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Abstract:According to the data from the sixth nationwide population census, 178 million people in China (13%) were over 60 years old in 2010. Aging is an independent risk factor for many chronic diseases. Epidemiological studies show that more than 50% of the elderly have 3 or more chronic diseases with distinct characteristics. The concept of geriatric multimorbidity indicates that the clinical focus of geriatrics has shifted from the traditional model of subspecialties to the integrative medicine which include comprehensive evaluation and treatment. In 2012, the American Geriatrics Society (ACS) provided the stepwise patient-centered care approach for diagnosis and treatment of older adults with multiple chronic conditions. This review aimed to describe the basement, development, comprehensive evaluation, and management system of geriatric multimorbidity.

Abstract:Objective To observe the changes of bone mineral density (BMD) and atherosclerosis indexes with the increase of age. Methods A total of 400 healthy participants who were selected through physical examination from 1500 self-estimated healthy individuals from several communities of Shenyang City from September 2007 to June 2008 were followed up in 2011 for their BMD, ankle-brachial index (ABI), pulse wave velocity (PWV), and carotid intima-media thickness (CIMT). They were assigned into four different age groups, ＜50 years, 50-59 years, 60-69 years, and ≥70 years. The women were divided into another 4 groups, premenopausal, 1-10 years since menopause, 11-20 years since menopause, and＞20 years since menopause. Results There were significant differences in total hip BMD among the women from different age groups and among those with menopause or not(P＜0.01). But for men, there was no difference in total hip BMD in those younger than 70 years. Significant differences were also found in lumbar spine BMD among women younger than 70 years and among those with menopause shorter than 20 years. No difference was found in lumbar spine BMD among the men in different age groups. No difference was seen in ABI among the women of different age groups younger than 70 years and among the menopause groups shorter than 20 years since menopause. Neither were the men from different age groups. There were significant differences in PWV among women from different age groups and among the groups with menopause or not. In men, PWV was higher in ≥70 years group than in other age groups. The differences of CIMT were significant in both women and men among age groups. In women, the BMD, ABI, PWV, and CIMT were correlated with age. In men, the total hip BMD, PWV, and CIMT were correlated with age. Conclusion The changes of BMD and atherosclerosis indices with aging are different between women and men.

Abstract:Objective To evaluate the relationship between aging-related cardiovascular subclinical state and estimated glomerular filtration rate (GFR) in healthy population in Shenyang. Methods In the cross-sectional study, 505 healthy people in Shenyang area were devided into ≤60 years and ＞60 years group. The physical condition, blood pressure, blood biochemical examination and cardiovascular ultrasound were performed. GFR was evaluated by Cockcroft-Gault equation (GFRCG), Chinese modified MDRD formula (GFRMDRD), Chronic Kidney Disease Epidemiology Collaboration equation (GFRCKD-EPI). Cardiac systolic function was assessed by the left ventricular ejection fraction (LVEF). Cardiac diastolic function was assessed by the ratio between mitral E/A ratio, deceleration time of the early mitral velocity (MV-DT), left atrial volume index(LAVI). Vascular structure and stiffness were assessed by carotid intema-media thickness (IMT), ankle brachial index (ABI) and pulse wave velocity (PWV). Results In ≤60 years group, GFRCG was significantly negative correlated with IMT (r＝-0.238, P＜0.01) and PWV (r＝-0.281, P＜0.01). There was significant negative correlation between GFRMDRD and LVEF (r＝-0.221, P＜0.01). GFRCKD-EPI was significantly negatively correlated with IMT (r＝-0.360, P＜0.01) and PWV (r＝-0.327, P＜0.01). After adjusting for age, body mass index (BMI), waist-hip ratio (WHR), blood pressure, blood lipid, and GFRCG was significantly positively correlated with LAVI (r＝0.168, P＜0.05). There was significant negative correlation between GFRMDRD and LVEF (r＝-0.212, P＜0.01). A significant positive correlation of GFRCKD-EPI with LAVI (r＝0.195, P＜0.01), and negative correlation with EA (r＝-0.137, P＜0.05) were observed. In ＞60 years group, GFRMDRD was positively correlated with ABI (r＝-0.167, P＜0.05), which remained significant (r＝0.175, P＜0.05) even after adjusting for confounding variables. Conclusion In aging process, there is decline in renal function, arterial stiffness and cardiac diastolic function. Our results confirm that there is interaction of cardiovascular system and renal function even in healthy people.

Abstract:Objective To sum up the demands of inpatients from geriatric department where the ward round is made by a interdisciplinary team, and the problems that the team can solve, in order to popularize the interdisciplinary care model suitable for Chinese patients. Methods A policy and procedures of ward round for geriatric inpatients made by a interdisciplinary team were established. The data of this model for the inpatients in geriatric ward of our hospital from 2011-09-01 to 2012-08-31 were collected and statistically analyzed. Results There were totally 274 patients hospitalized in the geriatric ward during that period, including 198 (72.3%) over 65 years old with a age of (75.4±7.0) years. Among those older than 65 years, 134 (67.7%) elderly inpatients received the interdisciplinary care. They all had multimorbidities, and 96 (71.6%), 55 (41%), 52 (38.8%), and 13(9.7%) got advices and treatments on nutrition, psychiatric disorder, rehabilitation therapy, and medication and/or dose adjustment, respectively. After interdisciplinary care, 130 cases(97.0%) recovered and were discharged from hospital, and four cases (3.0%) died. Conclusion Elderly inpatients with multimorbidities have a high demand for interdisciplinary care. Our new model of interdisciplinary team is an important working pattern for multimorbid elderly patients.

Abstract:Objective To investigate the relationship between plasma level of homocysteine and mild cognitive impairment (MCI) in elderly patients with leukoaraiosis (LA). Methods A total of 110 elderly inpatients with confirmed LA hospitalized in our department from August 2011 to Jan 2013 were enrolled in this study. And another 40 sex- and age-matched individuals served as normal control. The LA patients were divided into the MCI group (LA+MCI group, n＝60) and non MCI group (LA group, n＝50), and were also divided into another 3 groups according to the plasma level of homocysteine: low level group (＜16μmol/L, n＝31), middle level group (16μmol/L≤Hcy＜30μmol/L, n＝45), and high level group (≥30μmol/L, n＝34). Mini-mental state examination (MMSE), Montreal cognitive assessment (MoCA) and the activities of daily living (ADL) were used to evaluate the cognitive function. Results In comparison to normal individuals, plasma level of homocysteine was higher in the LA patients with or without MCI (P＜0.01, for all). In all the LA patients, their score and fasting blood glucose was negatively correlated with the plasma level of homocysteine (P＜0.01, for all). Compared with the LA patients with lower homocysteine, those with middle and high levels had lower MoCA score (P＜0.05), and the patients of higher homocysteine had significantly lower score than those of middle level (P＜0.05). Conclusion LA patients accompanied with MCI have higher plasma level of homocysteine, and the higher the level is, the more severe MCI is.

Abstract:Objective p66shc (66-kilodalton isoform of Shc gene products) gene, encoding a phosphotyrosine signal adapter protein, is confirmed to extend life span by 30%. Our aim was to determine the expression of Shc-related phosphotyrosine adaptor proteins in rat vascular aging in order to elucidate the value of vascular aging in the diagnosis and treatment of atherosclerosis. Methods A total of 60 Wistar rats were divided into 4 groups according to age, that is 4, 10, 16 and 24 months old rats respectively. Aorta plasma levels of malondialdehyde (MDA) and superoxide dismutase (SOD) were detected, and the compliance of rat carotid segment was measured by constant liquid injection. Western blotting was used to detect the expression of p66shc and caspase-3 in the healthy rats of different ages. Results With aging, aorta wall was thickened with more severe fibrosis. MDA content in the rats of 16 and 24 months old was evidently ascended when compared with 4 and 10 months old (P＜0.01), but that of SOD was markedly declined (P＜0.01 compared with that of 4 month old rats; P＜0.05 compared with that of 10 month old rats). The carotid flexibility was increased, especially flexibility area was significantly different (P＜0.01 compared with that of 4 month old rats; P＜0.05 compared with that of 10 month old rats). The expression of p66shc and Caspase-3 at protein level was increased in a time-dependent manner. Conclusion The molecular mechanism of vascular aging might be associated with up-regulaton of p66shc and Caspase-3 with aging. Its underlying mechanism may provide theoretical basis for slowing down of vascular aging, and prevention and treatment of atherosclerosis.

Abstract:Arterial aging is one of most principal mechanisms of chronic diseases of the elderly. Studies upon arterial aging are the important approaches to deal with the burden of aging society all over the world. This article overviewed the association of arterial aging and elderly chronic disease, the morphology, and the biomarkers of arterial aging.

Abstract:Osteoporosis and arteriosclerosis are both multifactorial, degenerative diseases that accompany aging. Many studies have suggested associations between osteoporosis and arteriosclerosis. In recent years, there are many studies investigating the common pathogenetic pathways of osteoporosis and arteriosclerosis. The meaning of bone-vascular axis is the associations between osteoporosis and vascular calcification. The hot research topics include RANK/RANKL/OPG system, oxidized lipids, fibroblast growth factor-23/Klotho axis, fetuin-A, and circulating calcifying cells. In this paper, we summarized the above pathogentic pathways.

Abstract:Objective To evaluate the incidence and possible risk factors of clopidogrel resistance in elderly patients with diabetes and coronary heart disease treated with percutaneous coronary intervention, and to investigate the impact of clopidogrel resistance on post-procedural outcomes. Methods Total 232 elderly inpatients with diabetes and coronary heart disease who were treated with clopidogrel and percutaneous coronary intervention were consecutively enrolled in this study. After receiving TEG test, the patients were divided into two groups according to ADP dependent platelet inhibition ratio: the control group (ratio＞50%) and the study group (ratio＜50%). The profiles of clinical cardiovascular risk factors, lipid and glucose metabolic indices, inflammation indices were collected before coronary intervention and compared between two groups. The incidence of post-procedural in-hospital myocardial infarction and mortality were also compared between two groups. Results There was no difference in age, gender, body mass index, history of smoking, incidences of hypertension and hyperlipidermia, medication, levels of triglyceride, total cholesterol, low density lipoprotein cholesterol and hemoglobin A1c between two groups. The patients in study group had lower level of high density lipoprotein cholesterol(HDL-C) and higher levels of fasting glucose, glucosylated serum protein(GSP) and high sensitivity C reactive protein(hs-CRP) than patients in control group (P＜0.01 for all). The study group had higher rate of post-procedural myocardial infarction than the control group (P＜0.01). No difference of mortality rate was found between two groups. Conclusions Clopidogrel resistance is common in elderly patients with diabetes and coronary heart disease. Elderly patients with clopidogrel resistance showed higher risk of in-hospital myocardial infarction after coronary intervention. Elevated levels of fasting glucose, GSP and hs-CRP and low level of HDL-C may suggest high risk of clopidogrel resistance in elderly patients with diabetes and coronary heart disease.

Abstract:Objective To investigate the clinical and genetic characteristics of a large Chinese family with maternally inherited hypertension. Methods The mitochondrial DNA point mutation was detected by sequence analysis in 1865 patients with essential hypertension. Then the families were followed up, and the clinical data were collected for statistical analysis. Results The morbidity of hypertension in the maternal members was up to 55.6%, while that of the non-maternal members was only 15.6% (P＜0.01). The onset age of hypertension tended to be younger [from (62.0±6.2) years old for the second generation, (46.3±5.8) years old for the third generation, and to (23.3±2.9) years old for the forth generation]. The serum levels of blood glucose, total cholesterol and sodium in maternal members were significantly higher than those of non-maternal members (P＜0.05). The results of echocardiogram had no difference between the maternal and non-maternal groups. Genetic analysis of this family showed that the morbidity of hypertension offspring of affected mother was higher than those of affected father (P＜0.05), but no difference was seen between male and female members with hypertension (P＞0.05). Conclusion The morbidity of hypertension is higher in maternal members than in non-maternal members. Genetic analysis shows that it is a family with maternally inherited hypertension, which may be related with mitochondrial DNA point mutation. Our findings suggest that mitochondrial DNA mutation may be associated with maternally inherited hypertension, and play an important role in the incidence of hypertension.

Abstract:Objective To investigate the features and prognosis of the elderly individuals with severe hyperglycemia during hospitalization. Methods All hospitalized patients with age over 60 or older whose fasting or random blood glucose was greater than 20.0mmol/L in our hospital from Jan 1, 2010 to Dec 31, 2011 were enrolled in this study. The causes, medical management and prognosis of these patients were analyzed. Results The cohort of subjects included 100 participants, including 69 diabetic patients and 31 non-diabetic patients, and had 130 times of hyperglycemia, with 90 times for diabetic patients (69.2%) and 40 times for non-diabetic patients (30.8%). And 91% of them were not hospitalized in the Department of Endocrinology. Infection and acute diseases were the main causes of hyperglycemia. The mortality of patients who died within 3 months following hyperglycemia was 54.0% (64.8% vs 61.2% between diabetic group and non-diabetic group, P＞0.05). The main cause of death was multiple organ dysfuction. There were 27 patients having hyperosmolar state, and the mortality in patients with hyperosmolar state was significantly higher than in patients without hyperosmolar state (70.4% vs 47.9%, P＜0.05). Compared with patients whose glycemic was controlled in more than 2 d, the mortality of patients whose blood glucose were successfully controlled within 1 d was significantly lower (39.1% vs 80.6%, P＜0.01). After treatment, the mortality of patients whose blood glucose remained ≥16.7mmol/L was 100.0%. Conclusion Hyperosmolar state and multiple organ dysfunction significantly increase the mortality. Timely reduction of blood glucose (within 1d) and the level of blood glucose less than 16.7mmol/L help to decrease the mortality.

Abstract:Objective To investigate the relationship between hyperuricemia and carotid artery atherosclerosis in postmenopausal women. Methods A total of 196 consecutive postmenopausal patients with dyslipidemia and receiving carotid artery ultrasonography in First Affiliated Hospital, Dalian Medical University from January to June 2012 were enrolled in this study. Among them, 156 patients were diagnosed with atherosclerosis and carotid atherosclerotic plaque (group A) identified by color Doppler ultrasound examination, and the other 40 cases had no atherosclerosis (group B). The age, blood pressure, body mass index (BMI), blood estradiol (E2), blood glucose, blood lipid and uric acid levels were compared between the two groups. Results There was no significant difference in the age, blood pressure, blood glucose, blood levels of triglycerides and high-density lipoprotein, BMI value and E2 levels between the two groups. However, group A had significantly higher uric acid [(455.32±54.67) vs (374.32±45.76)μmol/L, P＝0.02] and low-density lipoprotein cholesterol (LDL-C) [(4.41±0.84) vs (4.11±0.81)mmol/L, P＝0.04] than group B. Uric acid levels showed positive correlation with triglycerides and LDL-C respectively (r＝0.315, r＝0.214), but negative correlation with high-density lipoprotein cholesterol (HDL-C) (r＝-0.243). Among the 124 patients with hyperuricemia out of group A, they had significantly higher levels of LDL-C [(4.49±0.81) vs (4.26±0.79)mmol/L, P＝0.04] and triglycerides [(2.66±0.34) vs (2.45±0.39)mmol/L, P＝0.02], and significantly lower level of HDL-C [(1.09±0.39) vs (1.21±0.40)mmol/L, P＝0.03] when compared with the patients with normal uric acid level from group A. Conclusion Besides blood lipid, uric acid level is closely related with the carotid atherosclerosis in postmenopausal women.

Abstract:Objective To investigate the clinical features of the first-onset depression in elderly patients by comparing the clinical manifestations and treatment outcomes in the young patients. Methods Sixty elderly patients with first-onset depression who met the CCMD-3 criteria in our department from January to December 2010 were enrolled in the study. Sixty sex and education-level matched young patients with first-onset depression were selected as controlled subjects. A self-made questionnaire was used to analyze the triggers of depression and collect the related data. Selective serotonin reuptake inhabitors (SSRIs) were used to treat depression in both groups for 8 weeks. Hamilton Depression Rating Scale (HAMD) and Hamilton Anxiety Scale (HAMA) were employed to evaluate the depressive and related symptoms in 1, 2, 4, and 8 weeks after the treatment. Results The most common initial symptom was physical complaints in the elderly with first-onset depression. The HAMD total score, anxiety/somatization scores in the elderly were significantly higher than those in younger patients. But the scores of sleep disorders, weight loss and diurnal variation was lower in these elderly than in the control group. HAMA total score and body factors were significantly higher in the elderly patients than the control group. After 8 weeks treatment of SSRIs, the cure rate was 51.7% for the elderly patients, which was significantly lower than that of the control group (91.7%, P＜0.01). Conclusion The most common initial symptoms of the elderly depression are physical complaints. Symptoms such as anxiety, hypochondria, memory loss and physical complaints are more common in the elderly than in the young. But the biological symptoms, such as heavy body weight at morning and light at night are less common in the elderly. The efficacy of SSRIs in the elderly is not as good as for the young depression.

Abstract:Objective To explore the changes and significance of lymphocyte subsets (CD3+, CD4+, CD8+ and CD19+ cells) and natural killer (NK) cells in type 2 diabetes mellitus (T2DM) patients with obstructive sleep apnea syndrome (OSAS). Methods Fifty patients with identified T2DM according to the WHO criteria for diagnosis of T2DM admitted to our hospital from June 2011 to June 2012 was enrolled in this study. Then, they were divided into T2DM group (n＝30) and T2DM+OSAS group (n＝20) according to the diagnosis and treatment guidelines of OSAS published in the Chinese Journal of Tuberculosis and Respiratory Disease in 2002. Another 25 healthy subjects without OSAS or T2DM, and 25 OSAS patients hospitalized in the same period were included as healthy control group and OSAS group, respectively. Minimal model of homeostasis was used to represent insulin resistance (HOMA-IR). Lymphocyte subsets in the peripheral blood and insulin levels in all four groups were detected by flow cytometry and radioimmunity. Multiple regression analysis was carried out to study the correlation of the percentages of lymphocyte subsets and NK cells with the apnea/hypopnea index (AHI), body mass index (BMI), fasting blood glucose (FBG), fasting insulin (FINS), and HOMA-IR. Results The patients of T2DM+OSAS group had significantly higher BMI, lower oxygen saturation (SpO2), and high incidence of cardio-cerebrovascular complications than those from normal control (P＜0.01). AHI, FBG, FINS and HOMA-IR were significantly higher, while the lowest SpO2 during the night was significantly lower in the OSAS, T2DM and T2DM+OSAS groups than in normal control (P＜0.05, P＜0.01). The percentages of CD3+, CD4+, CD19+ lymphocytes, NK cells and the ratio of CD4+/CD8+ were significantly lower in the above 3 groups than in normal control (P＜0.05), but there was no significant difference in the percentage of CD8+ cells(P＞0.05). Linear correlation analysis showed that the AHI was positively correlated with FINS and HOMA-IR. Multiple regression analysis indicated that there was significant correlation of HOMA-IR, ANH and FBG with the percentages of CD4+ T cells and NK cells. Conclusion Abnormal immunoregulation is involved in the incidence and development of T2DM and OSAS. Rational immunoregulatory therapy might be a new approach for T2DM patients with OSAS.

Abstract:Objective To determine the effect of allitridum on the ultra rapid delayed rectifier potassium current (IKUr) in single rabbit atrial cardiomyocyte, and investigate the mechanism of its anti-atrial arrhythmia. Methods The dual enzymatic method was used to separate single rabbit atrial cardiomyocyte. The drug was applied via extracellular supserfusion, and current was evoked and recorded using Axon MultiClamp 700B amplifier. Results Allitridum at 200μmol/L exerted obvious inhibitory effect on IKUr in normal rabbit atrial cardiomyocyte, and decreased the peak value from (14.5±3.2) to (7.9±1.2)pA/pF (P＜0.01, n＝15). Allitridum also resulted in a decrease in current-voltage curve, and the effect became more significant with the increase of depolarization potential, in a voltage-dependent manner. Allitridum also showed the inhibitory effect on IKUr in a dose-dependent manner, with its IC50 value of 149.6μmol/L. Allitridum caused a significant positive shift of the steady-state activation curve of IKUr, and then delayed the activation, while a markedly negative shift of the steady-state inactivation of IKUr, and so accelerated the inactivation. Furthermore, the drug markedly lengthened the time constants for IKUr recovery from inactivation, and decelerated the re-inactivation after inactivation. It decreased the channel open at many links, and reduced current density. Conclusion Allitridum derived from Chinese herb, garlic bulb, potently blocks IKUr, which might be the underlying cellular electrophysiological mechanism of its therapeutic effect on atrial arrhythmia.

Abstract:Objective Aging heart shows significantly reduced tolerance to myocardial ischemia/reperfusion (I/R) injury, so senescent heart is prone to be damaged by the injury. This study was designed to investigate the protective effect of acetaldehyde dehydrogenase 2 (ALDH2) agonist Alda-1 in aging rats after myocardial I/R injury. Methods A total of 40 aging male Sprague Dawley (SD) rats (at an age of 20 to 22 months) were randomized into I/R group (I/R) and Alda-1 group (I/R＋Alda). Another 40 adult rats at an age of 3 to 4 months served as adult control. Rat acute myocardial I/R model was established by ligation of left anterior descending artery for 30min followed by reperfusion for 4h. Alda-1(16mg/kg) and normal saline at the same volume were intravenously infused at a flow rate of 2ml/(kg·h) into the left ventricle of corresponding rats in 5min before reperfusion. The left ventricular pressure was monitored at the same time. At the end of 4 hours reperfusion, ALDH2 activity, reactive oxygen species (ROS) production, and protein carbonylation in the myocardial tissue were measured. Serum level of lactate dehydrogenase (LDH) was tested. Results A significant decrease in ALDH2 activity was observed in the aging hearts, but this effect was blocked by Alda-1. Compared with the adult hearts, myocardial I/R injury was significantly aggravated in aging hearts, which were evidenced by reduced±LVdP/dtmax and increased serum level of LDH (P＜0.05). ALDH2 activator infusion during reperfusion effectively suppressed the above mentioned ischemic injury in the aging hearts (P＜0.05). Furthermore, protein carbonylation and ROS production in the myocardium were increased in the aging hearts compared with the adult hearts (P＜0.05), which was attenuated by Alda-1 treatment. Conclusion Activating myocardial ALDH2 significantly improves the resistance ability to myocardial I/R injury in aging heart. ALDH2-induced cardiac protection may be through suppressing myocardial I/R-induced protein oxidative damage.

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Abstract:With the poplation aging, the prevalence of senile osteoporosis is gradually increased all over the world. Its main consequence, osteoporotic fractures, exerts greatly impact on individuals, families and society. High-risk populations for osteoporosis could be preliminarily screened out by using International Osteoporosis Foundation (IOF) one minute questionnaire of osteoporosis and osteoporosis self-assessment tool for Asia (OSTA) osteoporosis. The diagnosis of osteoporosis is based on a history of fragility fracture or results of bone mineral density determined by Dual energy X-ray absorptometry (DXA), and also need exclude secondary osteoporosis. Treatments include lifestyle adjustment, bone health supplements, and anti-osteoporosis medications. This article also compare the efficacy, safety and convenience of anti-osteoporosis drugs, and introduce new anti-osteoporosis drugs.