Impact of renal function variability on long-term prognosis in ischemic stroke patients with atrial fibrillation.

Background: Although renal dysfunction is associated with adverse clinical outcomes in patients with atrial fibrillation (AF) following stroke, the impact of renal function variability is unclear. Aim: This study aimed to assess the association between renal function variability and various adverse clinical outcomes in patients with transient ischemic attack (TIA)/ischemic stroke and atrial fibrillation (AF). Methods: We conducted a population-based study and retrospectively identified patients hospitalized with a diagnosis of TIA/ischemic stroke and AF during 2016-2020 using the Clinical Data Analysis and Reporting System of Hong Kong. Serial serum creatinine tested upon the onset of TIA/ischemic stroke and during their subsequent follow-up was collected. Renal function variability was calculated using the coefficient of variation of the estimated glomerular filtration rate (eGFR). Clinical endpoints that occurred during the study period were captured and included ischemic stroke/systemic embolism, intracerebral hemorrhage (ICH), total bleeding, major adverse cardiovascular events (MACE), cardiovascular, non-cardiovascular, and all-cause mortality. Competing risk regression and Cox proportional hazard regression models were used to assess the associations of renal function variability with the outcomes of interest. Results: A total of 3,809 patients (mean age 80 ± 10 years, 43% men) who satisfied the inclusion and exclusion criteria were followed up for a mean of 2.5 ± 1.5 years (9,523 patient-years). The mean eGFR was 66 ± 22 mL/min/1.73 m2 at baseline, and the median number of renal function tests per patient during the follow-up period was 20 (interquartile range 11-35). After accounting for potential confounders, a greater eGFR variability was associated with increased risks of recurrent ischemic stroke/systemic embolism [fully adjusted subdistribution hazard ratio 1.11, 95% confidence interval (CI) 1.03-1.20], ICH (1.17, 1.01-1.36), total bleeding (1.13, 1.06-1.21), MACE (1.22, 1.15-1.30), cardiovascular (1.49, 1.32-1.69), non-cardiovascular (1.43, 1.35-1.52), and all-cause mortality (fully adjusted hazard ratio 1.44, 1.39-1.50). Conclusion: Visit-to-visit renal function variability is independently associated with adverse clinical outcomes in TIA/ischemic stroke patients with AF. Further large-scale studies are needed to validate our results.

Sex Differences in Association Between Gut Microbiome and Essential Hypertension Based on Ambulatory Blood Pressure Monitoring.

BACKGROUND: Sex differences in the pathogenesis of hypertension exist. While gut microbiota (GM) has been associated with hypertension, it is unclear whether there are sex-linked differences in the association between GM and hypertension. METHODS: We conducted a cross-sectional study to investigate the sex differences in associations between GM characterized by shotgun sequencing, GM-derived short-chain fatty acids, and 24-hour ambulatory blood pressure in 241 Hong Kong Chinese (113 men and 128 women; mean age, 54±6 years). RESULTS: The hypertensive group was associated with GM alterations; however, significant differences in ß-diversity and GM composition in hypertensive versus normotensive groups were only observed in women and not in men under various statistical models adjusting for the following covariates: age, sex, body mass index, sodium intake estimated by spot urine analysis, blood glucose, triglycerides, low- and high-density lipoprotein cholesterol, smoking, menopause, and fatty liver status. Specifically, Ruminococcus gnavus, Clostridium bolteae, and Bacteroides ovatus were significantly more abundant in the hypertensive women, whereas Dorea formicigenerans was more abundant in the normotensive women. No bacterial species were found to be significantly associated with hypertension in men. Furthermore, total plasma short-chain fatty acids and propionic acid were independent predictors of systolic and diastolic blood pressure in women but not men. CONCLUSIONS: GM dysregulation was strongly associated with 24-hour ambulatory blood pressure in women but not men, which may be mediated through propionic acid. Our work suggests that sex differences may be an important consideration while assessing the role of GM in the development and treatment of hypertension.

Delays in Stroke Onset to Hospital Arrival Time During COVID-19.

BACKGROUND AND PURPOSE: The current coronavirus disease 2019 (COVID-19) pandemic represents a global public health crisis, disrupting emergency healthcare services. We determined whether COVID-19 has resulted in delays in stroke presentation and affected the delivery of acute stroke services in a comprehensive stroke center in Hong Kong. METHODS: We retrospectively reviewed all patients with transient ischemic attack and stroke admitted via the acute stroke pathway of Queen Mary Hospital, Hong Kong, during the first 60 days since the first diagnosed COVID-19 case in Hong Kong (COVID-19: January 23, 2020-March 24, 2020). We compared the stroke onset to hospital arrival (onset-to-door) time and timings of inpatient stroke pathways with patients admitted during the same period in 2019 (pre-COVID-19: January 23, 2019-March 24, 2019). RESULTS: Seventy-three patients in COVID-19 were compared with 89 patients in pre-COVID-19. There were no significant differences in age, sex, vascular risk factors, nor stroke severity between the 2 groups (P>0.05). The median stroke onset-to-door time was ≈1-hour longer in COVID-19 compared with pre-COVID-19 (154 versus 95 minutes, P=0.12), and the proportion of individuals with onset-to-door time within 4.5 hours was significantly lower (55% versus 72%, P=0.024). Significantly fewer cases of transient ischemic attack presented to the hospital during COVID-19 (4% versus 16%, P=0.016), despite no increase in referrals to the transient ischemic attack clinic. Inpatient stroke pathways and treatment time metrics nevertheless did not differ between the 2 groups (P>0.05 for all comparisons). CONCLUSIONS: During the early containment phase of COVID-19, we noted a prolongation in stroke onset to hospital arrival time and a significant reduction in individuals arriving at the hospital within 4.5 hours and presenting with transient ischemic attack. Public education about stroke should continue to be reinforced during the COVID-19 pandemic.

Sex differences in epidemiology and risk factors of acute coronary syndrome in Chinese patients with type 2 diabetes: a long-term prospective cohort study.

OBJECTIVE: Diabetic patients with acute coronary syndrome (ACS) are at higher risk of poor outcome than are non-diabetic patients with ACS. Few studies have focused on sex-related ACS incidence, ACS-related mortality or risk factors to affects sex specific ACS in Chinese with Type 2 diabetes mellitus (T2DM). Based on a hospital-based cohort of Chinese patients with T2DM, we aimed to investigate whether there was sex difference in ACS or ACS-related mortality or risk factors of ACS. METHODS: Totally 2,135 Hong Kong Chinese with T2DM were recruited during 1994-1996 and followed up until August 2012. We systematically analyzed sex-related ACS incidence and ACS-related mortality and risk factors with χ2-squared test, descriptive statistics and survival analysis. RESULTS: Regular follow-up was completed in 2,105 subjects (98.6%), with a median period of 14.53 years. The occurrence of ACS was recorded among 414 patients (19.7%) and ACS-related death among 104 patients (4.9%). ACS incidences increased with age in both men and women, and men had a higher prevalence of ACS than women across different age categories and different follow-up periods (log rank χ2=20.32, P<0.001). The transition of ACS incidences from slow to rapid increase were about 5 years earlier in men (at 51-55 years) than in women (55-60 years). Among ACS patients, cumulative ACS-related mortalities was similar between men and women (log rank χ2=0.063, P=0.802). Besides age and albuminuria, different profiles of risk factors accounted for the occurrence of ACS between men and women. CONCLUSIONS: Our findings demonstrated sex differences in ACS incidence and risk factors, but not in ACS-related mortality in Chinese patients withT2DM. These findings suggest that screening and prevention campaigns should be optimized for men and women, which may help to identify diabetic patients at higher risk of coronary heart disease.

Long-term risk of cardiovascular disease among type 2 diabetic patients with asymptomatic intracranial atherosclerosis: a prospective cohort study.

OBJECTIVE: To investigate whether asymptomatic middle cerebral artery (MCA) stenosis is associated with risk of cardiovascular disease (CVD) in Chinese with type 2 diabetes. METHODS: In this prospective cohort study, 2,144 Hong Kong Chinese with type 2 diabetes and without history of stroke or atrial fibrillation were recruited in 1994-1996 and followed up for a median of 14.51 years. Participants were assessed at baseline for MCA stenosis using transcranial Doppler. We performed survival analysis to assess the association between asymptomatic MCA stenosis and first CVD event, defined as ischemic stroke, acute coronary syndrome (ACS) or cardiovascular death. RESULTS: Of the 2,144 subjects, MCA stenosis at baseline was detected in 264 (12.3%). Rates of stroke, ACS and cardiovascular death per 100 were, respectively, 2.24, 2.92 and 1.11 among participants with stenosis, higher than among those without stenosis. Ten-year cumulative occurrence of stroke, ACS and cardiovascular death in subjects with MCA stenosis was 20%, 24% and 10%, respectively, higher than the corresponding values for subjects without stenosis(all P<0.001). After adjusting for covariates, MCA stenosis was found to be an independent predictor of stroke [hazard ratio (HR) 1.40, 95%CI 1.05-1.86; P = 0.02], ACS (HR 1.35, 95%CI 1.04-1.75; P = 0.02) and cardiovascular death(HR 1.56, 95%CI 1.04-2.33; P = 0.03). CONCLUSIONS: Asymptomatic MCA stenosis is a risk factor for CVD in Chinese with type 2 diabetes, and detection of asymptomatic MCA stenosis by transcranial Doppler can identify diabetic individuals at high risk of future CVD. This finding is particularly important for diabetic individuals in Asia, where intracranial atherosclerosis is common.

Statins for asymptomatic middle cerebral artery stenosis: The Regression of Cerebral Artery Stenosis study.

BACKGROUND: The progression of cerebral atherosclerosis increases the risk of stroke and vascular events. Given the known benefits of statins in retarding coronary and carotid atherosclerosis progression, we studied the effects of statins on asymptomatic middle cerebral artery (MCA) stenosis progression. METHODS: We conducted a randomized, double-blind, placebo-controlled study to evaluate the effects of simvastatin on the progression of MCA stenosis among stroke-free individuals who had mild to moderately elevated LDL cholesterol (3.0-5.0 mmol/l). Two hundred and twenty-seven subjects were randomized to either placebo (n = 114) or simvastatin 20 mg daily (n = 113). The severity of MCA stenosis at baseline and at the end of the study was graded by MRA into normal, minimal (<10%), mild (10-49%), moderate (50-90%) and severe (>90%). The primary outcome was the change in grading of MCA stenosis over 2 years. RESULTS: At the end of the study, the LDL cholesterol level decreased by 1.43 and 0.12 mmol/l for the active and placebo groups, respectively (p < 0.001). There was no significant difference in the proportion of patients having stable, progressive and regressive MCA stenosis between the placebo (72, 22 and 6%) and active groups (78.6, 15.5 and 5.8%). The all-cause mortality was significantly lower in the active group (n = 0) relative to the placebo group (n = 7, p = 0.014). Any clinical events were also lower in the active group (n = 5) than in the placebo group (n = 13, p = 0.052). CONCLUSIONS: Simvastatin 20 mg daily had no apparent effect upon the evolution of asymptomatic MCA stenosis over 2 years.

Middle cerebral artery stenosis increased the risk of vascular disease mortality among type 2 diabetic patients.

BACKGROUND: In Chinese populations, middle cerebral artery (MCA) stenosis is the most commonly identified intracranial vascular lesion, and has been shown to be associated with an increased risk of secondary stroke mortality, but has yet to be reported for primary events. We assess whether asymptomatic MCA stenosis is associated with mortality in Chinese type 2 diabetic patients. METHODS: The presence of MCA stenosis was determined by transcranial Doppler and mortality data were collated in the Hong Kong Death Registry. Cox proportional hazards regression was used to determine if the MCA stenosis (n = 272, 53.7% 2-vessel disease) in 2,197 diabetics was associated with all-cause or vascular disease mortality, including after adjustment for conventional vascular risk factors. Anthropometric and fasting biochemical parameters were compared between diabetic patients with MCA stenosis and without evidence of stenosis. RESULTS: A total of 191 deaths were identified (30.9% of vascular disease origin) during a follow-up of 18,279 patient years over 8.32 years. After adjustment for age, gender and diabetes duration, the hazard ratios for vascular mortality for 1- and 2-vessel disease were 2.47 (95% CI = 1.13-5.38) and 4.47 (95% CI = 2.24-8.82), p < 0.001 for trend, for increasing vascular mortality with increasing severity of cerebrovascular involvement, but 0.81 (95% CI = 0.45-1.47) and 2.23 (95% CI = 1.45-1.47), p = 0.001 for trend, for all-cause mortality. For vascular mortality, further adjustments for anthropometric and fasting biochemical parameters, or existing disease and treatment history increased the hazard ratios for 1-vessel disease slightly but attenuated the risk for 2-vessel disease evidently, 2.81 (95% CI = 1.10-7.16) and 2.85 (95% = CI 1.11-7.33), p = 0.026. CONCLUSION: The presence of MCA stenoses was an independent predictor of vascular mortality in these diabetics. More aggressive treatment of risk factors in these subjects merits further evaluation.

Increasing severity of cardiovascular risk factors with increasing middle cerebral artery stenotic involvement in type 2 diabetic Chinese patients with asymptomatic cerebrovascular disease.

OBJECTIVE: To identify determinants associated with increasing severity of middle cerebral artery (MCA) stenosis in asymptomatic Chinese type 2 diabetic patients with and without MCA stenosis determined using transcranial Doppler. Conventional risk factors contribute to the pathogenesis of ischemic stroke, and differences in the pattern of these may explain the heterogeneity of disease presentation in different populations. In Chinese patients, MCA stenosis is the most commonly identified intracranial vascular lesion. RESEARCH DESIGN AND METHODS: Anthropometric and fasting biochemical parameters were compared between type 2 diabetic patients with MCA stenosis in one (n = 185) or both (n = 200) vessels and 1,492 type 2 diabetic patients without evidence of stenosis. RESULTS: Increasing MCA stenotic vascular involvement was associated with significantly increasing age, duration of diabetes, systolic blood pressure, and LDL cholesterol, but with lower glucose levels. There was also an increased prevalence of hypertension, dyslipidemia, and use of blood pressure-and glucose-lowering agents in the patients with MCA stenosis. Concomitant significant increases in the prevalence of peripheral vascular disease and retinopathy were also observed in the patients with MCA stenosis. CONCLUSIONS: Transcranial Doppler examination identified stenosis in one or both MCAs in over one-fifth of the Chinese type 2 diabetic subjects without symptoms of cerebrovascular disease. A number of conventional cardiovascular risk factors were closely associated with MCA stenosis. This technique may allow the identification of a particularly high-risk group, and further studies are required to determine whether asymptomatic MCA stenosis is predictive of primary cerebrovascular events and whether intensive treatment of risk factors would reduce the risk.