Statins and risks of dementia among patients with heart failure: a population-based retrospective cohort study in Hong Kong.

Background: Heart failure (HF) and dementia frequently co-exist with shared pathological mechanisms and risk factors. Our study aims to investigate the association between statin therapy and the risks of dementia and its subtypes among patients with HF. Methods: The Hong Kong Clinical Data Analysis and Reporting System database was interrogated to identify patients with incident HF diagnosis from 2004 to 2018, using ICD 9/ICD 10 codes. Inverse probability of treatment weighting (IPTW) was used to balance baseline covariates between statin users (N = 54,004) and non-users (N = 50,291). The primary outcomes were incident all-cause dementia, including subtypes of Alzheimer's disease, vascular dementia, and unspecified dementia. Cox proportional-hazard model with competing risk regression was performed to estimate the sub-distribution hazards ratio (SHR) with corresponding 95% confidence intervals (CI) of the risks of all-cause dementia and its subtypes that are associated with statin use. Findings: Of all eligible patients with HF (N = 104,295), the mean age was 74.2 ± 13.6 years old and 52,511 (50.3%) were male. Over a median follow-up of 9.9 years (interquartile range [IQR]: 6.4-13.0), 10,031 (9.6%) patients were diagnosed with dementia, among which Alzheimer's disease (N = 2250), vascular dementia (N = 1831), and unspecified dementia (N = 5950) were quantified separately. After IPTW, statin use was associated with a 20% lower risk of incident dementia compared with non-use (multivariable-adjusted SHR 0.80, 95% CI 0.76-0.84). Stratified by subtypes of dementia, statin use was associated with a 28% lower risk of Alzheimer's disease (SHR 0.72, 95% CI 0.63-0.82), 18% lower risk of vascular dementia (SHR 0.82, 95% CI 0.70-0.95), and a 20% lower risk of unspecified dementia (SHR 0.80, 95% CI 0.75-0.85). Interpretation: In patients with HF, statin use was associated with a significantly lower risk of all-cause dementia and its subtypes, including Alzheimer's disease, vascular dementia, and unspecified dementia. Both randomized trials and experimental studies to validate the potential neuroprotective effect of statin are warranted. Funding: No funding was provided for this study.

Statin Therapy Is Associated With a Lower Risk of Heart Failure in Patients With Atrial Fibrillation: A Population-Based Study.

BACKGROUND: Whether statin use can reduce the risk of heart failure (HF) remains controversial. The present study evaluates the association between statin use and HF in patients with atrial fibrillation. METHODS AND RESULTS: Patients with newly diagnosed atrial fibrillation from 2010 to 2018 were included. An inverse probability of treatment weighting was used to balance baseline covariates between statin users (n=23 239) and statin nonusers (n=29 251). The primary outcome was incident HF. Cox proportional hazard models with competing risk regression were used to evaluate the risk of HF between statin users and nonusers. The median age of the cohort was 74.7 years, and 47.3% were women. Over a median follow-up of 5.1 years, incident HF occurred in 3673 (15.8%) statin users and 5595 (19.1%) statin nonusers. Statin use was associated with a 19% lower risk of HF (adjusted subdistribution hazard ratio, 0.81 [95% CI, 0.78-0.85]). Restricted to the statin users, duration of statin use was measured during follow-up; compared with short-term use (3 months to <2 years), there was a stepwise reduction in the risk of incident HF among those with 2 to <4 years of statin use (subdistribution hazard ratio, 0.86 [95% CI, 0.84-0.88]), 4 to <6 years of statin use (subdistribution hazard ratio, 0.74 [95% CI, 0.72-0.76]), and ≥6 years of statin use (subdistribution hazard ratio, 0.71 [95% CI, 0.69-0.74]). Subgroup analysis showed consistent reductions in the risk of HF with statin use. CONCLUSIONS: Statin use was associated with a decreased risk of incident HF in a duration-dependent manner among patients with atrial fibrillation.

Morphological and functional types of tricuspid regurgitation: prognostic value in patients undergoing tricuspid annuloplasty during left-sided valvular surgery.

BACKGROUND: The nonuniform benefit of tricuspid annuloplasty may be explained by the proportionality of tricuspid regurgitation (TR) severity to right ventricular (RV) area. The purpose of this study was to delineate distinct morphological phenotypes of functional TR and investigate their prognostic implications in patients undergoing tricuspid annuloplasty during left-sided valvular surgery. METHODS: The ratios of pre-procedural effective regurgitant orifice area (EROA) with right ventricular end-diastolic area (RVDA) were retrospectively assessed in 290 patients undergoing tricuspid annuloplasty. Based on optimal thresholds derived from penalized splines and maximally selected rank statistics, patients were stratified into proportionate (EROA/RVDA ratio ≤ 1.74) and disproportionate TR (EROA/RVDA ratio > 1.74). RESULTS: Overall, 59 (20%) and 231 (80%) patients had proportionate and disproportionate TR, respectively. Compared to those with proportionate TR, patients with disproportionate TR were older, had a higher prevalence of atrial fibrillation, lower pulmonary pressures, more impaired RV function, and larger tricuspid leaflet tenting area. Over a median follow-up of 4.1 years, 79 adverse events (47 heart failure hospitalizations and 32 deaths) occurred. Patients with disproportionate TR had higher rates of adverse events than those with proportionate TR (32% vs 10%; P = 0.001) and were independently associated with poor outcomes on multivariate analysis. TR proportionality outperformed guideline-based classification of TR severity in outcome prediction and provided incremental prognostic value to both the EuroSCORE II and STS score (incremental χ2 = 6.757 and 9.094 respectively; both P < 0.05). CONCLUSIONS: Disproportionate TR is strongly associated with adverse prognosis and may aid patient selection and risk stratification for tricuspid annuloplasty with left-sided valvular surgery.

Incidence, Clinical Correlates, and Prognostic Impact of Dementia in Heart Failure: A Population-Based Cohort Study.

Background: Heart failure (HF) may increase the risk of dementia via shared risk factors. Objectives: The authors investigated the incidence, types, clinical correlates, and prognostic impact of dementia in a population-based cohort of patients with index HF. Methods: The previously territory-wide database was interrogated to identify eligible patients with HF (N = 202,121) from 1995 to 2018. Clinical correlates of incident dementia and their associations with all-cause mortality were assessed using multivariable Cox/competing risk regression models where appropriate. Results: Among a total cohort aged ≥18 years with HF (mean age 75.3 ± 13.0 years, 51.3% women, median follow-up 4.1 [IQR: 1.2-10.2] years), new-onset dementia occurred in 22,145 (11.0%), with age-standardized incidence rate of 1,297 (95% CI: 1,276-1,318) per 10,000 in women and 744 (723-765) per 10,000 in men. Types of dementia were Alzheimer's disease (26.8%), vascular dementia (18.1%), and unspecified dementia (55.1%). Independent predictors of dementia included: older age (≥75 years, subdistribution hazard ratio [SHR]: 2.22), female sex (SHR: 1.31), Parkinson's disease (SHR: 1.28), peripheral vascular disease (SHR: 1.46), stroke (SHR: 1.24), anemia (SHR: 1.11), and hypertension (SHR: 1.21). The population attributable risk was highest for age ≥75 years (17.4%) and female sex (10.2%). New-onset dementia was independently associated with increased risk of all-cause mortality (adjusted SHR: 4.51; P < 0.001). Conclusions: New-onset dementia affected more than 1 in 10 patients with index HF over the follow-up, and portended a worse prognosis in these patients. Older women were at highest risk and should be targeted for screening and preventive strategies.

Prediabetes Is Associated With Increased Risk of Heart Failure Among Patients With Atrial Fibrillation.

OBJECTIVE: To evaluate the association between prediabetes and heart failure (HF) and the association of HF with changes in glycemic status. RESEARCH DESIGN AND METHODS: Patients newly diagnosed with atrial fibrillation (AF) between 2015 and 2018 were divided into three groups (normoglycemia, prediabetes, and type 2 diabetes) according to their baseline glycemic status. The primary outcome was incident HF. The Fine and Gray competing risks model was applied, with death defined as the competing event. RESULTS: Among 17,943 patients with AF (mean age 75.5 years, 47% female), 3,711 (20.7%) had prediabetes, and 10,127 (56.4%) had diabetes at baseline. Over a median follow-up of 4.7 years, HF developed in 518 (14%) patients with normoglycemia, 646 (15.7%) with prediabetes, and 1,795 (17.7%) with diabetes. Prediabetes was associated with an increased risk of HF compared with normoglycemia (subdistribution hazard ratio [SHR] 1.12, 95% CI 1.03-1.22). In patients with prediabetes at baseline, 403 (11.1%) progressed to diabetes, and 311 (8.6%) reversed to normoglycemia at 2 years. Compared with remaining prediabetic, progression to diabetes was associated with an increased risk of HF (SHR 1.50, 95% CI 1.13-1.97), whereas reversion to normoglycemia was associated with a decreased risk (SHR 0.61, 95% CI 0.42-0.94). CONCLUSIONS: Prediabetes was associated with an increased risk of HF in patients with AF. Compared with patients who remained prediabetic, those who progressed to diabetes at 2 years experienced an increased risk of HF, whereas those who reversed to normoglycemia incurred a lower risk of HF.

Chronic kidney disease begets heart failure and vice versa: temporal associations between heart failure events in relation to incident chronic kidney disease in type 2 diabetes.

AIM: To investigate the interplay of incident chronic kidney disease (CKD) and/or heart failure (HF) and their associations with prognosis in a large, population-based cohort with type 2 diabetes (T2DM). METHODS: Patients aged ≥18 years with new-onset T2DM, without renal disease or HF at baseline, were identified from the territory-wide Clinical Data Analysis Reporting System between 2000 and 2015. Patients were followed up until December 31, 2020 for incident CKD and/or HF and all-cause mortality. RESULTS: Among 102 488 patients (median age 66 years, 45.7% women, median follow-up 7.5 years), new-onset CKD occurred in 14 798 patients (14.4%), in whom 21.7% had HF. In contrast, among 9258 patients (9.0%) with new-onset HF, 34.6% had CKD. The median time from baseline to incident CKD or HF (4.4 vs. 4.1 years) did not differ. However, the median (interquartile range) time until incident HF after CKD diagnosis was 1.7 (0.5-3.6) years and was 1.2 (0.2-3.4) years for incident CKD after HF diagnosis (P < 0.001). The crude incidence of CKD was higher than that of HF: 17.6 (95% confidence interval [CI] 17.3-17.9) vs. 10.6 (95% CI 10.4-10.9)/1000 person-years, respectively, but incident HF was associated with a higher adjusted-mortality than incident CKD. The presence of either condition (vs. CKD/HF-free status) was associated with a three-fold hazard of death, whereas concomitant HF and CKD conferred a six to seven-fold adjusted hazard of mortality. CONCLUSION: Cardiorenal complications are common and are associated with high mortality risk among patients with new-onset T2DM. Close surveillance of these dual complications is crucial to reduce the burden of disease.

A historical cohort study of glycemic control in patients with concurrent type 2 diabetes and substance use disorder treated in a primary care setting.

BACKGROUND: Substance use disorder (SUD) is a known barrier to patient-self-management, which can hinder efforts to achieve treatment goals in type 2 diabetes (T2D) when the conditions coexist. OBJECTIVE: Identify the association between SUD and glycemic control in patients with T2D treated in a primary care setting. METHODS: This retrospective cohort study included patients with T2D treated by providers at family medicine clinics at an academic medical center and its affiliated regional sites from January 2014 to October 2019. Study index date was the first A1c recorded when T2D and SUD diagnoses had both been documented in the medical record. Glycemic control, measured by hemoglobin A1c (A1c), was identified at baseline and over a 12-month follow-up period and was compared between SUD and non-SUD patients. RESULTS: Of 9568 included patients with T2D, 468 (4.9%) had a SUD diagnosis. In 237 SUD and 4334 non-SUD patients with A1c data, mean (SD) baseline A1c was 8.2% (2.5) and 7.9% (2.1), respectively (P = 0.043). A1c reduction was statistically greater in SUD patients than non-SUD patients (-0.31% versus -0.06%, respectively; P = 0.015), although the clinical significance is modest. In a multivariable linear regression analysis, follow-up A1c was lower in the SUD versus non-SUD patients (coefficient -0.184, 95% CI -0.358, -0.010; P = 0.038). CONCLUSIONS: Patients with T2D and SUD had higher baseline A1c but this difference was minimized over a 12-month follow-up period. Additional research is warranted to determine long-term glycemic control and barriers to attaining and maintaining glycemic control in patients with T2D and SUD.

Arkansas community's attitudes toward the regulation of medical cannabis and the pharmacist's involvement in Arkansas medical cannabis.

OBJECTIVES: This study explored the attitudes of the Arkansas community toward medical cannabis (MC) regulation and the role of pharmacists in dispensing MC before the product became available and examined whether participants' demographics (e.g., age, gender) and characteristics (e.g., history of cannabis use) were associated with these attitudes. DESIGN: Cross-sectional survey. SETTING AND PARTICIPANTS: Using social media, a university research registry, and posted flyers, we invited residents of Arkansas to participate in the self-administered online survey study during a 3-month period, February to April, in 2018. OUTCOME MEASURES: Five questions that inquired about participants' attitudes toward MC regulation and pharmacists' roles regarding MC use. RESULTS: Participants (n = 1343) who completed at least 1 of the 5 questions were included. The majority were aged 40-64 years (52.2%), female (69.1%), and white (88.7%). Most participants reported a history of cannabis use (81.8%) and possession or intention to apply for an MC card (52.9%). Among the conditions approved for MC use, pain (20.3%), arthritis (15.4%), and posttraumatic stress disorder (14.5%) were reported frequently. Likewise, prescription use for mood disorders (46.1%) and pain (37.4%) were also reported. In multivariable regression analyses, participants' history of cannabis use was associated with a preference for lesser oversight of MC, disagreement with MC being available through a pharmacy only, and disagreement on whether MC should be regulated before it is legalized for recreational use (all P < 0.001). It was also associated with a decrease in agreement that pharmacists are well-trained to improve patient safety (P < 0.001) and counsel patients regarding appropriate MC use (P = 0.032). CONCLUSION: Participants who had previously used cannabis were in favor of fewer restrictions and negatively perceived pharmacists' involvement in ensuring appropriate dispensing and MC use. The findings may highlight the need for Arkansas pharmacists to explore alternative ways to promote the safe and proper MC use.

Loss of Sigma-1 Receptor Chaperone Promotes Astrocytosis and Enhances the Nrf2 Antioxidant Defense.

Sigma-1 receptor (Sig-1R) functions as a chaperon that interacts with multiple proteins and lipids and is implicated in neurodegenerative and psychiatric diseases. Here, we used Sig-1R KO mice to examine brain expression profiles of astrocytes and ubiquitinated proteins, which are both hallmarks of central nervous system (CNS) pathologies. Our results showed that Sig-1R KO induces increased glial fibrillary acidic protein (GFAP) expression in primary neuron-glia cultures and in the whole brain of fetus mice with concomitantly increased accumulations of ubiquitinated proteins. Astrogliosis was also observed in the neuron-glia culture. Upon proteasome or autophagy inhibitor treatments, the pronounced ubiquitinated proteins were further increased in Sig-1R KO neurons, indicating that the Sig-1R regulates both protein degradation and quality control systems. We found that Nrf2 (nuclear factor erythroid 2-related factor 2), which functions to overcome the stress condition, was enhanced in the Sig-1R KO systems especially when cells were under stressful conditions. Mutation or deficiency of Sig-1Rs has been observed in neurodegenerative models. Our study identifies the critical roles of Sig-1R in CNS homeostasis and supports the idea that functional complementation pathways are triggered in the Sig-1R KO pathology.