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Aim To provide a contemporary analysis of incidence trends of infective endocarditis (IE) with its changing epidemiology over the past two decades in Europe. Methods A systematic review was conducted at the Mayo Clinic, Rochester. Ovid EBM Reviews, Ovid Embase, Ovid Medline, Scopus and Web of Science were searched for studies published between 1 January 2000 and 30 November 2020. All studies were independently reviewed by four referees and those that included a population-based incidence of IE in patients, irrespective of age, in Europe were included. Least squares regression was used to estimate pooled temporal trends in IE incidence. Results Of 9138 articles screened, 18 studies were included in the review. Elderly men predominated in all studies. IE incidence increased 4.1% per year (95% CI 1.8% to 6.4%) in the pooled regression analysis of eight studies that included comprehensive and consistent trends data. When trends data were weighted according to population size of individual countries, an increase in yearly incidence of 0.27 cases per 100 000 people was observed. Staphylococci and streptococci were the most common pathogens identified. The rate of surgical intervention ranged from 10.2% to 60.0%, and the rate of inpatient mortality ranged from 14.3% to 17.5%. In six studies that examined the rate of injection drug use, five of them reported a rate of less than 10%. Conclusion Based on findings from our systematic review, IE incidence in Europe has doubled over the past two decades in Europe. Multiple factors are likely responsible for this striking increase. Trial registeration number CRD42020191196.

In prediabetes, anthropometric characteristics as well as insulin action do not alter the hepatic response to glucagon. The postprandial suppression or lack of suppression of glucagon secretion is an important factor governing postprandial glucose tolerance independent of insulin secretion.

Abstract Background The objective of this paper was to examine temporal changes of infective endocarditis (IE) incidence and epidemiology in North America. Methods A systematic review was conducted at Mayo Clinic, Rochester. Ovid EBM Reviews, Ovid Embase, Ovid Medline, Scopus, and Web of Science were searched for studies published between January 1, 2000, and May 31, 2020. Four referees independently reviewed all studies, and those that reported a population-based incidence of IE in patients aged 18 years and older in North America were included. Results Of 8588 articles screened, 14 were included. Overall, IE incidence remained largely unchanged throughout the study period, except for 2 studies that demonstrated a rise in incidence after 2014. Five studies reported temporal trends of injection drug use (IDU) prevalence among IE patients with a notable increase in prevalence observed. Staphylococcus aureus was the most common pathogen in 7 of 9 studies that included microbiologic findings. In-patient mortality ranged from 3.7% to 14.4%, while the percentage of patients who underwent surgery ranged from 6.4% to 16.0%. Conclusions The overall incidence of IE has remained stable among the 14 population-based investigations in North America identified in our systematic review. Standardization of study design for future population-based investigations has been highlighted for use in subsequent systematic reviews of IE.

INTRODUCTION: We examined national Google Trends and local healthcare utilization after 3 high-impact gastroenterology publications. METHODS: Changes in US Google Trends and Olmsted County health utilization were studied. RESULTS: Publication views within 30 days were 51,458 ( Imperiale ), 49,759 ( Pimentel ), and 18,750 ( Gomm ). Colonoscopy searches ( P = 0.04) and Cologuard tests performed ( P < 0.01) increased while colonoscopies decreased ( P < 0.01). Searches for rifaximin ( P = 0.05), irritable bowel syndrome ( P < 0.01), diarrhea ( P < 0.01), and rifaximin prescriptions ( P = 0.02) increased. Increase in hydrogen-2 blocker searches ( P = 0.02) and prescriptions ( P < 0.01) and gastroesophageal reflux disease ( P < 0.01) and dementia office visits ( P < 0.01) occurred. DISCUSSION: High-impact gastroenterology publications influence Google searches and local population-based healthcare utilization.

The importance of coronary artery disease (CAD) surveillance, as recently underscored by the American Heart Association, is heightened by the obesity/diabetes epidemics. The need for surveillance is especially great for subclinical CAD, as the greatest increases in obesity/diabetes are occurring among younger age groups, where clinically-recognized CAD is infrequent. Yet few methods for such population-based surveillance exist. Using one such method, unbiased heart autopsy data, we previously showed that declines in grade of CAD observed since 1981 ended in the mid-1990s and may have reversed. In order to assess and interpret the factors underlying these observations, it is necessary to first examine trends in CAD risk factors among heart autopsied decedents and investigate the extent to which they mirror trends in the general population. Rochester Epidemiology Project (REP) medical records linkage resources were used to identify 1) all Olmsted County residents age 16-64 years who died from non-natural causes and went to autopsy 1981-2009 (96% autopsy rate) and 2) all Olmsted County residents age 16-64 years 1981-2009. We randomly selected two population subjects per decedent, stratified by calendar year. All REP inpatient/ ambulatory records were reviewed for CAD risk factors. Compared to population subjects, decedents were older and more likely to be male, smokers, alcohol abusers, and treated for hypertension; however, risk factor trends for both groups were generally of similar magnitude and direction, i.e., smoking, alcohol use, and blood pressure declined and anti-hypertensive medication use, diagnosed hyperlipidemia, and body mass index increased ( Table ). These population-based longitudinal data indicate that temporal trends in risk factors among autopsied decedents parallel those for the general population, supporting the concept that data on autopsied decedents can provide insight into trends in CAD risk and the changing burden of atherosclerosis within the source population. Characteristics of all 1) non-elderly adult Olmsted County residents who died non-natural deaths and were autopsied and 2) non-elderly adult Olmsted County residents with respect to CAD risk factors and calendar year trends CAD Risk Factor Autopsied Decedents (N=315) Population Subjects (N=672) P Value Autopsied Decedents, Temporal Trend Population Subjects, Temporal Trend N Calendar Year Estimate P value N Calendar Year Estimate P Value Age at Index, Mean (SD) 37.5 (14.0) 34.1 (13.6) <0.01 1 315 0.172 0.06 1 672 −0.059 0.33 1 Sex, % Male 236 (75%) 339 (50%) <0.01 2 315 0.008 0.60 2 672 −0.008 0.39 2 Race, % Non-White 29 (9%) 85 (13%) 0.14 3 305 0.054 0.04 3 589 0.023 0.12 3 Of Ever Smokers, Current = Yes 128/184 (70%) 118/210 (56%) 0.01 3 184 −0.040 0.048 3 210 −0.052 <0.01 3 Of Ever Alcohol Use, Current = Yes 175/238 (74%) 284/364 (78%) 0.08 3 238 −0.065 <0.01 3 364 −0.027 0.09 3 Mention of Alcoholism, Yes 80 (25%) 41 (6%) <0.01 3 315 0.014 0.35 3 672 0.042 0.04 3 Closest Systolic BP, Mean (SD) 124.1 (16.6) 120.3 (15.7) 0.34 3 285 −0.179 0.09 3 600 −0.156 0.02 3 Closest Diastolic BP, Mean (SD) 76.2 (11.6) 74.0 (10.5) 0.53 3 285 −0.194 0.01 3 600 −0.112 0.02 3 Closest BP on Medication, Yes 44 (14%) 36 (5%) <0.01 3 283 0.046 0.03 3 599 0.063 <0.01 3 Hyperlipidemia Diagnosis, Yes 32 (10%) 65 (10%) 0.32 3 315 0.114 <0.01 3 672 0.078 <0.01 3 Closest Fasting Glucose, Mean (SD) 95.8 (26.0) 95.0 (27.6) 0.63 3 177 0.270 0.23 3 335 0.505 <0.01 3 Closest BMI, Mean (SD) 26.1 (5.8) 25.9 (5.4) 0.52 3 280 0.080 0.04 3 593 0.091 <0.01 3 1 Unadjusted, Chi-square; 2 Unadjusted, Wilcoxon rank sum test; 3 Adjusted for age and sex, linear or logistic regression; BP = Blood Pressure; BMI = Body Mass Index

Introduction: Triple oral antithrombotic therapy (TOAT) (aspirin, clopidogrel, and warfarin) is associated with an increased risk of bleeding. Despite this, the optimal management of patients with indications for warfarin following percutaneous coronary intervention (PCI) has not been established. We sought to compare long-term clinical outcomes between patients receiving TOAT with those receiving dual antiplatelet therapy (DAPT) (aspirin and clopidogrel) after PCI. Hypothesis: Patients with clinical indications for warfarin have higher baseline risk which is largely responsible for the observed differences in outcomes between patients receiving TOAT vs. DAPT. Methods: Retrospective analysis of prospectively collected data from 9,009 patients. The primary outcome was a composite of all-cause mortality, ischemic or embolic events (myocardial infarction or stroke), or bleeding. Secondary outcomes were death plus ischemic or embolic events, death plus bleeding, death, MI, stroke, and bleeding. A 2:1 propensity matched analysis was also performed. Results: In 9,009 patients, 812 received TOAT and 8,197 received DAPT. Median follow-up was 61 months. The primary end point occurred in 2,749 patients. At 1 year, 22% of patients treated with TOAT had the primary endpoint versus 11% of DAPT patients (p<0.001). At 1 year, secondary end points of death or ischemic or embolic events (19% vs. 10%, p<0.001), and death or bleeding events (15% vs. 5%, p<0.001) also occurred with a higher frequency with TOAT. After propensity matched analysis the above differences were no longer significant with 1 year primary endpoint rates of 19% vs. 17% respectively (HR 1.95%, CI 0.88, 1.47; p = 0.33). Following propensity matching the only significant difference between TOAT and DAPT groups was minor bleeding (5% vs. 2%; HR 2.65, 95% CI 1.39, 5.03; p=0.003). Conclusions: In a large single center registry with comprehensive follow up, patients treated with TOAT had higher rates of ischemic and bleeding events. However, when baseline risks are accounted for event rates are similar, other than minor bleeding, indicating patient risk characteristics are largely responsible for the observed differences in outcomes.

Background. Apical hypertrophic cardiomyopathy (AHCM) has been considered a ``benign” form of HCM in Asian and non-Asian patients (pt). However, data on long-term outcome of pt with AHCM are limited. The purpose of this study was to determine the natural history of pt with AHCM followed at a tertiary referral center in North America. Methods. Between July 1976 and September 2006, 193 pt with the diagnosis of AHCM were seen at the Hypertrophic Cardiomyopathy Clinic. The last echocardiographic exam was reviewed in all pt. Follow-up data were obtained where possible (clinic visit). Results. Mean age at diagnosis 56±17 years, mean age at first presentation at our center was 58±17 years. Symptoms included chest pain in 69 pt (36 %), and exertional dyspnea ≥NYHA II in 97 pt (50 %). A family history of either HCM and/or sudden cardiac death was reported by 36 pt (19 %). Coronary artery disease was proven in 40 pt (21 %). Median follow up was 50 months (1–318) and obtained in 124 pt (64 %). The following events were reported at the last clinic visit: heart failure in =5 pt, syncope in =0 pt, ventricular tachycardia in =7 pt, ICD implantation in 22 pt, and stroke in 22 pt. Death from all causes occurred in 51 of 193 pt (26 %) at a mean age of 72 years (14–78). Kaplan-Meier survival analysis was used to examine survival from all causes of death since first presentation. Observed survival in patients with AHCM was significantly less than expected in an age- and gender matched Minnesota white population (p=0.009). The observed survival at 5, 10 and 15 years was 87 %, 82 %, and 57 % respectively, while the expected survival for these time points was 91 %, 81 %, and 72 %. Conclusions. AHCM in this predominantly North American patient population is associated with an increased mortality. Patients with AHCM have a high incidence of significant cardiovascular symptoms and ventricular arrhythmias. As the disease is less benign than previously suspected, careful longitudinal care by a cardiologist is warranted.

Introduction: Plasma aldosterone (Aldo) increases Na and water reabsorption and mediates inflammation. Our recent findings in a general population cohort showed Aldo strongly associated with hypertension (HTN), obesity, chronic kidney disease (CKD) and lower natriuretic peptide levels (NPs) during a first visit (V1), even when Aldo was within the normal range. It is undefined whether Aldo itself (V1) and/or its increase after 4-year (second visit, V2) can predict new onset cardiovascular and metabolic diseases. Hypotheses: We hypothesized that: 1) Aldo-V1 predicts new onset disease at V2; 2) The increase of Aldo between V1 and V2 predicts new onset disease-V2; and 3) Aldo-V2 remains associated with cardiovascular and metabolic disease-V2. Methods: We defined the correlations between Aldo-V1 and Aldo-V2 with cardiometabolic diseases and medications at V2, in a general community cohort (N=1368) from Olmsted County, MN. Associations were adjusted for age, sex and BMI; Aldo was analyzed as continuous variable and according to tertiles. Results: After 4 years, Aldo-V1 continuous variable predicted new onset of central obesity (p=0.0113, OR=1.36, CI=1.07-1.73), HTN (p=0.0012, OR=1.36, CI=1.13-1.63) and use of antilipemic drugs (p=0.0119, OR=1.25, CI=1.05-1.48); while Aldo-V1 in the 3 rd tertile predicted new onset of type 2 diabetes (T2DM) (p=0.0392, OR=1.96, CI=1.03-3.70), use of antilipemic therapy (p=0.0162, OR=1.59, CI=1.09-2.31) and HTN (p=0.049, OR1.44, CI=1.00-2.08) at V2. Secondly, we observed that the increase in Aldo between V1 and V2 predicted new HTN-V2. Finally, we found higher Aldo-V2, but still within the normal range and Aldo-V2 remained associated with HTN, obesity and CKD, when analyzed as continuous variable and when in the 3 rd tertile. Conclusions: In the general community, Aldo-V1 predicts new onset HTN, central obesity, T2DM and use of antilipemic therapy. Importantly, the increase of aldosterone between V1 and V2 also predicts new onset HTN. Finally, Aldo-V2 correlates with HTN, obesity and CKD as we found at V1. Further studies are warranted to evaluate aldosterone as therapeutic target to delay disease progression, and to support its role as prognostic biomarker to identify high-risk subjects.

Objective Activated platelets serve as a catalyst for thrombin generation. Furthermore, oral MHT may carry greater thrombotic risk than transdermal products. This study compared effects of oral and transdermal MHT on platelet characteristics including platelet‐derived microvesicles (MV) in recently menopausal women. Methods Platelets and MV were prepared from blood of a subset of women (n=117) enrolled in the Kronos Early Estrogen Prevention Study prior to and after 4 years of treatment with either oral conjugated equine estrogen (0.45 mg, oCEE), transdermal 17β estradiol (50 µg/day, tE2), each with intermittent progesterone (200 mg/day for 12 days a month), or placebo pills and patch. Results Platelet count, and activated platelet P‐selectin and fibrinogen‐binding receptor expression were similar across groups. Numbers of tissue factor positive and platelet‐derived MV increased significantly in the tE2 compared to placebo. Conclusions Four years of MHT did not increase thrombogenic characteristics of platelets. Thrombotic risk associated with oral MHT most likely involves liver‐derived proteins than platelets per se. Differential effects of oCEE and tE2 on circulating MV may reflect the hormonal composition of the two formulations on non‐genomic pathways in circulating platelets. Funding This work was supported by grants from the Aurora Foundation to the Kronos Longevity Research Institute, NIH HL90639, UL1TR00013 1 , American Heart Association‐ Scientist Development Grant, AHA 08‐30503Z, American Heart Association, Grant‐in‐Aid, 12GRNT12050147, and the Mayo Foundation.

Background Break down of the blood brain barrier and activation of brain cells are implicated in progression of deposition of β‐amyloid that is associated with the pathophysiology of Alzheimer's disease. A previous study from our group indicated that deposition of β‐amyloid may be reduced in the brains of menopausal women treated with transdermal 17β‐estradiol. This study aimed to determine the association of peripheral microvesicles carrying markers of cells of the neurovascular unit with β‐amyloid in the brains of menopausal women and if the association was affected by prior menopausal hormone treatments (MHT). Methods Menopausal women previously enrolled in the Kronos Early Estrogen Prevention Study at Mayo Clinic underwent β‐amyloid positron emission tomography (PET) imaging of their brains 3 years following treatment with either placebo (PL, n=29), transdermal 17β‐estradiol (tE2; n=21), or oral conjugated equine estrogen (oCEE; n=17) for 4 years. Microvesicles (MV) were isolated from peripheral venous blood by differential centrifugation and analyzed by flow cytometry using fluorophore conjugated antibodies directed toward total tau, β‐amyloid 1‐42 (Ab1‐42), neuron specific class III β‐tubulin (Tuj1), microglia ionized calcium adaptor molecule 1(Iab‐1), glial fibrillar acid protein (GFAP), and low density lipoprotein receptor‐related protein 1. Principal components analysis was used to reduce the dimensionality of the 6 brain markers to 2 principal components (PCs). Proportional odds ordinal logistic regression analysis was used to regress deposition of β‐amyloid on the 2 PCs with and without adjustment for MHT group. Results Number of blood MV positive for Ab1‐42 differed significantly among MHT groups (median [IQR]: 6.06 [2.11, 12.55] in the PL; 2.49 [0.73, 3.59] in the tE2 and 4.96 [0.83, 10.31] in the oCEE; P=0.036). The first 2 PCs explain 58% of the variance of the 6 markers. PC#1 represented a contrast between MV‐Iab‐1 and the MV‐GFAP and MV‐Tuj1. In multivariable models, brain β‐amyloid load positively associated with the first PC after adjustment for MHT (P= 0.006). Conclusion MV derived from cells of the neurovascular unit can be detected in peripheral blood, and, when combined into summary scores, showed an association with deposition of β‐amyloid in the brain that is independent of MHT. Support or Funding Information Supported by grants from NIH P50 AG044170 and the Mayo Foundation This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .