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.

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.

Perceived stress and pain interference in acute rehabilitation following spinal cord injury: Resilience as a moderator.

PURPOSE/OBJECTIVE: Higher levels of resilience is associated with improved pain outcomes in chronic pain and other neurological populations, but the role of resilience in pain following spinal cord injury (SCI) remains unclear. This study examined resilience as a moderator in the relationship between perceived stress and both pain intensity and interference during acute rehabilitation for SCI. RESEARCH METHOD/DESIGN: Individuals admitted to inpatient rehabilitation acutely following SCI (N = 57) completed measures of perceived stress, resilience, pain intensity, and interference. The Johnson-Neyman procedure was used to examine significance of conditional relationships that emerged. RESULTS: Resilience was found to moderate the relationship between perceived stress and pain interference, but not pain intensity, during inpatient rehabilitation. CONCLUSIONS/IMPLICATIONS: When resilience is low, perceived stress has a more profound and adverse impact on pain interference during inpatient rehabilitation, suggesting therapeutic strategies that build components of resilience are needed during acute rehabilitation following SCI. The relationship between stress, resilience, and pain may differ postinpatient rehabilitation for SCI and warrants further investigation. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Association Between Triglycerides and Incident Cognitive Impairment in Black and White Adults in the Reasons for Geographic and Racial Differences in Stroke Study.

Background Elevated nonfasting triglycerides were associated with non-Alzheimer dementia in a recent study. However, this study neither evaluated the association of fasting triglycerides with incident cognitive impairment (ICI) nor adjusted for high-density lipoprotein cholesterol or hs-CRP (high-sensitivity C-reactive protein), known risk markers for ICI and dementia. Methods and Results We examined the association between fasting triglycerides and ICI among 16 170 participants in the REGARDS (Reasons for Geographic and Racial Differences in Stroke) study without cognitive impairment or a history of stroke at baseline in 2003 to 2007 and who had no stroke events during follow-up through September 2018. Overall, 1151 participants developed ICI during the median follow-up of 9.6 years. The relative risk for ICI associated with fasting triglycerides of ≥150 mg/dL versus <100 mg/dL including adjustment for age and geographic region of residence was 1.59 (95% CI, 1.20-2.11) among White women and 1.27 (95% CI, 1.00-1.62) among Black women. After multivariable adjustment, including adjustment for high-density lipoprotein cholesterol and hs-CRP, the relative risk for ICI associated with fasting triglycerides ≥150 mg/dL versus <100 mg/dL was 1.50 (95% CI, 1.09-2.06) among White women and 1.21 (95% CI, 0.93-1.57) among Black women. There was no evidence of an association between triglycerides and ICI among White or Black men. Conclusions Elevated fasting triglycerides were associated with ICI in White women after full adjustment including high-density lipoprotein cholesterol and hs-CRP. The current results suggest that the association between triglycerides and ICI is stronger in women than men.

Characteristics of patients with diabetes and a history of myocardial infarction initiating PCSK9 and SGLT2 inhibitors.

Study objective: Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) and sodium-glucose cotransporter-2 inhibitors (SGLT2i) reduce the risk for atherosclerotic cardiovascular disease (ASCVD) events in patients with diabetes and ASCVD. We assessed factors associated with initiating either medication among patients with diabetes and a prior myocardial infarction (MI). Setting/participants: US adults ≥19 years old with private health insurance (MarketScan) or government health insurance (Medicare) who had diabetes and a prior MI and initiated a PCSK9i or an SGLT2i in 2017 or 2018. Main outcome measures: PCSK9i or SGLT2i initiation was identified using pharmacy claims. Results: Overall, 8102 patients initiated a PCSK9i (n = 1501; 18.5%) or an SGLT2i (n = 6601; 81.5%). Patients with 2 and ≥3 versus 1 prior MI (risk ratio [RR]: 1.32 [95%CI: 1.17-1.48] and 1.68 [1.41-2.01], respectively), prior coronary revascularization (1.47 [1.31-1.64]), prior stroke (1.28 [1.06-1.56]), history of peripheral artery disease (1.27 [1.14-1.41]), receiving cardiologist care (1.51 [1.36-1.67]) or taking ezetimibe (2.57 [2.35-2.82]) were more likely to initiate a PCSK9i versus an SGLT2i. Patients with a history of short-term (RR 1.07 [95%CI 1.05-1.09]) or long-term (1.07 [1.04-1.09]) diabetes complications, and taking a low/moderate- and high-intensity statin dosage (1.61 [1.51-1.70] and 1.68 [1.58-1.77], respectively) were more likely to initiate an SGLT2i versus a PCSK9i. Among patients who initiated a PCSK9i, 2.9% subsequently initiated an SGLT2i; 0.8% who initiated an SGLT2i subsequently initiated a PCSK9i. Conclusion: The decision to initiate PCSK9i or SGLT2i is explained by having very high cardiovascular disease risk for those initiating PCSK9i and diabetes complications for those initiating SGLT2i.

Reactions to Multiple Ascending Doses of the Microtubule Stabilizer TPI-287 in Patients With Alzheimer Disease, Progressive Supranuclear Palsy, and Corticobasal Syndrome: A Randomized Clinical Trial.

Importance: Basket-design clinical trials that allow investigation of treatment effects on different clinical syndromes that share the same molecular pathophysiology have not previously been attempted in neurodegenerative disease. Objective: To assess the safety, tolerability, and pharmacodynamics of the microtubule stabilizer TPI-287 (abeotaxane) in Alzheimer disease (AD) or the 4-repeat tauopathies (4RT) progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS). Design, Setting, and Participants: Two parallel-design, double-blind, placebo-controlled phase 1 randomized clinical trials in AD and 4RT were conducted from December 20, 2013, through May 4, 2017, at the University of California, San Francisco, and University of Alabama at Birmingham. A total of 94 patients with clinically diagnosed AD (n = 39) and 4RT (n = 55) were screened; of these, 3 refused to participate, and 10 with AD and 11 with 4RT did not meet inclusion criteria. A total of 29 patients with AD, 14 with PSP, and 30 with ß-amyloid-negative CBS (determined on positron emission tomography findings) were enrolled. Data were analyzed from December 20, 2013, through May 4, 2017, based on modified intention to treat. Interventions: Randomization was 8:3 drug to placebo in 3 sequential dose cohorts receiving 2.0, 6.3, or 20.0 mg/m2 of intravenous TPI-287 once every 3 weeks for 9 weeks, with an optional 6-week open-label extension. Main Outcomes and Measures: Primary end points were safety and tolerability (maximal tolerated dose) of TPI-287. Secondary and exploratory end points included TPI-287 levels in cerebrospinal fluid (CSF) and changes on biomarker, clinical, and neuropsychology measures. Results: A total of 68 participants (38 men [56%]; median age, 65 [range, 50-85] years) were included in the modified intention-to-treat analysis, of whom 26 had AD (14 women [54%]; median age, 63 [range, 50-76] years), and 42 had 4RT (16 women [38%]; median age, 69 [range, 54-83] years). Three severe anaphylactoid reactions occurred in TPI-287-treated patients with AD, whereas none were seen in patients with 4RT, leading to a maximal tolerated dose of 6.3 mg/m2 for AD and 20.0 mg/m2 for 4RT. More falls (3 in the placebo group vs 11 in the TPI-287 group) and a dose-related worsening of dementia symptoms (mean [SD] in the CDR plus NACC FTLD-SB [Clinical Dementia Rating scale sum of boxes with frontotemporal dementia measures], 0.5 [1.8] in the placebo group vs 0.7 [1.6] in the TPI-287 group; median difference, 1.5 [95% CI, 0-2.5]; P = .03) were seen in patients with 4RT. Despite undetectable TPI-287 levels in CSF, CSF biomarkers demonstrated decreased chitinase-3-like protein-1 (YKL-40) levels in the 4RT treatment arm (mean [SD], -8.4 [26.0] ng/mL) compared with placebo (mean [SD], 10.4 [42.3] ng/mL; median difference, -14.6 [95% CI, -30.0 to 0.2] ng/mL; P = .048, Mann-Whitney test). Conclusions and Relevance: In this randomized clinical trial, TPI-287 was less tolerated in patients with AD than in those with 4RT owing to the presence of anaphylactoid reactions. The ability to reveal different tau therapeutic effects in various tauopathy syndromes suggests that basket trials are a valuable approach to tau therapeutic early clinical development. Trial Registration: ClinicalTrials.gov identifiers: NCT019666666 and NCT02133846.

Effects of virtual walking on spinal cord injury-related neuropathic pain: A randomized, controlled trial.

PURPOSE: This study is an examination of the efficacy of a virtual walking protocol to treat spinal cord injury (SCI)-related pain. METHOD: A total of 59 individuals with SCI and neuropathic pain (NP) were randomly assigned to receive 20 min of virtual walking, the treatment condition, or virtual wheeling, the control condition. Although having NP was a requirement to participate in the study, participants also underwent pain classification of up to 3 worst pain sites to also examine the effects of virtual walking on nonneuropathic pain. Pain outcomes included changes in pain severity across all pain types, NP unpleasantness, and severity of various sensory qualities of NP. DESIGN: This was a randomized, controlled, single-blinded trial. RESULTS: There was no significant difference in change in pain between groups, though there was a significant pre- to posttreatment reduction across all pain types in the virtual walking condition, but not the control condition. Specific to NP, there was a significant reduction in pain unpleasantness, but not neuropathic pain intensity. NP experienced as "cold," "deep," and with increased skin sensitivity were significantly reduced following virtual walking compared with the control condition. CONCLUSION: Results from this trial suggest that virtual walking treatment may benefit certain aspects of NP, such as associated unpleasantness, as well as certain sensory qualities of that pain. Efficacy of this treatment modality to reduce overall pain severity remains unclear, and may be modulated by other injury, individual, or personality characteristics. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Genome sequencing for early-onset or atypical dementia: high diagnostic yield and frequent observation of multiple contributory alleles.

We assessed the results of genome sequencing for early-onset dementia. Participants were selected from a memory disorders clinic. Genome sequencing was performed along with C9orf72 repeat expansion testing. All returned sequencing results were Sanger-validated. Prior clinical diagnoses included Alzheimer's disease, frontotemporal dementia, and unspecified dementia. The mean age of onset was 54 (41-76). Fifty percent of patients had a strong family history, 37.5% had some, and 12.5% had no known family history. Nine of 32 patients (28%) had a variant defined as pathogenic or likely pathogenic (P/LP) by American College of Medical Genetics and Genomics standards, including variants in APP, C9orf72, CSF1R, and MAPT Nine patients (including three with P/LP variants) harbored established risk alleles with moderate penetrance (odds ratios of ∼2-5) in ABCA7, AKAP9, GBA, PLD3, SORL1, and TREM2 All six patients harboring these moderate penetrance variants but not P/LP variants also had one or two APOE ε4 alleles. One patient had two APOE ε4 alleles with no other established contributors. In total, 16 patients (50%) harbored one or more genetic variants likely to explain symptoms. We identified variants of uncertain significance (VUSs) in ABI3, ADAM10, ARSA, GRID2IP, MME, NOTCH3, PLCD1, PSEN1, TM2D3, TNK1, TTC3, and VPS13C, also often along with other variants. In summary, genome sequencing for early-onset dementia frequently identified multiple established or possible contributory alleles. These observations add support for an oligogenic model for early-onset dementia.