Association between serum chloride levels with mortality in incident peritoneal dialysis patients

Background and aimsLower serum chloride (Cl) levels have been associated with excess mortality in pre-dialysis chronic kidney disease patients. However, the relationship between serum Cl levels and clinical outcomes in continuous ambulatory peritoneal dialysis (CAPD) patients is unclear.Methods and resultsIn this retrospective cohort study, we enrolled 1656 eligible incident patients undergoing CAPD from 2006 to 2013, and followed until December 2018. Cox regression analyses were used to examine the association between baseline and time-varying serum Cl levels and mortality. During a median follow-up of 46 months, 503 patients (30.4%) died. In analyses of baseline serum Cl, the adjusted hazard ratios (HR) for tertile 1 (<100.0 mmol/L), tertile 2 (100.0–103.0 mmol/L) versus tertile 3 (>103.0 mmol/L) were 2.34 [95% confidence interval (CI) 1.43–3.82] and 1.73 (95% CI 1.24–2.42) for all-cause mortality, 2.86 (95% CI 1.47–5.56) and 1.90 (95% CI 1.19–3.02) for cardiovascular disease (CVD) mortality, respectively. And a linear relationship was observed between serum Cl and mortality. Further, the inverse association between serum Cl and CVD mortality was particularly accentuated in the patients who were ≥50 years or with a history of diabetes. Similarly, lower time-varying serum Cl levels were also associated with a significant increased risk of all-cause and CVD death.ConclusionLower serum Cl levels predicted higher risk of all-cause and CVD mortality in CAPD patients.     

The interaction between hyperuricemia and low-density lipoprotein cholesterol increases the risk of 1-year post-discharge all-cause mortality in ST-segment elevation myocardial infarction patients

Background and aimsHyperuricemia is a known risk factor for cardiovascular diseases, but little is known on whether the association between hyperuricemia and poor outcomes in ST-segment elevation myocardial infarction (STEMI) is modified by low-density lipoprotein cholesterol (LDL-c). This study aimed to investigate the effect of the interaction between hyperuricemia and LDL-c on the risk of 1-year post-discharge all-cause mortality in STEMI patients.Methods and resultsA total of 1396 STEMI patients were included. Cox proportional hazards models were used to determine the association between hyperuricemia and 1-year all-cause mortality in the overall population and subgroups stratified based on LDL-c levels (<3.0 mmol/L or ≥3.0 mmol/L). Multivariate analysis indicated that hyperuricemia was associated with 1-year mortality (HR: 2.66; 95% CI: 1.30–5.47; p = 0.008). However, the prognostic effect of hyperuricemia was only observed in patients with LDL-c level ≥3.0 mmol/L (HR: 12.90; 95% CI: 2.98–55.77; p < 0.001), but not in those with LDL-c level <3.0 mmol/L (HR: 0.91, 95% CI: 0.30–2.79, p = 0.875). The interaction between hyperuricemia and LDL-c levels had a significant effect on 1-year mortality.ConclusionHyperuricemia was associated with increased 1-year post-discharge mortality in patients with LDL-c level≥ 3.0 mmol/L, but not in those with LDL-c level< 3.0 mmol/L.     

Prediabetes and incident heart failure in hypertensive patients: Results from the Swedish Primary Care Cardiovascular Database

Backgrounds and aimsThe cardiovascular risk conferred by concomitant prediabetes in hypertension is unclear. We aimed to examine the impact of prediabetes on incident heart failure (HF) and all-cause mortality, and to describe time in therapeutic blood pressure range (TTR) in a hypertensive real-world primary care population.Methods and resultsIn this retrospective cohort study, 9628 hypertensive individuals with a fasting plasma glucose (FPG) in 2006–2010 but no diabetes, cardiovascular or renal disease were followed to 2016; median follow-up was 9 years. Prediabetes was defined as FPG 5.6–6.9 mmol/L, and in a secondary analysis as 6.1–6.9 mmol/L. Study outcomes were HF and all-cause mortality. Hazard ratios (HR) were compared for prediabetes with normoglycemia using Cox regression. All blood pressure values from 2001 to the index date (first FPG in 2006–2010) were used to calculate TTR. At baseline, 51.4% had prediabetes. The multivariable-adjusted HR (95% confidence intervals) was 0.86 (0.67–1.09) for HF and 1.06 (0.90–1.26) for all-cause mortality. For FPG defined as 6.1–6.9 mmol/L, the multivariable-adjusted HR were 1.05 (0.80–1.39) and 1.42 (1.19–1.70), respectively. The prediabetic group had a lower TTR (p < 0.05).ConclusionsPrediabetes was not independently associated with incident HF in hypertensive patients without diabetes, cardiovascular or renal disease. However, prediabetes was associated with all-cause mortality when defined as FPG 6.1–6.9 mmol/L (but not as 5.6–6.9 mmol/L). TTR was lower in the prediabetic group, suggesting room for improved blood pressure to reduce incident heart failure in prediabetes.     

High-density lipoprotein cholesterol to apolipoprotein A1 ratio and all-cause mortality among incident peritoneal dialysis patients

Background and aimsThe ratio of high-density lipoprotein cholesterol to apolipoprotein A1 (HAR) is associated with all-cause mortality in nonchronic kidney disease patients, but its role in predicting all-cause mortality in patients undergoing peritoneal dialysis (PD) is still unclear. The purpose of this study was to investigate the relationship between HAR and all-cause mortality in patients with PD.Methods and resultsThe medical records of 1199 patients with PD from November 1, 2005, to August 31, 2019, were collected retrospectively. The main outcome was defined as all-cause mortality. The HAR was divided into three groups by X-tile software. The association between HAR and all-cause mortality was evaluated by Cox models. The Kaplan–Meier method was used for the survival curve. The median follow-up period was 35 months (interquartile range: 20–57 months), with a total of 326 deaths recorded. After multiple adjustments, the risk of all-cause mortality in the high HAR group was 1.96-fold higher than that in the low HAR group (hazard ratio: 1.96; 95% CI, 1.22 to 3.15; P = 0.005). The restricted cubic splines showed that the risk of all-cause mortality increased gradually when HAR was >0.37. In the stratified analysis, a high HAR was linked to a high risk of all-cause mortality in males, patients under 55 years old, and patients without diabetes or cardiovascular disease (CVD).ConclusionThis study suggests that HAR is independently related to all-cause mortality in PD patients, especially in males, patients under 55 years old, and patients without diabetes or CVD.     

Association between the visceral adiposity index and risks of all-cause and cause-specific mortalities in a large cohort: Findings from the UK biobank

Background and aimsThe visceral adiposity index (VAI) has been recently established as a measure of visceral fat distribution and is shown to be associated with a wide range of adverse health events. However, the precise associations between the VAI score and all-cause and cause-specific mortalities in the general population remain undetermined.Methods and resultsIn this large-scale prospective epidemiological study, 357,457 participants (aged 38–73 years) were selected from the UK Biobank. We used Cox competing risk regression models to estimate the association between the VAI score and all-cause, cardiovascular disease (CVD), cancer, and other mortalities. The VAI score was significantly correlated with an increased risk of all-cause mortality (hazard ratio [HR], 1.200; 95% confidence interval [CI], 1.148–1.255; P < 0.0001), cancer mortality (HR, 1.224; 95% CI, 1.150–1.303; P < 0.0001), CVD mortality (HR, 1.459; 95% CI, 1.148–1.255; P < 0.0001), and other mortalities (HR, 1.200; 95% CI, 1.148–1.255; P < 0.0001) after adjusting for a series of confounders. In addition, the subgroup analyses showed that HRs were significantly higher in participants who were male, aged below 65 years, and body mass index less than 25.ConclusionIn summary, VAI was positively associated with an increased risk of all-cause and cause-specific mortalities in a nationwide, well-characterised population identified in a UK Biobank. The VAI score might be a complementary traditional predictive indicator for evaluating the risk of adverse health events in the population of Western adults aged 38 years and older.     

Prognostic utility of the prognostic nutritional index combined with serum sodium level in patients with heart failure

Background and aimsBoth malnutrition and hyponatremia (serum sodium <135 mmol/L) can be induced by the impaired absorption function of the edematous intestinal wall caused by heart failure (HF) and are prognostic factors of mortality in HF. However, little is known about the interrelationship of nutritional status and hyponatremia in mortality risk prediction in HF.Methods and resultsThis study enrolled 2882 HF patients admitted to the HF care unit of Fuwai Hospital, Beijing, China from 2008 to 2018; 71.3% were male and the mean age was 56.64 ± 15.96 years. Nutritional status was assessed by prognostic nutritional index (PNI), calculated as serum albumin (g/L) + 5 × total lymphocyte count (10⁹/L). Lower PNI indicates worse nutritional status. Patients were divided into 8 groups based on baseline PNI quartiles (Q1: <43.6, Q2: 43.6–48.55, Q3: 48.55–63.25, Q4: >63.25) and sodium level (normal sodium and hyponatremia). After adjustment, patients in the PNI Q1 associated with hyponatremia had a 2.12-fold higher risk of all-cause death (95% confidence interval [CI]: 1.67–2.70) compared with those in the PNI Q4 with normal sodium. A refinement in risk prediction was observed after adding PNI quartile and serum sodium category to the original model (ΔC-statistic = 0.018, 95% CI: 0.007–0.025; net re-classification index = 0.459, 95% CI: 0.371–0.548; integrated discrimination improvement = 0.025, 95% CI: 0.018–0.032).ConclusionHF patients with both the lowest PNI quartile and hyponatremia are at higher risk of all-cause mortality. The combination of PNI and serum sodium level enhanced the predictive value for all-cause mortality in hospitalized HF patients.Clinical trial registrationURL: ClinicalTrials.gov; Unique Identifier: NCT02664818.     

Prognostic Value of Increased Mitral Valve Gradient After Transcatheter Edge-to-Edge Repair for Primary Mitral Regurgitation

ObjectivesThis study sought to evaluate the prognostic value of an increased mean mitral valve pressure gradient (MVG) in patients with primary mitral regurgitation (MR) after transcatheter edge-to-edge repair (TEER).BackgroundConflicting data exist regarding impact of increased mean MVG on outcomes after TEER.MethodsThis study included 419 patients with primary MR (mean age 80.6 ± 10.4 years; 40.6% female) who underwent TEER. Patients were divided into quartiles (Qs) based on discharge echocardiographic mean MVG. Primary outcome was the composite endpoint of all-cause mortality and heart failure hospitalization. Secondary outcomes included all-cause mortality and the secondary composite endpoint of all-cause mortality, heart failure hospitalization, and mitral valve reintervention.ResultsThe median number of MitraClips used was 2 per patient. MR reduction ≤moderate was achieved in 407 (97.1%) patients. Mean MVG was 1.9 ± 0.3 mm Hg, 3.0 ± 0.1 mm Hg, 4.0 ± 0.1 mm Hg, and 6.0 ± 1.2 mm Hg in Q1, Q2, Q3, and Q4, respectively. There was no significant differences across quartiles in the primary outcome (15.4%, 19.6%, 22.0%, and 21.9% in Q1-Q4, respectively; P = 0.63), all-cause mortality (15.9% vs 18.6% vs 19.4% vs 17.1%, respectively; P = 0.91), and the secondary composite endpoint at 2 years (33.3% vs 29.5% vs 22.0% vs 31.6%, respectively; P = 0.37). After multivariate adjustment for baseline clinical and procedural variables, the mean MVG in Q4 compared with Q1 to Q3 was not independently associated with the primary outcome (HR: 1.22; 95% CI: 0.82-1.83; P = 0.33), all-cause mortality, and the secondary composite endpoint.ConclusionsIncreased mean MVG was not independently associated with adverse events after TEER in patients with primary MR.     

Association of Age of Onset of Hypertension With Cardiovascular Diseases and Mortality

BackgroundThe relations of hypertension onset age with cardiovascular diseases (CVD) and all-cause mortality remain inconclusive.ObjectivesThis study sought to examine the associations of hypertension onset age with CVD and all-cause mortality.MethodsThis prospective study included 71,245 participants free of hypertension and CVD in the first survey (July 2006 to October 2007) of the Kailuan study, a prospective cohort study in Tangshan, China. All participants were followed biennially until December 31, 2017. A total of 20,221 new-onset hypertension cases were identified during follow-up. We randomly selected 1 control participant for each new-onset hypertensive participant, matching for age (±1 year) and sex, and included 19,887 case-control pairs. We used weighted Cox regression models to calculate the average hazard ratios of incident CVD and all-cause mortality across the age groups.ResultsDuring an average follow-up of 6.5 years, we identified 1,672 incident CVD cases and 2,008 deaths. After multivariate adjustment, with the increase in hypertension onset age, the hazards of outcomes were gradually attenuated. The average hazard ratio (95% confidence interval) of CVD and all-cause mortality were 2.26 (1.19 to 4.30) and 2.59 (1.32 to 5.07) for the hypertension onset age <45 years old group, 1.62 (1.24 to 2.12) and 2.12 (1.55 to 2.90) for the 45- to 54-year age group, 1.42 (1.12 to 1.79) and 1.30 (1.03 to 1.62) for the 55- to 64-year age group, and 1.33 (1.04 to 1.69) and 1.29 (1.11 to 1.51) for the ≥65-year age group, respectively (p for interaction = 0.38 for CVD and <0.01 for death).ConclusionsHypertension was associated with a higher risk for CVD and all-cause mortality, and the associations were stronger with a younger age of onset.     

Effect of Mitral Valve Gradient After MitraClip on Outcomes in Secondary Mitral Regurgitation: Results From the COAPT Trial

ObjectivesThe authors sought to evaluate the association between mean mitral valve gradient (MVG) and clinical outcomes among patients who underwent MitraClip treatment for secondary mitral regurgitation (SMR) in the COAPT (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation) trial.BackgroundIn the COAPT trial, patients with heart failure (HF) and severe SMR who remained symptomatic despite guideline-directed medical therapy had marked 2-year reductions in mortality and HF hospitalizations after treatment with MitraClip.MethodsMitraClip-treated patients were divided into quartiles (Q) based on discharge echocardiographic MVG (n = 250). Endpoints including all-cause mortality, HF hospitalization, and health status measures at 2 years were compared between quartiles.ResultsMean MVG after MitraClip was 2.1 ± 0.4 mm Hg, 3.0 ± 0.2 mm Hg, 4.2 ± 0.5 mm Hg, and 7.2 ± 2.0 mm Hg in Q1 (n = 63), Q2 (n = 61), Q3 (n = 62), and Q4 (n = 64), respectively. There was no difference across quartiles in the 2-year composite endpoint of all-cause mortality or HF hospitalization (43.2%, 49.2%, 40.6%, and 40.9%, respectively; p = 0.80), nor in improvements in New York Heart Association functional class, Kansas City Cardiomyopathy Questionnaire score, or 6-min walk time. Results were similar after adjustment for baseline clinical and echocardiographic characteristics, post-procedure MR grade, and number of clips (all-cause mortality or HF hospitalization Q4 [44.6%] vs. Q1 to Q3 [40.3%]; adjusted hazard ratio: 1.23, 95% confidence interval: 0.60 to 2.51; p = 0.57).ConclusionsAmong HF patients with severe SMR, higher MVGs on discharge did not adversely affect clinical outcomes following MitraClip. These findings suggest that in select patients with HF and SMR otherwise meeting the COAPT inclusion criteria, the benefits of MR reduction may outweigh the effects of mild-to-moderate mitral stenosis after MitraClip.     

Association between monocyte count to high-density lipoprotein cholesterol ratio and mortality in patients undergoing peritoneal dialysis

Background and aimsPrevious studies had demonstrated that elevated monocyte count to high-density lipoprotein cholesterol ratio (MHR), a novel marker of inflammation, was associated with higher cardiovascular events and mortality in patients with pre-dialysis chronic kidney disease, diabetes, and coronary heart disease. However, the association between MHR and mortality in patients undergoing peritoneal dialysis (PD) has received little attention. The aim of this study was to investigate the association between MHR and all-cause and cardiovascular mortality in PD patients.Methods and resultsIn this single center retrospective cohort study, PD patients who had catheter insertion in our PD center from January 1, 2006 to December 31, 2016 were enrolled. All patients were divided into three groups according to the tertiles of baseline MHR levels and followed up until December 31, 2018. The associations of MHR levels with all-cause and cardiovascular mortality were assessed by using Cox proportional hazards models. Of 1584 patients, mean age was 46.02 ± 14.65 years, 60.1% were male, and 24.2% had diabetes. The mean MHR level was 0.39 ± 0.23. During a median follow up time of 45.6 (24.6–71.8) months, 349 patients died, and 181 deaths were caused by cardiovascular disease. After adjusting for confounders, the highest MHR tertile was significantly associated with all-cause and cardiovascular mortality with a hazard ratio of 1.43 (95%CI = 1.06–1.93, P = 0.019), 1.54 (95%CI = 1.01–2.35, P = 0.046), respectively.ConclusionHigher MHR level was an independent risk factor for all-cause and cardiovascular mortality in PD patients.     

Association between body mass index and mortality in atrial fibrillation patients with and without diabetes mellitus: Insights from a multicenter registry study in China

Background and aimsThe aim of this study was to evaluate the association between body mass index (BMI) and mortality in atrial fibrillation (AF) patients with and without diabetes mellitus (DM).Methods and resultsA total of 1991 AF patients were enrolled and divided into two groups according to whether they have DM at recruitment. Baseline information was collected and a mean follow-up of 1 year was carried out. The primary outcome was defined as all-cause mortality with the secondary outcomes including cardiovascular mortality, stroke and major adverse events (MAEs). Univariable and multivariable Cox regression were performed to estimate the association between BMI and 1-year outcomes in AF patients with and without DM. 309 patients with AF (15.5%) had comorbid DM at baseline. Patients with DM were more likely to have cardiovascular comorbidities, receive relevant medications but carry worse 1-year outcomes. Multivariable Cox regressions indicated that elevated BMI was related with reduced risk of all-cause mortality, cardiovascular mortality and major adverse events. Compared to normal weight, overweight [HR (95% CI): 0.548 (0.405–0.741), p < 0.001] and obesity [HR (95% CI): 0.541 (0.326–0.898), p = 0.018] were significantly related with decreased all-cause mortality for the entire cohort. Remarkably reduced all-cause mortality in the overweight [HR (95% CI): 0.497 (0.347–0.711), p < 0.001] and obesity groups [HR (95% CI): 0.405 (0.205–0.800), p = 0.009] could also be detected in AF patients without DM, but not in those with DM.ConclusionElevated BMI was associated with reduced mortality in patients with AF. This association was modified by DM. The obesity paradox confined to AF patients without DM, but could not be generalized to those with DM.     

Subclinical atherosclerosis in adolescents and young adults and the risk of cardiovascular disease: The Strong Heart Family Study (SHFS)

Background and aimsRates of cardiovascular disease (CVD) among American Indians (AI) have been increasing. Although we have observed an association between atherosclerosis and CVD in older adults, the potential association among young AI is unclear. Therefore, we aim to describe the prevalence of atherosclerosis among young AI and determine its association with CVD and all-cause mortality.Methods and resultsWe evaluated AI participants from the Strong Heart Family Study (SHFS), who were <40 years old and CVD free at the baseline examination, 2001–2003 (n = 1376). We used carotid ultrasound to detect baseline atherosclerotic plaque. We identified CVD events and all-cause mortality through 2019, with a median follow-up of 17.8 years. We used shared frailty Cox Proportional Hazards models to assess the association between atherosclerosis and time to CVD event or all-cause mortality, while controlling for covariates.Among 1376 participants, 71 (5.2%) had atherosclerosis at baseline. During follow-up, 120 (8.7%) had CVD events and 104 (7.6%) died from any cause. CVD incidence was higher in participants who had baseline atherosclerosis (13.51/1000 person-years) than in those who did not (4.95/1000 person-years, p = 0.0003). CVD risk and all-cause mortality were higher in participants with atherosclerosis, while controlling for covariates (CVD HR = 1.85, 95%CI = 1.02–3.37, p = 0.0420; all-cause mortality HR = 2.04, 95%CI = 1.07–3.89, p = 0.0291).ConclusionsAmong young AI, atherosclerosis was independently associated with incident CVD and all-cause mortality later in life. Thus, atherosclerosis begins early in life and interventions in adolescents and young adults to slow the progression of disease could prevent or delay CVD events later in life.     

The prognostic impact of uric acid in acute heart failure according to coexistence of diabetes mellitus

Background and aimsIncreased uric acid levels predict higher mortality in heart failure (HF) patients. Patients with diabetes mellitus (DM) appear to have increased xanthine oxidase activity. We aimed to study if the association between uric acid and mortality in acute HF was different according to the coexistence of DM.Methods and resultsWe studied a cohort of patients hospitalized due to acute HF in 2009–2010. Patients with no uric acid measurement upon admission were excluded from the analysis. Follow-up: 2 years; endpoint: all-cause mortality. Patients with elevated uric acid (>80.0 mg/L) were compared with those with lower values. We used a multivariate Cox-regression analysis to assess the prognostic impact of uric acid (both continuous and categorical variable: cut-off 80.0 mg/L). The analysis was stratified according to coexistence of DM. We studied 569 acute HF patients, 44.6%male, mean age 76 years, 290 were diabetic. Median admission uric acid: 81.2 mg/L and 52.2%had uric acid >80.0 mg/L. Elevated uric acid predicted all-cause mortality in acute HF only in patients with DM. The multivariate-adjusted HR of 2-year mortality was 1.68 (95 % CI: 1.15–2.46) for diabetic HF patients with uric acid>80.0 mg/L compared to those with lower levels (p = 0.008) and 1.10 (95 % CI: 1.03–1.18) per each 10 mg/L increase in uric acid (p = 0.007). In non-diabetic HF patients, uric acid was not associated with mortality.ConclusionsIncreased uric acid predicts ominous outcome in acute HF patients with diabetes, however, it is not prognostic associated in non-diabetics. Uric acid may play a different role in acute HF depending on DM status.     

Statin use and the risk of CVD events,stroke, and all-cause mortality in patients with diabetes: A systematic review and meta-analysis

AimsConsidering the lack of evidence on statin use and the risk of cardiovascular disease (CVD) in patients with diabetes in primary and secondary prevention, this study aimed to evaluate the effect of statin use in individuals with diabetes for primary and secondary prevention.Data synthesisThe MEDLINE, Web of Science, Embase, ClinicalTrials.gov, and Cochrane Central Register for Controlled Trials databases were searched. We included studies that assessed the effect of statin use in individuals with diabetes for at least 1 year. The outcomes included CVD, all-cause mortality, and stroke. A total of 24 studies including 2,152,137 patients with diabetes were included in the meta-analysis. Compared with statin non-users, patients who received statins showed a lower risk of CVD events (primary prevention: risk ratio [RR] = 0.80, 95% confidence interval [CI] 0.69–0.94, P = 0.006; secondary prevention: RR = 0.75, 95% CI 0.65–0.87, P < 0.0001). No association was observed between statin and non-statin users and the risk of all-cause mortality. The pooled results also revealed that statin use reduced the risk of ischemic stroke in patients with diabetes (primary prevention: RR = 0.83, 95% CI 0.70–0.97, P = 0.020; secondary prevention: RR = 0.74, 95% CI 0.63–0.85, P < 0.0001).ConclusionsStatin use significantly reduced the risk of CVD events and stroke, but not all-cause mortality, in individuals with diabetes undergoing both primary and secondary prevention. More data are required to verify the effects of statins in patients with diabetes.Systematic review registrationPROSPERO CRD42021281132.     

Interplay of Coronary Artery Calcium and Risk Factors for Predicting CVD/CHD Mortality: The CAC Consortium

ObjectivesThis study sought to evaluate the association and burden of coronary artery calcium (CAC) with long-term, cause-specific mortality across the spectrum of baseline risk.BackgroundAlthough CAC is a known predictor of short-term, all-cause mortality, data on long-term and cause-specific mortality are inadequate.MethodsThe CAC Consortium cohort is a multicenter cohort of 66,636 participants without coronary heart disease (CHD) who underwent CAC testing. The following risk factors (RFs) were considered: 1) current cigarette smoking; 2) dyslipidemia; 3) diabetes mellitus; 4) hypertension; and 5) family history of CHD.ResultsDuring the 12.5-years median follow-up, 3,158 (4.7%) deaths occurred; 32% were cardiovascular disease (CVD) deaths. Participants with CAC scores ≥400 had a significantly increased risk for CHD and CVD mortality (hazard ratio [HR]: 5.44; 95% confidence interval [CI]: 3.88 to 7.62; and HR: 4.15; 95% CI: 3.29 to 5.22, respectively) compared with CAC of 0. Participants with ≥3 RFs had a smaller increased risk for CHD and CVD mortality (HR: 2.09; 95% CI: 1.52 to 2.85; and HR: 1.84; 95% CI: 1.46 to 2.31, respectively) compared with those without RFs. Across RF strata, CAC added prognostic information. For example, participants without RFs but with CAC ≥400 had significantly higher all-cause, non-CVD, CVD, and CHD mortality rates compared with participants with ≥3 RFs and CAC of 0.ConclusionsAcross the spectrum of RF burden, a higher CAC score was strongly associated with long-term, all-cause mortality and a greater proportion of deaths due to CVD and CHD. Absence of CAC identified people with a low risk over 12 years of follow-up, with most deaths being non-CVD in nature, regardless of RF burden.     

Early Invasive Strategy Based on the Time of Symptom Onset of Non-ST-Segment Elevation Myocardial Infarction

BackgroundA limitation of the current guidelines regarding the timing of invasive coronary angiography for patients with non–ST-segment elevation acute coronary syndrome is the randomization time. To date, no study has reported the clinical outcomes of invasive strategy timing on the basis of the time of symptom onset.ObjectivesThe aim of this study was to investigate the effect of invasive strategy timing from the time of symptom onset on the 3-year clinical outcomes of patients with non–ST-segment elevation myocardial infarction (NSTEMI).MethodsAmong 13,104 patients from the Korea Acute Myocardial Infarction Registry–National Institutes of Health, 5,856 patients with NSTE myocardial infarction were evaluated. The patients were categorized according to symptom-to-catheter (StC) time (<48 or ≥48 hours). The primary outcome was 3-year all-cause mortality.ResultsOverall, 3,919 patients (66.9%) were classified into the StC time <48 hours group. This group had lower all-cause mortality than the group with StC time ≥48 hours (7.3% vs 13.4%; P < 0.001). The lower risk for all-cause mortality in the group with StC time <48 hours group was consistent in all subgroups. Notably, emergency medical service use (HR: 0.31; 95% CI: 0.19-0.52) showed a lower risk for all-cause mortality than no emergency medical service use (HR: 0.54; 95% CI: 0.46-0.65; P value for interaction = 0.008).ConclusionsAn early invasive strategy on the basis of StC time was associated with a decreased risk for all-cause mortality in patients with NSTEMI. Because the study was based on a prospective registry, the results should be considered hypothesis generating, highlighting the need for further research. (iCReaT Study No. C110016)     

Predicted and Observed Mortality at 10 Years in Patients With Bifurcation Lesions in the SYNTAX Trial

BackgroundPercutaneous coronary intervention (PCI) of bifurcation lesions is associated with higher rates of adverse events, and currently it is unclear whether PCI or coronary artery bypass grafting (CABG) is the safer treatment for these patients at very long-term follow-up.ObjectivesThe aim of this study was to investigate the impact of bifurcation lesions on individual predicted and observed all-cause 10-year mortality in the SYNTAX (Synergy Between PCI With Taxus and Cardiac Surgery) trial.MethodsIn the SYNTAXES (SYNTAX Extended Survival) study, 10-year observed and individual predicted mortality derived from the SYNTAX score 2020 (SS-2020) was compared between patients with ≥1 bifurcation (n = 1,300) and those with no bifurcations (n = 487).ResultsAmong patients treated with PCI, patients with >1 bifurcation lesion compared with those without bifurcation lesions had a significantly higher risk for all-cause death (19.8% vs 30.1%; HR: 1.55; 95% CI: 1.12-2.14; P = 0.007), whereas following CABG, mortality was similar in patients with and those without bifurcation lesions (23.3% vs 23.0%; HR: 0.81; 95% CI: 0.59-1.12; P = 0.207; P_interaction = 0.006). In PCI patients, a 2-stent vs a 1-stent technique was associated with higher mortality (33.3% vs 25.9%; HR: 1.51; 95% CI: 1.06-2.14; P = 0.021). According to the SS-2020, among those with ≥1 bifurcation, there was equipoise for all-cause mortality between PCI and CABG in 2 quartiles of the population, whereas CABG was superior to PCI in the 2 remaining quartiles.ConclusionsBifurcation lesions require special attention from the heart team, considering the higher 10-year all-cause mortality associated with PCI. Careful evaluation of bifurcation lesion complexity and calculation of individualized 10-year prognosis using the SS-2020 may therefore be helpful in decision making. (Synergy Between PCI With TAXUS and Cardiac Surgery: SYNTAX Extended Survival [SYNTAXES], NCT03417050; Taxus Drug-Eluting Stent Versus Coronary Artery Bypass Surgery for the Treatment of Narrowed Arteries [SYNTAX], NCT00114972)     

10-Year All-Cause Mortality Following Percutaneous or Surgical Revascularization in Patients With Heavy Calcification

ObjectivesThe aim of this study was to assess 10-year all-cause mortality in patients with heavily calcified lesions (HCLs) undergoing percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG).BackgroundLimited data are available on very long term outcomes in patients with HCLs according to the mode of revascularization.MethodsThis substudy of the SYNTAXES (Synergy Between PCI With Taxus and Cardiac Surgery Extended Survival) study assessed 10-year all-cause mortality according to the presence of HCLs within lesions with >50% diameter stenosis and identified during the calculation of the anatomical SYNTAX (Synergy Between PCI With Taxus and Cardiac Surgery) score among 1,800 patients with the 3-vessel disease and/or left main disease randomized to PCI or CABG in the SYNTAX trial. Patients with HCLs were further stratified according to disease type (3-vessel disease or left main disease) and assigned treatment (PCI or CABG).ResultsThe 532 patients with ≥1 HCL had a higher crude mortality rate at 10 years than those without (36.4% vs 22.3%; HR: 1.79; 95% CI: 1.49-2.16; P < 0.001). After adjustment, an HCL remained an independent predictor of 10-year mortality (HR: 1.36; 95% CI: 1.09-1.69; P = 0.006). There was a significant interaction in mortality between treatment effect (PCI and CABG) and the presence or absence of HCLs (P_interaction = 0.005). In patients without HCLs, mortality was significantly higher after PCI than after CABG (26.0% vs 18.8%; HR: 1.44; 95% CI: 0.97-1.41; P = 0.003), whereas in those with HCLs, there was no significant difference (34.0% vs 39.0%; HR: 0.85; 95% CI: 0.64-1.13; P = 0.264).ConclusionsAt 10 years, the presence of an HCL was an independent predictor of mortality, with a similar prognosis following PCI or CABG. Whether HCLs require special consideration when deciding the mode of revascularization beyond their current contribution to the anatomical SYNTAX score deserves further evaluation. (Synergy Between PCI With TAXUS and Cardiac Surgery: SYNTAX Extended Survival [SYNTAXES], NCT03417050; SYNTAX Study: TAXUS Drug-Eluting Stent Versus Coronary Artery Bypass Surgery for the Treatment of Narrowed Arteries [SYNTAX], NCT00114972)     

Systolic Blood Pressure and Outcomes in Patients With Heart Failure With Reduced Ejection Fraction

BackgroundNational guidelines recommend that systolic blood pressure (SBP) in patients with heart failure with reduced ejection fraction (HFrEF) and hypertension be maintained below 130 mm Hg.ObjectivesThis study sought to determine associations of SBP <130 mm Hg with outcomes in patients with HFrEF.MethodsOf the 25,345 patients in the Medicare-linked OPTIMIZE-HF registry, 10,535 had an ejection fraction (EF) ≤40%. Of these, 5,615 had stable SBP (≤20 mm Hg admission to discharge variation), and 3,805 (68%) had a discharge SBP <130 mm Hg. Propensity scores for SBP <130 mm Hg, estimated for each of the 5,615 patients, were used to assemble a matched cohort of 1,189 pairs of patients with SBP <130 versus ≥130 mm Hg, balanced on 58 baseline characteristics (mean age 76 years; mean EF 28%, 45% women, 13% African American). This process was repeated in 3,946 patients, after excluding 1,669 patients (30% of 5,615) with a discharge SBP <110 mm Hg and assembled a second matched balanced cohort of 1,099 pairs of patients with SBP 110 to 129 mm Hg versus ≥130 mm Hg.ResultsThirty-day all-cause mortality occurred in 7% and 4% of matched patients with SBP <130 mm Hg versus ≥130 mm Hg, respectively (hazard ratio [HR]: 1.76; 95% confidence interval [CI]: 1.24 to 2.48; p = 0.001). HRs (95% CIs) for all-cause mortality, all-cause readmission, and HF readmission at 1 year, associated with SBP <130 mm Hg, were 1.32 (1.15 to 1.53; p < 0.001), 1.11 (1.01 to 1.23; p = 0.030), and 1.24 (1.09 to 1.42; p = 0.001), respectively. HRs (95% CIs) for 30-day and 1-year all-cause mortality associated with SBP 110 to 129 mm Hg (vs. ≥130 mm Hg) were 1.50 (1.03 to 2.19; p = 0.035), and 1.19 (1.02 to 1.39; p = 0.029), respectively.ConclusionsAmong hospitalized older patients with HFrEF, SBP <130 mm Hg is associated with poor outcomes. This association persisted when the analyses were repeated after excluding patients with SBP <110 mm Hg. There is an urgent need for randomized controlled trials to evaluate optimal SBP reduction goals in patients with HFrEF.     

Impact of Surgical and Transcatheter Aortic Valve Replacement in Low-Gradient Aortic Stenosis: A Meta-Analysis

ObjectivesThe aim of this study was to assess the impact of aortic valve replacement (AVR) on survival in patients with each subclass of low-gradient (LG) aortic stenosis (AS) and to compare outcomes following surgical AVR (SAVR) and transcatheter AVR (TAVR).BackgroundLG severe AS encompasses a wide variety of pathophysiology, including classical low-flow, LG (LF-LG), paradoxical LF-LG, and normal-flow, LG (NF-LG) AS, and uncertainty exists regarding the impact of AVR on each subclass of LG AS.MethodsPubMed and Embase were queried through October 2020 to identify studies comparing survival with different management strategies (SAVR, TAVR, and conservative) in patients with LG AS. Pairwise meta-analysis comparing AVR versus conservative management and network meta-analysis comparing SAVR versus TAVR versus conservative management were performed.ResultsThirty-two studies with a total of 6,515 patients and a median follow-up time of 24.2 months (interquartile range: 36.5 months) were included. AVR was associated with a significant decrease in all-cause mortality in classical LF-LG (hazard ratio [HR]: 0.42; 95% confidence interval [CI]: 0.36 to 0.48), paradoxical LF-LG (HR: 0.41; 95% CI: 0.29 to 0.57), and NF-LG (HR: 0.41; 95% CI: 0.27 to 0.62) AS compared with conservative management. SAVR and TAVR were each associated with a decrease in all-cause mortality in classical LF-LG (HR: 0.46 [95% CI: 0.38 to 0.55] and 0.49 [95% CI: 0.37 to 0.64], respectively), paradoxical LF-LG (HR: 0.42 [95% CI: 0.28 to 0.65] and 0.42 [95% CI: 0.25 to 0.72], respectively), and NF-LG (HR: 0.40 [95% CI: 0.21 to 0.77] and 0.46 [95% CI: 0.26 to 0.84], respectively) AS compared with conservative management. No significant difference was observed between SAVR and TAVR.ConclusionsIn all subclasses of LG AS, AVR was associated with a significant decrease in all-cause mortality regardless of surgical or transcatheter approach.