Effects of sodium-glucose cotransporter 2 inhibitors on cardiovascular and renal outcomes in people with diabetes and advanced chronic kidney disease.

AIMS/HYPOTHESIS: Although the benefits of sodium-glucose cotransporter 2 inhibitor (SGLT2i) use in chronic kidney disease (CKD) are well established, the effects of these therapeutic agents in patients with advanced CKD are less certain. We hypothesised that the continued use of these drugs, even when renal function deteriorates to stage 4 CKD or worse, is safe and associated with improved cardiorenal survival. METHODS: This is a retrospective cohort study utilising data from medical records from two institutions. All patients with type 2 diabetes mellitus who were prescribed an SGLT2i between 1 January 2016 and 31 December 2021, who subsequently had eGFR <30 ml/min per 1.73 m2 recorded on two occasions at least 90 days apart, were identified. The date on which the eGFR first reached any level less than 30 ml/min per 1.73 m2 was defined as the index date. Individuals were then categorised into the SGLT2i continuation group or the discontinuation group according to the use of SGLT2i after the index date. Inverse probability of treatment weighting (IPTW) was performed to minimise confounding. Outcomes of interest included heart failure outcomes, cardiovascular outcomes, renal outcomes and safety outcomes. RESULTS: According to the eligibility criteria, 337 patients in the continuation group and 358 in the discontinuation group were identified. After IPTW, continuation of SGLT2i use was associated with significantly lower risks of the composite of major adverse cardiovascular events compared with discontinuation of SGLT2i use (HR 0.65 [95% CI 0.43, 0.99]), largely driven by reduced risk of myocardial infarction during follow-up (subdistribution HR [SHR] 0.43 [95% CI 0.21, 0.89]). The incidences of an eGFR decline of 50% or more (SHR 0.58 [95% CI 0.42, 0.81]) and all-cause hospital admission (SHR 0.77 [95% CI 0.64, 0.94]) were also significantly lower in the continuation group. None of the studied safety outcomes were significantly different when comparing the two groups. Blood haemoglobin levels were significantly higher in the continuation group at the end of follow-up (114.6 g/l vs 110.4 g/l, with a difference of 4.12 g/l; p=0.047). CONCLUSIONS/INTERPRETATION: In patients with CKD who were treated with an SGLT2i, continuation of SGLT2i use after eGFR declined to 30 ml/min per 1.73 m2 or less was associated with lower risks of cardiovascular and renal events compared with discontinuation of SGLT2i use. Continued use of SGLT2i throughout the course of CKD should be considered to optimise patient outcomes.

Incidence and progression of diabetic retinopathy in patients treated with glucagon-like peptide-1 receptor agonists versus sodium-glucose cotransporter 2 inhibitors: A population-based cohort study.

AIM: Glucagon-like peptide 1 receptor agonists (GLP1RA) and sodium-glucose cotransporter 2 inhibitors (SGLT2i) are both recommended for patients with diabetes, yet their effects on the development or progression of diabetic retinopathy (DR) are largely unknown. METHODS: In this retrospective cohort study, data were collected from a nationwide database. Patients with diabetes who initiated treatment with a GLP1RA or SGLT2i between 1 May 2016 and 31 December 2017, were identified. Patients were divided into those with or without a previous diagnosis of DR and then categorized into the GLP1RA and the SGLT2i groups according to drug use. The primary outcome of interest in the DR group was the composite of new-onset proliferative DR, vitreous haemorrhage and tractional retinal detachment (RD). In the non-DR group, the primary outcome was the composite of newly diagnosed DR of any severity, vitreous haemorrhage and RD. RESULTS: In total, 97 413 patients were identified. After matching, 1517 patients were treated with a GLP1RA and 3034 with an SGLT2i in the DR cohort. In the non-DR cohort, 9549 initiated a GLP1RA and 19 098 initiated an SGLT2i. In patients with pre-existing DR, the incidence of any DR progression event was significantly higher in the GLP1RA group than the SGLT2i group (subdistribution hazard ratio 1.50, 95% confidence interval 1.01-2.23), primarily because of the increased risk of tractional RD. In patients without DR at baseline, the risks of all ocular outcomes were similar between the GLP1RA and SGLT2i groups. CONCLUSIONS: In patients with diabetes mellitus and established DR, GLP1RA treatment was associated with increased risks of DR progression compared with SGLT2i use.

Evaluations of secondary hypertension and laboratory data in the elderly population.

Secondary hypertension in the elderly poses many challenges and requires a comprehensive diagnostic and management approach. This review explores the prevalence, diagnostic strategies, and treatment modalities for secondary hypertension in elderly patients, focusing on etiologies including primary aldosteronism, renal vascular disease, renal parenchymal disease, obstructive sleep apnea, thyroid disorders, Cushing's syndrome, pheochromocytomas and paragangliomas, and drug-induced hypertension. Key considerations include age-related changes in physiology and atypical presentations of underlying conditions necessitating thorough screening with a combination of clinical evaluation, laboratory tests, and imaging studies. Collaboration among healthcare providers is essential to ensure a timely diagnosis and personalized management tailored to the unique needs of elderly patients. Further research is needed to address knowledge gaps and optimize clinical strategies for managing secondary hypertension in this population.

Major adverse cardiovascular and limb events in people with diabetes treated with GLP-1 receptor agonists vs SGLT2 inhibitors.

AIMS/HYPOTHESIS: This study aimed to assess the real-world outcomes of people with diabetes mellitus treated with glucagon-like peptide-1 receptor agonists (GLP1RAs) compared with those treated with sodium-glucose cotransporter 2 inhibitors (SGLT2is) in terms of major adverse cardiovascular and limb events. Peripheral artery disease is a common cause of morbidity in people with diabetes. Previous cardiovascular outcome trials have demonstrated the benefits of GLP1RAs and SGLT2is for reducing various cardiovascular events, but the safety and efficacy of these drugs on limb outcomes remain subject to debate and ambiguity. METHODS: A retrospective cohort study was conducted in which data were collected from the Taiwan National Health Insurance Research Database. In total, 379,256 individuals with diabetes receiving either GLP1RA or SGLT2i with treatment initiated between 1 May 2016 and 31 December 2019 were identified. The primary outcome was major adverse limb events (MALE), defined as the composite of newly diagnosed critical limb ischaemia, percutaneous transluminal angioplasty or peripheral bypass for peripheral artery disease, and non-traumatic amputation. The secondary outcome was major adverse cardiac events, which was a composite of cardiovascular death, non-fatal myocardial infarction and non-fatal ischaemic stroke. Other examined outcomes included death from any cause and hospitalisation for heart failure. Propensity score matching was performed at a 1:4 ratio between the GLP1RA and SGLT2i groups to mitigate possible selection bias. RESULTS: A total of 287,091 patients were eligible for analysis, with 81,152 patients treated with SGLT2i and 20,288 patients treated with GLP1RA after matching. The incidence of MALE was significantly lower in the GLP1RA group than in the SGLT2i group (3.6 vs 4.5 events per 1000 person-years; subdistribution HR 0.80; 95% CI 0.67, 0.96), primarily due to a lower incidence of critical limb ischaemia. The reduced risks of MALE associated with GLP1RA use were particularly noticeable in people with diabetic peripheral neuropathy (subdistribution HR 0.66 vs 1.11; p for interaction 0.006). CONCLUSIONS/INTERPRETATION: In people with diabetes, GLP1RA use was associated with significantly reduced risks of MALE compared with SGLT2i within the first 2 years after initiation, especially among people with diabetic neuropathy.

Mortality risk in patients with underweight or obesity with peripheral artery disease: a meta-analysis including 5,735,578 individuals.

OBJECTIVES: The "obesity paradox" - in which patients with obesity exhibit superior survival than normal-weight counterparts - has been reported for several diseases. However, obesity is a well-known risk factor for cardiovascular disease, and whether the obesity paradox is present in peripheral artery disease (PAD) is unknown. METHODS: A comprehensive search for studies that reported mortality in patients with PAD grouped by BMI identified 12 studies. We compared the survival of underweight patients with those who were not underweight, and patients with obesity against those without. Underweight was defined by a BMI value of <18.5 kg/m2 in most studies and obesity by BMI ≥ 30 kg/m2. Subgroup analyses were performed according to length of follow-up, presentation of PAD, and mode of revascularization. Meta-regression analyses were conducted, with covariates including age, sex, presence of coronary artery disease (CAD) and diabetes mellitus (DM). RESULTS: The mortality risk of underweight patients with PAD was significantly higher compared to those who are not underweight (HR 1.72, 95% CI 1.38-2.14; I2 = 84.2%). In contrast, the mortality risk of patients with obesity with PAD was significantly lower than those without (HR 0.78, 95% CI 0.62-0.97; I2 = 89.8%). These findings remained consistent regardless of the presentation of PAD, revascularization, age, sex, or presence of CAD. The risk of death in the short-term of underweight patients (HR 1.50, 95% CI 0.47-4.72) and patients with obesity (HR 0.86, 95% CI 0.66-1.13) were not significantly different from their counterparts. The meta-regression showed that of the association between obesity and better survival was more pronounced in studies with a greater proportion of patients with concomitant CAD (regression coefficient -0.029, 95% CI -0.054 to -0.004). CONCLUSIONS: In patients with PAD, mortality is higher among underweight patients and lower among patients with obesity. The mechanisms underlying the obesity paradox in patients with PAD remain to be elucidated, and further evidence is required to guide optimal weight control strategies in these patients.

A Dose Response Association Between Body Mass Index and Mortality in Patients with Peripheral Artery Disease: A Meta-analysis Including 5 729 272 Individuals.

OBJECTIVE: Obesity is a significant risk factor for atherosclerotic cardiovascular disease; however, the "obesity paradox", in which obese patients enjoy superior survival, has been observed in various cardiovascular conditions. Whether this phenomenon exists for peripheral artery disease (PAD) remains uncertain. The goal of this study was to evaluate the relationship between body mass index (BMI) and mortality in patients with PAD. METHODS: A comprehensive literature search identified seven eligible cohort studies that reported the association between BMI and all cause mortality in patients with PAD. A dose response meta-analysis was done for all cause mortality, short term (30 day or in hospital) mortality and long term mortality. The dose response association between BMI and mortality was also assessed in patients who received endovascular therapy (EVT). RESULTS: The non-linear dose response analysis showed that higher BMI values were associated with a lower mortality risk from the range between 15 kg/m2 to approximately 33 - 34 kg/m2. The risk of mortality increased slightly thereafter. This relationship was consistent with that of long term mortality but was not apparent in short term mortality. A U shaped relationship was also observed between BMI and mortality in patients who received EVT with the lowest mortality observed at around 30 kg/m2. CONCLUSION: The obesity paradox was evident in the analysis of long term survival among patients with PAD, with the lowest mortality rates observed in obese patients. However, this association was not observed for short term or in hospital mortality.

The feasibility, efficacy, and safety of RDN procedure using CO2 angiography through radial artery in severe chronic kidney disease patients.

The recent evidence regarding the effectiveness of renal denervation (RDN) in blood pressure control is becoming increasingly substantial. However, many studies have excluded populations with severely impaired kidney function, even though these individuals have a higher prevalence of hypertension compared to the general population, and controlling their blood pressure is more challenging. The effectiveness and safety of RDN in patients with severe chronic kidney disease (CKD) lack strong evidence support. Concerns about worsening kidney function still exist, particularly in patients with CKD stage 5. We conducted an observational study involving 10 patients who were using at least 3 different antihypertensive medications and had an estimated glomerular filtration rate (eGFR) < 45 mL/min/1.73 m2 but had not undergone dialysis. For these patients, we performed RDN via the radial artery approach, with the assistance of carbon dioxide (CO2) angiography. Utilizing this approach, the systolic 24-hour ambulatory blood pressure monitoring did not exhibit a significant decrease at 3 months; however, a significant reduction was observed at 6 months after RDN. We also minimized contrast agent usage, observed no kidney function decline 3 months post-RDN, and experienced no vascular-related complications. Using the radial artery approach and CO2 angiography assistance for RDN may be an effective and safe blood pressure control method for patients with severe kidney impairment.

Long-term exposure to air pollution and the risks of venous thromboembolism: a nationwide population-based retrospective cohort study.

OBJECTIVES: To delineate the effects of exposure to air pollution on the risk of venous thromboembolism (VTE). BACKGROUND: The association between air pollution and arterial occlusive diseases has been well reported in the literature. VTE is the third most common acute cardiovascular syndrome; however, its relationship with exposure to air pollution has been controversial. METHODS: This study linked data from the Taiwan National Health Insurance Research Database with that from the Taiwan Environmental Protection Administration. Patients who were first admitted for VTE between January 1, 2001, and December 31, 2013, were analyzed. A time-stratified, case-crossover design was employed. Three different exposure periods were defined: exposure for 1 month, one quarter, and 1 year. Four control periods were designated for each exposure period. The association between exposure to air pollutants and the risk of VTE was tested using logistic regression analysis. Subgroup analyses were also performed, stratified by age, sex, type of VTE, the use of hormone therapy, and level of urbanization at the site of residence. RESULTS: Exposures to particulate matter (PM) smaller than 2.5 µm (PM2.5) and those smaller than 10 µm (PM10) were associated with higher risks of VTE, with longer exposures associated with higher risk. The concentration of PM2.5 exposure for 1 month was linearly associated with a greater risk of VTE up to 28.0 µg/m3, beyond which there was no association. PM2.5 exposure for one quarter or 1 year remained significantly associated with higher risks of VTE at higher concentrations. The increased risk in VTE associated with exposure to PM2.5 was more prominent in older patients and in patients not under hormone therapy. Similar results were observed for PM10 exposures. CONCLUSIONS: Exposure to PM, particularly PM2.5, leads to an increased risk of VTE, with possible accumulative effects. With increased PM production in industrializing countries, the effects of PM on VTE occurrence warrant further attention.

Efficacy and Safety of Direct Oral Anticoagulants for Stroke Prevention in Older Patients With Atrial Fibrillation: A Network Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Although older patients with atrial fibrillation are at heightened risk of thromboembolic and bleeding events, their optimal treatment choice remains uncertain. METHODS AND RESULTS: This meta-analysis was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We searched the PubMed, EMBASE, and Cochrane databases for randomized controlled trials that compared thromboembolic or bleeding outcomes between a direct oral anticoagulant (DOAC) and a vitamin K antagonist (VKA) and reported outcomes for patients aged ≥75 years with atrial fibrillation. The efficacy outcome was the composite of stroke and systemic embolism. Safety outcomes included major bleeding, any clinically relevant bleeding, and intracranial hemorrhage. Each DOAC and VKA was compared pairwise in a network meta-analysis. High- and low-dose regimens and factor IIa and Xa inhibitors were also compared. Seven randomized controlled trials were included in the analysis. Stroke and systemic embolism risks did not differ significantly among DOACs. There were no significant differences in major bleeding between each DOAC and VKA. Intracranial hemorrhage risk was significantly lower with dabigatran, apixaban, and edoxaban than with VKA and rivaroxaban, which had similar risks. High-dose regimens led to lower risks of stroke or systemic embolism compared with VKA and low-dose regimens, with both doses having similar bleeding risks. CONCLUSIONS: In patients aged ≥75 years with atrial fibrillation, DOACs were associated with fewer thromboembolic events compared with VKA, whereas dabigatran, apixaban, and edoxaban were associated with lower risks of intracranial hemorrhage compared with VKA and rivaroxaban. REGISTRATION: URL: www.crd.york.ac.uk/prospero/. Unique identifier: CRD42022329557.

Differential effects of sodium-glucose cotransporter 2 inhibitors on cardiovascular and renal outcomes according to renal function: a dose-response meta-analysis involving 10 randomized clinical trials and 71 553 individuals.

BACKGROUND: The main target of sodium-glucose cotransporter 2 inhibitors (SGLT2i), the sodium-glucose cotransporters 2, is found in the kidneys, and their activity is reduced in patients with chronic kidney disease (CKD). How the efficacy of SGLT2i may vary in patients with different levels of renal impairment has not been fully elucidated. METHODS: We searched the PubMed databases for relevant studies published through May 25, 2022. Randomized control trials comparing SGLT2i with placebo and reporting cardiovascular or renal outcomes were included. The primary outcome was the composite of major adverse cardiovascular events (MACE), which were defined as cardiovascular death (CV death), nonfatal myocardial infarction (MI), and nonfatal ischemic stroke. Secondary outcomes included the components of MACE, all-cause mortality, hospitalization for heart failure (HHF), the composite of CV death and HHF, and composite renal outcomes. Linear meta-regression analysis was used to assess the effects of estimated glomerular filtration rate (eGFR) on the risks associated with SGLT2i treatment vs placebo for all outcomes. Nonlinear meta-regression analysis was also performed for MACE to investigate the combined influence of reduced drug efficacy in CKD but possible greater risk reduction in a population with higher risk at baseline. Further analyses were performed by including additional study-level covariates, including the prevalence of diabetes mellitus (DM), heart failure (HF), and atherosclerotic cardiovascular disease (ASCVD). RESULTS: Risk ratios for MACE, CV death, nonfatal MI, HHF, and composite renal outcomes associated with SGLT2i treatment were not significantly related to baseline eGFR values. A positive association was observed between eGFR values and the risk of stroke with SGLT2i use (regression coefficient ß = .0109, 95% confidence interval [CI] 0.0029-0.0188). A similar positive association was observed between eGFR values and the composite outcome of CV death and HHF (ß = .0025, 95% CI 0.0000-0.0051). The results of the meta-regression analyses, including the additional covariates of DM, HF, and ASCVD, were consistent with the results of the primary analyses for most outcomes. CONCLUSION: The protective effects of SGLT2i for reducing most adverse cardiovascular and renal outcomes persisted in patients with variable degrees of renal impairment. The observed benefits such as preventing CV death, HF worsening, or stroke may be greater for patients with more severe CKD. Considering the cardiovascular and renal benefits associated with SGLT2i treatment, patients with CKD should be treated aggressively to improve outcomes. PROSPERO REGISTRATION NUMBER: CRD42021273500.

Analysis of Left Ventricular Indexes and Mortality Among Asian Adults With Hemodynamically Significant Chronic Aortic Regurgitation.

Importance: Chronic hemodynamically significant aortic regurgitation (AR) is associated with excess risk of death, yet data for Asian patients are lacking, and whether Asian patients can abide by Western guidelines as to when aortic valve surgery should be performed is unknown. Objective: To assess AR presentation and cutoffs of left ventricular ejection fraction (LVEF), LV end-systolic dimension index (LVESDi), and LV end-systolic volume index (LVESVi) that are associated with risk of death in Asian patients with AR. Design, Setting, and Participants: This retrospective cohort study included consecutive patients with chronic, moderately severe to severe AR from 3 tertiary referral centers (2 in Japan and 1 in Taiwan) from June 11, 2008, through November 19, 2020, with follow-up through November 11, 2021. Exposures: Aortic regurgitation severity, graded by a comprehensive integrated approach. Main Outcomes and Measures: The primary outcome was the association between volume-derived LVEF, LVESDi, and LVESVi and all-cause death (ACD). The secondary outcome was the association of these LV indexes with cardiovascular death (CVD). Clinical and echocardiographic data were analyzed retrospectively. A de novo disk-summation method was used to derive LV volumes and volume-derived LVEF. Results: Of 1259 patients (mean [SD] age, 64 [17] years; 934 [74%] male), 515 (41%) were Japanese and 744 (59%) were Taiwanese. The median follow-up was 4.1 years (IQR, 1.56-7.24 years). The mean (SD) body surface area was 1.67 (0.21) m2; LVEF, 55% (11%); LVESDi, 24.7 (5.7) mm/m2; LVESVi, 50.1 (28.0) mL/m2; and indexed mid-ascending aorta size, 24.7 (5.5) mm/m2. Aortic valve surgery occurred in 483 patients (38%); 240 patients (19%) died during follow-up. Overall mean (SD) 8-year survival was 74% (2%). Separate multivariate models adjusted for covariates demonstrated independent associations of LVEF, LVESDi, and LVESVi with ACD (LVEF: hazard ratio [HR] per 10%, 0.80; 95% CI, 0.70-0.92; P = .002; LVESDi: HR, 1.04; 95% CI, 1.01-1.06; P = .002; LVESVi: HR per 10 mL/m2, 1.11; 95% CI, 1.05-1.17; P < .001) and CVD (LVEF: HR per 10%, 0.69; 95% CI, 0.56-0.85; P < .001; LVESDi: HR, 1.05; 95% CI, 1.01-1.09; P = .01; LVESVi per 10 mL/m2: HR, 1.15; 95% CI, 1.06-1.24; P < .001). In the total cohort, spline curves showed that mortality started to increase for an LVEF of 53% or less, LVESDi of 22 mm/m2 or greater, and LVESVi of 46 mL/m2 or greater for both ACD and CVD. Early surgery was beneficial in 3 strata of LVESDi (<20, 20 to <25, and ≥25 mm/m2) and 2 strata of LVESVi (<46 and ≥46 mL/m2). Conclusions and Relevance: This multicenter cohort study of Asian patients with hemodynamically significant AR found cutoff values of LVEF, LVESDi, and LVESVi that were associated with increased risk of death. These findings suggest that Western guidelines seem applicable in Asian patients and, most importantly, that indexed LV parameters with a lower cutoff could be used in discriminating patients with excess mortality risk.

Association of Statin Therapy With Major Adverse Cardiovascular and Limb Outcomes in Patients With End-stage Kidney Disease and Peripheral Artery Disease Receiving Maintenance Dialysis.

Importance: Controversy exists regarding whether statin therapy has benefits for patients with kidney failure, and the consequences of statin therapy for patients with kidney failure and concomitant peripheral artery disease (PAD) are particularly uncertain. Objective: To evaluate the association of statin therapy with cardiovascular (CV) and limb outcomes among patients with kidney failure and concomitant PAD and dyslipidemia who are receiving long-term maintenance dialysis. Design, Setting, and Participants: This retrospective cohort study used data from the Taiwan National Health Insurance Research Database. A total of 20 731 patients with kidney failure receiving long-term maintenance dialysis who were diagnosed with PAD and dyslipidemia between January 1, 2001, and December 31, 2013, were identified, and 10 767 patients met study criteria. Data were analyzed from June 8, 2021, to June 2, 2022. Main Outcomes and Measures: Primary outcomes were all-cause death and the composite of endovascular therapy (EVT) and amputation. Other outcomes of interest included CV events (CV death, acute myocardial infarction, ischemic stroke, and hospitalization for heart failure), major adverse limb events (new-onset claudication, new-onset critical limb ischemia, EVT, and nontraumatic amputation), and all-cause readmission. All outcomes were examined at 1 year and 3 years of follow-up. To minimize selection bias, propensity score matching on a 1:1 ratio was performed among patients receiving statin therapy (statin group) and patients not receiving statin therapy (nonstatin group). A defined daily dose (DDD) approach was used to evaluate whether the association of statin therapy with the risk of primary outcomes was dose dependent. Results: Among 20 731 patients with kidney failure and concomitant PAD and dyslipidemia receiving long-term maintenance dialysis, 10 767 patients (5593 women [51.9%]; mean [SD] age, 68.5 [11.5] years; all of Taiwanese ethnicity) met the predetermined study criteria; of those, 3597 patients were receiving statin therapy, and 7170 were not. A total of 6470 patients (mean [SD] age, 66.4 [11.3] years; 3359 women [51.9%]) were included in the 1:1 propensity score-matched cohort, with 3235 patients in each group (statin and nonstatin). The incidence and risk of CV and all-cause death were significantly lower in the statin group vs the nonstatin group at 3 years of follow-up (CV death: 611 patients [18.9%] vs 685 patients [21.2%]; hazard ratio [HR], 0.86 [95% CI, 0.77-0.96]; P = .008; all-cause death: 1078 patients [33.3%] vs 1138 patients [35.2%]; HR, 0.92 [95% CI, 0.84-0.996]; P = .04). Statin use was also associated with a significantly lower incidence and risk of the composite adverse limb outcome of EVT and amputation at 3 years of follow-up (314 patients [9.7%] vs 361 patients [11.2%]; subdistribution HR, 0.85 [95% CI, 0.73-0.99]; P = .04). Results of subgroup analyses were consistent with those of the primary analysis across all subgroup variables. In the adjusted dose-response analysis, the risk reduction associated with statin use increased in a dose-dependent manner for both all-cause death (HR: 0.95 for DDD <0.50, 0.92 for DDD 0.50-0.99, 0.85 for DDD 1.00-1.49, and 0.79 for DDD ≥1.50; P = .002 for trend) and the composite outcome of EVT and amputation (subdistribution HR: 0.79 for DDD <0.50, 0.78 for DDD 0.50-0.99, 0.82 for DDD 1.00-1.49, and 0.58 for DDD ≥1.50; P = .002 for trend) compared with no statin therapy; however, not all findings in the DDD analysis were statistically significant. Conclusions and Relevance: In this cohort study, statin therapy was associated with reductions in the risk of all-cause death, CV death, and the composite adverse limb outcome of EVT and amputation. These findings suggest that statin therapy may have protective CV and limb benefits for patients with kidney failure and concomitant PAD who are receiving long-term maintenance dialysis.

Comparison Between Bicuspid and Tricuspid Aortic Regurgitation: Presentation, Survival, and Aorta Complications.

Background: Although the Asian population is growing globally, data in Asian subjects regarding differences between bicuspid aortic valve (BAV) and tricuspid aortic valve (TAV) in aortic regurgitation (AR) remain unexplored. Objectives: The aim of this study was to examine differences between Asian BAV-AR and TAV-AR in significant AR, including aorta complications. Methods: The study included 711 consecutive patients with chronic moderate to severe and severe AR from 2008 to 2020. Outcomes included all-cause death, aortic valve surgery (AVS), and incidence of aortic dissection (AD). Results: There were 149 BAV-AR (mean age: 48 ± 16 years) and 562 TAV-AR (mean age: 68 ± 15 years; P < 0.0001) patients; baseline indexed left ventricle and indexed aorta size were larger in TAV-AR. Total follow-up was 4.8 years (IQR: 2.0-8.4 years), 252 underwent AVS, and 185 died during follow-up; 18 cases (only 1 BAV) of AD occurred, with a mean maximal aorta size of 60 ± 9 mm. The 10-year AVS incidence was higher in TAV-AR (51% ± 4%) vs BAV-AR (40% ± 5%) even after adjustment for covariates (P < 0.0001). The 10-year survival was higher in BAV-AR (86% ± 4%) vs TAV-AR (57% ± 3%; P < 0.0001) and became insignificant after age adjustment (P = 0.33). Post-AVS 10-year survival was 93% ± 5% in BAV-AR and 78% ± 5% in TAV-AR, respectively (P = 0.08). The 10-year incidence of AD was higher in TAV-AR (4.8% ± 1.5%) than in BAV-AR (0.9% ± 0.9%) and was determined by aorta size ≥45 mm (P ≤ 0.015). Compared with an age- and sex-matched population in Taiwan, TAV-AR (HR: 3.1) had reduced survival (P < 0.0001). Conclusions: Our findings suggest that TAV-AR patients were at a later stage of AR course and had a high AD rate as opposed to BAV-AR patients in Taiwan, emphasizing the importance of early referral for timely management. Surgery on the aorta with a lower threshold in TAV-AR should be considered.