Comparing PCSK9 Monoclonal Antibody Treatment Strategies Following Myocardial Infarction Using Negative Control Outcomes: A Target Trial Emulation Study.

BACKGROUND: Initiation of proprotein convertase subtilisin/kexin type 9 monoclonal antibody (PCSK9 mAb) for lipid-lowering following myocardial infarction (MI) is likely affected by patients' prognostic factors, potentially leading to bias when comparing real-world treatment effects. METHODS: Using target-trial emulation, we assessed potential confounding when comparing two treatment strategies post-MI: initiation of PCSK9 mAb within 1 year and no initiation of PCSK9 mAb. We identified MI hospitalizations during July 2015-June 2020 for patients aged ≥18 years in Optum's de-identified Clinformatics Data Mart (CDM) and MarketScan, and those aged ≥66 in the US Medicare claims database. We estimated a 3-year counterfactual cumulative risk and risk difference (RD) for 10 negative control outcomes using the clone-censor-weight approach to address time-varying confounding and immortal person-time. RESULTS: PCSK9 mAb initiation within 1-year post-MI was low (0.7% in MarketScan and 0.4% in both CDM and Medicare databases). In CDM, there was a lower risk for cancer (RD = -3.6% [95% CI: -4.3%, -2.9%]), decubitus ulcer (RD = -7.7% [95% CI: -11.8%, -3.7%]), fracture (RD = -8.1% [95% CI: -9.6%, -6.6%]), influenza vaccine (RD = -9.3% [95% CI: -17.5%, -1.1%]), and visual test (RD = -0.6% [95% CI: -0.7%, -0.6%]) under the PCSK9 mAb initiation versus no initiation strategy. Similar differences persisted in the MarketScan and Medicare databases. In each database, ezetimibe and low-density lipoprotein testing were unbalanced between treatment strategies. CONCLUSION: A comparative effectiveness study of these treatments using the current approach would likely bias results due to the low number of PCSK9 mAb initiators.

Ambulatory Care Fragmentation and Total Health Care Costs.

BACKGROUND: The magnitude of the relationship between ambulatory care fragmentation and subsequent total health care costs is unclear. OBJECTIVE: To determine the association between ambulatory care fragmentation and total health care costs. RESEARCH DESIGN: Longitudinal analysis of 15 years of data (2004-2018) from the national Reasons for Geographic and Racial Differences in Stroke (REGARDS) study, linked to Medicare fee-for-service claims. SUBJECTS: A total of 13,680 Medicare beneficiaries who are 65 years and older. MEASURES: We measured ambulatory care fragmentation in each calendar year, defining high fragmentation as a reversed Bice-Boxerman Index ≥0.85 and low as <0.85. We used generalized linear models to determine the association between ambulatory care fragmentation in 1 year and total Medicare expenditures (costs) in the following year, adjusting for baseline demographic and clinical characteristics, a time-varying comorbidity index, and accounting for geographic variation in reimbursement and inflation. RESULTS: The average participant was 70.9 years old; approximately half (53%) were women. One-fourth (26%) of participants had high fragmentation in the first year of observation. Those participants had a median of 9 visits to 6 providers, with the most frequently seen provider accounting for 29% of visits. By contrast, participants with low fragmentation had a median of 8 visits to 3 providers, with the most frequently seen provider accounting for 50% of visits. High fragmentation was associated with $1085 more in total adjusted costs per person per year (95% CI $713 to $1457) than low fragmentation. CONCLUSIONS: Highly fragmented ambulatory care in 1 year is independently associated with higher total costs the following year.

Associations among claims-based care fragmentation, self-reported gaps in care coordination, and self-reported adverse events.

BACKGROUND: Fragmentation of care (that is, the use of multiple ambulatory providers without a dominant provider) may increase the risk of gaps in communication among providers. However, it is unclear whether people with fragmented care (as measured in claims) perceive more gaps in communication among their providers. It is also unclear whether people who perceive gaps in communication experience them as clinically significant (that is, whether they experience adverse events that they attribute to poor coordination). METHODS: We conducted a longitudinal study using data from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study, including a survey on perceptions of healthcare (2017-2018) and linked fee-for-service Medicare claims (for the 12 months prior to the survey) (N = 4,296). We estimated correlation coefficients to determine associations between claims-based and self-reported numbers of ambulatory visits and ambulatory providers. We then used logistic regression to determine associations between claims-based fragmentation (measured with the reversed Bice-Boxerman Index [rBBI]) and self-reported gaps in care coordination and, separately, between claims-based fragmentation and self-reported adverse events that the respondent attributed to poor coordination. RESULTS: The correlation coefficient between claims-based and self-report was 0.37 for the number of visits and 0.38 for the number of providers (p < 0.0001 for each). Individuals with high fragmentation by claims (rBBI ≥ 0.85) had a 23% increased adjusted odds of reporting any gap in care coordination (95% CI 3%, 48%) and, separately, a 61% increased adjusted odds of reporting an adverse event that they attributed to poor coordination (95% CI 11%, 134%). CONCLUSIONS: Medicare beneficiaries with claims-based fragmentation also report gaps in communication among their providers. Moreover, these gaps appear to be clinically significant, with beneficiaries reporting adverse events that they attribute to poor coordination.

Ambulatory Care Fragmentation, Emergency Department Visits, and Race: a Nationwide Cohort Study in the U.S.

BACKGROUND: It is unclear whether highly fragmented ambulatory care (i.e., care spread across multiple providers without a dominant provider) increases the risk of an emergency department (ED) visit. Whether any such association varies with race is unknown. OBJECTIVE: We sought to determine whether highly fragmented ambulatory care increases the risk of an ED visit, overall and by race. DESIGN AND PARTICIPANTS: We analyzed data for 14,361 participants ≥ 65 years old from the nationwide prospective REasons for Geographic and Racial Differences in Stroke (REGARDS) cohort study, linked to Medicare claims (2003-2016). MAIN MEASURES: We defined high fragmentation as a reversed Bice-Boxerman Index ≥ 0.85 (≥ 75th percentile). We used Poisson models to determine the association between fragmentation (as a time-varying exposure) and ED visits, overall and stratified by race, adjusting for demographics, medical conditions, medications, health behaviors, psychosocial variables, and physiologic variables. KEY RESULTS: The average participant was 70.5 years old; 53% were female, and 33% were Black individuals. Participants with high fragmentation had a median of 9 visits to 6 providers, with 29% of visits by the most frequently seen provider; participants with low fragmentation had a median of 7 visits to 3 providers, with 50% of visits by the most frequently seen provider. Overall, high fragmentation was associated with more ED visits than low fragmentation (adjusted risk ratio [aRR] 1.31, 95% confidence interval [CI] 1.29, 1.34). The magnitude of this association was larger among Black (aRR 1.48, 95% CI 1.44, 1.53) than White participants (aRR 1.23, 95% CI 1.20, 1.25). CONCLUSIONS: Highly fragmented ambulatory care was an independent predictor of ED visits, especially among Black individuals.

Recurrent Atherosclerotic Cardiovascular Disease Events Potentially Prevented with Guideline-Recommended Cholesterol-Lowering Therapy following Myocardial Infarction.

PURPOSE: Many adults with atherosclerotic cardiovascular disease (ASCVD) who are recommended to take a statin, ezetimibe and/or a proprotein convertase subtilisin/kexin type 9 inhibitor (PCSK9i) by the 2018 American Heart Association/American College of Cardiology cholesterol guideline do not receive these medications. We estimated the percentage of recurrent ASCVD events potentially prevented with guideline-recommended cholesterol-lowering therapy following a myocardial infarction (MI) hospitalization. METHODS: We conducted simulations using data from US adults with government health insurance through Medicare or commercial health insurance in the MarketScan database. We used data from patients with an MI hospitalization in 2018-2019 to estimate the percentage receiving guideline-recommended therapy. We used data from patients with an MI hospitalization in 2013-2016 to estimate the 3-year cumulative incidence of recurrent ASCVD events (i.e., MI, coronary revascularization or ischemic stroke). The low-density lipoprotein cholesterol (LDL-C) reduction with guideline-recommended therapy was derived from trials of statins, ezetimibe and PCSK9i, and the associated ASCVD risk reduction was estimated from a meta-analysis by the Cholesterol-Lowering Treatment Trialists Collaboration. RESULTS: Among 279,395 patients with an MI hospitalization in 2018-2019 (mean age 75 years, mean LDL-C 92 mg/dL), 27.3% were receiving guideline-recommended cholesterol-lowering therapy. With current cholesterol-lowering therapy use, 25.3% (95%CI: 25.2%-25.4%) of patients had an ASCVD event over 3 years. If all patients were to receive guideline-recommended therapy, 19.8% (95%CI: 19.5%-19.9%) were estimated to have an ASCVD event over 3 years, representing a 21.6% (95%CI: 20.5%-23.6%) relative risk reduction. CONCLUSION: Implementation of guideline-recommended cholesterol-lowering therapy could prevent a substantial percentage of recurrent ASCVD events.

The Projected Impact of Population-Wide Achievement of LDL Cholesterol <70 mg/dL on the Number of Recurrent Events Among US Adults with ASCVD.

PURPOSE: Adults with atherosclerotic cardiovascular disease (ASCVD) are recommended high-intensity statins, with those at very high risk for recurrent events recommended adding ezetimibe and/or a proprotein convertase subtilisin/kexin type 9 inhibitor if their low-density lipoprotein cholesterol (LDL-C) is ≥70 mg/dL. We estimated the number of recurrent ASCVD events potentially averted if all adults in the United States (US) ≥45 years of age with ASCVD achieved an LDL-C <70 mg/dL. METHODS: The number of US adults with ASCVD and LDL-C ≥70 mg/dL was estimated from the National Health and Nutrition Examination Survey 2009-2016 (n = 596). The 10-year cumulative incidence of recurrent ASCVD events was estimated from the REasons for Geographic And Racial Differences in Stroke study (n = 5390), weighted to the US population by age, race, and sex. The ASCVD risk reduction by achieving an LDL-C <70 mg/dL was estimated from meta-analyses of lipid-lowering treatment trials. RESULTS: Overall, 14.7 (95% CI, 13.7-15.8) million US adults had ASCVD, of whom 11.6 (95% CI, 10.6-12.5) million had LDL-C ≥70 mg/dL. The 10-year cumulative incidence of ASCVD events was 24.3% (95% CI, 23.2-25.6%). We projected that 2.823 (95% CI, 2.543-3.091) million ASCVD events would occur over 10 years among US adults with ASCVD and LDL-C ≥70 mg/dL. Overall, 0.634 (95% CI, 0.542-0.737) million ASCVD events could potentially be averted if all US adults with ASCVD achieved and maintained LDL-C <70 mg/dL. CONCLUSION: A substantial number of recurrent ASCVD events could be averted over 10 years if all US adults with ASCVD achieved, and maintained, an LDL-C <70 mg/dL.

Trends in Recurrent Coronary Heart Disease After Myocardial Infarction Among US Women and Men Between 2008 and 2017.

BACKGROUND: Rates for recurrent coronary heart disease (CHD) events have declined in the United States. However, few studies have assessed whether this decline has been similar among women and men. METHODS: Data were used from 770 408 US women and 700 477 US men <65 years of age with commercial health insurance through MarketScan and ≥66 years of age with government health insurance through Medicare who had a myocardial infarction (MI) hospitalization between 2008 and 2017. Women and men were followed up for recurrent MI, recurrent CHD events (ie, recurrent MI or coronary revascularization), heart failure hospitalization, and all-cause mortality (Medicare only) in the 365 days after MI. RESULTS: From 2008 to 2017, age-standardized recurrent MI rates per 1000 person-years decreased from 89.2 to 72.3 in women and from 94.2 to 81.3 in men (multivariable-adjusted P interaction by sex <0.001). Recurrent CHD event rates decreased from 166.3 to 133.3 in women and from 198.1 to 176.8 in men (P interaction <0.001). Heart failure hospitalization rates decreased from 177.4 to 158.1 in women and from 162.9 to 156.1 in men (P interaction=0.001). All-cause mortality rates decreased from 403.2 to 389.5 in women and from 436.1 to 417.9 in men (P interaction=0.82). In 2017, the multivariable-adjusted rate ratios comparing women with men were 0.90 (95% CI, 0.86-0.93) for recurrent MI, 0.80 (95% CI, 0.78-0.82) for recurrent CHD events, 0.99 (95% CI, 0.96-1.01) for heart failure hospitalization, and 0.82 (95% CI, 0.80-0.83) for all-cause mortality. CONCLUSIONS: Rates of recurrent MI, recurrent CHD events, heart failure hospitalization, and mortality in the first year after an MI declined considerably between 2008 and 2017 in both men and women, with proportionally greater reductions for women than men. However, rates remain very high, and rates of recurrent MI, recurrent CHD events, and death continue to be higher among men than women.

Inflammation biomarkers and incident coronary heart disease: the Reasons for Geographic And Racial Differences in Stroke Study.

BACKGROUND: Individual inflammation biomarkers are associated with incident coronary heart disease (CHD) events. However, there is limited research on whether the risk for incident CHD is progressively higher with a higher number of inflammation biomarkers in abnormal levels. METHODS: We used data from 15,758 Reasons for Geographic and Racial Differences in Stroke (REGARDS) study participants aged ≥45 years without a history of CHD at baseline in 2003-2007. Abnormal levels of baseline high-sensitivity C-reactive protein, leukocyte count and serum albumin were defined as ≥3.8 mg/L (3rd tertile), ≥6.3 x 109 cells/L (3rd tertile), and <4.0 g/dL (1st tertile), respectively. The outcome was a composite of incident myocardial infarction or CHD death. RESULTS: Overall, 38.9% (n = 6,123) had 0, 36.6% (n = 5,774) had 1, 19.8% (n = 3,113) had 2 and 4.7% (n = 748) had 3 biomarkers of inflammation in abnormal levels. Over a median follow-up of 11.4 years, 954 (6.1%) participants had incident CHD. The rate of incident CHD per 1000 person-years for individuals with 0, 1, 2, and 3 biomarkers of inflammation in abnormal levels was 4.4 (95% confidence interval [CI]: 3.9-5.0), 6.3 (95% CI: 5.6-6.9), 8.8 (95% CI: 7.8-9.9), and 10.6 (95% CI: 8.1-13.1), respectively. Multi-variable adjusted hazard ratios for incident CHD associated with 1, 2 and 3 versus no inflammation biomarker in abnormal levels were 1.26 (95% CI: 1.07-1.49), 1.72 (95% CI: 1.43-2.07), and 1.84 (95% CI: 1.37-2.47), respectively (P-trend < .001). CONCLUSIONS: The number of inflammation markers in abnormal levels was associated with increased risk of incident CHD after multi-variable adjustment.

Frailty, gaps in care coordination, and preventable adverse events.

BACKGROUND: Older US adults often receive care from multiple ambulatory providers. Seeing multiple providers may be clinically appropriate but creates challenges for communication. Whether frailty is a risk factor for gaps in communication among older adults and subsequent preventable adverse events is unknown. METHODS: We conducted a cross-sectional analysis of community-dwelling US adults ≥ 65 years of age in the REasons for Geographic And Racial Differences in Stroke (REGARDS) study who attended an in-home study examination in 2013-2016 and completed a survey on experiences with healthcare in 2017-2018 (n = 5,024). Using 5 frailty indicators (low body mass index, exhaustion, slow walk, weakness, and history of falls), we characterized participants into 3 mutually exclusive groups: not frail (0 indicators), intermediate-frail (1-2 indicators), and frail (3-5 indicators). We used survey data on self-reported gaps in care coordination and self-reported adverse events that participants attributed to poor communication among providers (a drug-drug interaction, repeat testing, an emergency department visit, or a hospital admission). RESULTS: Overall, 2,398 (47.7%) participants were not frail, 2,436 (48.5%) were intermediate-frail, and 190 (3.8%) were frail. The prevalence of any gap in care coordination was 37.0%, 40.8%, and 51.1% among participants who were not frail, intermediate-frail and frail, respectively. The adjusted prevalence ratio (PR) for any gap in care coordination among intermediate-frail and frail versus not frail participants was 1.09 (95% confidence interval [95%CI] 1.02-1.18) and 1.34 (95%CI 1.15-1.56), respectively. The prevalence of any preventable adverse event was 7.0%, 11.3% and 20.0% among participants who were not frail, intermediate-frail and frail, respectively. The adjusted PR for any preventable adverse event among those who were intermediate-frail and frail versus not frail was 1.47 (95%CI 1.22-1.77) and 2.24 (95%CI 1.60-3.14), respectively. CONCLUSION: Among older adults, frailty is associated with an increased prevalence for self-reported gaps in care coordination and preventable adverse events. Targeted interventions to address patient-reported concerns regarding care coordination among intermediate-frail and frail older adults may be warranted.

Risk for recurrent cardiovascular disease events among patients with diabetes and chronic kidney disease.

BACKGROUND: Adults who have experienced multiple cardiovascular disease (CVD) events have a very high risk for additional events. Diabetes and chronic kidney disease (CKD) are each associated with an increased risk for recurrent CVD events following a myocardial infarction (MI). METHODS: We compared the risk for recurrent CVD events among US adults with health insurance who were hospitalized for an MI between 2014 and 2017 and had (1) CVD prior to their MI but were free from diabetes or CKD (prior CVD), and those without CVD prior to their MI who had (2) diabetes only, (3) CKD only and (4) both diabetes and CKD. We followed patients from hospital discharge through December 31, 2018 for recurrent CVD events including coronary, stroke, and peripheral artery events. RESULTS: Among 162,730 patients, 55.2% had prior CVD, and 28.3%, 8.3%, and 8.2% had diabetes only, CKD only, and both diabetes and CKD, respectively. The rate for recurrent CVD events per 1000 person-years was 135 among patients with prior CVD and 110, 124 and 171 among those with diabetes only, CKD only and both diabetes and CKD, respectively. Compared to patients with prior CVD, the multivariable-adjusted hazard ratio for recurrent CVD events was 0.92 (95%CI 0.90-0.95), 0.89 (95%CI: 0.85-0.93), and 1.18 (95%CI: 1.14-1.22) among those with diabetes only, CKD only, and both diabetes and CKD, respectively. CONCLUSION: Following MI, adults with both diabetes and CKD had a higher risk for recurrent CVD events compared to those with prior CVD without diabetes or CKD.

Ambulatory Care Fragmentation and Subsequent Hospitalization: Evidence From the REGARDS Study.

BACKGROUND: Previous studies have suggested that highly fragmented ambulatory care increases the risk of subsequent hospitalization, but those studies used claims only and were not able to adjust for many clinical potential confounders. OBJECTIVE: The objective of this study was to determine the association between fragmented ambulatory care and subsequent hospitalization, adjusting for demographics, medical conditions, medications, health behaviors, psychosocial variables, and physiological variables. DESIGN: Longitudinal analysis of data (2003-2016) from the nationwide REasons for Geographic And Racial Differences in Stroke (REGARDS) study, linked to Medicare fee-for-service claims. SUBJECTS: A total of 12,693 Medicare beneficiaries 65 years and older from the REGARDS study who had at least 4 ambulatory visits in the first year of observation and did not have a hospitalization in the prior year. MEASURES: We defined high fragmentation as a reversed Bice-Boxerman score above the 75th percentile. We used Cox proportional hazards models to determine the association between fragmentation as a time-varying exposure and incident hospitalization in the 3 months following each exposure period. RESULTS: The mean age was 70.4 years; 54% were women, and 33% were African American. During the first year of observation, participants with high fragmentation had a median of 8 ambulatory visits with 6 providers, whereas participants with low fragmentation had a median of 7 visits with 3 providers. Over 11.8 years of follow-up, 6947 participants (55%) had a hospitalization. High fragmentation was associated with an increased hazard of hospitalization (adjusted hazard ratio=1.18; 95% confidence interval: 1.12, 1.24). CONCLUSION: Highly fragmented ambulatory care is an independent risk factor for hospitalization.

Healthcare Fragmentation and Incident Acute Coronary Heart Disease Events: a Cohort Study.

BACKGROUND: Highly fragmented ambulatory care (i.e., care spread across many providers without a dominant provider) has been associated with excess tests, procedures, emergency department visits, and hospitalizations. Whether fragmented care is associated with worse health outcomes, or whether any association varies with health status, is unclear. OBJECTIVE: To determine whether fragmented care is associated with the risk of incident coronary heart disease (CHD) events, overall and stratified by self-rated general health. DESIGN AND PARTICIPANTS: We conducted a secondary analysis of the nationwide prospective Reasons for Geographic and Racial Differences in Stroke (REGARDS) cohort study (2003-2016). We included participants who were ≥ 65 years old, had linked Medicare fee-for-service claims, and had no history of CHD (N = 10,556). MAIN MEASURES: We measured fragmentation with the reversed Bice-Boxerman Index. We used Cox proportional hazards models to determine the association between fragmentation as a time-varying exposure and adjudicated incident CHD events in the 3 months following each exposure period. KEY RESULTS: The mean age was 70 years; 57% were women, and 34% were African-American. Over 11.8 years of follow-up, 569 participants had CHD events. Overall, the adjusted hazard ratio (HR) for the association between high fragmentation and incident CHD events was 1.14 (95% confidence interval (CI) 0.92, 1.39). Among those with very good or good self-rated health, high fragmentation was associated with an increased hazard of CHD events (adjusted HR 1.35; 95% CI 1.06, 1.73; p = 0.01). Among those with fair or poor self-rated health, high fragmentation was associated with a trend toward a decreased hazard of CHD events (adjusted HR 0.54; 95% CI 0.29, 1.01; p = 0.052). There was no association among those with excellent self-rated health. CONCLUSION: High fragmentation was associated with an increased independent risk of incident CHD events among those with very good or good self-rated health.

Differences in ambulatory care fragmentation by race.

BACKGROUND: More fragmented ambulatory care (i.e., care spread across many providers without a dominant provider) has been associated with more subsequent healthcare utilization (such as more tests, procedures, emergency department visits, and hospitalizations) than less fragmented ambulatory care. It is not known if race and socioeconomic status are associated with fragmented ambulatory care. METHODS: We conducted a longitudinal analysis of data from the REasons for Geographic and Racial Differences in Stroke (REGARDS) study, using the REGARDS baseline visit plus the first year of follow-up. We included participants ≥65 years old, who had linked fee-for-service Medicare claims, and ≥ 4 ambulatory visits in the first year of follow-up. We used Tobit regression to determine the associations between race, annual household income, and educational attainment at baseline and fragmentation score in the subsequent year (as measured with the reversed Bice-Boxerman Index). Covariates included other demographic characteristics, medical conditions, medication use, health behaviors, and psychosocial variables. Additional analyses categorized visits by the type of provider (primary care vs. specialist). RESULTS: The study participants (N = 6799) had an average age of 73.0 years, 53% were female, and 30% were black. Nearly half had low annual household income (<$35,000) and 41% had a high school education or less. Overall, participants had a median of 10 ambulatory visits to 4 providers in the 12 months following their baseline study visit. Participants in the highest quintile of fragmentation scores had a median of 11 visits to 7 providers. Black race was associated with an absolute adjusted 3% lower fragmentation score compared to white race (95% confidence interval (2% lower to 4% lower; p < 0.001). This difference was explained by blacks seeing fewer specialists than whites. Income and education were not independent predictors of fragmentation scores. CONCLUSIONS: Among Medicare beneficiaries, blacks had less fragmented ambulatory care than whites, due to lower utilization of specialty care. Future research is needed to determine the effect of fragmented care on health outcomes for blacks and whites.

Risk for ischemic stroke and coronary heart disease associated with migraine and migraine medication among older adults.

BACKGROUND: Migraine has been associated with cardiovascular disease (CVD) events among middle-aged adults. The objective of this study was to determine the risk for ischemic stroke and coronary heart disease (CHD) events among older adults with versus without migraine. METHODS: This retrospective cohort study was conducted using data from US adults ≥66 years of age with Medicare health insurance between 2008 and 2017. After stratification by history of CVD, patients with a history of migraine were matched 1:4 to those without a history of migraine, based on calendar year, age, and sex. Patients were followed through December 31, 2017 for ischemic stroke and CHD events including myocardial infarction or coronary revascularization. All analyses were done separately for patients with and without a history of CVD. RESULTS: Among patients without a history of CVD (n = 109,950 including n = 21,990 with migraine and n = 87,960 without migraine), 1789 had an ischemic stroke and 3552 had a CHD event. The adjusted hazard ratio (HR) among patients with versus without migraine was 1.20 (95% confidence interval [95%CI], 1.07-1.35) for ischemic stroke and 1.02 (95%CI, 0.93-1.11) for CHD events. Compared to patients without migraine, those with migraine who were taking an opioid medication had a higher risk for ischemic stroke (adjusted HR 1.43 [95%CI, 1.20-1.69]), while those taking a triptan had a lower risk for CHD events (adjusted HR 0.79 [95%CI, 0.67-0.93]). Among patients with a history of CVD (n = 79,515 including n = 15,903 with migraine and n = 63,612 without migraine), 2960 had an ischemic stroke and 7981 had a CHD event. The adjusted HRs (95%CI) for ischemic stroke and CHD events associated with migraine were 1.27 (1.17-1.39) and 0.99 (0.93-1.05), respectively. Patients with migraine taking an opioid medication had a higher risk for ischemic stroke (adjusted HR 1.21 [95%CI, 1.07-1.36]), while those taking a triptan had a lower risk for CHD events (adjusted HR 0.83 [95%CI, 0.72-0.95]), each versus those without migraine. CONCLUSIONS: Older adults with migraine are at increased risk for ischemic stroke. The risk for ischemic stroke among older adults with migraine may differ by migraine medication classes.

Potential Cardiovascular Disease Events Prevented with Adoption of the 2017 American College of Cardiology/American Heart Association Blood Pressure Guideline.

BACKGROUND: Over 10 years, achieving and maintaining 2017 ACC/AHA guideline goals could prevent 3.0 million (UR, 1.1-5.1 million), 0.5 million (UR, 0.2-0.7 million), and 1.4 million (UR, 0.6-2.0 million) cardiovascular disease (CVD) events compared with maintaining current blood pressure (BP) levels, achieving 2003 Seventh Joint National Committee Report goals, and achieving 2014 Eighth Joint National Committee goals, respectively. We estimated the number of cardiovascular disease events prevented and treatment-related serious adverse events incurred over 10 years among US adults with hypertension by achieving 2017 ACC/AHA guideline-recommended BP goals compared with (1) current BP levels, (2) achieving 2003 Seventh Joint National Committee Report BP goals, and (3) achieving 2014 Eighth Joint National Committee panel member report BP goals. METHODS: US adults aged ≥45 years with an indication for BP treatment were grouped according to recommendations for antihypertensive drug therapy in the 2017 ACC/AHA guideline, 2003 Seventh Joint National Committee Report, and 2014 Eighth Joint National Committee. Population sizes were estimated from the 2011 to 2014 National Health and Nutrition Examination Surveys. Rates for fatal and nonfatal CVD events (stroke, coronary heart disease, or heart failure) were estimated from the REGARDS (REasons for Geographic And Racial Differences in Stroke) study, weighted to the US population. CVD risk reductions with treatment to BP goals and risk for serious adverse events were obtained from meta-analyses of BP-lowering trials. CVD events prevented and treatment-related nonfatal serious adverse events over 10 years were calculated. Uncertainty surrounding main data inputs was expressed in uncertainty ranges (UR). RESULTS: Over ten years, achieving and maintaining 2017 ACC/AHA guideline goals compared with current BP levels, achieving 2003 Seventh Joint National Committee Report goals, or achieving 2014 Eighth Joint National Committee goals could prevent 3.0 million (UR, 1.1-5.1 million), 0.5 million (UR, 0.2-0.7 million), or 1.4 million (UR, 0.6-2.0 million) CVD events, respectively. Compared with current BP levels, achieving and maintaining 2017 goals could prevent 71.9 (UR, 26.6-122.3) CVD events per 1000 treated. Achieving 2017 guideline BP goals compared with current BP levels could also lead to nearly 3.3 million more serious adverse events over 10 years (UR, 2.2-4.4 million). CONCLUSIONS: Achieving and maintaining 2017 ACC/AHA BP goals could prevent a greater number of CVD events than achieving 2003 Seventh Joint National Committee Report or 2014 Eighth Joint National Committee BP goals but could also lead to more serious adverse events.

Projections of incident atherosclerotic cardiovascular disease and incident type 2 diabetes across evolving statin treatment guidelines and recommendations: A modelling study.

BACKGROUND: Experimental and observational research has suggested the potential for increased type 2 diabetes (T2D) risk among populations taking statins for the primary prevention of atherosclerotic cardiovascular disease (ASCVD). However, few studies have directly compared statin-associated benefits and harms or examined heterogeneity by population subgroups or assumed treatment effect. Thus, we compared ASCVD risk reduction and T2D incidence increases across 3 statin treatment guidelines or recommendations among adults without a history of ASCVD or T2D who were eligible for statin treatment initiation. METHODS AND FINDINGS: Simulations were conducted using Markov models that integrated data from contemporary population-based studies of non-Hispanic African American and white adults aged 40-75 years with published meta-analyses. Statin treatment eligibility was determined by predicted 10-year ASCVD risk (5%, 7.5%, or 10%). We calculated the number needed to treat (NNT) to prevent one ASCVD event and the number needed to harm (NNH) to incur one incident case of T2D. The likelihood to be helped or harmed (LHH) was calculated as ratio of NNH to NNT. Heterogeneity in statin-associated benefit was examined by sex, age, and statin-associated T2D relative risk (RR) (range: 1.11-1.55). A total of 61,125,042 U.S. adults (58.5% female; 89.4% white; mean age = 54.7 years) composed our primary prevention population, among whom 13-28 million adults were eligible for statin initiation. Overall, the number of ASCVD events prevented was at least twice as large as the number of incident cases of T2D incurred (LHH range: 2.26-2.90). However, the number of T2D cases incurred surpassed the number of ASCVD events prevented when higher statin-associated T2D RRs were assumed (LHH range: 0.72-0.94). In addition, females (LHH range: 1.74-2.40) and adults aged 40-50 years (LHH range: 1.00-1.14) received lower absolute benefits of statin treatment compared with males (LHH range: 2.55-3.00) and adults aged 70-75 years (LHH range: 3.95-3.96). Projected differences in LHH by age and sex became more pronounced as statin-associated T2D RR increased, with a majority of scenarios projecting LHHs < 1 for females and adults aged 40-50 years. This study's primary limitation was uncertainty in estimates of statin-associated T2D risk, highlighting areas in which additional clinical and public health research is needed. CONCLUSIONS: Our projections suggest that females and younger adult populations shoulder the highest relative burden of statin-associated T2D risk.

Association Between Patients' Self-Reported Gaps in Care Coordination and Preventable Adverse Outcomes: a Cross-Sectional Survey.

BACKGROUND: Whether patients' reports of gaps in care coordination reflect clinically significant problems is unclear. OBJECTIVE: To determine any association between patient-reported gaps in care coordination and patient-reported preventable adverse outcomes. DESIGN AND PARTICIPANTS: We administered a cross-sectional survey on experiences with healthcare to participants in the national Reasons for Geographic and Racial Differences in Stroke (REGARDS) study who were ≥ 65 years old. Of the 15,817 participants in REGARDS at the time of our survey (August 2017-November 2018), 11,138 completed the survey. We restricted the sample to participants who reported ≥ 2 ambulatory visits and ≥ 2 ambulatory providers in the past year (N = 7568). MAIN MEASURES: We considered 7 gaps in ambulatory care coordination, elicited with previously validated questions. We considered 4 outcomes: (1) a test that was repeated because the doctor did not have the result of the first test, (2) a drug-drug interaction that occurred due to multiple prescribers, (3) an emergency department visit that could have been prevented by better communication among providers, and (4) a hospital admission that could have been prevented by better communication among providers. We used logistic regression to determine the association between ≥ 1 gap in care coordination and ≥ 1 preventable outcome, adjusting for potential confounders. KEY RESULTS: The average age of the sample was 77.0 years; 55% were female, and 34% were African-American. More than one-third of participants (38.1%) reported ≥ 1 gap in care coordination and nearly one-tenth (9.8%) reported ≥ 1 preventable outcome. Having ≥ 1 gap in care coordination was associated with an increased odds of ≥ 1 preventable outcome (adjusted odds ratio 1.55; 95% confidence interval 1.33, 1.81). CONCLUSIONS: Participants' reports of gaps in care coordination were associated with an increased odds of preventable adverse outcomes. Future interventions should leverage patients' observations to detect and resolve gaps in care coordination.

Agreement of claims-based methods for identifying sepsis with clinical criteria in the REasons for Geographic and Racial Differences in Stroke (REGARDS) cohort.

BACKGROUND: Claims-based algorithms are commonly used to identify sepsis in health services research because the laboratory features required to define clinical criteria may not be available in administrative data. METHODS: We evaluated claims-based sepsis algorithms among adults in the US aged ≥65 years with Medicare health insurance enrolled in the REasons for Geographic And Racial Differences in Stroke (REGARDS) study. Suspected infections from baseline (2003-2007) through December 31, 2012 were analyzed. Two claims-based algorithms were evaluated: (1) infection plus organ dysfunction diagnoses or sepsis diagnoses (Medicare-Implicit/Explicit) and (2) Centers for Medicare and Medicaid Services Severe Sepsis/Septic Shock Measure diagnoses (Medicare-CMS). Three classifications based on clinical criteria were used as standards for comparison: (1) the sepsis-related organ failure assessment (SOFA) score (REGARDS-SOFA), (2) "quick" SOFA (REGARDS-qSOFA), and (3) Centers for Disease Control and Prevention electronic health record criteria (REGARDS-EHR). RESULTS: There were 2217 suspected infections among 9522 participants included in the current study. The total number of suspected infections classified as sepsis was 468 for Medicare-Implicit/Explicit, 249 for Medicare-CMS, 541 for REGARDS-SOFA, 185 for REGARDS-qSOFA, and 331 for REGARDS-EHR. The overall agreement between Medicare-Implicit/Explicit and REGARDS-SOFA, REGARDS-qSOFA, and REGARDS-EHR was 77, 79, and 81%, respectively, sensitivity was 46, 53, and 57%, and specificity was 87, 82, and 85%. Comparing Medicare-CMS and REGARDS-SOFA, REGARDS-qSOFA, and REGARDS-EHR, agreement was 77, 87, and 85%, respectively, sensitivity was 27, 41, and 36%, and specificity was 94, 92, and 93%. Events meeting the REGARDS-SOFA classification had a lower 90-day mortality rate (140.7 per 100 person-years) compared with the Medicare-CMS (296.1 per 100 person-years), REGARDS-qSOFA (238.6 per 100 person-years), Medicare-Implicit/Explicit (219.4 per 100 person-years), and REGARDS-EHR classifications (201.8 per 100 person-years). CONCLUSION: Claims-based sepsis algorithms have high agreement and specificity but low sensitivity when compared with clinical criteria. Both claims-based algorithms identified a patient population with similar 90-day mortality rates as compared with classifications based on qSOFA and EHR criteria but higher mortality relative to SOFA criteria.

Trends in Blood Pressure Control Among US Adults With Hypertension, 1999-2000 to 2017-2018.

Importance: Controlling blood pressure (BP) reduces the risk for cardiovascular disease. Objective: To determine whether BP control among US adults with hypertension changed from 1999-2000 through 2017-2018. Design, Setting, and Participants: Serial cross-sectional analysis of National Health and Nutrition Examination Survey data, weighted to be representative of US adults, between 1999-2000 and 2017-2018 (10 cycles), including 18 262 US adults aged 18 years or older with hypertension defined as systolic BP level of 140 mm Hg or higher, diastolic BP level of 90 mm Hg or higher, or use of antihypertensive medication. The date of final data collection was 2018. Exposures: Calendar year. Main Outcomes and Measures: Mean BP was computed using 3 measurements. The primary outcome of BP control was defined as systolic BP level lower than 140 mm Hg and diastolic BP level lower than 90 mm Hg. Results: Among the 51 761 participants included in this analysis, the mean (SD) age was 48 (19) years and 25 939 (50.1%) were women; 43.2% were non-Hispanic White adults; 21.6%, non-Hispanic Black adults; 5.3%, non-Hispanic Asian adults; and 26.1%, Hispanic adults. Among the 18 262 adults with hypertension, the age-adjusted estimated proportion with controlled BP increased from 31.8% (95% CI, 26.9%-36.7%) in 1999-2000 to 48.5% (95% CI, 45.5%-51.5%) in 2007-2008 (P < .001 for trend), remained stable and was 53.8% (95% CI, 48.7%-59.0%) in 2013-2014 (P = .14 for trend), and then declined to 43.7% (95% CI, 40.2%-47.2%) in 2017-2018 (P = .003 for trend). Compared with adults who were aged 18 years to 44 years, it was estimated that controlled BP was more likely among those aged 45 years to 64 years (49.7% vs 36.7%; multivariable-adjusted prevalence ratio, 1.18 [95% CI, 1.02-1.37]) and less likely among those aged 75 years or older (37.3% vs 36.7%; multivariable-adjusted prevalence ratio, 0.81 [95% CI, 0.65-0.97]). It was estimated that controlled BP was less likely among non-Hispanic Black adults vs non-Hispanic White adults (41.5% vs 48.2%, respectively; multivariable-adjusted prevalence ratio, 0.88; 95% CI, 0.81-0.96). Controlled BP was more likely among those with private insurance (48.2%), Medicare (53.4%), or government health insurance other than Medicare or Medicaid (43.2%) vs among those without health insurance (24.2%) (multivariable-adjusted prevalence ratio, 1.40 [95% CI, 1.08-1.80], 1.47 [95% CI, 1.15-1.89], and 1.36 [95% CI, 1.04-1.76], respectively). Controlled BP was more likely among those with vs those without a usual health care facility (48.4% vs 26.5%, respectively; multivariable-adjusted prevalence ratio, 1.48 [95% CI, 1.13-1.94]) and among those who had vs those who had not had a health care visit in the past year (49.1% vs 8.0%; multivariable-adjusted prevalence ratio, 5.23 [95% CI, 2.88-9.49]). Conclusions and Relevance: In a series of cross-sectional surveys weighted to be representative of the adult US population, the prevalence of controlled BP increased between 1999-2000 and 2007-2008, did not significantly change from 2007-2008 through 2013-2014, and then decreased after 2013-2014.

[Mortality in survivors of torture ad prison during the chilean dictatorship between 1973 and 1990]. / Estudio descriptivo de mortalidad en sobrevivientes de tortura y prisión política en el período de la dictadura militar en Chile, 1973-1990.

BACKGROUND: Studies on the long-term consequences of torture in survivors in Chile have only addressed the consequences for mental health, leaving aside the physical consequences. AIM: To report the causes of death in the universe of victims of the Chilean civic-military dictatorship recognized by the Reports of the National Commission for Political Prison and Torture (CNPPT) and the Advisory Commission for the qualification of Disappeared Detainees, Politically Executed individuals and Victims of Political Prison and Torture. MATERIAL AND METHODS: The causes of death, age at the time of death, sex, political context of death and opportunity of repair up to June 2016 are described in 38,254 victims of the Chilean civic-military dictatorship. RESULTS: Of the universe of 38,254 victims, 9,152 (23.9%) died until June 2016. The median age at death was 68 years. The main causes of death were malignant tumors in 28%, cardiovascular diseases in 27%, respiratory diseases in 10%, digestive diseases in 9% and external causes in 8%. CONCLUSIONS: These results can inform prevention and treatment strategies for victims of the Chilean dictatorship.