive drug use in men. CONCLUSIONS Arterial stiffness is related to thigh muscle volume in men. Sarcopenia and atherosclerosis may share a common pathway and interact with each other to facilitate mutual abnormalities.

Association of Endothelin-1 Gene Variant With Hypertension

Abstract—Endothelin-1 (ET-1) is a powerful vasoconstrictor peptide produced by endothelial and smooth muscle cells. Many lines of biological evidence suggest that the ET-1 gene is a candidate gene for hypertension. Moreover, recent association studies suggested that a G/T polymorphism with an amino acid substitution (Lys/Asn) at codon 198 in exon 5 of the ET-1 gene interacts with body mass index (BMI) in association with blood pressure. They suggested that T carriers are more sensitive to weight gain than GG homozygotes in association with blood pressure. However, association studies are often irreproducible, and the first study often suggests a stronger genetic effect than is found by subsequent studies. We therefore assessed the interaction in 2 large Japanese populations. The present study showed a nonsignificant but similar trend to the results of previous reports. Moreover, in line with previous reports, this study revealed a significant interaction between the ET-1 K198N (G/T) polymorphism and BMI in association with hypertension in our populations (P =0.027). The interaction was significant, even after adjustment for gender and age (P =0.045) and for all confounding factors (P =0.044). T carriers were more sensitive to weight gain than GG homozygotes in association with hypertension. Considering the combined impact of obesity and hypertension on the development of cardiovascular and cerebrovascular disorders, T allele carriers might represent elective targets for therapy to lower their body weight.

Postprandial Hypotension Is Associated With Asymptomatic Cerebrovascular Damage in Essential Hypertensive Patients

offelucidate the relationship between postprandial hypotension (PPH) and asymptomatic cerebrovascular damage, we evaluated changes in blood pressure after a meal by 24-hour blood pressure monitoring in 70 hospitalized essential hypertensive patients aged >/=50 years. They received a diet containing standard nutritional ingredients with 120 mmol (7 g) NaCl and were free from medication for at least 1 week. PPH was defined as the mean reduction of systolic blood pressure during 2 hours after a meal. Patients were divided into three groups according to mean values of PPH after 3 meals: PPH-1 (n=16, 5 mm Hg</=PPH<10 mm Hg), PPH-2 (n=18, PPH>/=10 mm Hg), and normal (n=36, PPH<5 mm Hg). As asymptomatic cerebrovascular damage, lacunae and leukoaraiosis were evaluated by magnetic resonance imaging. PPH did not correlate with daytime or nighttime blood pressure or the nondipper phenomenon; however, PPH was significantly related to asymptomatic cerebrovascular damage. The prevalence of lacunae in the normal, PPH-1, and PPH-2 groups was 44%, 69%, and 83%, respectively (chi2=8.22, P<0.05). The number of lacunae in the normal, PPH-1, and PPH-2 groups was 1.0+/-1.3, 1.3+/-1.2, and 1. 9+/-1.4, respectively (F[2,67]=3.2, P<0.05). The prevalence of advanced leukoaraiosis in the normal, PPH-1, and PPH-2 groups was 44%, 50%, and 83%, respectively (chi2=7.63, P<0.05). Severity score of leukoaraiosis in the normal, PPH-1, and PPH-2 groups was 1.5+/-0. 7, 1.7+/-0.8, and 2.1+/-0.7, respectively (F[2,67]=4.3, P<0.05). These findings indicate that elderly hypertensive patients with marked PPH should be considered to have advanced cerebrovascular damage even in the absence of abnormal neurological findings.

Relation of left ventricular hypertrophy and geometry to asymptomatic cerebrovascular damage in essential hypertension

Increased left ventricular (LV) mass and abnormal geometry have a powerful prognostic value for cardiovascular morbidity and mortality including stroke. However, there have been no studies on the association between LV hypertrophy and preclinical brain damage in essential hypertensive patients. In the present study, we investigated the relation between LV hypertrophy and asymptomatic cerebrovascular damage identified by magnetic resonance imaging in 150 essential hypertensive patients, with an emphasis on LV geometry. Patients were divided into the following 4 groups according to their LV mass index and relative wall thickness; normal ventricular geometry (n = 50), concentric remodeling (n = 22), eccentric hypertrophy (n = 44), and concentric LV hypertrophy (n = 34). Lacunar lesions and leukoaraiosis were evaluated. The prevalence of lacunae was significantly higher in patients with LV remodeling than in patients with normal LV (chi-square 19.6, p = 0.0002). The number of lacunae was significantly higher in patients with LV hypertrophy than in patients with normal LV or concentric remodeling (F [3,146] = 8.03, p<0.0001). The severity of leukoaraiosis was also significantly greater in patients with LV hypertrophy than in patients with a normal left ventricle (chi-square 14.5, p = 0.02). Stepwise regression analysis confirmed that LV mass index and relative wall thickness, in addition to age and systolic blood pressure, were independent predictors for asymptomatic cerebrovascular damage, even in the absence of neurologic abnormalities. In hypertensive patients, LV hypertrophy, and especially concentric LV hypertrophy, provides important prognostic information on the presence of pre-clinical brain damage.

Silent cerebral microbleeds associated with arterial stiffness in an apparently healthy subject

Silent cerebral microbleeds (MBs) are a common finding in stroke patients, especially those with intracerebral hemorrhage, and are thought to be a marker of future cerebral hemorrhage. Clinically, two distinct forms of MBs have been documented, those observed with either or both stroke or small vessel disease (SVD) and those associated with cerebral amyloid angiopathy. We investigated a possible association between MBs and arterial stiffness in a general population. Subjects were 443 apparently healthy individuals with a mean age of 67.1±8.1 years. The presence of MBs, lacunar infarcts and periventricular hyperintensity (PVH) was determined by 3-tesla magnetic resonance imaging. Carotid intima-media thickness (IMT) was measured by ultrasonography. Arterial stiffness was evaluated by brachial-to-ankle pulse wave velocity (baPWV), and the Framingham stroke risk score (FSRS) was obtained as an integrated cerebrovascular risk factor. The prevalence of MBs was 5.0%. Both baPWV and FSRS were significantly higher in subjects with MBs (1820±308 vs. 1645±325 cm/s, P=0.014 and 12.1±8.6 vs. 8.9±7.5%, P=0.047, respectively). Odds ratio of a high baPWV, defined as ⩾1500 cm/s, for the presence of MBs was 6.05 even after correction for confounding parameters, including age and hypertension. This association with high baPWV remained irrespective of MBs location, whether strictly located in the lobes or in the basal ganglia and infratentorial regions. These findings indicate an association between arterial stiffness and the presence of MBs. Assessment of arterial stiffness may be useful in identifying subjects at high risk for the presence of MBs.

Quadriceps sarcopenia and visceral obesity are risk factors for postural instability in the middle-aged to elderly population.

Aim:  Aging shifts body composition to comprising more fat and less muscle. Sarcopenia, particularly in the knee extensors, and obesity, particularly visceral obesity, either alone or in combination, may exacerbate age‐related physical disability. We investigated the association between age‐related quadriceps (Qc) sarcopenia and visceral obesity, as measured by cross‐sectional area (CSA), on postural instability.

Abdominal fat, adipose-derived hormones and mild cognitive impairment: the J-SHIPP study.

Background/Aim: Lower body weight in later life has been shown to be associated with dementia. However, abdominal fat distribution under conditions of mild cognitive impairment (MCI) and the possible involvement of leptin and adiponectin in MCI have not been fully investigated. Methods: We analyzed 517 middle-aged-to-elderly community-dwelling persons. Abdominal subcutaneous fat and visceral fat areas were determined using computed tomography, and plasma leptin and adiponectin concentrations were measured in fasting samples. MCI was assessed using the Japanese version of the MCI screening method. Results: In men, the abdominal subcutaneous fat area was significantly lower in participants with MCI than in those with normal cognitive function [median (interquartile range): 107.4 (85.9, 133.1) cm2 vs. 136.4 (93.1, 161.4) cm2; p = 0.002]. Logistic regression analyses with confounding factors including age and abdominal subcutaneous fat area showed that a 10 mg/l increase in plasma adiponectin had a protective effect against the development of MCI in men (odds ratio: 0.46; 95% CI: 0.20–0.97; p = 0.041). In contrast, MCI was not found to be associated with abdominal fat area or adipose-derived hormones in women. Conclusion: Reduced amounts of subcutaneous fat and low levels of plasma adiponectin were found to be associated with MCI in men.

Association of central systolic blood pressure with intracerebral small vessel disease in Japanese.

BACKGROUND Recent studies have reported the association between advanced arterial stiffness and brain small vessel diseases (SVDs). Two possible hemodynamic mechanisms, increases in central blood pressure (BP) and pulsatile flow load to the brain, have been speculated to link arterial stiffness and SVD. The carotid flow augmentation index (AI) has been proposed as an index of pulsatile flow to the brain. We compared its association with brain SVD with that of central BP in a general population. METHODS Subjects were 500 individuals free from symptomatic cardiovascular diseases with a mean age of 66.9 +/- 8.4 years. Brachial-ankle pulse wave velocity (baPWV) was measured as an index of arterial stiffness. Carotid flow AI was obtained by Doppler ultrasonography. The presence of silent cerebral lacunar infarcts (SCI) was determined as a manifestation of SVD by 3-tesla magnetic resonance imaging (MRI). Second peak radial systolic BP (SBP2) and pulse pressure (PP2) were used as estimates of central BP. RESULTS baPWV was significantly associated with radial BP2 (r = 0.55, P < 0.0001) but not with carotid flow AI (r = 0.03, P = 0.51). Radial BPs and baPWV, but not flow AI, were significantly higher in subjects with SCI. Radial SBP2 had higher odds ratio for the presence of SCI than brachial SBP, PP, and radial PP2. Logistic regression analysis showed that radial SBP2, but not flow AI, was independently related to the presence of SCI. CONCLUSION These findings indicate that the SBP2, an estimate of central SBP, is significantly associated with the presence of SVD in an apparently healthy general population.

Association of GNAS1 Gene Variant With Hypertension Depending on Smoking Status

The &bgr;-adrenoceptor (&bgr;-AR) Gs protein system has been shown to have important roles in the cardiovascular system. The gene encoding the &agr;-subunit of Gs proteins (GNAS1) is a candidate genetic determinant for hypertension. We studied the GNAS1 T393C polymorphism in >2000 Japanese individuals. &khgr;2 test showed a marginally significant difference in the frequencies of the alleles (P =0.036) and genotypes (P =0.094) between hypertensives and normotensives. Because hypertension is considered to be a complex disorder resulting from interactions between genetic and environmental factors, we further analyzed the T393C polymorphism, with consideration of interactions between the polymorphism and confounding factors in regression models. These analyses showed a significant interaction between the polymorphism and cigarette smoking in the pathogenesis of hypertension (P =0.0005). The interaction was reflected in a significant association of the polymorphism with hypertension in nonheavy smokers (P =0.0028; odds ratio, 1.52; 95% confidence interval, 1.16 to 2.00). A significant interaction between the polymorphism and aging in the pathogenesis of hypertension was also shown in nonheavy smokers. These findings may be helpful in conducting further molecular and biological studies on the relationship among cigarette smoking, the &bgr;-AR-Gs protein system, and hypertension.

Abnormal nocturnal blood pressure profile is associated with mild cognitive impairment in the elderly: the J-SHIPP study

Mild cognitive impairment (MCI), a syndrome characteristic of the transition phase between normal cognitive function and dementia, has been shown to carry the risk of progression to dementia. Dysregulation of blood pressure (BP) is thought to be an indicator of cerebrovascular damage, including cognitive impairment. Here, we investigated the possible association of circadian BP variation with MCI in community-dwelling persons exhibiting no definitive dementia. Our study enrolled 144 persons (68±7 years). Nocturnal BP profile was defined as dipper, with a 10–19% drop in nocturnal systolic BP; extreme dipper, ⩾20% drop; non-dipper, 0–10% drop; and riser, any increase in nocturnal BP. MCI was assessed using the MCI screen, a cross-validated, staff-administered battery of tests. Subjects with MCI (n=38) were significantly older (74±6, 67±6 years, P<0.001) and had higher frequency of apolipoprotein E ɛ4 allele (36.8, 18.9%, P=0.018). Although the ambulatory measured BP and the percent changes in nocturnal systolic BP (−10±12% and −12±8%, respectively; P=0.291) did not differ between MCI subjects and normal controls, frequency of MCI was significantly higher in the extreme dippers (32.0%), non-dippers (30.0%) and risers (50.0%) than in dippers (13.2%, P=0.018). Multiple logistic regression analysis identified a blunted nocturnal BP decline, non-dipping or increase in nocturnal BP and extreme drop in BP as potent determinants of MCI (odds ratio 3.062, P=0.039), after adjustment for possible confounding factors, including apolipoprotein E ɛ4 genotype. Abnormal nocturnal BP profile was found to be a strong indicator of MCI in otherwise apparently healthy community-dwelling elderly persons.