<h3>Importance</h3><p>Familial hypercholesterolemia (FH) is a genetic disorder that often results in severely high low-density lipoprotein cholesterol (LDL-C) and high risk of premature coronary heart disease (CHD). However, the impact of FH variants on CHD risk among individuals with moderately elevated LDL-C is not well quantified.</p><h3>Objective</h3><p>To assess CHD risk associated with FH variants among individuals with moderately (130-189 mg/dL) and severely (≥190 mg/dL) elevated LDL-C and to quantify excess CHD deaths attributable to FH variants in US adults.</p><h3>Design, Setting, and Participants</h3><p>A total of 21 426 individuals without preexisting CHD from 6 US cohort studies (Atherosclerosis Risk in Communities study, Coronary Artery Risk Development in Young Adults study, Cardiovascular Health Study, Framingham Heart Study Offspring cohort, Jackson Heart Study, and Multi-Ethnic Study of Atherosclerosis) were included, 63 of whom had an FH variant. Data were collected from 1971 to 2018, and the median (IQR) follow-up was 18 (13-28) years. Data were analyzed from March to May 2023.</p><h3>Exposures</h3><p>LDL-C, cumulative past LDL-C, FH variant status.</p><h3>Main Outcomes and Measures</h3><p>Cox proportional hazards models estimated associations between FH variants and incident CHD. The Cardiovascular Disease Policy Model projected excess CHD deaths associated with FH variants in US adults.</p><h3>Results</h3><p>Of the 21 426 individuals without preexisting CHD (mean [SD] age 52.1 [15.5] years; 12 041 [56.2%] female), an FH variant was found in 22 individuals with moderately elevated LDL-C (0.3%) and in 33 individuals with severely elevated LDL-C (2.5%). The adjusted hazard ratios for incident CHD comparing those with and without FH variants were 2.9 (95% CI, 1.4-6.0) and 2.6 (95% CI, 1.4-4.9) among individuals with moderately and severely elevated LDL-C, respectively. The association between FH variants and CHD was slightly attenuated when further adjusting for baseline LDL-C level, whereas the association was no longer statistically significant after adjusting for cumulative past LDL-C exposure. Among US adults 20 years and older with no history of CHD and LDL-C 130 mg/dL or higher, more than 417 000 carry an FH variant and were projected to experience more than 12 000 excess CHD deaths in those with moderately elevated LDL-C and 15 000 in those with severely elevated LDL-C compared with individuals without an FH variant.</p><h3>Conclusions and Relevance</h3><p>In this pooled cohort study, the presence of FH variants was associated with a 2-fold higher CHD risk, even when LDL-C was only moderately elevated. The increased CHD risk appeared to be largely explained by the higher cumulative LDL-C exposure in individuals with an FH variant compared to those without. Further research is needed to assess the value of adding genetic testing to traditional phenotypic FH screening.</p>

Self-rated health (SRH) is an in-dividual's self-evaluation of well-being, as influenced by social and biological factors, that correlates with cardiovascular risk factors, car-diovascular disease (CVD), and cardiac and all-cause mortality. 1,2 Coronary artery calcium (CAC) scoring, which quantifies the burden of calcified coronary athero-sclerosis by cardiac computed to-mography, serves as a more exact and personalized measure of CVD risk than traditional 10-year athero-sclerotic CVD risk scores by capturing lifetime exposure to traditional risk factors, additional risk enhancers, and genetic predisposition. A study in middle-aged adults found that a general self-assessment rating of overall health correlated poorly with CAC 3 ; however , it is not clear whether these results would apply to older adults. Therefore, in a community-based sample of adults 73 to 95 years old without known CVD, we studied whether SRH including overall life satisfaction, perceived heart attack risk, and attitude toward CVD prevention is correlated with individual CAC burden. Methods The Atherosclerosis Risk in Communities Study (ARIC) is a large prospective cohort study of adults across 4 US communities. 4 Our cross-sectional analysis included a total of 2290 ARIC participants without coronary heart disease at visit 7 (years 2018 to 2019), aged 73 to 95 (female, 61%; Black, 22%); 92% of these participants had survey data reporting both their perceived cardiovascular health and their overall satisfaction with life. Data were analyzed in 2022. Three queries that were included as part of the ARIC CAC study questionnaire were investigated. The first question stated "Overall, how satisfied are you with life these days?" and was rated on a scale of 0 to 10, with 0 noted as not at all satisfied and 10 noted as completely satisfied. The second question stated "Compared to other people your age and sex, how would you rate your risk of a heart attack?" and was scored on a 5-point scale for which the options were much higher than average, higher than average, about average, lower than average, and much lower than average. The final question stated "Please rate how strongly you agree or disagree with the following statement: Taking medication helps prevent a heart attack in people your age" and was scored on a 5-point scale for which the options were strongly agree, agree, neither agree nor disagree, disagree, and strongly disagree. Data were stratified by sex. Mean CAC scores in Agatston units and standard deviation as well as median with interquartile interval were calculated for each category. Spearman rank correlation coefficients were calculated for the variables of SRH responses to each topic and CAC. A 2-tailed P value of .05 was set as the threshold for statistical significance. All analyses were conducted using Stata software , version 15 (StataCorp LLC).

Accumulating evidence supports a link between sleep disorders, disturbed sleep, and adverse brain health, ranging from stroke to subclinical cerebrovascular disease to cognitive outcomes, including the development of Alzheimer disease and Alzheimer disease-related dementias. Sleep disorders such as sleep-disordered breathing (eg, obstructive sleep apnea), and other sleep disturbances, as well, some of which are also considered sleep disorders (eg, insomnia, sleep fragmentation, circadian rhythm disorders, and extreme sleep duration), have been associated with adverse brain health. Understanding the causal role of sleep disorders and disturbances in the development of adverse brain health is complicated by the common development of sleep disorders among individuals with neurodegenerative disease. In addition to the role of sleep disorders in stroke and cerebrovascular injury, mechanistic hypotheses linking sleep with brain health and biomarker data (blood-based, cerebrospinal fluid-based, and imaging) suggest direct links to Alzheimer disease-specific pathology. These potential mechanisms and the increasing understanding of the "glymphatic system," and the recognition of the importance of sleep in poststroke recovery, as well, support a biological basis for the indirect (through the worsening of vascular disease) and direct (through specific effects on neuropathology) connections between sleep disorders and brain health. Given promising evidence for the benefits of treatment and prevention, sleep disorders and disturbances represent potential targets for early treatment that may improve brain health more broadly. In this scientific statement, we discuss the evidence supporting an association between sleep disorders and disturbances and poor brain health ranging from stroke to dementia and opportunities for prevention and early treatment.

Comparative effectiveness evaluation of newer P2Y12 inhibitors (prasugrel and ticagrelor) compared with clopidogrel after acute coronary syndrome (ACS) is limited in real-world US populations. The objective of this study was to evaluate cardiovascular events based on ticagrelor, prasugrel, and clopidogrel use in a real-world patient setting. This retrospective cohort study used the IBM MarketScan database (January 1, 2013, to December 31, 2018) to create three propensity score-matched pairs: ticagrelor vs. clopidogrel (N = 21,719), prasugrel vs. clopidogrel (N = 11,513), and prasugrel vs. ticagrelor (N = 11,065). The primary outcome was a composite of myocardial ischemia, unstable angina, stroke, and heart failure hospitalization. These groups were compared in a time-to-event analysis for the primary outcome at 30, 90, and 180 days following P2Y12 inhibitors initiation after percutaneous coronary intervention. Compared with clopidogrel, ticagrelor use suggested a 10% reduction in the primary outcome at 90 days (hazard ratio (HR): 0.90, 95% confidence interval (CI): 0.82–0.99). There were no differences for all other matched pairs or follow-up combinations. In the subgroup analysis of females, the results suggested a risk reduction of 27% for prasugrel at 30 days (HR: 0.73, 95% CI: 0.53–1.00) and 17% for ticagrelor at 90 days (HR: 0.83, 95% CI: 0.70–0.98) when compared with clopidogrel. Among patients treated with bare-metal stents, the results suggested that prasugrel vs. ticagrelor was associated with a 55% and 33% reduced risk for the primary outcome at 30 days and 180 days, respectively. With limited evidence in the United States comparing these drugs, this study helps inform clinicians when choosing P2Y12 inhibitors after ACS.

<p>We examined the associations between lung function and incident dementia and cognitive decline in 12,688 participants of the ARIC study who provided lung function measurements in 1990-1992. Cognitive tests were administered up to seven times, and dementia was ascertained through 2019. We used shared parameter models to jointly model proportional hazard models and linear mixed-effect models to estimate lung function-associated dementia rate and cognitive change, respectively. Higher forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) were associated with reduced dementia rate (n=2452 developed dementia); hazard ratios per 1L higher FEV1 and FVC were 0.79 (95%CI: 0.71-0.89) and 0.81 (95%CI: 0.74-0.89), respectively. Each 1L higher FEV1 and FVC was associated with 0.08 (95%CI: 0.05-0.12) SD and 0.05 (95%CI: 0.02-0.07) SD attenuation of 30-year cognitive decline, respectively. One percent higher FEV1/FVC was associated with 0.008 (95% CI: 0.004-0.012) SD less cognitive decline. We observed statistical interaction between FEV1 and FVC, suggesting that cognitive declines depended on values of specific FEV1 and FVC (as compared to FEV1, FVC, or FEV1/FVC% models that suggested linear incremental associations). Our findings may have important implications for reducing burden of cognitive decline that is attributable to environmental exposures and associated lung function impairment.</p>

Venous thromboembolism (VTE) affects 1.2 million people per year in the United States. With several clinical changes in diagnosis and treatment approaches in the past decade, we evaluated contemporary post-VTE mortality risk profiles and trends. Incident VTE cases were identified from the 2011–2019 Medicare 20% Sample, which is representative of nearly all Americans aged 65 and older. The social deprivation index was linked from public data; race/ethnicity and sex were self-reported. The all-cause mortality risk 30 days and 1 year after incident VTE was calculated in demographic subgroups and by prevalent cancer diagnosis status using model-based standardization. Risks for major cancer types, risk differences by age, sex, race/ethnicity, and socio-economic status (SES), and trends over time are also reported. The all-cause mortality risk among older US adults following incident VTE was 3.1% (95% CI 3.0–3.2) at 30 days and 19.6% (95% CI 19.2–20.1) at 1 year. For cancer-related VTE events, the age-sex-race-standardized risk was 6.0% at 30 days and 34.7% at 1 year. The standardized 30-day and 1-year risks were higher among non-White beneficiaries and among those with low SES. One-year mortality risk decreased 0.28 percentage points per year (95% CI 0.16–0.40) on average across the study period, with no trend observed for 30-day mortality risk. In sum, all-cause mortality risk following incident VTE has decreased slightly in the last decade, but racial and socio-economic disparities persist. Understanding patterns of mortality among demographic subgroups and in cancer-associated events is important for targeting efforts to improve VTE management.

Rationale: The autonomic nervous system extensively innervates the lungs but its role in COPD outcomes has not been well-studied. Objective: We assessed relationships between cardiovascular autonom...

In closely monitored randomized controlled trials (RCTs), newer P2Y12 agents (ticagrelor and prasugrel) reduced cardiovascular outcomes compared with clopidogrel following percutaneous coronary intervention (PCI) in acute coronary syndrome. However, these RCTs indicated a higher bleeding risk with these newer agents. This study evaluated the comparative safety of each P2Y12 inhibitor on hospitalizations due to major bleeding in a real-world population. This retrospective, propensity score-matched (PSM) cohort study utilized the IBM MarketScan database over 6 years (2013–2018) to identify incident users of P2Y12 inhibitors with age ≥18 years. The primary safety outcome was hospitalization due to any major bleeding event including gastrointestinal, intracranial, and other serious forms of bleeding. In pairwise comparisons using Cox-proportional hazards models, ticagrelor, prasugrel, and clopidogrel users were compared for the primary safety outcome at 30, 90, and 180 days following the first prescription of P2Y12 inhibitor after PCI. There were 21,719 (ticagrelor vs. clopidogrel), 11,513 (prasugrel vs. clopidogrel), and 11,065 (prasugrel vs. ticagrelor) PSM pairs. Overall, the risk of major bleeding was similar for all P2Y12 inhibitors. Hospitalization for major bleeding was generally lower among ticagrelor users vs. clopidogrel and higher among prasugrel users compared with clopidogrel. Importantly, a 66% higher risk of major bleeding at 90 days is suggested with prasugrel compared with clopidogrel (hazard ratio 1.66; 95% confidence interval, 1.11–2.48). This study indicated a higher short-term bleeding risk with prasugrel compared with clopidogrel, which concurs with the results of RCTs.

Objectives: We investigated the relationship between the cognitive status of participants’ spouses and participants’ own cognitive outcomes, controlling for mid-life factors. Methods: Participants (n = 1845; baseline age 66–90 years) from the prospective Atherosclerosis Risk in Communities Study were followed from 2011 to 2019. We used linear regression and Cox proportional hazard models to estimate whether spouses of people with MCI/dementia had lower cognitive functioning and elevated risk of incident dementia. Results: Having a spouse with MCI/dementia was associated with a deficit in cognitive function (b = −0.09 standard deviations; 95% CI = −0.18, 0.00). Adjustment for mid-life risk factors attenuated this association (b = −0.02 standard deviations; 95% CI = −0.10, 0.06). We observed no significant relationship between spousal MCI/dementia status and incident dementia (hazard ratio = 0.97; 95% CI = 0.69, 1.38). Discussion: Spousal cognitive status is not associated with poor cognitive outcomes independent of mid-life factors.

Background ACC/AHA guidelines caution against the use of antihypertensive therapy in the setting of

<h3>Importance</h3><p>Good sleep is essential for health, yet associations between sleep and dementia risk remain incompletely understood. The Sleep and Dementia Consortium was established to study associations between polysomnography (PSG)–derived sleep and the risk of dementia and related cognitive and brain magnetic resonance imaging endophenotypes.</p><h3>Objective</h3><p>To investigate association of sleep architecture and obstructive sleep apnea (OSA) with cognitive function in the Sleep and Dementia Consortium.</p><h3>Design, Setting, and Participants</h3><p>The Sleep and Dementia Consortium curated data from 5 population-based cohorts across the US with methodologically consistent, overnight, home-based type II PSG and neuropsychological assessments over 5 years of follow-up: the Atherosclerosis Risk in Communities study, Cardiovascular Health Study, Framingham Heart Study (FHS), Osteoporotic Fractures in Men Study, and Study of Osteoporotic Fractures. Sleep metrics were harmonized centrally and then distributed to participating cohorts for cohort-specific analysis using linear regression; study-level estimates were pooled in random effects meta-analyses. Results were adjusted for demographic variables, the time between PSG and neuropsychological assessment (0-5 years), body mass index, antidepressant use, and sedative use. There were 5946 participants included in the pooled analyses without stroke or dementia. Data were analyzed from March 2020 to June 2023.</p><h3>Exposures</h3><p>Measures of sleep architecture and OSA derived from in-home PSG.</p><h3>Main Outcomes and Measures</h3><p>The main outcomes were global cognitive composite<i>z</i>scores derived from principal component analysis, with cognitive domains investigated as secondary outcomes. Higher scores indicated better performance.</p><h3>Results</h3><p>Across cohorts, 5946 adults (1875 females [31.5%]; mean age range, 58-89 years) were included. The median (IQR) wake after sleep onset time ranged from 44 (27-73) to 101 (66-147) minutes, and the prevalence of moderate to severe OSA ranged from 16.9% to 28.9%. Across cohorts, higher sleep maintenance efficiency (pooled β per 1% increase, 0.08; 95% CI, 0.03 to 0.14;<i>P</i> &lt; .01) and lower wake after sleep onset (pooled β per 1-min increase, −0.07; 95% CI, −0.13 to −0.01 per 1-min increase;<i>P</i> = .02) were associated with better global cognition. Mild to severe OSA (apnea-hypopnea index [AHI] ≥5) was associated with poorer global cognition (pooled β, −0.06; 95% CI, −0.11 to −0.01;<i>P</i> = .01) vs AHI less than 5; comparable results were found for moderate to severe OSA (pooled β, −0.06; 95% CI, −0.11 to −0.01;<i>P</i> = .02) vs AHI less than 5. Differences in sleep stages were not associated with cognition.</p><h3>Conclusions and Relevance</h3><p>This study found that better sleep consolidation and the absence of OSA were associated with better global cognition over 5 years of follow-up. These findings suggest that the role of interventions to improve sleep for maintaining cognitive function requires investigation.</p>

Introduction: Cardiovascular health may be used for prevention of cerebral vascular disease. We evaluated whether improvement of cardiovascular health within midlife and from midlife to late-life w...

Objective: Reproductive factors, including parity, may contribute to dementia risk, due to hormonal, physiological, social, and demographic factors. We hypothesized that higher parity would be asso...