Prevalence and Prognostic Significance of Polyvascular Disease in Patients Hospitalized With Acute Decompensated Heart Failure: The ARIC Study.

BACKGROUND: Polyvascular disease is associated with increased mortality rates and decreased quality of life. Whether its prevalence or associated outcomes differ for patients hospitalized with heart failure with reduced vs preserved ejection fraction (HFrEF vs HFpEF, respectively) is uncertain. METHODS: The Atherosclerosis Risk in Communities (ARIC) study conducted hospital surveillance of acute decompensated heart failure (ADHF) from 2005-2014. Polyvascular disease (coexisting disease in ≥ 2 arterial beds) was identified based on the finding of prevalent coronary artery disease, peripheral artery disease or cerebrovascular disease. Mortality risks associated with polyvascular disease were analyzed separately for HFpEF and HFrEF, with adjustment for potential confounders. All analyses were weighted by the inverse of the sampling probability. RESULTS: Of 24,937 weighted (5460 unweighted) hospitalizations due to ADHF (52% female, 32% Black, mean age 75 years), polyvascular disease was prevalent in 22% with HFrEF and in 17% with HFpEF. One-year mortality risks increased sequentially with 0, 1 and ≥ 2 arterial bed involvement, both for patients with HFrEF (29%-32%-38%; P trend = 0.0006) and for those with HFpEF (26%-32%-37%; P trend < 0.0001). After adjustments, polyvascular disease was associated with a 26% higher mortality hazard for patients with HFrEF (HR = 1.26; 95% CI: 1.07-1.50) and a 29% higher hazard for patients with HFpEF (HR = 1.29; 95% CI: 1.03-1.62), with no interaction by HF type (P interaction = 0.9). CONCLUSION: Patients hospitalized with ADHF and coexisting polyvascular disease have an increased risk of death, irrespective of HF type. Clinical attention should be directed toward polyvascular disease, with implementation of secondary prevention strategies to improve the prognosis of this high-risk population. SUMMARY: Polyvascular disease is known to be associated with myocardial infarction, stroke or cardiovascular death and is a major risk factor for decreased quality of life. This study sought to evaluate the relationship between polyvascular disease and mortality in patients hospitalized with acute decompensated heart failure (ADHF), and to understand whether the associations differ based on ejection fraction. Patients hospitalized with ADHF and coexisting polyvascular disease had an increased risk of death, irrespective of heart failure type, implying the need for increased clinical attention directed toward polyvascular disease, along with implementation of secondary prevention strategies to improve prognosis. TWEET: Patients hospitalized with acute HF and coexisting polyvascular disease face an increased risk of death, irrespective of HF type.

Defecatory disorders are a common cause of chronic constipation in Parkinson disease.

BACKGROUND AND AIMS: Up to 50% of patients with Parkinson disease have constipation (PD-C), but the prevalence of defecatory disorders caused by rectoanal dyscoordination in PD-C is unknown. We aimed to compare anorectal function of patients with PD-C versus idiopathic chronic constipation (CC). METHODS: Anorectal pressures, rectal sensation, and rectal balloon expulsion time (BET) were measured with high-resolution anorectal manometry (HR-ARM) in patients with PD-C and control patients with CC, matched for age and sex. RESULTS: We identified 97 patients with PD-C and 173 control patients. Eighty-six patients with PD-C (89%) had early PD, and 39 (40%) had a defecatory disorder, manifest by a prolonged rectal balloon expulsion time (37 patients) or a lower rectoanal pressure difference during evacuation (2 patients). PD-C patients with a prolonged BET had a greater anal resting pressure (p = 0.02), a lower rectal pressure increment (p = 0.005), greater anal pressure (p = 0.047), and a lower rectoanal pressure difference during evacuation (p < 0.001). Rectal sensory thresholds were greater in patients with abnormal BET. In the multivariate model comparing CC and PD-C (AUROC = 0.76), PD-C was associated with a lower anal squeeze increment (odds ratio [OR] for PD-C, 0.93 [95% CI, 0.91-0.95]), longer squeeze duration (OR, 1.05 [95% CI, 1.03-1.08]), lower rectal pressure increment (OR per 10 mm Hg, 0.72 [95% CI, 0.66-0.79]), and negative rectoanal gradient during evacuation (OR per 10 mm Hg, 1.16 [95% CI, 1.08-1.26]). CONCLUSIONS: Compared with CC, PD-C was characterized by impaired squeeze pressure, longer squeeze duration, lower increase in rectal pressure, and a more negative rectoanal gradient during evacuation.

Peripheral artery disease, chronic kidney disease, and recurrent admissions for acute decompensated heart failure: The ARIC study.

BACKGROUND AND AIMS: Peripheral artery disease (PAD) has not only been associated with recurrent hospitalization for acute decompensated heart failure (ADHF) but is also associated with chronic kidney disease (CKD), a known risk factor for worse heart failure outcomes. The interaction of CKD with PAD in post-discharge ADHF outcomes is not well known. METHODS: Since 2005, hospitalizations for ADHF were sampled from 4 US regions by the Atherosclerosis Risk in Communities (ARIC) study and classified by physician review. We examined the adjusted association of PAD with 1-year ADHF readmissions, in patients with and without CKD (defined by glomerular filtration rate [GFR] ≤60 mL/min/1.73 m2 [stage 3a or worse]). RESULTS: From 2005 to 2018, there were 1049 index hospitalizations for patients with ADHF (mean age 77 years, 66 % white) with creatinine data, who were discharged alive. Of these, 155 (15 %) had PAD and 66 % had CKD. In comparison to those without PAD, patients with PAD had more comorbid conditions and higher 1-year ADHF readmission rates, irrespective of CKD status. After adjustment, PAD was associated with a greater risk of 1-year ADHF readmissions, both for patients with concomitant CKD (HR, 1.70; 95 % CI: 1.29-2.24) and those without CKD (HR, 1.97; 95 % CI: 1.14-3.40); p-interaction = 0.8. CONCLUSION: Among patients hospitalized with ADHF, those with concurrent PAD have more prevalent cardiovascular comorbidities and higher likelihood of 1-year ADHF readmission, irrespective of CKD status. Integrating a more holistic approach in management of patients with concomitant heart failure, PAD and CKD may be an important strategy to improve the prognosis in this vulnerable population.

Mortality in Patients Hospitalized With Acute Myocardial Infarction Without Standard Modifiable Risk Factors: The ARIC Study Community Surveillance.

Background Prevention strategies targeting standard modifiable cardiovascular risk factors (SMuRFs; diabetes, hypertension, smoking, hypercholesterolemia) are critical to improving cardiovascular disease outcomes. However, acute myocardial infarction (AMI) among individuals who lack 1 or more SMuRFs is not uncommon. Moreover, the clinical characteristics and prognosis of SMuRFless individuals are not well characterized. Methods and Results We analyzed AMI hospitalizations from 2000 to 2014 captured by the ARIC (Atherosclerosis Risk in Community) study community surveillance. AMI was classified by physician review using a validated algorithm. Clinical data, medications, and procedures were abstracted from the medical record. Main study outcomes included short- and long-term mortality within 28 days and 1 year of AMI hospitalization. Between 2000 and 2014, a total of 742 (3.6%) of 20 569 patients with AMI were identified with no documented SMuRFs. Patients without SMuRFs were less likely to receive aspirin, nonaspirin antiplatelet therapy, or beta blockers and less often underwent angiography and revascularization. Compared with those with one or more SMuRFs, patients without SMuRFs had significantly higher 28-day (odds ratio, 3.23 [95% CI, 1.78-5.88]) and 1-year (hazard ratio, 2.09 [95% CI, 1.29-3.37]) adjusted mortality. When examined across 5-year intervals from 2000 to 2014, the incidence of 28-day mortality significantly increased for patients without SMuRFs (7% to 15% to 27%), whereas it declined for those with 1 or more SMuRFs (7% to 5% to 5%). Conclusions Individuals without SMuRFs presenting with AMI have an increased risk of all-cause mortality with an overall lower prescription rate for guideline-directed medical therapy. These findings highlight the need for evidence-based pharmacotherapy during hospitalization and the need to discover new markers and mechanisms for early risk identification in this population.

Temporal trends and outcomes of patients with chronic limb-threatening ischemia with and without history of coronary artery disease: insights from the us national inpatient sample database.

BACKGROUND: The burden and prognostic significance of coronary artery disease (CAD) in adults with peripheral artery disease and chronic limb-threatening ischemia (CLTI) is unknown. METHODS: Temporal trends in prevalence of significant CAD (history of myocardial infarction or coronary revascularizations) in hospitalizations for CLTI were determined using the 2000 to 2018 National Inpatient Sample (NIS) database. A multivariable regression analysis of outcomes was performed based on presence or absence of CAD. RESULTS: Among 13 575 099 hospitalizations for CLTI (41% female, 69% white, mean age 69 years), 23% had concomitant CAD, of which 11% underwent lower extremity arterial revascularization (43.6% endovascular and 56.4% surgical). The prevalence of concomitant CAD with CLTI increased from 15.3% in 2000 to 23.1% in 2018. Furthermore, the frequency of endovascular revascularization in adults with CAD and CLTI increased from 15.1% to 48.3%, while there was a decreasing trend of surgical revascularization, from 84.9% to 51.7%. After multivariate adjustments, CLTI with CAD was associated with increased risk of in-hospital mortality (OR, 1.40; 95% CI, 1.32-1.47; P less than .0001) and bleeding requiring transfusion (OR, 1.10; 95% CI, 1.06-1.12; P less than .0001) compared with patients with CLTI without CAD. As compared with surgical revascularization, endovascular revascularization was associated with lower risk of in-hospital mortality in both patients with CLTI with CAD (OR, 0.69; 95% CI, 0.63-0.76; P less than .001) and CLTI without CAD (OR, 0.71; 95% CI, 0.67-0.76; P less than .001). CONCLUSIONS: Prevalence of CAD has increased in adults presenting with CLTI and is associated with poor outcomes, warranting the need for effective interventions and secondary prevention in this high-risk population.

Duodenal Mucosal Expression of COVID-19-Related Genes in Health, Diabetic Gastroenteropathy, and Functional Dyspepsia.

CONTEXT: SARS-CoV-2 infects the gastrointestinal tract and may be associated with symptoms that resemble diabetic gastroparesis. Why patients with diabetes who contract COVID-19 are more likely to have severe disease is unknown. OBJECTIVE: We aimed to compare the duodenal mucosal expression of SARS-CoV-2 and inflammation-related genes in diabetes gastroenteropathy (DGE), functional dyspepsia (FD), and healthy controls. METHODS: Gastrointestinal transit, and duodenal mucosal mRNA expression of selected genes were compared in 21 controls, 39 DGE patients, and 37 FD patients from a tertiary referral center. Pathway analyses were performed. RESULTS: Patients had normal, delayed (5 FD [13%] and 13 DGE patients [33%]; P = 0.03 vs controls), or rapid (5 FD [12%] and 5 DGE [12%]) gastric emptying (GE). Compared with control participants, 100 SARS-CoV-2-related genes were increased in DGE (FDR < 0.05) vs 13 genes in FD; 71 of these 100 genes were differentially expressed in DGE vs FD but only 3 between DGE patients with normal vs delayed GE. Upregulated genes in DGE include the SARS-CoV2 viral entry genes CTSL (|Fold change [FC]|=1.16; FDR < 0.05) and CTSB (|FC|=1.24; FDR < 0.05) and selected genes involved in viral replication (eg, EIF2 pathways) and inflammation (CCR2, CXCL2, and LCN2, but not other inflammation-related pathways eg, IL-2 and IL-6 signaling). CONCLUSION: Several SARS-CoV-2-related genes were differentially expressed between DGE vs healthy controls and vs FD but not between DGE patients with normal vs delayed GE, suggesting that the differential expression is related to diabetes per se. The upregulation of CTSL and CTSB and replication genes may predispose to SARS-CoV2 infection of the gastrointestinal tract in diabetes.

Prognostic significance of obstructive coronary artery disease in patients admitted with acute decompensated heart failure: the ARIC study community surveillance.

AIMS: We aimed to investigate the impact of obstructive coronary artery disease (CAD) in patients with acute decompensated heart failure (ADHF), and examine potential differences in prognostic utility for heart failure with reduced (HFrEF) versus preserved ejection fraction (HFpEF). METHODS AND RESULTS: The Atherosclerosis Risk in Communities study conducted hospital surveillance of ADHF from 2005 to 2014. Obstructive CAD was defined as ≥50% or ≥75% stenosis, respectively, for the left main and other major epicardial arteries. Adjusted associations between obstructive CAD and 30-, 60-, and 90-day mortality were analysed. A total of 934 (4146 weighted) patients admitted with ADHF (mean age 72 years, 46% women, 30% Black, 30% HFpEF) had available angiography (61% performed in hospital). Obstructive CAD was more prevalent with HFrEF than HFpEF, whether at the left main (15% vs. 11%), left anterior descending (LAD) (48% vs. 30%), left circumflex (37% vs. 32%), right coronary (42% vs. 32%), or multiple coronary arteries (45% vs. 33%). In-hospital revascularization was performed in 25% and 22% of patients with HFrEF and HFpEF, respectively. Obstructive CAD was associated with higher adjusted mortality, particularly with left main or LAD involvement, and had a more pronounced association with 90-day mortality in HFrEF (odds ratio [OR] 2.77; 95% confidence interval [CI] 1.53-5.02) than HFpEF (OR 0.94; 95% CI 0.36-2.41) (p-interaction = 0.05). CONCLUSION: Patients hospitalized with ADHF and coexisting obstructive CAD have higher short-term mortality, warranting the need for effective interventions and secondary prevention.

P2Y12 inhibitor versus aspirin monotherapy for secondary prevention of cardiovascular events: meta-analysis of randomized trials.

Aim: To compare the efficacy and safety of P2Y12 inhibitor or aspirin monotherapy for secondary prevention in patients with atherosclerotic cardiovascular disease (ASCVD). Methods and results: Medline, Embase, and Cochrane Central databases were searched to identify randomized trials comparing monotherapy with a P2Y12 inhibitor versus aspirin for secondary prevention in patients with ASCVD (cardiovascular, cerebrovascular, or peripheral artery disease). The primary outcome was major adverse cardiac events (MACE). Secondary outcomes were myocardial infarction (MI), stroke, all-cause mortality, and major bleeding. A random-effects model was used to calculate risk ratios (RR) and the corresponding 95% confidence interval (CI) and heterogeneity among studies was assessed using the Higgins I2 value. A total of 9 eligible trials (5 with clopidogrel and 4 with ticagrelor) with 61 623 patients were included in our analyses. Monotherapy with P2Y12 inhibitors significantly reduced the risk of MACE by 11% (0.89, 95% CI 0.84-0.95, I2 = 0%) and MI by 19% (0.81, 95% CI 0.71-0.92, I2 = 0%) compared with aspirin monotherapy. There was no significant difference in the risk of stroke (0.85, 95% CI 0.73-1.01), or all-cause mortality (1.01, 95% CI 0.92-1.11). There was also no significant difference in the risk of major bleeding with P2Y12 inhibitor monotherapy compared with aspirin (0.94, 95% CI 0.72-1.22, I2 = 42.6%). Results were consistent irrespective of the P2Y12 inhibitor used. Conclusion: P2Y12 inhibitor monotherapy for secondary prevention is associated with a significant reduction in atherothrombotic events compared with aspirin alone without an increased risk of major bleeding.

Prognostic value of shock index in patients admitted with non-ST-segment elevation myocardial infarction: the ARIC study community surveillance.

AIMS: Shock index (SI), defined as the ratio of heart rate (HR) to systolic blood pressure (SBP), is easily obtained and predictive of mortality in patients with ST-segment elevation myocardial infarction. However, large-scale evaluations of SI in patients with non-ST-segment elevation myocardial infarction (NSTEMI) are lacking. METHODS AND RESULTS: Hospitalizations for acute myocardial infarction were sampled from four US areas by the Atherosclerosis Risk in Communities (ARIC) study and classified by physician review. Shock index was derived from the HR and SBP at first presentation and considered high when ≥0.7. From 2000 to 2014, 18 301 weighted hospitalizations for NSTEMI were sampled and had vitals successfully obtained. Of these, 5753 (31%) had high SI (≥0.7). Patients with high SI were more often female (46% vs. 39%) and had more prevalent chronic kidney disease (40% vs. 32%). TIMI (Thrombolysis in Myocardial Infarction) risk scores were similar between the groups (4.3 vs. 4.2), but GRACE (Global Registry of Acute Coronary Syndrome) score was higher with high SI (140 vs. 118). Angiography, revascularization, and guideline-directed medications were less often administered to patients with high SI, and the 28-day mortality was higher (13% vs. 5%). Prediction of 28-day mortality by SI as a continuous measurement [area under the curve (AUC): 0.68] was intermediate to that of the GRACE score (AUC: 0.87) and the TIMI score (AUC: 0.54). After adjustments, patients with high SI had twice the odds of 28-day mortality (odds ratio = 2.02; 95% confidence interval: 1.46-2.80). CONCLUSION: The SI is easily obtainable, performs moderately well as a predictor of short-term mortality in patients hospitalized with NSTEMI, and may be useful for risk stratification in emergency settings.

Clinical and Echocardiographic Characteristics of Patients Hospitalized With Acute Versus Chronic Heart Failure With Preserved Ejection Fraction (From the ARIC Study).

An expanding number of therapies are now indicated for comorbidity management in heart failure with preserved ejection fraction (HFpEF). Whether comorbidity burdens differ for patients with HFpEF who are hospitalized for acute decompensated heart failure (ADHF) versus those with chronic stable heart failure (CSHF) who are hospitalized for other causes is uncertain. Since 2005, the Atherosclerosis Risk in Communities (ARIC) study has conducted adjudicated community surveillance of hospitalized heart failure. Hospitalized ADHF and CSHF were sampled identically, using prespecified discharge codes and demographic strata, but were differentiated by signs or symptoms of acute or worsening heart failure upon physician review of the medical record. HFpEF was defined by an ejection fraction ≥50%. All events were weighted by the inverse of the sampling probability for statistical analyses. From 2005 to 2014, 13,706 weighted (2,936 unweighted) hospitalizations (mean age 77 years, 64% women, 29% Black) were sampled among patients with HFpEF and adjudicated ADHF (86%) or CSHF (14%). Comorbidity prevalence was high both for ADHF and CSHF hospitalizations, irrespective of gender. Women hospitalized with ADHF versus CSHF had greater prevalence of hypertension (89% vs 84%) diabetes mellitus (48% vs 39%) and renal disease (85% vs 74%). Echocardiographic features such as left ventricular hypertrophy and valvular abnormalities were more common with ADHF than CSHF, for both genders. However, the 28-day and 1-year mortality risk were comparable for ADHF and CSHF. In conclusion, hospitalized patients with HFpEF have a high comorbidity burden and risk of death, irrespective of the cause of hospitalization.