Hongwei Ji

Northern Shanghai Study: cardiovascular risk and its associated factors in the Chinese elderly—a study protocol of a prospective study design

Introduction Cardiovascular (CV) diseases are the leading cause of death and disability in the world. Increasing lifespans and ageing populations also contribute to an increasing CV burden. However, in China, there were few well-designed cohort studies focusing on the elderly population, let alone an established CV risk score. The objective of this study is to establish a CV risk score based on a community-dwelling Chinese elderly population, determining the profile of the associated CV risk factors and target organ damages (TODs), so as to guide the later intervention. Methods and analysis The Northern Shanghai Study is an ongoing prospective community-based study. After enrolment, clinical examination, anthropometric measurement and a questionnaire will be administered to each participant at baseline and after every 2 years in the follow-up. Our tests and examinations include: blood/urine sample and biochemical measurements, office blood pressure recording, carotid ultrasonograph, echocardiograph, pulse wave velocity, pulse wave analysis, 4-limb blood pressure recording, body mass index, etc. Baseline measurement will also include the assessments on TODs and the conventional CV risk factors. In the follow-up, the incidence of CV events and mortality will be recorded. The Northern Shanghai Risk Score will be calculated, with considerations on CV risk factors and TODs. Ethics and dissemination This study was approved by the Shanghai Tenth Peoples Hospital Institutional Review Board. All participants signed a written consent form. Trial registration number NCT02368938; Pre-results.

Comparison of Carotid‐Femoral and Brachial‐Ankle Pulse‐Wave Velocity in Association With Target Organ Damage in the Community‐Dwelling Elderly Chinese: The Northern Shanghai Study

Background Carotid‐femoral pulse‐wave velocity (cf‐PWV) and brachial‐ankle PWV (ba‐PWV) are the 2 most frequently applied PWV measurements. However, little is known about the comparison of hypertensive target organ damage (TOD) with cf‐PWV and ba‐PWV. Methods and Results A total of 1599 community‐dwelling elderly subjects (age >65 years) in northern Shanghai were recruited from June 2014 to August 2015. Both cf‐PWV and ba‐PWV were measured using SphygmoCor and VP1000 systems, respectively. Within the framework of comprehensive cardiovascular examinations, risk factors were assessed, and asymptomatic TOD, including left ventricular mass index, peak transmitral pulsed Doppler velocity/early diastolic tissue Doppler velocity (E/Ea), carotid intima‐media thickness, arterial plaque, creatinine clearance rate, and urinary albumin‐creatinine ratio were all evaluated. Both PWVs were significantly associated with male sex, age, waist/hip circumference, fasting plasma glucose, and systolic blood pressure, and ba‐PWV was also significantly related to body mass index. Both PWVs were significantly correlated with most TOD. When cf‐PWV and ba‐PWV were both or separately put into the stepwise linear regression model together with cardiovascular risk factors and treatment, only cf‐PWV, but not ba‐PWV, was significantly associated with carotid intima‐media thickness and creatinine clearance rate (P<0.05). When cf‐PWV and ba‐PWV were both or separately put into the same full‐mode model after adjustment for confounders, only cf‐PWV, but not ba‐PWV, showed significant association with carotid intima‐media thickness and creatinine clearance rate (P<0.05). Similar results were observed in logistic regression analysis. Conclusions Taken together, in the community‐dwelling elderly Chinese, cf‐PWV seems to be more closely associated with hypertensive TOD, especially vascular and renal TOD, as compared with ba‐PWV. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT02368938.

Measuring the Carotid to Femoral Pulse Wave Velocity (Cf-PWV) to Evaluate Arterial Stiffness

For the elderly, arterial stiffening is a good marker for aging evaluation and it is recommended that the arterial stiffness be determined noninvasively by the measurement of carotid to femoral pulse wave velocity (cf-PWV) (Class I; Level of Evidence A). In literature, numerous community-based or disease-specific studies have reported that higher cf-PWV is associated with increased cardiovascular risk. Here, we discuss strategies to evaluate arterial stiffness with cf-PWV. Following the well-defined steps detailed here, e.g., proper position operator, distance measurement, and tonometer position, we will obtain a standard cf-PWV value to evaluate arterial stiffness. In this paper, a detailed stepwise method to record a good quality PWV and pulse wave analysis (PWA) using a non-invasive tonometry-based device will be discussed.

VASCULAR AGEING AND PRECLINICAL TARGET ORGAN DAMAGE IN COMMUNITY-DWELLING ELDERLY: THE NORTHERN SHANGHAI STUDY

Objective: Vascular aging represents a mediating step between risk factors and cardiovascular (CV) events. And preclinical target organ damage (TOD) integrates the cumulative effects of CV risk factors with aging which can be detected before clinical events occur. This study is focusing on the relationships between healthy vascular aging (HVA) and preclinical TOD. Design and method: Cross-sectional data from the Northern Shanghai Study (NSS, Clinicaltrials.gov NCT02368938), prospectively recruited from June 2014 to June 2017 [n = 2098, 45.52% men, aged 71.3 ± 6.1 years]. Preclinical TODs were assessed in all the participants. Other clinical information was obtained by standard questionaire. HVA was defined as absence of hypertension and a relatively normal cf-PWV (presented per age decade and blood pressure category). We fitted logistic regression models to assess the probability of Non-HVA in association with all the preclinical TOD. Figure. No caption available. Results: In this analysis, 642 (30.6%) elderly participants had HVA, the prevalence of HVA decreased from 30.84% (aged 65–66) to 20.72% (aged over 75). Increased age, increased SBP, increased fasting glucose, increased BMI and family history of premature cardiovascular disease (CVD) were significantly associated with accelerated vascular aging (Non-HVA) (p = 0.005 to p < 0.001). After multivariate adjustments, accelerated vascular aging was associated with left ventricular diastolic dysfunction (LVDD) (OR (95%CI), 1.525 (1.171, 1.988), p = 0.003), left ventricular hypertrophy (LVH) (OR (95%CI), 1.858 (1.228, 2.811), p = 0.002) and micro-albuminuria (MAU) (OR (95%CI), 1.525 (1.171, 1.988), p = 0.002). Conclusions: Management of metabolic profile may help to prevent or delay vascular aging. And accelerated vascular aging is associated with LVH, LVDD and MAU, which provide a potential vascular target to reverse or terminate cardiac and renal TOD.

PULSE PRESSURE AMPLIFICATION AND AUGMENTATION INDEX IN ASSOCIATION WITH CARDIAC STRUCTURAL AND FUNCTIONAL DAMAGE: THE NORTHERN SHANGHAI STUDY

Objective: To investigate and compare the associations of pulse pressure amplification (PPA) and augmentation index (Aix) with asymptomatic cardiac structural and functional damage in an elderly Chinese population. Figure. No caption available. Design and method: 1940 participants (mean age of 71.6 years) were included in the present study. Central blood pressure (BP) parameters were measured by SphygmoCor device. PPA and Aix were calculated as the ratio of central and brachial pulse pressures and the ratio of augmentation pressure and aortic pulse pressure, respectively. Cardiac structural and functional parameters including left ventricular mass index (LVMI), the ratio of peak early diastolic transmitral flow velocity and early diastolic lateral mitral annular velocity (E/Ea), were evaluated using standardized methods. Results: In correlation analysis, both PPA and Aix significantly correlated with LVMI and E/Ea ratio. When PPA and Aix separately put into same multivariate full-mode linear regression models, both PPA and Aix significantly associated with LVMI (regression coefficient [&bgr;] = 4.664, per 10% increase of PPA, P < 0.001; &bgr; = 1.998, per 10% increase of Aix, P = 0.02) and E/Ea ratio (&bgr; = 0.499, per 10% increase of PPA, P < 0.01; &bgr; = 0.152, per 10% increase of Aix, P = 0.18). When PPA and Aix both put into same multivariate stepwise linear regression models, only PPA were stayed in the model. When PPA and Aix separately put into same multivariate full-mode logistic regression models, only PPA was significantly associated with left ventricular hypertrophy (Odds ratio[OR]:1.242, 95% confidence interval[CI]:1.026–1.505, per 10% increase of PPA) and dysfunction (OR: 1.407, 95%CI: 1.087–1.820, per 10% increase of PPA). When PPA and Aix both put into same multivariate stepwise logistic regression models, only PPA were stayed in the model. In all multivariate models, brachial systolic BP was included and significantly associated with cardiac damage. Conclusions: PPA showed stronger BP-independent association with cardiac structural and functional damage than Aix.

ASSOCIATION OF ASYMPTOMATIC TARGET ORGAN DAMAGES WITH SECRETED FRIZZLED RELATED PROTEIN 5 IN THE ELDERLY: THE NORTHERN SHANGHAI STUDY

Objective: Secreted frizzled related protein 5 (SFRP5) is a novel anti-inflammatory adipokine which is implicated in metabolic and cardiovascular disease (CVD). However, little is known about the relevance of SFRP5 with asymptomatic hypertensive target organ damages (TOD). We aimed to investigate the association between SFRP5 and TOD in a large population study. Figure. No caption available. Design and method: Associations between plasma SFRP5 and cardiovascular risk factors as well as TOD were investigated in 1745 participants from Northern Shanghai Study. Plasma SFRP5 level was measured by an enzyme-linked immunosorbent assay. Results: Plasma SFRP5 level was negatively associated with body mass index, waist/hip ratio and fasting blood glucose (all P < 0.001). Lower plasma SFRP5 level was observed in men than in women (4.19 vs 5.13 ng/ml, P < 0.001), in smokers than in nonsmokers (4.34 vs 4.78 ng/ml, P < 0.05). Additionally, plasma SFRP5 level was also lower in diabetes than those without diabetes (4.30 vs 4.81 ng/ml, P < 0.05). Further, an inverse association was observed between SFRP5 and pulse wave velocity as well as carotid intima-media thickness (both P < 0.05). Moreover, multivariate logistic regression analysis showed lower SFRP5 level was associated with increased arterial stiffness in the elderly (OR 0.83, 95% CI 0.71 to 0.99 per 1-SD increase, P < 0.05). Conclusions: Plasma SFRP5 level was inversely correlated with conventional cardiovascular risk factors and low plasma SFRP5 was also significantly associated with arterial stiffening in the elderly Chinese population.

COMPARISON OF ANKLE-BRACHIAL INDEX AND UPSTROKE TIME PER CARDIAC CYCLE IN ASSOCIATION WITH TARGET ORGAN DAMAGE IN ELDERLY CHINESE: THE NORTHERN SHANGHAI STUDY

Objective: Recent studies indicated that upstroke time per cardiac cycle (UTCC) in lower extremity is equivalent to ankle-brachial index (ABI) in diagnosing peripheral arterial disease and in predicting cardiovascular mortality. In the present study, we aim to compare ABI and UTCC in relation to target organ damage (TOD) Figure. No caption available. Design and method: 1841 elderly participants (mean age of 70 years) derived from the Northern Shanghai Study were included in the present study. ABI and UTCC were measured using VP-1000 device (Omron, Japan). TOD including left ventricular hypertrophy and diastolic dysfunction, carotid intima-media thickness and plaque, carotid-femoral pulse wave velocity (CF-PWV) and renal damage, were all evaluated. Results: ABI and UTCC both were significantly correlated with CF-PWV, carotid plaque and eGFR, but not with cardiac damage. Compared with ABI, UTCC showed stronger correlation with CF-PWV. When ABI and UTCC separately put into same multivariate full-mode logistic regression models, both ABI (Odds Ratio [OR]:2.273; 95% Confidence Interval [CI]:1.632–3.165) and UTCC (OR:1.627; 95%CI: 1.182–2.240) significantly associated with carotid plaque, but only UTCC significantly associated with increased CF-PWV (OR:1.664; 95%CI:1.147–2.416) and renal damage (OR:1.625; 95%CI:1.068–2.472). When ABI and UTCC both put into same multivariate stepwise logistic regression models, consistent results were observed. In ROC curve analysis, UTCC was better than ABI in discriminating increased CF-PWV (AUC:0.68 vs. 0.57; P < 0.001) and renal damage (AUC:0.67 vs. 0.60; P = 0.012). Conclusions: Compared with ABI, UTCC showed stronger association with vascular and renal damage in this elderly cohort. In combination with previous findings, UTCC may be a useful tool for diagnosing PAD and stratifying cardiovascular risk.

DETERMINANTS OF RENAL FUNCTIONAL IMPAIRMENT, THE IMPORTANCE OF FASTING PLASMA GLUCOSE CONTROL: THE NORTHERN SHANGHAI STUDY

Objective: Chronic kidney disease is a global health problem. However, the causes of renal functional impairment in the general elderly population remains unclear. The aim of this study was to investigate the determinants of renal functional impairment, within a framework of cardiovascular (CV) risk assessment in a community-dwelling elderly cohort. Design and method: From June 2014 to August 2015, a total of 912 community-dwelling elderly subjects (aged > = 65 years) from the northern Shanghai were recruited. CV risk factors were assessed, and renal function was evaluated by estimated glomerular filtration rate (e-GFR) at baseline and during 2-year follow-up. Rapid decline in e-GFR was defined as an e-GFR slope (decline in e-GFR) > 5 ml/min per 1.73 m2 per year. Results: The average decline in e-GFR was 0.104 ml/min/1.73m2 per year, while the increasing risk of having rapid decline in e-GFR was 1.25-fold every additional year. Decline in e-GFR was significantly different between diabetics and non-diabetics (p = 0.03). In full adjustment model, decline in e-GFR (p = 0.03) and rapid decline in e-GFR (OR 1.37, CI 1.07–1.75) were both significantly associated with fasting plasma glucose. Similar result of the association of rapid decline in e-GFR with fasting plasma glucose was obtained in the diabetes (full adjustment, OR 1.57, CI 1.05–2.34). Conclusions: In the community-dwelling elderly Chinese, the average decline in e-GFR was 0.104 ml/min/1.73m2 per year, and renal functional impairment was significantly associated with hyperglycemia in the old Chinese. Figure. No caption available.

COMPARISON OF ARTERIAL STIFFNESS PARAMETERS IN HYPERTENSIVE AND TYPE-2 DIABETIC PATIENTS: THE NORTHERN SHANGHAI STUDY

Objective: Both hypertension and diabetes are powerful risk factors of cardiovascular disease, however, their contribution to arterial stiffness is different. This study was designed to compare different arterial stiffness parameters among hypertensive and type-2 diabetic patients in a community-based elderly cohort. Design and method: 2,098 (aged 70.3 ± 5.6 years) participants were recruited till June 2017. All participants were divided into 4 groups: I. without hypertension and without diabetes (normal group), II. without hypertension and with diabetes (DM group), III. with hypertension and without diabetes(HTN group), and IV. with hypertension and with diabetes (DM+HTN group). Three arterial stiffness parameters were measured with validated devices, including carotid-femoral pulse wave velocity (PWV), augmentation index (AIx), and pulse pressure amplification (PPA). Results: The body mass index (BMI) was significantly lower in normal group than in the other 3 groups (P <  = 0.02). Mean age, current smoker rate, physical activity, and education level were similar among 4 groups (P> = 0.22). Spearman correlation analysis showed that arterial stiffness parameters significantly correlated with age, mean blood pressure and heart rate. Generalized linear model with Tukey adjustment was applied to pairwise compare arterial stiffness parameters. Potential confounders including age, gender, BMI, mean blood pressure, heart rate, LDL-C, and use of insulin were adjusted in the model. Compared with normal group, PWV in the other 3 groups were significantly higher (P < 0.01), and PWV in DM+HTN group was significantly higher than DM group and HTN group (P < 0.001). The AIx in DM group and in DM+HTN group were significantly lower than in normal group (P < 0.001), while AIx in HTN group and normal group were similar (P = 0.49). As for PPA, they did not differ between participants with diabetes and without diabetes (with/without hypertension, P = 0.99 and P = 0.12, respectively), while PPA in patients with hypertension were significantly higher than those without hypertension (P < 0.001). Figure. No caption available. Conclusions: In the community-based elderly cohort, PWV is associated with both DM and HTN. AIx is associated with DM but not HTN, and PPA is associated with HTN but not DM. This result may improve the cardiovascular risk assessment in the future.

HEALTHY ORGAN AGEING IS ASSOCIATED WITH LOW CVD RISK IN CHINESE ELDERLY: THE NORTHERN SHANGHAI STUDY

Objective: Aging on organ level represents the decline of organ function. And the decline of cardiovascular function is associated with the cardiovascular risk. This study is focusing on the prevalence, correlates of healthy organ aging (HOA) and the relationship between cardiovascular risk and HOA. Design and method: This analysis is nested in Northern Shanghai Study (NSS, Clinicaltrials.gov NCT02368938), participants prospectively recruited from June 2014 to June 2017 [n = 2098, 45.52% men, aged 71.3 ± 6.1 years]. To calculate the 10-year Framingham CVD risk, 847 participants aged 65–74 years of age without CVD were finally included in this analysis [40.4% of 2098, 48.76% men, aged 67.9 ± 2.8 years]. Preclinical TODs including left ventricular hypertrophy, left ventricular diastolic dysfunction, micro-albuminuria, CKD, carotid hypertrophy and lower-extremity atherosclerosis were assessed in all the participants. Other clinical information was obtained by standard questionaire. Healthy organ aging was defined as absence of any preclinical TOD. We fitted logistic regression models to assess the cardiovascular risk in association with healthy organ aging. Results: In this analysis, 104 (12.3%) elderly participants had HOA without any preclinical TOD. With the increasing number of TOD, the average 10-year CVD risk increased in both gender. The prevalence of HOA decreased from 17.48% (aged 65–66) to 6.10% (aged over 71). Age, systolic blood pressure, metabolic syndrome and smoking were significantly associated with HOA (p = 0.004 to p < 0.001). After multivariate adjustments, HOA was significantly associated with low CVD risk (<10%) (OR (95%CI), 0.409 (0.260, 0.643), p < 0.001). And the results were stable after stratifying for gender. However, after stratifying for family history of premature CVD, this significance disappeared in the subgroup with family history of premature CVD. Figure. No caption available. Conclusions: Smoking cessation, management of blood pressure and improve metabolic profile may help to delay and prevent organ aging. And HOA is beneficial in terms of the prevention of CVD.