Maya Ohara

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 ± 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 < 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.

Association of Postural Instability With Asymptomatic Cerebrovascular Damage and Cognitive Decline The Japan Shimanami Health Promoting Program Study

Background and Purpose— Asymptomatic cerebral small-vessel disease (cSVD) in elderly individuals are potent risk factors for stroke. In addition to common clinical risk factors, postural instability has been postulated to be associated with cSVD in older frail patients. Here, we conducted a cross-sectional study to understand the possible link between postural instability and asymptomatic cSVD further, namely periventricular hyperintensity, lacunar infarction, and microbleeds, as well as cognitive function, in a middle-aged to elderly general population (n=1387). Methods— Postural instability was assessed based on one-leg standing time (OLST) and posturography findings. cSVD was evaluated by brain magnetic resonance imaging. Mild cognitive impairment was assessed using a computer-based questionnaire, and carotid intima-media thickness as an index of atherosclerosis was measured via ultrasonography. Results— Frequency of short OLST, in particular <20 s, increased linearly with severity of cSVD (lacunar infarction lesion: none, 9.7%; 1, 16.0%; >2, 34.5%; microbleeds lesion: none, 10.1%; 1, 15.3%; >2, 30.0%; periventricular hyperintensity grade: 0, 5.7%; 1, 11.5%; >2, 23.7%). The association of short OLST with lacunar infarction and microbleeds but not periventricular hyperintensity remained significant even after adjustment for possible covariates (lacunar infarction, P=0.009; microbleeds, P=0.003; periventricular hyperintensity, P=0.601). In contrast, no significant association was found between posturographic parameters and cSVD, whereas these parameters were linearly associated with OLST. Short OLST was also significantly associated with reduced cognitive function independent of covariates, including cSVD (P=0.002). Conclusions— Postural instability was found to be associated with early pathological changes in the brain and functional decline, even in apparently healthy subjects.

Sarcopenic obesity and arterial stiffness, pressure wave reflection and central pulse pressure: The J-SHIPP study

more prevalent in decedents compared to the general population (18% vs 7%). Furthermoremarkedly elevated Lp(a) levels (N80th percentile) were more prevalent in decedents with obstructive CAD compared to minor disease (22% vs 6%), however this did not reach statistical significance (p= 0.18, Fig. 2J). As novel therapies that effectively reduce Lp(a) levels (such as PCSK9 inhibitors) are emerging, the potential benefits of population-based screening for elevated Lp(a) in reducing premature cardiac death warrant further investigation. No significant association was identified between atheroma burden and HDL, ApoA1, triglycerides, HbA1c or cotinine (Fig. 2C, D, F, G, H). Although numerous associations between elevated HDL and cardiovascular risk reduction have been reported [9], a causal relationship has not been demonstrated. Smoking exposure, as indicated by elevated cotinine levels, was prevalent amongst sudden cardiac decedents (~50%) however did not correlate with atheroma severity. The current study has identified elevated levels of total cholesterol and apolipoprotein B in decedents with premature ischemic heart disease. Furthermore the severity of coronary diseasewas associatedwith the degree of hypercholesterolemia, which appears to be a dominant risk factor for premature cardiac death. The significant dyslipidemia in this group is likely partially attributed to FH, which is prevalent but underdiagnosed in the community. As age-standardized mortality rates in peoplewithuntreateddyslipidemiaor FHare reduced tonearnormalwith statin therapy, the need for effective screening programs to identify and treat high-risk young individuals is paramount. Programs targeting the identification and cascade screening of index cases (including decedents with premature CAD) or universal screening of the young may be cost-effective means of reducing premature cardiovascular mortality [10].

Clinical characteristics of high plasma adiponectin and high plasma leptin as risk factors for arterial stiffness and related end-organ damage

OBJECTIVE The relationship between plasma levels of adiponectin and cardiovascular events is inconclusive. We evaluated the clinical characteristics of people with high plasma adiponectin and high plasma leptin levels. METHODS Thousand seven hundred participants recruited from visitors to the Anti-Aging Doc were divided into four groups by combining the bipartiles of plasma adiponectin and leptin levels in men and women separately: AL, high adiponectin and high leptin; Al, high adiponectin and low leptin; al, low adiponectin and low leptin; aL, low adiponectin and high leptin. Body composition, including visceral fat area and thigh muscle cross-sectional area (CSA), brachial-ankle pulse wave velocity (baPWV), periventricular hyperintensity, and urinary albumin excretion, were determined. RESULTS Twenty percent of the studied population fell within the AL group. This group had a significantly higher visceral fat area than the Al group. Thigh muscle CSA was lowest in the AL group among groups. baPWV, brain white matter lesions, and albuminuria findings in the AL group were significantly higher than those of the Al group. Multiple and logistic regression analyses with confounding parameters further confirmed that plasma adiponectin was not an independent determinant for brain and renal small vessel-related disease. CONCLUSION These findings suggest that the plasma level of adiponectin alone is not enough for the risk stratification of cardiovascular disease. Leptin resistance associated with skeletal muscle loss in addition to obesity may need to be addressed to identify high risk people with high plasma adiponectin levels.

Portable indices for sarcopenia are associated with pressure wave reflection and central pulse pressure: the J-SHIPP study.

Objective: 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. Methods: 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 cm2. Results: 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. Conclusion: These findings indicate the clinical usefulness of noninvasive methods for assessment of sarcopenia, which is a risk factor for cardiovascular disease.

Orthostatic hypertension as a predisposing factor for masked hypertension: The J-SHIPP study

Masked hypertension (HT) is a known risk factor for cardiovascular outcomes. Postural blood pressure (BP) dysregulation is another BP phenomenon representing cardiovascular frailty. Given their several shared risk factors, we suspected an inter-relationship between these two BP phenomena. Here we investigated a possible relationship between masked HT and postural BP dysregulation in a general population. Study subjects were 884 apparently healthy individuals (aged 66.3±8.9 years). Masked HT was assessed on the basis of the ambulatory monitored average awake BP and office-measured BP values. Orthostatic BP change was measured at our office after a subject was asked to actively stand up. A strong inverse relationship was noted for orthostatic systolic BP (SBP) change and office-to-awake SBP differences (office−awake BP) (r=−0.422, P<0.001), and these relationships were replicated in the second-visit measurements (n=101, r=−0.326, P=0.001). Multivariate analysis revealed that the inverse association was independent (β=−0.23, P<0.001) of possible covariates, including baseline office BP and antihypertensive treatment. Orthostatic HT (OHT), which is defined as postural increases in SBP >10 mm Hg, 3 min after standing (P=0.001), but not transient HT at only 1 min (P=0.767), was associated with greater office-to-awake SBP differences than in orthostatic normotensive subjects. Among apparently normotensive subjects, the frequency of masked HT was therefore significantly greater in subjects who showed OHT 3 min after standing (52.1%) compared with controls (27.5%) (odds ratio=3.01, P=0.001). We observed an intra-individual relationship between the postural BP change and the office-to-awake BP differences, and subjects who showed OHT were likely to have masked HT irrespective of antihypertensive treatment.

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

ObjectiveOsteoporosis 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. MethodsThirty-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. ResultsAt 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. ConclusionsChanges 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.

Office-based simple frailty score and central blood pressure predict mild cognitive impairment in an apparently healthy Japanese population: J-SHIPP study

Frailty is associated with cognitive impairment and can be used to identify people at high risk for dementia. We developed a simple frailty (SF) score using a combination of low hand grip strength (<32.5 kg in men, <19.5 kg in women), and short one-leg standing time (<20 seconds). These can be easily measured in the clinician’s office when seeing patients. We investigated the possible association between SF score and mild cognitive impairment (MCI) in a cross-sectional study with 838 independent middle-aged to elderly participants (319 men, mean age 65.1years). In total, 118 participants were diagnosed with MCI. A SF score of 2 was significantly associated with the presence of MCI (odds ratio 4.6, 95% confidence interval: 1.9–6.9, p = 0.0001) even after adjustment for age and sex. Stepwise regression analyses showed that a SF score of 2 was associated with the presence of MCI, independently of central pulse pressure and silent cerebral infarcts. These findings indicate that the SF score is a useful frailty parameter to predict MCI in an apparently independent population.

Muscle mass decline, arterial stiffness, white matter hyperintensity, and cognitive impairment: Japan Shimanami Health Promoting Program study

There is a close association between frailty and cognitive impairment. However, the underlying contribution of sarcopenia to the development of cognitive impairment is unclear. We investigated the possible association between muscle mass decline and cognitive impairment in a cross‐sectional study of 1518 subjects aged 55 years or above. We also evaluated arterial stiffness and white matter hyperintensities (WMHs) as possible underlying mechanisms for this association.

Association of office-based frailty score with hypertensive end organ damage in the J-SHIPP cross-sectional study

BACKGROUND Frailty, a geriatric syndrome reflecting a state of reduced physiological reserve and increased vulnerability, is an independent risk factor for cardiovascular morbidity and mortality. However, the relationship between frailty and hypertensive end-organ damage is not fully established. METHOD AND RESULTS We performed a cross-sectional study to investigate the association between frailty and end-organ damage in 1125 apparently healthy middle-aged to elderly subjects. We performed a simple frailty (SF) score that was easily obtainable in the office, in combination with low hand grip power and short one-leg standing (OLS) time. The association between SF score and hypertensive end-organ damage and other frailty-related parameters was evaluated. Odds ratio of SF score 1 to score 0 for the presence of hypertension was 1.9 [1.4-2.5, p<.0001] and that of SF score 2 was 3.3 [2.1-5.3, p<.0001]. SF score was also significantly associated with brachial-ankle pulse wave velocity (baPWV) and central pulse pressure (PP2). SF score was significantly associated with higher frailty index calculated from 21 parameters, lower cognitive test score, % vital capacity, skeletal muscle mass, and thigh muscle cross-sectional area. SF score was positively associated with stage of brain white matter hyperintenisty, plasma levels of B-type natriuretic peptide, and urinary protein excretion, even after correction for confounding parameters including baPWV and PP2. CONCLUSIONS These findings indicate that frailty is significantly associated with end-organ damage in elderly subjects. SF score may be a useful clinical tool to identify frail subjects and advanced end-organ damage in elderly subjects.