Management instructions for elderly patients with hypertension.

Aim: To compare the understanding of hypertension and antihypertensive treatment in Japanese patients (aged <75 years vs. ≥75 years) with blood pressure (BP) targets as per the 2014 Japanese guidelines.Methods: A 10-question survey was administered before and after treatment.Results: Majority of patients aged ≥75 years did not achieve their BP targets (75%); >50% of these patients had little knowledge of hypertension and poor understanding of their physician's explanation of it.Conclusions: Elderly patients with hypertension (aged ≥75 years) require daily BP monitoring and detailed and repeated explanation of hypertension and BP targets.

Questionnaire Survey From the Viewpoint of Concordance in Patient and Physician Satisfaction Concerning Hypertensive Treatment in Elderly Patients　- Patients Voice Study.

BACKGROUND: Patient-physician concordance is an important concern in the treatment of elderly patients with hypertension (HT). Treatment that considers concordance is necessary for mutual understanding and therapeutic satisfaction between patients and physicians. However, there have been no studies addressing concordance that objectively analyzed both patient and physician satisfaction before and after treatment.Methods and Results:An exploratory open-label, multicenter, intervention study was conducted. Patients with HT undergoing treatment with angiotensin-receptor blocker (ARB) or a calcium-channel blocker (CCB) monotherapy were enrolled. Medication was switched to an ARB/CCB combination tablet and taken for 12 weeks. Physicians and patients participated in satisfaction surveys concerning treatment. Discrepancies in satisfaction levels between patients and physicians were found at baseline for the following survey items: treatment, involvement in treatment, understanding of HT, reliance, medication, and blood pressure. After treatment, the satisfaction levels of both patients and physicians increased; discrepancies in satisfaction between the groups also improved. CONCLUSIONS: The rates of satisfaction were relatively higher for patients compared with physicians at baseline. After HT treatment addressing concordance, both patient and physician satisfaction rates and the gap in satisfaction rates between patients and physicians improved. This indicates that addressing concordance has clinical significance in the treatment of elderly HT patients. (UMIN000017270).

The Impact of Autophagy on Cardiovascular Senescence and Diseases.

The risk of cardiovascular disease increases with age, causing chronic disability, morbidity, and mortality in the elderly. Cardiovascular aging and disease are characterized by heart failure, cardiac ischemia-reperfusion injury, cardiomyopathy, hypertension, arterial stiffness, and atherosclerosis. As a cell ages, damaged organelles and abnormal proteins accumulate. A system for removing these cytoplasmic substrates is essential for maintaining homeostasis. Autophagy assists tissue homeostasis by forming a pathway by which these substances are degraded. Growing evidence suggests that autophagy plays a role in age-related and disease states of the cardiovascular system, and it may even be effective in preventing or treating cardiovascular disease. On the other hand, overexpression of autophagy in the heart and arteries can produce detrimental effects. We summarize the current understanding of the close relationship between autophagy and cardiovascular senescence.

Metabolomic analysis of akt1-mediated muscle hypertrophy in models of diet-induced obesity and age-related fat accumulation.

Akt1 is a serine/threonine kinase that promotes cell growth and survival. Previously, Akt1 activation in a double transgenic (DTG) mouse model fed a high-fat/high-sucrose (HF/HS) diet was found to promote type IIb muscle growth and to lead to a significant reduction in obesity. Here, we have used metabolomics to examine the metabolic perturbations in blood serum and liver and gastrocnemius tissues of the DTG mice. Multivariate statistics highlighted consistent metabolic changes in gastrocnemius muscle following Akt1 activation, which included significant reductions of serine and histidine-containing dipeptides (anserine and carnosine), in addition to increased concentrations of phosphorylated sugars. In addition, Akt1-mediated regression in obesity could be associated with increased glycolysis in gastrocnemius muscle as well as increased gluconeogenesis, glycogenolysis, and ketogenesis in the liver. In old DTG animals, Akt1 activation was found to improve glucose metabolism and confer a beneficial effect in the regression of age-related fat accumulation. This study identifies metabolic changes induced by Akt1-mediated muscle growth and demonstrates a cross-talk between distant organs that leads to a regression of fat mass. The current findings indicate that agents that promote Akt1 induction in muscle have utility in the regression of obesity.

[Dipper, non-dipper pattern].

The circadian rhythms of blood pressure is regulated by various mechanisms, such as the autonomic nerve system, the renin-angiotensin system and hormones. Non-dippers are defined as those with a nighttime blood pressure reduction of less than 10% of daytime blood pressure. Many reports say that non-dippers have increased risk of cardiovascular or cerebrovascular disease. Ambulatory blood pressure monitoring (ABPM) is a useful tool for diagnostic and management of abnormal blood pressure variability in hypertensive individuals. Antihypertensive agents have the potential to provide blood pressure control of non-dipper patients. 24-hour blood pressure control with ABPM may be necessary for patients to get better prognosis by blood pressure lowering therapy.

Relationship between defecation status and blood pressure level or blood pressure variability.

Blood pressure variability is an independent predictor of cardiovascular disease. Defecation status has also been associated with the risk of developing cardiovascular disease. This study aimed to investigate the association between blood pressure variability and defecation status. A total of 184 participants who could measure their home blood pressure for at least 8 days monthly, both at baseline and 1 year later, were included in this study. All participants had their home blood pressure measured using HEM-9700T (OMRON Healthcare). Day-to-day variability of systolic blood pressure was assessed using the coefficient of variation of home systolic blood pressure during 1 month. Data on defecation status was obtained using a questionnaire survey. Eighty-nine patients had an elevated coefficient of variation at 1 year. The proportion of participants with elevated coefficient of variation at 1 year was significantly higher in the no daily bowel movement group than in the daily bowel movement group (72% vs. 42%, P = 0.001). In multivariable logistic regression analysis with the elevated coefficient of variation at 1 year as the objective variable and age, sex, no daily bowel movement, taking medications, including antihypertensive drugs, laxatives, and intestinal preparations, and coefficient of variation at baseline as independent variables, no daily bowel movement was independently associated with the elevated coefficient of variation at 1 year (odds ratio: 3.81, 95% confidence interval: 1.64-8.87, P = 0.0019). In conclusion, no daily bowel movement was independently associated with elevated day-to-day blood pressure variability at 1 year. Relationship between defecation status and blood pressure level or blood pressure variability.

Triglyceride-glucose index predicts future chronic kidney disease development in all populations, including normotensive and isolated diastolic hypertension.

Hypertension and insulin resistance are established risk factors for chronic kidney disease. However, the association between chronic kidney disease and insulin resistance in detailed hypertension pattern groups such as isolated diastolic hypertension remains unclear. Triglyceride-glucose index has been noted as an indicator of insulin resistance. This study investigated the association between the triglyceride-glucose index and chronic kidney disease in four blood pressure groups: isolated diastolic hypertension, isolated systolic hypertension, systolic diastolic hypertension, and normotension. Using a database of 41,811 middle-aged men who had two or more annual health checkups from 2007 to 2019, those with chronic kidney disease at the first visit, antihypertensive/diabetes/dyslipidemia medication users, and incomplete data were excluded. Four groups were categorized using the 140/90 mmHg threshold. A COX proportional hazards model was used to assess the triglyceride-glucose index with incident chronic kidney disease. Participants were divided: isolated diastolic hypertension: 2207 (6.72%), isolated systolic hypertension: 2316 (7.06%), systolic-diastolic hypertension: 3299 (10.05%), normal: 24,996 (76.17%). The follow-up period was 6.78 years. Adjusted hazard ratios (HRs) and 95% CIs per unit increase in triglyceride-glucose index: isolated diastolic hypertension (HR = 1.31, 95% CI (1.06-1.62)), isolated systolic hypertension (HR = 1.36, 95% CI (1.12-1.64)), systolic-diastolic hypertension (HR = 1.40, 95% CI (1.19-1.64)), normal (HR = 1.18, 95% CI (1.09-1.28)). Triglyceride-glucose index is relevant for predicting chronic kidney disease development in all subtypes of hypertension. The results may lead to early prediction and prevention of the development of chronic kidney disease.

Effectiveness of digital health interventions for telemedicine/telehealth for managing blood pressure in adults: a systematic review and meta-analysis.

This systematic review and meta-analysis included randomized controlled trials or observational studies that compare digital health interventions (DHIs) for telemedicine/telehealth versus usual care for managing blood pressure (BP) in adults. We searched PubMed, Cochrane CENTRAL, and IchuShi-Web, and used a random-effects meta-analysis of the weighted mean difference (MD) between the comparison groups to pool data from the included studies. The outcome included the pooled MD of office BP from baseline to each follow-up period. This meta-analysis considered 117 studies with 68677 participants as eligible. The 3-month intervention period reduced office systolic BP (SBP) compared with usual care in 38 studies (MD: -3.21 mmHg [95% confidence interval: -4.51 to -1.90]), with evidence of heterogeneity. Office SBP across intervention periods demonstrated comparable effects (3-, 6- [54 studies], 12- [43 studies], and >12-month periods [9 studies]). The benefits for office diastolic BP were similar to those for office SBP. Additionally, the interventions significantly reduced the office SBP compared with the control, regardless of the mode of intervention delivery (smartphone apps [38 studies], text messages [35 studies], and websites [34 studies]) or type of facility (medical [74 studies] vs. non-medical [33 studies]). The interventions were more effective in 41 hypertension cohorts compared with 66 non-hypertension cohorts (-4.81 mmHg [-6.33, -3.29] vs. -2.17 mmHg [-3.15, -1.19], P = 0.006 for heterogeneity). In conclusion, DHIs for telemedicine/telehealth improved BP management compared with usual care. The effectiveness with heterogeneity should be considered, as prudent for implementing evidence-based medicine. This meta-analysis considered 117 studies with 68677 participants eligible. The DHIs for telemedicine/telehealth reduced office BP compared with usual care, regardless of intervention duration, intervention delivery mode, facility type, and cohort type. Additionally, the DHIs reduced the risk of uncontrolled BP compared with usual care, regardless of intervention duration, intervention delivery mode, and facility type. BP blood pressure, DHI digital health intervention, MD mean difference, RR risk ratio, SBP systolic blood pressure.

Waon therapy upregulates Hsp90 and leads to angiogenesis through the Akt-endothelial nitric oxide synthase pathway in mouse hindlimb ischemia.

BACKGROUND: Thermal therapy, namely Waon therapy, has previously been reported to regulate nitric oxide (NO) and endothelial NO synthase (eNOS) and augment ischemia-induced angiogenesis in mice and improve limb ischemia in patients with peripheral artery disease. The aim of this study was to clarify the precise mechanism by which Waon therapy augments angiogenesis in mice with hindlimb ischemia. METHODS AND RESULTS: Unilateral hindlimb ischemia was induced in apolipoprotein E-deficient mice and Waon therapy was performed for 5 weeks. Heat shock protein 90 (Hsp90), phosphorylated-Akt, and phosphorylated-eNOS were detected in arterial endothelial cells of ischemic hindlimbs and all were upregulated by Waon therapy compared to controls. Waon therapy also increased serum concentrations of nitrite and nitrate. Capillary density and the ischemic limb/normal side blood perfusion ratio monitored by laser Doppler perfusion imaging in the Waon therapy group were significantly increased beyond those in the control group. The effect of Waon therapy on angiogenesis through the activation of the Hsp90/Akt/eNOS pathway was attenuated by the administration of a Hsp90 inhibitor. CONCLUSIONS: It is suggested that Waon therapy upregulates Hsp90, which contributes to the activation of the Akt/eNOS/NO pathway, and induces angiogenesis in mice with hindlimb ischemia.

Insufficient blood pressure control is independently associated with increased arterial stiffness.

Hypertension is a risk factor for atherosclerosis. Achieving the therapeutic target value of blood pressure (BP) prevents the onset of cardiovascular events; however, it is not clear how antihypertensive drug use and BP control status relate to arterial stiffness. The purpose of this study is to investigate the relationship between BP control status with or without antihypertensive drugs and arterial stiffness. Nine hundred eighty individuals (mean age: 68 ± 11 years) who participated in a community-based cohort study were enrolled. Arterial stiffness was evaluated using the cardio-ankle vascular index (CAVI). Higher BP was defined as a systolic BP ≥ 140 mmHg or diastolic BP ≥ 90 mmHg. Participants were divided into four groups: normal, non higher BP without antihypertensive drugs (n = 421); untreated, higher BP without antihypertensive drugs (n = 174); good control, non higher BP with antihypertensive drugs (n = 209); and poor control, higher BP with antihypertensive drugs (n = 176). In multivariable logistic analysis adjusted for age, sex, dyslipidemia and diabetes mellitus medication use, obesity, smoking, alcohol drinking, and heart rate at the CAVI measurement for a high CAVI-using a borderline cutoff value of 8.0-the other three groups were significantly associated with a high CAVI when compared with the normal group. By contrast, multivariable logistic analysis of a high CAVI using an abnormal cutoff value of 9.0 demonstrated that the poor control and untreated groups were significantly associated with a high CAVI, whereas the good control group was not. In conclusion, even with antihypertensive drugs, poor BP control is independently associated with a high CAVI.

The relationship between day-to-day variability in home blood pressure measurement and multiple organ function.

Blood pressure variability (BPV) is associated with the prognosis of cardiovascular diseases. However, it is unclear how BPV is related to various organs. The aim of this study is to investigate the association between BPV and multiple organ functions. A total of three hundred fifteen participants (114 males; mean age: 70 ± 9 years) participated in a community health checkup held in Tarumizu City. Home blood pressure (BP) was measured using a HEM-9700T (OMRON Healthcare, Kyoto, Japan). Day-to-day BPV was evaluated by the coefficient of variation (CV) of home BP measured in the morning for one month. N-terminal pro B-type natriuretic peptide (NT-pro BNP) and high-sensitivity (hs-)troponin T were measured as cardiac biomarkers. Liver stiffness and renal function were evaluated using the Fibrous-4 (Fib4) index and estimated glomerular filtration rate (eGFR), respectively. NT-pro BNP and hs-troponin T were divided by the median value. Fib4 index greater than 2.67 and eGFR less than 60 mL/min/1.73 m2 were defined as high Fib4 index and low eGFR, respectively. In a multivariable logistic regression analysis, the CV of systolic BP was significantly associated with high NT-pro BNP, high Fib 4 index, and low eGFR, but not with high hs-troponin T. In contrast, the CV of diastolic BP was not associated with low eGFR, and the other three biomarkers had the same results as systolic BP. In conclusion, day-to-day BPV of systolic BP is independently associated with NT-pro BNP, eGFR, and Fib4 index, but not with hs-troponin T. In contrast, diastolic BPV was not found to be associated with eGFR.

Association of blood pressure and dietary intake of Sunomono, Japanese vinegared side dishes, in community-dwelling Japanese: A cross-sectional study.

Objective: Vinegar has been reported to have a hypotensive effect. We aimed to investigate the relationship between the consumption of vinegar-based side dishes and blood pressure. Research methods & procedures: This cross-sectional study included 746 individuals (257 men and 489 women) aged ≥40 years from Tarumizu, Kagoshima, Japan. Nutrient intake was estimated based on the brief-type self-administered diet history questionnaire. The intake frequency of vinegar-based side dishes (Sunomono and pickles) was determined using a self-administered diet history questionnaire. Participants who did not consume vinegar-based side dishes for a month were defined as having no Sunomono or pickle eating habit. Blood pressure was categorized into four groups according to the Japanese Society of Hypertension Guidelines for the Management of Hypertension. The association between the intake of vinegar-based side dishes and blood pressure categories was analyzed using ordinal logistic regression analysis adjusted for age, body mass index, smoking history, excessive alcohol intake, living situation, energy intake, protein intake, sodium intake, potassium intake, and seaweed intake. Results: Approximately 13.6% men and 6.1% women had no Sunomono eating habits. In men, eating Sunomono, but not pickles, was significantly related to blood pressure categories (estimate, -0.702; 95% CI, -1.122 to -0.310), whereas more frequent consumption of Sunomono did not show an improvement in the blood pressure category. The relationship between eating Sunomono and blood pressure categories was not recognized in women. Conclusion: This was the first study assessing the association between consumption of vinegar-based side dishes and blood pressure categories. We highlighted the effect of Sunomono consumption on blood pressure categories in men. Consumption of Sunomono may improve blood pressure in men.

Effect of febuxostat on left ventricular diastolic function in patients with asymptomatic hyperuricemia: a sub analysis of the PRIZE Study.

Hyperuricemia is related to an increased risk of cardiovascular events from a meta-analysis and antihyperuricemia agents may influence to cardiac function. We evaluated the effect of febuxostat on echocardiographic parameters of diastolic function in patients with asymptomatic hyperuricemia as a prespecified endpoint in the subanalysis of the PRIZE study. Patients in the PRIZE study were assigned randomly to either add-on febuxostat treatment group or control group with only appropriate lifestyle modification. Of the 514 patients in the overall study, 65 patients (31 in the febuxostat group and 34 in the control group) who had complete follow-up echocardiographic data of the ratio of peak early diastolic transmitral flow velocity (E) to peak early diastolic mitral annular velocity (e') at baseline and after 12 and 24 months were included. The primary endpoint was a comparison of the changes in the E/e' between the two groups from baseline to 24 months. Interestingly, e' was slightly decreased in the control group compared with in the febuxostat group (treatment p = 0.068, time, p = 0.337, treatment × Time, p = 0.217). As a result, there were significant increases in E/e' (treatment p = 0.045, time, p = 0.177, treatment × time, p = 0.137) after 24 months in the control group compared with the febuxostat group. There was no significant difference in the serum levels of N-terminal-pro brain natriuretic peptide and high-sensitive troponin I between the two groups during the study period. In conclusions, additional febuxostat treatment in patients with asymptomatic hyperuricemia for 24 months might have a potential of preventable effects on the impaired diastolic dysfunction.

Clinical characteristics of older adults with hypertension and unrecognized cognitive impairment.

To treat older patients with hypertension, it is important to detect cognitive impairment at an early stage because of its potential influence on treatment efficacy and functional prognosis. In this study, we aimed to identify the incidence and determinants of cognitive impairment in hypertensive patients aged 65 years and above who visited our outpatient clinic and were not previously diagnosed with cognitive impairment. Among 312 patients with hypertension, we found that 35% (n = 109) and 7.7% (n = 24) had cognitive impairment and dementia, respectively, as defined by the Mini-Mental State Examination (≤27 or ≤23, respectively). Patients with cognitive impairment were older, had lower levels of education, and had lower instrumental activities of daily living (IADL) scores than those without cognitive impairment. Multiple regression analysis revealed that age and IADL were associated with cognitive impairment in patients with hypertension. Regarding the treatment of hypertension, the office and home blood pressure levels, number of antihypertensive medications prescribed, and proportion of the use of each antihypertensive drug was equivalent between patients with and without cognitive impairment. Finally, patients with unrecognized cognitive impairment showed distinct clinical characteristics, including high antihypertensive medication burden and preserved IADL, when compared to hypertensive patients in the different cohorts of definitive mild cognitive impairment of a similar age. These findings suggest that older hypertensive patients are at a high risk of masked cognitive decline, even if they are functionally independent.

Insulin-like 6 is induced by muscle injury and functions as a regenerative factor.

The insulin-like family of factors are involved in the regulation of a variety of physiological processes, but the function of the family member termed insulin-like 6 (Insl6) in skeletal muscle has not been reported. We show that Insl6 is a myokine that is up-regulated in skeletal muscle downstream of Akt signaling and in regenerating muscle in response to cardiotoxin (CTX)-induced injury. In the CTX injury model, myofiber regeneration was improved by the intramuscular or systemic delivery of an adenovirus expressing Insl6. Skeletal muscle-specific Insl6 transgenic mice exhibited normal muscle mass under basal conditions but elevated satellite cell activation and enhanced muscle regeneration in response to CTX injury. The Insl6-mediated regenerative response was associated with reductions in muscle cell apoptosis and reduced serum levels of creatine kinase M. Overexpression of Insl6 stimulated proliferation and reduced apoptosis in cultured myogenic cells. Conversely, knockdown of Insl6 reduced proliferation and increased apoptosis. These data indicate that Insl6 is an injury-regulated myokine that functions as a myogenic regenerative factor.

Hypertension, cardiovascular disease, and nocturia: a systematic review of the pathophysiological mechanisms.

Nocturia significantly impairs quality of life, especially in the elderly population, and urinary retention is a main target of treatment for urologists. In addition to nocturia, cardiovascular diseases are common in the elderly population, and a systematic review showed that hypertension and heart failure are often associated with nocturia. One possible pathogenic mechanism underlying the development of hypertension is an increase in blood pressure due to excessive salt intake in people with high-salt sensitivity. From Guyton's natriuretic curve, we can infer that salt-sensitive hypertensive patients who consume too much salt do not excrete salt during the daytime and are forced to excrete salt at night, resulting in increased urine production and nocturia. In patients with heart failure, the nocturnal supine position leads to an increase in central fluid volume due to an increase in venous return from the periphery, and the secretion of natriuretic peptide is stimulated by the stretching of the atria and ventricles. Thus, natriuresis due to hypertension and hydrodiuresis due to heart failure may cause nocturia, which can effectively be treated by the administration of thiazide diuretics and loop diuretics in the morning, respectively. Because cardiovascular diseases, such as hypertension and heart failure, can cause nocturia and because the treatment methods differ depending on the cause, it is necessary to pay close attention to nocturia in the management of lifestyle-related diseases, such as cardiovascular disease.

Association of Lectin-Like Oxidized Low-Density Lipoprotein Receptor-1 With Angiotensin II Type 1 Receptor Impacts Mitochondrial Quality Control, Offering Promise for the Treatment of Vascular Senescence.

Lectin-like oxidized low-density lipoprotein (ox-LDL) causes vascular senescence and atherosclerosis. It has been reported that ox-LDL scavenger receptor-1 (LOX-1) is associated with the angiotensin II type 1 receptor (AT1R). While mitochondria play a crucial role in the development of vascular senescence and atherosclerosis, they also undergo quality control through mitochondrial dynamics and autophagy. The aim of this study was to investigate (1) whether LOX-1 associates with AT1R, (2) if this regulates mitochondrial quality control, and (3) whether AT1R inhibition using Candesartan might ameliorate ox-LDL-induced vascular senescence. We performed in vitro and in vivo experiments using vascular smooth muscle cells (VSMCs), and C57BL/6 and apolipoprotein E-deficient (ApoE KO) mice. Administration of oxidized low-density lipoprotein (ox-LDL) to VSMCs induced mitochondrial dysfunction and cellular senescence accompanied by excessive mitochondrial fission, due to the activation of fission factor Drp1, which was derived from the activation of the Raf/MEK/ERK pathway. Administration of either Drp1 inhibitor, mdivi-1, or AT1R blocker candesartan attenuated these alterations. Electron microscopy and immunohistochemistry of the co-localization of LAMP2 with TOMM20 signal showed that AT1R inhibition also increased mitochondrial autophagy, but this was not affected by Atg7 deficiency. Conversely, AT1R inhibition increased the co-localization of LAMP2 with Rab9 signal. Moreover, AT1R inhibition-induced mitochondrial autophagy was abolished by Rab9 deficiency, suggesting that AT1R signaling modulated mitochondrial autophagy derived from Rab9-dependent alternative autophagy. Inhibition of the Raf/MEK/ERK pathway also decreased the excessive mitochondrial fission, and Rab9-dependent mitochondrial autophagy, suggesting that AT1R signaling followed the Raf/MEK/ERK axis modulated both mitochondrial dynamics and autophagy. The degree of mitochondrial dysfunction, reactive oxygen species production, vascular senescence, atherosclerosis, and the number of fragmented mitochondria accompanied by Drp1 activation were all higher in ApoE KO mice than in C57BL/6 mice. These detrimental alterations were successfully restored, and mitochondrial autophagy was upregulated with the administration of candesartan to ApoE KO mice. The association of LOX-1 with AT1R was found to play a crucial role in regulating mitochondrial quality control, as cellular/vascular senescence is induced by ox-LDL, and AT1R inhibition improves the adverse effects of ox-LDL.

Estrogen Plays a Crucial Role in Rab9-Dependent Mitochondrial Autophagy, Delaying Arterial Senescence.

Background The risk of cardiovascular disease is known to increase after menopause. Mitochondria, which undergo quality control via mitochondrial autophagy, play a crucial role in the regulation of cellular senescence. The aim of this study was to investigate whether the effect of estrogen-mediated protection from senescence on arteries is attributed to the induction of mitochondrial autophagy. Methods and Results We used human umbilical vein cells, vascular smooth muscle cells, and 12-week-old female C57BL/6 mice. The administration of 17ß-estradiol (E2) to cells inhibited cellular senescence and mitochondrial dysfunction. Furthermore, E2 increased mitochondrial autophagy, maintaining mitochondrial function, and retarding cellular senescence. Of note, E2 did not modulate LC3 (light chain 3), and ATG7 (autophagy related 7) deficiency did not suppress mitochondrial autophagy in E2-treated cells. Conversely, E2 increased the colocalization of Rab9 with LAMP2 (lysosomal-associated membrane protein 2) signals. The E2-mediated effects on mitochondrial autophagy were abolished by the knockdown of either Ulk1 or Rab9. These results suggest that E2-mediated mitochondrial autophagy is associated with Rab9-dependent alternative autophagy. E2 upregulated SIRT1 (sirtuin 1) and activated LKB1 (liver kinase B1), AMPK (adenosine monophosphate-activated protein kinase), and Ulk1, indicating that the effect of E2 on the induction of Rab9-dependent alternative autophagy is mediated by the SIRT1/LKB1/AMPK/Ulk1 pathway. Compared with the sham-operated mice, ovariectomized mice showed reduced mitochondrial autophagy and accelerated mitochondrial dysfunction and arterial senescence; these detrimental alterations were successfully rescued by the administration of E2. Conclusions We showed that E2-induced mitochondrial autophagy plays a crucial role in the delay of vascular senescence. The Rab9-dependent alternative autophagy is behind E2-induced mitochondrial autophagy.

The relationship between home blood pressure measurement and room temperature in a Japanese general population.

Blood pressure (BP) is influenced by various factors, and it is known that temperature and BP have a negative relationship. However, few reports have examined the relationship between BP and temperature throughout the day in the same participant over time. Therefore, this study aimed to investigate the relationship between BP and temperature in the morning and evening in the same participants during a time period of ~1 year. In total, 401 participants, who participated in a community-based health checkup survey in Tarumizu, Japan, were enrolled. Five participants were excluded due to missing data. All participants measured their BP and the room temperature at home using a blood pressure monitor (HEM-9700T, OMRON Healthcare, Kyoto, Japan). The mean systolic BP (SBP) and diastolic BP (DBP) in the morning were significantly higher than the mean of the measurements taken in the evening (SBP: morning vs. evening 128 ± 15 mmHg vs. 122 ± 14 mmHg, P < 0.0001; DBP: morning vs. evening 77 ± 10 mmHg vs. 72 ± 8 mmHg, P < 0.0001). Using a linear mixed model with participants as a random effect, SBP and DBP were significantly associated with temperature in both the morning and evening. In the morning, in almost every month except July, a significant association between SBP and temperature was observed. However, there was a significant relationship between evening BP and temperature in all months. In conclusion, BP was significantly related to temperature in both the morning and evening during the year-long study. Furthermore, BP and temperature were significantly associated in all months except morning measurements in July.

Cerebrovascular and cardiovascular diseases caused by drugs of abuse.

Drugs such as stimulants, sedatives, sleeping pills, and narcotics are associated with drug abuse and are therefore regulated by law. Physical dependence on these drugs is sometimes difficult to control despite an awareness of the problems they cause in daily life and the harm they can cause to the body. Drug dependence is a social problem worldwide, and the physical implications are serious. Many of these drugs cause cerebrovascular and cardiovascular diseases, which often require emergency medical treatment. Differential diagnosis is essential because of the likelihood of life-threatening events, especially among young people who exhibit cerebrovascular and cardiovascular diseases without any of the typical risk factors. Drugs of abuse, especially stimulants, induce a hyperadrenergic state that evokes vasoconstriction and tachycardia, as well as subsequent ischemic and hemorrhagic stroke, acute coronary syndrome, arrhythmias, and aortic dissection. Chronic drug abuse can also cause cardiac hypertrophy and left ventricular dysfunction. As a treatment for these conditions, sedative drugs can be effective but the use of vasodilators may also be required. There are concerns that the use of both alpha- and beta-adrenergic receptor blockers may cause tachycardia and increased blood pressure. Therefore, careful differential diagnosis and selection of therapeutic agents is required.