Stephen Sidney

BACKGROUND: We aimed to examine how coronary artery calcium (CAC) and its progression relate to cognitive function in midlife, an important time for cognitive aging. METHODS: We studied participants enrolled in the prospective CARDIA (Coronary Artery Risk Development in Young Adults) study, a longitudinal cohort of Black and White adults aged 18 to 30 years at baseline, who completed CAC measurements using computed tomography at year 15 (2000–2001; our baseline), had at least 1 follow-up CAC measurement at years 20 (2005–2006) or 25 (2010–2011), and completed cognitive assessments with a battery of 5 tests at years 30 (2015–2016) or 35 (2020–2022). CAC progression was defined as: (1) CAC >0 at follow-up among participants with baseline CAC=0; (2) an annualized change of ≥10 units at follow-up among those with 00 (9%) was associated with lower processing speed, verbal memory, and global cognition, whereas CAC progression (26%) was associated with lower processing speed and global cognition after adjusting for demographics, education, physical activity, depressive symptoms, APOE ε4 allele, and baseline CAC score. The standardized cognitive differences (95% CI) for CAC progression versus no progression were −0.14 (95% CI, −0.23 to −0.06) for the Digit Symbol Substitution Test and −0.09 (95% CI, −0.17 to −0.01) for the Montreal Cognitive Assessment. CONCLUSIONS: CAC progression was associated with worse midlife processing speed and global cognition, independent of baseline CAC score and established risk factors. Repeated CAC assessments may offer clinical value for identifying individuals at increased risk for midlife cognitive decline.

BACKGROUND: The magnitude of cognitive changes after incident heart failure (HF) is unclear. We assessed whether incident HF is associated with changes in cognition after accounting for pre-HF cognitive trajectories and known determinants of cognition. METHODS: This pooled cohort study included adults without HF, stroke, or dementia from 6 US population-based studies from 1971 to 2019. Linear mixed-effects models estimated cognitive change with incident HF diagnosis and the rate of cognitive change over the years after HF, controlling for pre-HF cognitive trajectories and participant factors. Outcomes included change in global cognition (primary outcome), executive function, and memory (secondary outcomes). Cognitive outcomes were standardized to a t score metric (mean [SD], 50 [10]); a 1-point difference represented a 0.1-SD difference in cognition. RESULTS: We included 29 614 adults (mean [SD] age was 61 [10] years, 55% female, 70% White). During a median follow-up of 6.6 (Q1–Q3, 5.0–19.8) years, 1407 (5%) adults received an incident diagnosis of HF. Incident HF diagnosis was associated with initial decreases in global cognition (−1.1 points [95% CI, −1.4 to −0.8]) and executive function (−0.6 points [95% CI, −1.0 to −0.3]). Larger decreases in global cognition after HF were seen with older age, female sex, and White race. Participants with incident HF diagnosis demonstrated faster and long-term declines in global cognition (−0.1 points per year [95% CI, −0.2 to −0.1]) and executive function (−0.2 points per year [95% CI, −0.2 to −0.1]). The change in memory with incident HF diagnosis was not statistically significant but showed a similar trend with an initial decline of −0.5 points (95% CI, −1.4 to +0.3) and a slope of −0.1 points per year (95% CI, −0.3 to 0.0). CONCLUSIONS: In this pooled cohort study, incident HF diagnosis was associated with initial decreases in global cognition and executive function and faster, persistent declines in these domains at follow-up.

Background: We examined the association between acute cardiovascular disease (CVD) events and wildfire air pollution in California in 2018. Methods: The study included adult (≥18 years) members of Kaiser Permanente Northern California, an integrated health care system. Outcomes included CVD events (hospitalizations for acute myocardial infarction, heart failure, or stroke, and CVD death) and death from any cause. Fine particulate air pollution (particulate matter 2.5 ) exposure was assessed in categories (Good 3 , Moderate 12–34 μg/m ³ , High ≥35 μg/m ³ ) and continuously. Poisson time series regression was used to model daily event rates during July 1 to December 31, 2018, using a spline to adjust for long‐term time trends. We calculated rate ratios (RR) to estimate the association between wildfire air pollution and daily rate of CVD events and deaths. Results: Our study included 3.2 million adults with a total follow‐up of 587.9 million person‐days. High PM _2.5 concentrations during the Mendocino Complex wildfire in July to August was associated with an increased rate of CVD events (RR, 1.231 [95% CI, 1.039–1.458]) and death (RR, 1.358 [95% CI, 1.128–1.635]) compared with Good PM _2.5 concentrations. In contrast, there was no evidence of increased risk during the Camp wildfire in November (RR for CVD events, 0.966 [95% CI, 0.894–1.044]; RR for all‐cause mortality, 0.985 [95% CI, 0.904–1.074] High versus Good PM _2.5 concentrations). Conclusions: There was some evidence of increased rates of CVD events and death during wildfires, but results were inconsistent. With ongoing climate change, large wildfires are a pressing public health concern and future work is needed to understand differences in health outcomes by wildfire.

While the age-adjusted mortality rate from heart disease (HD) and stroke decreased between 2011 and 2019, the number of deaths due to HD and stroke increased in association with the rapid growth rate of the population aged 65 years and older.¹ From 2019 to 2020, the estimated age-adjusted mortality rate increased by 15.9%, largely due to COVID-19 mortality,² with increases in age-adjusted mortality from HD (4.3%) and stroke (6.4%). We examined relative contributions of aging vs underlying disease risk in the total population and in major race and ethnicity groups.

Rationale: People with chronic obstructive pulmonary disease (COPD) have an increased risk of cardiovascular disease and may be more susceptible to air pollution exposure. However, no study has examined the association between long-term fine particulate matter exposure (≤2.5 μm in aerodynamic diameter) and risk of cardiovascular events in this potentially vulnerable population. Objectives: To estimate the association between long-term fine particulate matter and risk of cardiovascular events among adults with COPD. Methods: This retrospective cohort study included 169,714 adults with COPD who were members of the Kaiser Permanente Northern California health plan during 2007–2016. Electronic health record data were linked to 1 km modeled particulate matter ≤2.5 μm in aerodynamic diameter exposure estimates. We fit Cox proportional hazard models, adjusting for age, sex, race/ethnicity, calendar year, smoking, body mass index, comorbidities, medications, and socioeconomic status. In low exposure analyses, we examined effects below the current regulation limit (12 μg/m3). Measurements and Main Results: Among adults with COPD, a 10-μg/m3 increase in 1-year mean fine particulate matter exposure was associated with an elevated risk of cardiovascular mortality (hazard ratio, 1.10; 95% confidence interval [CI], 1.01–1.20). Effects were stronger in low exposure analyses (hazard ratio, 1.88; 95% CI, 1.56–2.27). Fine particulate matter exposure was not associated with acute myocardial infarction or stroke in overall analyses. Conclusions: Long-term fine particulate matter exposure was associated with an increased risk of cardiovascular mortality among adults with COPD. Current regulations may not sufficiently protect those with COPD.

Background: Moderate-to-vigorous intensity physical activity (MVPA) is associated with favorable self-rated mental and physical health. Conversely, poor self-rated health in these domains could precede unfavorable shifts in activity. We evaluated bidirectional associations of accelerometer-estimated time spent in stationary behavior (SB), light intensity physical activity (LPA), and MVPA with self-rated health over 10 years in in the CARDIA longitudinal cohort study. Methods: Participants (n = 894, age: 45.1 ± 3.5; 63% female; 38% black) with valid accelerometry wear and self-rated health at baseline (2005–6) and 10-year follow-up (2015–6) were included. Accelerometry data were harmonized between exams and measured mean total activity and duration (min/day) in SB, LPA, and MVPA; duration (min/day) in long-bout and short-bout SB (≥30 min vs. < 30 min) and MVPA (≥10 min vs. < 10 min) were also quantified. The Short-Form 12 Questionnaire measured both a mental component score (MCS) and physical component score (PCS) of self-rated health (points). Multivariable linear regression associated baseline accelerometry variables with 10-year changes in MCS and PCS. Similar models associated baseline MCS and PCS with 10-year changes in accelerometry measures. Results: Over 10-years, average (SD) MCS increased 1.05 (9.07) points, PCS decreased by 1.54 (7.30) points, and activity shifted toward greater SB and less mean total activity, LPA, and MVPA (all p < 0.001). Only baseline short-bout MVPA was associated with greater 10-year increases in MCS (+ 0.92 points, p = 0.021), while baseline mean total activity, MVPA, and long-bout MVPA were associated with greater 10-year changes in PCS (+ 0.53 to + 1.47 points, all p < 0.005). In the reverse direction, higher baseline MCS and PCS were associated with favorable 10-year changes in mean total activity (+ 9.75 cpm, p = 0.040, and + 15.66 cpm, p < 0.001, respectively) and other accelerometry measures; for example, higher baseline MCS was associated with − 13.57 min/day of long-bout SB (p < 0.001) and higher baseline PCS was associated with + 2.83 min/day of MVPA (p < 0.001) in fully adjusted models. Conclusions: The presence of bidirectional associations between SB and activity with self-rated health suggests that individuals with low overall activity levels and poor self-rated health are at high risk for further declines and supports intervention programming that aims to dually increase activity levels and improve self-rated health.

We examined the longitudinal association between blood pressure (BP) and stroke incidence in young and middle-aged adults. BP measured during 9 examinations of the CARDIA study (Coronary Artery Risk Development in Young Adults) from 1985-1986 to 2015-2016 was used to classify participants (n=5079) according to the 2017 Hypertension Clinical Practice Guidelines. We used the highest BP obtained through the third examination (1990–1991) to define baseline BP categories; time-dependent categories (accounting for change in BP over time) were determined incorporating follow-up measurements. BP groups at ages 30 and 40 years were also defined. Stroke events were adjudicated until 2018. Mean age at baseline was 29.8 years. Stroke occurred in 100 participants. Stroke incidence (per 100 000 person-years) was higher ( P <0.001) in Black (120 [95% CI, 95–149]) versus White (29 [95% CI, 18–46]) participants. After adjustment with Cox models for sociodemographic and cardiovascular risk factors, stage 2 hypertension was associated with a higher risk of stroke at baseline (hazard ratio, 3.72 [95% CI, 2.12–6.54]), as a time-dependent variable (hazard ratio, 5.84 [95% CI, 3.43–9.95]), at age 30 (hazard ratio, 4.14 [95% CI, 2.19–7.82]) and at age 40 (hazard ratio, 5.59 [95% CI, 3.35–9.31]), compared with normal BP. Elevated BP and stage 1 hypertension showed more modest increases in risk. As a continuous variable, systolic BP ≥90 mm Hg at age 40 was directly associated with stroke risk. These findings call for primordial prevention strategies to reduce population BP levels among young and middle-aged adults, particularly in Black young adults given ≈4-fold higher stroke incidence, including within values traditionally considered to be normal.

Background: Non-alcoholic fatty liver disease (NAFLD) is associated with cardiovascular disease (CVD) risk factors that have been linked to cognitive decline. Whether NAFLD is associated with cognitive performance in midlife remains uncertain.Methods: Coronary Artery Risk Development in Young Adults study participants with CT examination and cognitive assessment at Y25 (2010–2011; n = 2809) were included. Cognitive function was reassessed at Y30. NAFLD was defined according to liver attenuation and treated both continuously and categorically (using ≤ 40 and ≤ 51 Hounsfield units to define severity) after exclusion for other causes of liver fat. Cognitive tests including the Digit Symbol Substitution (processing speed), Rey Auditory Verbal Learning (verbal memory), and Stroop (executive function) were analyzed with standardized z-scores. Linear models were constructed to (a) examine the cross-sectional associations of NAFLD with cognitive scores and (b) evaluate its predictive role in 5-year change in cognitive performance.Results: Participants’ mean age (Y25) was 50.1 (SD 3.6) years (57% female; 48% black), with 392 (14%) having mild NAFLD and 281 (10%) having severe NAFLD. NAFLD was positively associated with CVD risk factors and inversely associated with cognitive scores. However, after adjustment for CVD risk factors, no associations were shown between NAFLD and cognitive scores (all βs ≈ 0). Similarly, no associations were observed with 5-year cognitive decline. CVD history, hypertension, smoking, diabetes and hypertriglyceridemia showed stronger associations with baseline cognitive scores and were predictive of subsequent cognitive decline (allP ≤ .05).Conclusion: Among middle-aged adults, inverse associations between NAFLD and cognitive scores were attenuated after adjustment for CVD risk factors, with the latter predictive of poorer cognitive performance both at baseline and follow-up.