The clinical impact of estimating low-density lipoprotein cholesterol (LDL-C) using different equations in the general population.

BACKGROUND: Low-density lipoprotein cholesterol (LDL-C) is associated with atherosclerotic cardiovascular disease (ASCVD). Friedewald, Sampson, and Martin-Hopkins equations are used to calculate LDL-C. This study compares the impact of switching between these equations in a large geographically defined population. MATERIALS AND METHODS: Data for individuals who had a lipid panel ordered clinically between 2010 and 2019 were included. Comparisons were made across groups using the two-sample t-test or chi-square test as appropriate. Discordances between LDL measures based on clinically actionable thresholds were summarized using contingency tables. RESULTS: The cohort included 198,166 patients (mean age 54 years, 54% female). The equations perform similarly at the lower range of triglycerides but began to diverge at a triglyceride level of 125 mg/dL. However, at triglycerides of 175 mg/dL and higher, the Martin-Hopkins equation estimated higher LDL-C values than the Samson equation. This discordance was further exasperated at triglyceride values of 400 to 800 mg/dL. When comparing the Sampson and Friedewald equations, at triglycerides are below 175 mg/dL, 9% of patients were discordant at the 70 mg/dL cutpoint, whereas 42.4% were discordant when triglycerides are between 175 and 400 mg/dL. Discordance was observed at the clinically actionable LDL-C cutpoint of 190 mg/dL with the Friedewald equation estimating lower LDL-C than the other equations. In a high-risk subgroup (ASCVD risk score > 20%), 16.3% of patients were discordant at the clinical cutpoint of LDL-C < 70 mg/dL between the Sampson and Friedewald equations. CONCLUSIONS: Discordance at clinically significant LDL-C cutpoints in both the general population and high-risk subgroups were observed across the three equations. These results show that using different methods of LDL-C calculation or switching between different methods could have clinical implications for many patients.

Advanced Heart Failure Characteristics and Outcomes in Women and Men.

BACKGROUND: The epidemiology and pathophysiology of heart failure (HF) differ in women and men. Whether these differences extend to the subgroup of patients with advanced HF is not well defined. METHODS AND RESULTS: This is a retrospective cohort study of all adult Olmsted County, Minnesota residents with advanced HF (European Society of Cardiology criteria) from 2007 to 2017. Differences in survival and hospitalization risks in women and men following advanced HF development were examined using Cox proportional hazard regression and Andersen-Gill models, respectively. Of 936 individuals with advanced HF, 417 (44.6%) were women and 519 (55.4%) were men (self-reported sex). Time from development of HF to advanced HF was similar in women and men (median 3.2 versus 3.6 years). Women were older at diagnosis (mean age 79 versus 75 years), less often had coronary disease and hyperlipidemia, but more often had hypertension and depression (P<0.05 for each). Advanced HF with preserved ejection fraction was more prevalent in women than men (60% versus 30%, p<0.001). There were no differences in adjusted risks of all-cause mortality (hazard ratio [HR], 0.89 [95% CI, 0.77-1.03]), cardiovascular mortality (HR, 0.85 [95% CI, 0.70-1.02]), all-cause hospitalizations (HR, 1.04 [95% CI, 0.90-1.20]), or HF hospitalizations (HR, 0.91 [95% CI, 0.75-1.11]) between women and men. However, adjusted cardiovascular mortality was lower in women versus men with advanced HF with reduced ejection fraction (HR, 0.72 [95% CI, 0.56-0.93]). CONCLUSIONS: Women more often present with advanced HF with preserved ejection fraction and men with atherosclerotic disease and advanced HF with reduced ejection fraction. Despite these differences, survival and hospitalization risks are largely comparable in women and men with advanced HF.

Systemic correlates of cutaneous manifestations of lupus erythematosus.

BACKGROUND: We aimed to investigate the prevalence of skin disease among patients with systemic lupus erythematosus (SLE) and determine whether LE skin disease had clinical or serologic correlates with SLE. METHODS: We reviewed records of 335 patients with SLE (seen at Mayo Clinic, Rochester, Minnesota, USA) and abstracted skin manifestations, fulfilled mucocutaneous SLE criteria, and clinical and serologic parameters. RESULTS: Of the 231 patients with skin manifestations, 57 (24.7%) had LE-specific conditions, 102 (44.2%) had LE-nonspecific conditions, and 72 (31.2%) had both. LE skin disease was associated with photosensitivity, anti-Smith antibodies, and anti-U1RNP antibodies (all P < 0.001). Patients without LE skin disease more commonly had elevated C-reactive protein levels (P = 0.01). Patients meeting 2-4 mucocutaneous American College of Rheumatology criteria less commonly had cytopenia (P = 0.004) or anti-double-stranded DNA antibodies (P = 0.004). No significant associations were observed for systemic involvement (renal, hematologic, neurologic, and arthritis) when comparing patients with or without LE skin involvement. LE skin involvement was not significantly associated with internal SLE disease flare, number of medications, or overall survival. CONCLUSIONS: LE skin disease commonly occurs in patients with SLE. The presence of LE skin disease had no mitigating impact on the severity of SLE sequelae, disease flares, number of medications, or overall survival.

The impact of multimorbidity and functional limitation on quality of life in patients with heart failure: A multi-site study.

BACKGROUND: Multimorbidity and functional limitation are associated with poor outcomes in heart failure (HF). However, the individual and combined effect of these on health-related quality of life in patients with HF is not well understood. METHODS: Patients aged ≥30 years with two or more HF diagnostic codes and one or more HF-related prescription drugs from four U.S. institutions were mailed a survey to measure patient-centric factors including functional status (activities of daily living [ADLs]) and health-related quality of life (PROMIS-29 Health Profile). Patients with HF from January 1, 2013 to February 1, 2018 were included. Multimorbidity was defined as ≥2 non-cardiovascular comorbidities; functional limitation as any limitation in at least one of eight ADLs. Patients were categorized into four groups by multimorbidity (Yes/No) and functional limitation (Yes/No). We dichotomized the PROMIS-29 sub-scale scores at the median and calculated odd ratios for the four multimorbidity/functional limitation groups. RESULTS: A total of 3330 patients with HF returned the survey (response rate 31%); 3020 completed the questions of interest and were retained. Among these patients (45% female; mean age 73 [standard deviation: 12] years), 29% had neither multimorbidity nor functional limitation, 24% had multimorbidity only, 22% had functional limitation only, and 25% had both. After adjustment, having functional limitation only was associated with higher anxiety (odds ratio [OR]: 3.44, 95% confidence interval [CI]: 2.66-4.45), depression (OR: 3.11, 95% CI: 2.39-4.06), and fatigue (OR: 4.19, 95% CI: 3.25-5.40); worse sleep (OR: 2.14, 95% CI: 1.69-2.72) and pain (OR: 6.73, 95% CI: 5.15-8.78); and greater difficulty with social activities (OR: 9.40, 95% CI: 7.19-12.28) compared with having neither. Results were similar for having both multimorbidity and functional limitation. CONCLUSION: Patients with only functional limitation have similar poor health-related quality of life scores as those with both multimorbidity and functional limitation, underscoring the important role that physical functioning plays in the well-being of patients with HF.

Discordance Between Very Low-Density Lipoprotein Cholesterol and Low-Density Lipoprotein Cholesterol Increases Cardiovascular Disease Risk in a Geographically Defined Cohort.

BACKGROUND: Clinical risk scores are used to identify those at high risk of atherosclerotic cardiovascular disease (ASCVD). Despite preventative efforts, residual risk remains for many individuals. Very low-density lipoprotein cholesterol (VLDL-C) and lipid discordance could be contributors to the residual risk of ASCVD. METHODS AND RESULTS: Cardiovascular disease-free residents, aged ≥40 years, living in Olmsted County, Minnesota, were identified through the Rochester Epidemiology Project. Low-density lipoprotein cholesterol (LDL-C) and VLDL-C were estimated from clinically ordered lipid panels using the Sampson equation. Participants were categorized into concordant and discordant lipid pairings based on clinical cut points. Rates of incident ASCVD, including percutaneous coronary intervention, coronary artery bypass grafting, stroke, or myocardial infarction, were calculated during follow-up. The association of LDL-C and VLDL-C with ASCVD was assessed using Cox proportional hazards regression. Interaction between LDL-C and VLDL-C was assessed. The study population (n=39 098) was primarily White race (94%) and female sex (57%), with a mean age of 54 years. VLDL-C (per 10-mg/dL increase) was significantly associated with an increased risk of incident ASCVD (hazard ratio, 1.07 [95% CI, 1.05-1.09]; P<0.001]) after adjustment for traditional risk factors. The interaction between LDL-C and VLDL-C was not statistically significant (P=0.11). Discordant individuals with high VLDL-C and low LDL-C experienced the highest rate of incident ASCVD events, 16.9 per 1000 person-years, during follow-up. CONCLUSIONS: VLDL-C and lipid discordance are associated with a greater risk of ASCVD and can be estimated from clinically ordered lipid panels to improve ASCVD risk assessment.

Results of Patch Testing to Botanicals: Review of the Mayo Clinic Experience Over 2 Decades (1997-2017).

Background: Botanicals are increasingly incorporated into skincare products. Although allergic contact dermatitis due to botanicals is recognized, data describing the prevalence of positive patch tests to botanicals are sparse. Objective: To report the Mayo Clinic experience of patch testing to selected botanical products in the standard, extended standard, fragrance, and plant series. Methods: IRB-approved retrospective study of the Mayo Clinic experience with patch testing to botanicals from 1997 to 2017. Results: In total, 12,169 people were patch tested to botanicals in the standard, extended standard, fragrance, and plant series; 4032 were men and 8137 were women. The mean age of the population tested was 54 (standard deviation 17.7) years. Almost 11% (1320/12,169) of the patch-tested population exhibited positive reactions to at least 1 botanical agent. Myroxylon pereirae resin 25% was the most common positive allergen in the series. Patients who had positive reactions to at least 1 botanical agent were more (19.8%) likely to have a positive reaction to at least 1 additional botanical than those patients who did not have any positive tests. Most patients presented with generalized involvement (334) or involvement of the hands (284) or face (232). Conclusion: Physicians should be aware of the high prevalence of allergic contact dermatitis and patch test positivity associated with botanical products.

Patient Awareness of Heart Failure Diagnosis: A Community Study.

Background Heart failure (HF) is a complex disease that contributes to a high number of hospitalizations, deaths, and economic health care costs each year. However, among patients with HF, there is a lack of awareness of their HF diagnosis that has not been fully examined. Methods and Results Residents from 3 counties of southeast Minnesota with a first-ever International Classification of Diseases, Ninth Revision (ICD-9) code 428 or Tenth Revision (ICD-10) code I50 between January 1, 2013 and March 31, 2016 (N=2461) were prospectively surveyed to measure HF self-awareness. A total of 1114 patients returned the survey (response rate, 45%), and 787 had validated HF upon medical record review. Among these 787 patients with HF (mean age, 76 years; 53% men), 37% (n=293) were aware of their HF diagnosis. After adjustment, being a woman (odds ratio [OR], 1.56 [95% CI, 1.10-2.22]), having HF with reduced ejection fraction (OR, 1.58 [95% CI, 1.13-2.22]), attending the HF clinic (OR, 4.07 [95% CI, 2.25-7.36]), and having coronary artery disease (OR, 1.65 [95% CI, 1.16-2.37]) were all associated with increased awareness of an HF diagnosis. Conversely, having diabetes was associated with decreased awareness of an HF diagnosis (adjusted OR, 0.69 [95% CI, 0.50-0.95]). Conclusions Awareness of an HF diagnosis is low in a community population of patients with HF. Strategies to improve patient awareness of their diagnosis should be implemented to improve self-care behaviors and outcomes in patients with HF.

Association Between Fluctuations in Blood Lipid Levels Over Time With Incident Alzheimer Disease and Alzheimer Disease-Related Dementias.

BACKGROUND AND OBJECTIVES: Prevention strategies for Alzheimer disease and Alzheimer disease-related dementias (AD/ADRDs) are urgently needed. Lipid variability, or fluctuations in blood lipid levels at different points in time, has not been examined extensively and may contribute to the risk of AD/ADRD. Lipid panels are a part of routine screening in clinical practice and routinely available in electronic health records (EHR). Thus, in a large geographically defined population-based cohort, we investigated the variation of multiple lipid types and their association to the development of AD/ADRD. METHODS: All residents living in Olmsted County, Minnesota on the index date January 1, 2006, aged 60 years or older without an AD/ADRD diagnosis were identified. Persons with ≥3 lipid measurements including total cholesterol, triglycerides, low-density lipoprotein cholesterol (LDL-C), or high-density lipoprotein cholesterol (HDL-C) in the 5 years before index date were included. Lipid variation was defined as any change in individual's lipid levels over time regardless of direction and was measured using variability independent of the mean (VIM). Associations between lipid variation quintiles and incident AD/ADRD were assessed using Cox proportional hazards regression. Participants were followed through 2018 for incident AD/ADRD. RESULTS: The final analysis included 11,571 participants (mean age 71 years; 54% female). Median follow-up was 12.9 years with 2,473 incident AD/ADRD cases. After adjustment for confounding variables including sex, race, baseline lipid measurements, education, BMI, and lipid-lowering treatment, participants in the highest quintile of total cholesterol variability had a 19% increased risk of incident AD/ADRD, and those in highest quintile of triglycerides, variability had a 23% increased risk. DISCUSSION: In a large EHR derived cohort, those in the highest quintile of variability for total cholesterol and triglyceride levels had an increased risk of incident AD/ADRD. Further studies to identify the mechanisms behind this association are needed.

Changes in Kidney Function After Diagnosis of Advanced Heart Failure.

BACKGROUND: Kidney function and its association with outcomes in patients with advanced heart failure (HF) has not been well-defined. METHODS AND RESULTS: We conducted a retrospective cohort study comprising all adult residents of Olmsted County, Minnesota, with HF who developed advanced HF from 2007 to 2017. Patients were grouped by estimated glomerular filtration rate (eGFR) at advanced HF diagnosis using the 2021 Chronic Kidney Disease Epidemiology Collaboration equation. A linear mixed effects model was fitted to assess the relationship between development of advanced HF and longitudinal eGFR trajectory. A total of 936 patients with advanced HF (mean age 77 years, 55% male, 93.7% White) were included. Twenty-two percent of these patients had an eGFR of <30 at advanced HF diagnosis, 22% had an eGFR of 30-44, 23% had an eGFR of 45-59, and 32% had an eGFR of ≥60 mL/min/1.73 m2. The eGFR decreased faster after advanced HF (7.6% vs 10.9% annual decline before vs after advanced HF), with greater decreases after advanced HF in those with diabetes and preserved ejection fraction. An eGFR of <30 mL/min/1.73 m2 was associated with worse survival after advanced HF compared with an eGFR of ≥60 mL/min/1.73 m2 (adjusted hazard ratio 1.30, 95% confidence interval 1.07-1.57). CONCLUSIONS: eGFR deteriorated faster after patients developed advanced HF. An eGFR of <30 mL/min/1.73 m2 at advanced HF diagnosis was associated with higher mortality.

Variability in Lipid Levels and Risk for Cardiovascular Disease: An Electronic Health Record-Based Population Cohort Study.

Background Larger within-patient variability of lipid levels has been associated with increased risk of cardiovascular disease (CVD); however, measures of lipid variability require ≥3 measurements and are not currently used clinically. We investigated the feasibility of calculating lipid variability within a large electronic health record-based population cohort and assessed associations with incident CVD. Methods and Results We identified all individuals ≥40 years of age who resided in Olmsted County, MN, on January 1, 2006 (index date), without prior CVD, defined as myocardial infarction, coronary artery bypass graft surgery, percutaneous coronary intervention, or CVD death. Patients with ≥3 measurements of total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, or triglycerides during the 5 years before the index date were retained. Lipid variability was calculated using variability independent of the mean. Patients were followed through December 31, 2020 for incident CVD. We identified 19 652 individuals (mean age 61 years; 55% female), who were CVD-free and had variability independent of the mean calculated for at least 1 lipid type. After adjustment, those with highest total cholesterol variability had a 20% increased risk of CVD (Q5 versus Q1 hazard ratio, 1.20 [95% CI, 1.06-1.37]). Results were similar for low-density lipoprotein cholesterol and high-density lipoprotein cholesterol. Conclusions In a large electronic health record-based population cohort, high variability in total cholesterol, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol was associated with an increased risk of CVD, independent of traditional risk factors, suggesting it may be a possible risk marker and target for intervention. Lipid variability can be calculated in the electronic health record environment, but more research is needed to determine its clinical utility.

Trends in Patch Testing of Black Patients: The Mayo Clinic Decade Experience (January 1, 2011, to December 31, 2020).

Background: Trends in patch testing for allergic contact dermatitis (ACD) have not been well characterized in Black patients. Despite similar incidence of ACD in Black and White patients, there are differences in allergen profiles. Understanding patch testing trends in Black patients furthers knowledge that has considerable impact on the management of ACD in the Black population. Objective: The purpose of this study was to review the results of patch testing in Black patients at Mayo Clinic over a decade. Methods: We retrospectively reviewed the results of patch testing to the standard, extended standard, or hairdresser series in 149 Black patients seen at Mayo Clinic (Rochester, MN; Scottsdale, AZ; and Jacksonville, FL) from January 1, 2011, to December 31, 2020. Results: During the 10-year period, 149 Black patients (mean age, 49.2 years [SD, 17.1 years]; female 67.1%) were patch tested at Mayo Clinic to the standard, extended standard, or hairdresser series. Most common sites of dermatitis were generalized (30.9%), hands (18.8%), leg (16.8%), trunk (16.1%), and arm (14.8%). Overall, 109 patients (73.2%) had at least 1 positive reaction and 74 patients (50%) had 2 or more positive reactions. Overall, the 10 allergens with the highest reaction rates (from highest to lowest) identified in our study population were 4-amino-2-hyroxytoluene (33.3%), thimerosal (20.4%), nickel sulfate (18.9%), methylisothiazolinone (16.5%), methyldibromo glutaronitrile (13.4%), methyldibromo glutaronitrile/phenoxyethanol (12.5%), captan (12.5%), carmine (12.5%), methylchloroisothiazolinone/methylisothiazolinone (11.5%), and hydroperoxide of linalool 1% (11.3%). Conclusions: We describe patch test results in Black patients over a decade at Mayo Clinic. The top 10 allergens were preservatives, hair dyes, and fragrances. Differing patterns of allergens may occur in Black patients due to different patterns of exposures related to cultural practices.

Predictors of Metformin Failure: Repurposing Electronic Health Record Data to Identify High-Risk Patients.

CONTEXT: Metformin is the first-line drug for treating diabetes but has a high failure rate. OBJECTIVE: To identify demographic and clinical factors available in the electronic health record (EHR) that predict metformin failure. METHODS: A cohort of patients with at least 1 abnormal diabetes screening test that initiated metformin was identified at 3 sites (Arizona, Mississippi, and Minnesota). We identified 22 047 metformin initiators (48% female, mean age of 57 ± 14 years) including 2141 African Americans, 440 Asians, 962 Other/Multiracial, 1539 Hispanics, and 16 764 non-Hispanic White people. We defined metformin failure as either the lack of a target glycated hemoglobin (HbA1c) (<7%) within 18 months of index or the start of dual therapy. We used tree-based extreme gradient boosting (XGBoost) models to assess overall risk prediction performance and relative contribution of individual factors when using EHR data for risk of metformin failure. RESULTS: In this large diverse population, we observed a high rate of metformin failure (43%). The XGBoost model that included baseline HbA1c, age, sex, and race/ethnicity corresponded to high discrimination performance (C-index of 0.731; 95% CI 0.722, 0.740) for risk of metformin failure. Baseline HbA1c corresponded to the largest feature performance with higher levels associated with metformin failure. The addition of other clinical factors improved model performance (0.745; 95% CI 0.737, 0.754, P < .0001). CONCLUSION: Baseline HbA1c was the strongest predictor of metformin failure and additional factors substantially improved performance suggesting that routinely available clinical data could be used to identify patients at high risk of metformin failure who might benefit from closer monitoring and earlier treatment intensification.

Rethinking blood eosinophil counts: Epidemiology, associated chronic diseases, and increased risks of cardiovascular disease.

Background: The distribution and determinants of blood eosinophil counts in the general population are unclear. Furthermore, whether elevated blood eosinophil counts increase risk for cardiovascular disease (CVD) and other chronic diseases, other than atopic conditions, remains uncertain. Objective: We sought to describe the distribution of eosinophil counts in the general population and determine the association of eosinophil count with prevalent chronic disease and incident CVD. Methods: A population-based adult cohort was followed from January 1, 2006, to December 31, 2020. Electronic health record data regarding demographic characteristics, prevalent clinical characteristics, and incident CVD were extracted. Associations between blood eosinophil counts and demographic characteristics, chronic diseases, laboratory values, and risks of incident CVD were assessed using chi-square test, ANOVA, and Cox proportional hazards regression. Results: Blood eosinophil counts increased with age, body mass index, and reported smoking and tobacco use. The prevalence of chronic obstructive pulmonary disease, hypertension, cardiac arrhythmias, hyperlipidemia, diabetes mellitus, chronic kidney disease, and cancer increased as eosinophil counts increased. Eosinophil counts were significantly associated with coronary heart disease (hazard ratio [HR], 1.44; 95% CI, 1.12-1.84) and heart failure (HR, 1.62; 95% CI, 1.30-2.01) in fully adjusted models and with stroke/transient ischemic attack (HR, 1.37; 95% CI, 1.16-1.61) and CVD death (HR, 1.49; 95% CI, 1.10-2.00) in a model adjusting for age, sex, race, and ethnicity. Conclusions: Blood eosinophil counts differ by demographic and clinical characteristics as well as by prevalent chronic disease. Moreover, elevated eosinophil counts are associated with risk of CVD. Further prospective investigations are needed to determine the utility of eosinophil counts as a biomarker for CVD risk.

Activities of Daily Living and Outcomes in Patients with Advanced Heart Failure.

BACKGROUND: Functional debility is associated with worse outcomes in the general heart failure population, but the prevalence of difficulty with activities of daily living and clinical significance once patients develop advanced heart failure requires further examination. METHODS: This was a population-based, retrospective cohort study of Olmsted County, Minnesota adults with advanced heart failure from 2007-2018. Difficulty with 9 activities of daily living was assessed by questionnaire. Predictors of difficulty were assessed by a proportional odds model. Associations of difficulty with activities of daily living with mortality and hospitalization were examined using Cox and Andersen-Gill models. RESULTS: Among 765 patients with advanced heart failure, 565 (73.9%) reported difficulty with activities of daily living at diagnosis. Of those, 257 (45%) had moderate and 148 (26%) had severe difficulty. Independent predictors of difficulty included female sex (odds ratio [OR] 1.73; 95% confidence interval [CI], 1.26-2.36; P = .001), older age (OR per 10-year increase 1.17; 95% CI, 1.05-1.31; P = .005), dementia (OR 1.85; 95% CI, 1.06-3.24; P = .031), depression (OR 1.75; 95% CI, 1.28-2.40; P = .001), and morbid obesity (OR 1.49; 95% CI, 1.04-2.13; P = .031). Estimated 2-year mortality was 61.5%, 64.2%, and 67.6% in patients with no/minimal, moderate, and severe difficulty, respectively. The adjusted hazard ratios (95% CI) for death were 1.08 (0.90-1.28) and 1.17 (0.95-1.43) for moderate and severe difficulty, respectively, vs no/minimal difficulty (P = .33). There were no statistically significant associations of difficulty with activities of daily living and hospitalization risks. CONCLUSIONS: Most patients with advanced heart failure have difficulty completing activities of daily living and are at high risk of mortality regardless of impairment in activities of daily living.

Guideline-Directed Medical Therapy in Newly Diagnosed Heart Failure With Reduced Ejection Fraction in the Community.

BACKGROUND: Guideline-directed medical therapy (GDMT) dramatically improves outcomes in heart failure with reduced ejection fraction (HFrEF). Our goal was to examine GDMT use in community patients with newly diagnosed HFrEF. METHODS AND RESULTS: We performed a population-based, retrospective cohort study of all Olmsted County, Minnesota, residents with newly diagnosed HFrEF (EF ≤ 40%) 2007-2017. We excluded patients with contraindications to medication initiation. We examined the use of beta-blockers, HF beta-blockers (metoprolol succinate, carvedilol, bisoprolol), angiotensin converting enzyme inhibitors (ACEis), angiotensin receptor blockers (ARBs), angiotensin receptor neprilysin inhibitors (ARNIS), and mineralocorticoid receptor antagonists (MRAs) in the first year after HFrEF diagnosis. We used Cox models to evaluate the association of being seen in an HF clinic with the initiation of GDMT. From 2007 to 2017, 1160 patients were diagnosed with HFrEF (mean age 69.7 years, 65.6% men). Most eligible patients received beta-blockers (92.6%) and ACEis/ARBs/ARNIs (87.0%) in the first year. However, only 63.8% of patients were treated with an HF beta-blocker, and few received MRAs (17.6%). In models accounting for the role of an HF clinic in initiation of these medications, being seen in an HF clinic was independently associated with initiation of new GDMT across all medication classes, with a hazard ratio (95% CI) of 1.54 (1.15-2.06) for any beta-blocker, 2.49 (1.95-3.20) for HF beta-blockers, 1.97 (1.46-2.65) for ACEis/ARBs/ARNIs, and 2.14 (1.49-3.08) for MRAs. CONCLUSIONS: In this population-based study, most patients with newly diagnosed HFrEF received beta-blockers and ACEis/ARBs/ARNIs. GDMT use was higher in patients seen in an HF clinic, suggesting the potential benefit of referral to an HF clinic for patients with newly diagnosed HFrEF.

Development of Advanced Heart Failure: A Population-Based Study.

BACKGROUND: Some patients with heart failure (HF) will go on to develop advanced HF, characterized by severe HF symptoms despite attempts to optimize medical therapy. The goals of this study were to examine the risk of developing advanced HF in patients with newly diagnosed HF, identify risk factors for developing advanced HF, and evaluate the impact of advanced HF on outcomes. METHODS: This was a population-based, retrospective cohort study of Olmsted County, Minnesota, residents with a new clinical diagnosis of HF between 2007 and 2017. Risk factors for the development of advanced HF (2018 European Society of Cardiology criteria) were examined using cause-specific Cox proportional hazard regression models. The associations of development of advanced HF with risks of hospitalization and mortality were examined using the Andersen-Gill and Cox models, respectively. RESULTS: There were 4597 residents with incident HF from 2007 to 2017. The cumulative incidence of advanced HF was 11.5% (95% CI, 10.5%-12.5%) at 6 years after incident HF diagnosis overall and was 14.4% (95% CI, 12.3%-16.9%), 11.4% (95% CI, 8.9%-14.6%), and 11.7% (95% CI, 10.3%-13.2%) in patients with incident HF with reduced, mildly reduced, and preserved ejection fraction, respectively. Key demographics, comorbidities, and echocardiographic characteristics were independently associated with the development of advanced HF. Development of advanced HF was associated with increased risks of all-cause hospitalization (adjusted hazard ratio, 3.0 [95% CI, 2.7-3.4]; P<0.001), HF hospitalization (hazard ratio, 10.2 [95% CI, 8.7-12.1]), all-cause mortality (hazard ratio, 5.0 [95% CI, 4.5-5.6]; P<0.001), and cardiovascular mortality (hazard ratio, 7.8 [95% CI, 6.7-9.1]). CONCLUSIONS: In this population-based study, development of advanced HF was common and was associated with markedly increased morbidity and mortality.

Diabetes Mellitus in Advanced Heart Failure.

BACKGROUND: Diabetes mellitus is associated with increased rates of mortality in patients with less severe (stage C) heart failure (HF). The prevalence of diabetes and its complications in advanced (stage D) HF and their contributions to mortality risk are unknown. METHODS AND RESULTS: We conducted a retrospective population-based cohort study of all adult residents of Olmsted County, Minnesota, who had advanced HF between 2007 and 2017. Patients with diabetes were identified by using the criteria of the Healthcare Effectiveness Data and Information Set. Diabetes complications were captured by using the Diabetes Complications Severity Index. Of 936 patients with advanced HF, 338 (36.1%) had diabetes. Overall, median survival time after development of advanced HF was 13.1 (3.9-33.1) months; mortality did not vary by diabetes status (aHR 1.06, 95% CI 0.90-1.25; P = 0.45) or by glycated hemoglobin levels in those with diabetes (aHR 1.01 per 1% increase, 95% CI 0.93-1.10; P = 0.82). However, patients with diabetes and 4 (aHR 1.24, 95% CI 0.92-1.67) or 5-7 (aHR 1.49, 95% CI 1.09-2.03) diabetes complications were at increased risk of mortality compared to those with ≤ 3 complications. CONCLUSIONS: More than one-third of patients with advanced HF have diabetes. In advanced HF, overall prognosis is poor, but we found no evidence that diabetes is associated with a significantly higher mortality risk.