Postprandial hypotension as a risk marker for asymptomatic lacunar infarction.

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 ±â€Š9 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±â€Š11.3 mmHg; one lesion, n = 82, -5.2 ±â€Š11.8; two lesions, n = 18, -6.9 ±â€Š11.5; three lesions, n = 7, -13.4 ±â€Š11.3; and four lesions, n = 1, -27; P = 0.012). Although participants with PHYPO were older (P < 0.001) and had higher preprandial BP (P < 0.001) and faster pulse wave velocity (P = 0.001), multivariate analysis adjusted for these covariates indicated that postprandial BP decline was an independent determinant for the number of lacunar infarctions (P = 0.004). No significant associations were observed with grade of periventricular hyperintensity or frequency of microbleeds. These relationships were also found in an analysis based on central BP, whereas no superiority was seen in the analysis based on central BP. CONCLUSION: Postprandial BP decline is an overlooked risk marker for asymptomatic lacunar infarction in community residents.

Change in arterial stiffness associated with monthly bisphosphonate treatment in women with postmenopausal osteoporosis.

OBJECTIVE: Osteoporosis and atherosclerosis are the two most common diseases in postmenopausal women. In most cases, they are simultaneously present in the same individual and commonly lead to bone fracture or cardiovascular disease (CVD). Bisphosphonates (BPs) are frequently used in the treatment of osteoporosis and have the ability to increase lumbar spine bone mineral density (L-BMD). BPs may also protect against CVD. A single monthly 50-mg dose of minodronate (monthly minodronate) is now common practice and is highly anticipated to reduce the incidence of both bone fracture and CVD. A useful approach to independently predicting CVD is brachial-ankle pulse wave velocity (baPWV). Here, we directly compared the effects of monthly minodronate with those of a standard single weekly 35-mg dose of alendronate (weekly alendronate) on L-BMD and baPWV in postmenopausal women with osteoporosis across a 12-month period. METHODS: Thirty-eight postmenopausal women with osteoporosis were randomized into two treatment groups (group 1, weekly alendronate, n = 19; group 2, monthly minodronate, n = 19). L-BMD and baPWV were assessed at baseline and 12-month follow-up. RESULTS: At the end of the 12-month period, increases in L-BMD were similar between group 1 (7.6%) and group 2 (8.5%), but baPWV was significantly reduced in group 2 compared with group 1. The change in baPWV during the study period showed a significant negative correlation with the change in L-BMD. CONCLUSIONS: Changes in L-BMD in the monthly minodronate and weekly alendronate groups are generally comparable. Good control of changes in L-BMD in the postmenopausal phase might be associated with regression of CVD. Monthly minodronate is a promising new BP and potential first-line drug for the treatment of osteoporosis in postmenopausal women.

Association of hematological parameters with insulin resistance, insulin sensitivity, and asymptomatic cerebrovascular damage: the J-SHIP and Toon Health Study.

BACKGROUND: Elevated hematocrit levels have been suggested to be an independent determinant of insulin resistance and type 2 diabetes. To clarify the diagnostic significance of hematocrit level, we investigated the association with hemodynamic profiles, insulin resistance and insulin sensitivity, arterial properties, and asymptomatic cerebrovascular damage in a general Japanese population. METHODS: This study included 1,978 participants from two independent cohorts. Insulin sensitivity was assessed by the oral 75 g glucose tolerance test. Carotid ultrasonography was performed to evaluate atherosclerosis and wall shear stress. Periventricular hyperintensity and lacunar infarction were assessed by brain magnetic resonance imaging. RESULTS: Hematocrit quartile showed a stepwise association with insulin sensitivity (Q1: 2.2±0.7, Q2: 2.0±0.7, Q3: 1.9±0.7, Q4: 1.8±0.6, p<0.001) and insulin resistance (1.0±0.6, 1.2±0.7, 1.3±0.8, 1.5±1.0, p<0.001). Multiple linear regression analysis adjusted for possible covariates identified hematocrit as an independent determinant of insulin sensitivity (ß=-0.074, p=0.019) and insulin resistance (ß=0.115, p<0.001). However, this association was lost after further adjustment for visceral fat area and plasma alanine aminotransferase level. Further, no significant association was observed between hematocrit and carotid intima-media thickness (p=0.306) where as wall shear stress was inversely associated with the carotid atherosclerosis (r=-0.250, p<0.001). In contrast, a low hematocrit level was independently associated with periventricular hyperintensity (odds ratio 0.87 (95% CI 0.80-0.95), p=0.001). CONCLUSION: Hematocrit was positively associated with insulin resistance and insulin sensitivity. This association was epiphenomenon of visceral and hepatic adiposity. Conversely, low hematocrit was a significant risk factor for periventricular hyperintensity independent of insulin resistance.

[A case of Fisher syndrome with multiple cranial neuropathy and abnormal EEG findings].

A 69-year-old woman was admitted because of unconsciousness and multiple cranial neuropathy. She had suffered diarrhea 2 weeks previously. On examination, she was noted to have total external and internal ophthalmoplegia, bilateral facial palsy, dysphagia, dysarthria, neck weakness, distal motor weakness of all limbs, and ataxia. She had also presented with hyporeflexia and hypoesthesia, but with a bilateral pyramidal tract sign. A study of her cerebrospinal fluid revealed albuminocytologic dissociation, and nerve conduction study revealed demyelination of her peripheral nerves. Moreover, electroencephalography findings were abnormal and anti-GQ1b antibody was positive. We diagnosed Fisher syndrome with Guillain-Barré syndrome and Bickerstaff brainstem encephalitis. We administered intravenous immunoglobulin treatment for 5 days and her symptoms gradually improved. However, her external ophthalmoplegia continued for several months.

Postprandial hypertension, an overlooked risk marker for arteriosclerosis.

OBJECTIVE: Increased blood pressure (BP) variability is suggested to be a risk factor for cardiovascular disease. Although a postprandial decline in BP is a frequently observed phenomenon in the elderly, little attention has been paid to the clinical and diagnostic significance of postprandial BP change. Here, we aimed to clarify the possible association between postprandial BP dysregulation and arteriosclerosis. METHODS: The study subjects were 1339 apparently healthy middle-aged to elderly persons (66 ± 9 years old). Postprandial changes in BP were calculated by two readings on the same day, one just before lunch with a standardized Japanese meal and the second 30 min after lunch. Arteriosclerosis was assessed by carotid intima-media thickness and brachial-to-ankle pulse wave velocity. RESULTS: Mean preprandial and postprandial systolic BP was 127 ± 18 and 123 ± 18 mmHg respectively. One hundred and twelve subjects (8.4%) showed a greater than 20-mmHg postprandial decline in systolic BP, while 129 (9.6%) showed a greater than 10-mmHg increase. Arteriosclerosis was significantly higher in both postprandial hypotensive and hypertensive subjects. The postprandial changes in systolic BP were strongly associated with preprandial systolic BP (r = 0.335, p < 0.001). The association between postprandial hypotension and increased arteriosclerosis was therefore lost after adjustment for basal systolic BP. Multiple linear regression analysis adjusted for possible covariates, including basal BP, identified a postprandial increase in BP as an independent determinant of insulin resistance as assessed by HOMA-IR (ß = 0.093, p < 0.001), carotid thickness (ß = 0.086, p = 0.001) and pulse wave velocity (ß = 0.170, p < 0.001). CONCLUSION: Postprandial increase in BP is a novel risk marker for arteriosclerosis.

Liver enzyme and adipocytokine profiles are synergistically associated with insulin resistance: the J-SHIPP study.

AIM: Alanine aminotransferase (ALT) and γ-glutamyltransferase (GGT) are associated with insulin resistance and arteriosclerotic disease. Since adiposity raises liver enzyme levels and causes insulin resistance, adipocytokines are thought to underlie the relationship between liver enzymes and insulin resistance. To clarify this hypothesis, we conducted a cross-sectional epidemiological study in a Japanese general population. METHODS: The study subjects were 903 middle-aged to elderly persons. Plasma levels of adiponectin and leptin were measured, while other clinical parameters were obtained from personal health records of medical check-ups. Insulin resistance was assessed by a homeostasis model assessment index (HOMA-IR). RESULTS: Plasma levels of ALT (r=0.379, p<0.001), GGT (r=0.225, p<0.001), adiponectin (r= -0.346, p<0.001) and leptin (r=0.369, p<0.001) were significantly correlated with insulin resistance even on subgroup analysis by sex. Further, any combination of liver enzymes and adipocytokines was synergistically associated with insulin resistance (p<0.001) after adjustment for possible covariates (ALT*adiponectin: ß=-0.098, p<0.001, ALT*leptin: ß=0.129, p<0.001, GGT*adiponectin: ß=-0.054, p=0.054, GGT*leptin: ß=0.126, p<0.001); however, in simple obese subjects with normal adipocytokine levels, liver enzymes were not associated with insulin resistance (mean HOMA-IR: worsened adipocytokine +/visceral obesity +, 2.01±1.14; +/-, 1.39±0.84; -/+, 1.23± 0.55; -/-, 1.03±0.57; p<0.001). CONCLUSION: Plasma levels of ALT and GGT were independent determinants of insulin resistance only in subjects with a worsened adipocytokine profile. Use of liver enzyme levels as a marker of insulin resistance requires stratification by adipocytokine profile.

Potential utility of soluble p3-alcadein α plasma levels as a biomarker for sporadic Alzheimer's disease.

Alcadeins (Alcs) constitute a family of neuronal type I membrane proteins (α, ß, γ) that share identical localization and function to the amyloid-ß protein precursor (AßPP) in the brain. Alcs are proteolyzed in neurons through successive cleavages via secretases, resulting in non-aggregative p3-Alc, where p3 corresponds to the AßPP-fragment. We found p3-Alcα detected in human plasma reflected the pathological process of amyloid-ß accumulation in Alzheimer's disease (AD) patients and therefore investigated the utility of p3-Alcα as a plasma biomarker in AD. We measured p3-Alcα plasma levels in 83 sporadic-AD, 18 mild cognitive impaired (MCI), and 24 control subjects using the sandwich-ELISA system. Pooled samples with previously published data (171 AD and 45 controls) were also analyzed. The plasma p3-Alcα concentrations in patients with AD and MCI were significantly higher compared with control subjects (224.7 ± 40.4, 223.3 ± 53.9, and 189.1 ± 32.9 pg/ml, respectively; p = 0.0012). In AD patients, the plasma p3-Alcα concentration significantly correlated with age (r = 0.23, p = 0.037) and serum creatinine levels (r = 0.23, p = 0.0012). Even after adjusting for confounding factors of age, gender, renal function, and ApoE-ε4, high plasma p3-Alcα levels were correlated with significant AD risk, with an odds ratio 1.47 (95% confidence interval: 1.18-1.93, p = 0.0019) for every 10 pg/ml increase. Pooled analysis further confirmed these findings. Increased plasma p3-Alcα, evident in the early stages of cognitive impairment, suggests that Alc metabolites are useful plasma biomarkers of AD.