Health Literacy and Treatment Satisfaction Among Patients with Venous Thromboembolism.

BACKGROUND: Venous thromboembolism (VTE) treatment requires complex management, and patients with limited health literacy (HL) may perceive higher burden and lower benefits associated with their treatment. OBJECTIVE: To examine the association of HL with treatment satisfaction among patients with VTE. DESIGN: Retrospective cohort study PARTICIPANTS: Kaiser Permanente Southern and Northern California members who were taking oral anticoagulants (OAC) for incident VTE between 2015 and 2018 were surveyed. Main Measures HL was assessed using a 3-item HL assessment and dichotomized as having adequate or limited HL. High treatment burden and low treatment benefit were defined as Anti-Clot Treatment Scale (ACTS) scores below the 25th percentile of the distributions for ACTS Burdens and Benefits survey components, respectively. Using Poisson regression, multivariable adjusted risk ratios (RR) and 95% confidence intervals (CI) were calculated for the association of HL with high treatment burden and low treatment benefits. RESULTS: Among 2154 respondents, 397 (18.4%) had limited HL. Patients with limited vs adequate HL were older (47.9% vs 27.5% aged ≥ 75 years, p<0.001), more likely to use a non-English language when discussing their health (10.8% vs 1.7%, p<0.001), to have less than high school education (10.1% vs 1.7%, p<0.001), and to self-rate their health as fair or poor (47.6% vs 25.5%, p<0.001). After multivariable adjustment, patients with limited HL were more likely to have higher perceived treatment burden (RR 1.24, 95% CI 1.07, 1.45) and lower perceived treatment benefits (RR 1.21, 95% CI 1.08, 1.37). CONCLUSIONS: Limited HL was associated with lower OAC treatment satisfaction, though absolute differences in satisfaction scores were small. Further examination of the intersection of HL with VTE treatment satisfaction and compliance among older and non-English speaking patients is warranted.

Sociopolitical stress and acute cardiovascular disease hospitalizations around the 2016 presidential election.

Previous research suggests that stressors may trigger the onset of acute cardiovascular disease (CVD) events within hours to days, but there has been limited research around sociopolitical events such as presidential elections. Among adults ≥18 y of age in Kaiser Permanente Southern California, hospitalization rates for acute CVD were compared in the time period immediately prior to and following the 2016 presidential election date. Hospitalization for CVD was defined as an inpatient or emergency department discharge diagnosis of acute myocardial infarction (AMI) or stroke using International Classification of Diseases, 10th revision codes. Rate ratios (RR) and 95% confidence intervals (CIs) were calculated comparing CVD rates in the 2 d following the 2016 election to rates in the same 2 d of the prior week. In a secondary analysis, AMI and stroke were analyzed separately. The rate of CVD events in the 2 d after the 2016 presidential election (573.14 per 100,000 person-years [PY]) compared to the rate in the window prior to the 2016 election (353.75 per 100,000 PY) was 1.62 times higher (95% CI 1.17, 2.25). Results were similar across sex, age, and race/ethnicity groups. The RRs were similar for AMI (RR 1.67, 95% CI 1.00, 2.76) and stroke (RR 1.59, 95% CI 1.03, 2.44) separately. Transiently heightened cardiovascular risk around the 2016 election may be attributable to sociopolitical stress. Further research is needed to understand the intersection between major sociopolitical events, perceived stress, and acute CVD events.

Influenza vaccination and mortality among adults with heart failure in an integrated healthcare delivery system, 2009-2018.

BACKGROUND: Influenza infection can result in decompensation or exacerbation of heart failure (HF) symptoms, hospitalization, and death. OBJECTIVE: To examine the association of influenza vaccination with mortality and hospitalization during influenza and non-influenza seasons between 2009 and 2018. DESIGN, SETTING, AND PARTICIPANTS: In this prospective, observational cohort study, we included Kaiser Permanente Southern California members with a HF diagnosis prior to September 1 each year from 2009 to 2017. EXPOSURE: The first influenza vaccination in each season (September 1 to May 31) was recorded. Vaccinated/unvaccinated patients were matched 1:1 on age, sex, and ejection fraction at the vaccination date (n-total = 74,870). MAIN OUTCOMES: Patients were followed through the end of each influenza season for all-cause mortality. Secondary outcomes included cardiovascular mortality and all-cause hospitalization. In a sensitivity analysis, we examined mortality in the non-influenza season. RESULTS: Influenza vaccinated vs unvaccinated patients had more comorbidities and higher healthcare utilization. After multivariable adjustment for utilization, sociodemographics, comorbidities, and medications, influenza vaccinated vs unvaccinated patients had a lower risk of all-cause mortality and cardiovascular mortality during the influenza season (hazard ratio [HR] 0.66, 95% confidence interval [CI] 0.63, 0.70 and HR 0.68, 95% CI 0.63, 0.74, respectively) but a higher risk of all-cause hospitalization (HR 1.27, 95% CI 1.21, 1.31). There was no association between influenza vaccination and all-cause or cardiovascular mortality during the non-influenza season (HR 0.99, 95% CI 0.89, 1.09 and HR 1.00, 95% CI 0.84, 1.21, respectively). CONCLUSIONS: Influenza vaccination in HF patients was associated with a lower risk of mortality during the influenza season. Our findings provide support for recommendations of universal influenza vaccination in patients with HF.

Sex-Specific Trends in Acute Myocardial Infarction Within an Integrated Healthcare Network, 2000 Through 2014.

BACKGROUND: In recent decades, the rates of incident acute myocardial infarction (AMI) have declined in the United States, yet disparities by sex remain. In an integrated healthcare delivery system, we examined temporal trends in incident AMI among women and men. METHODS: We identified hospitalized AMI among members ≥35 years of age in Kaiser Permanente Southern California. The first hospitalization for AMI overall, and for ST-segment-elevation MI and non-ST-segment-elevation MI was identified by International Classification of Diseases, Ninth Revision, Clinical Modification primary discharge diagnosis codes in each calendar year from 2000 through 2014. Age- and sex-standardized incidence rates per 100 000 person-years were calculated by using direct adjustment to the 2010 US Census population. Average annual percent changes (AAPCs) and period percent changes were calculated, and trend tests were conducted using Poisson regression. RESULTS: We identified 45 331 AMI hospitalizations between 2000 and 2014. Age- and sex-standardized incidence rates of AMI declined from 322.4 (95% CI, 311.0-333.9) in 2000 to 174.6 (95% CI, 168.2-181.0) in 2014, representing an AAPC of -4.4% (95% CI, -4.2 to -4.6) and a period percent change of -46.6%. The AAPC for AMI in women was -4.6% (95% CI, -4.1 to -5.2) between 2000 and 2009 and declined to -2.3% (95% CI, -1.2 to -3.4) between 2010 and 2014. The AAPC for AMI in men was stable over the study period (-4.7% [95% CI, -4.4 to -4.9]). The AAPC for ST-segment-elevation MI hospitalization overall was -8.3% (95% CI, -8.0% to -8.6%).The AAPC in ST-segment-elevation MI changed among women in 2009 (2000-2009: -10.2% [95% CI, -9.3 to -11.1] and in 2010-2014: -5.2% [95% CI, -3.1 to -7.3]) while remaining stable among men (-8.0% [95% CI, -7.6 to -8.4]). The AAPC for non-ST-segment-elevation MI hospitalization was smaller than for ST-segment-elevation MI among both women and men (-1.9% [95% CI, -1.5 to -2.3] and -2.8% [95% CI, -2.5 to -3.2], respectively). CONCLUSIONS: These results suggest that the incidence of hospitalized AMI declined between 2000 and 2014; however, declines in AMI have slowed among women in comparison with men in recent years. Determining unmet care needs among women may reduce these sex-based AMI disparities.

Long-Term Levels of LDL-C and Cognitive Function: The CARDIA Study.

OBJECTIVES: It is uncertain if long-term levels of low-density lipoprotein-cholesterol (LDL-C) affect cognition in middle age. We examined the association of LDL-C levels over 25 years with cognitive function in a prospective cohort of black and white US adults. METHODS: Lipids were measured at baseline (1985-1986; age: 18-30 years) and at serial examinations conducted over 25 years. Time-averaged cumulative LDL-C was calculated using the area under the curve for 3,328 participants with ≥3 LDL-C measurements and a cognitive function assessment. Cognitive function was assessed at the Year 25 examination with the Digit Symbol Substitution Test [DSST], Rey Auditory Visual Learning Test [RAVLT], and Stroop Test. A brain magnetic resonance imaging (MRI) sub-study (N = 707) was also completed at Year 25 to assess abnormal white matter tissue volume (AWMV) and gray matter cerebral blood flow volume (GM-CBFV) as secondary outcomes. RESULTS: There were 15.6%, 32.9%, 28.9%, and 22.6% participants with time-averaged cumulative LDL-C <100 mg/dL, 101-129 mg/dL, 130-159 mg/dL, and ≥160 mg/dL, respectively. Standardized differences in all cognitive function test scores ranged from 0.16 SD lower to 0.09 SD higher across time-averaged LDL-C categories in comparison to those with LDL-C < 100 mg/dL. After covariate adjustment, participants with higher versus lower time-averaged LDL-C had a lower RAVLT score (p-trend = 0.02) but no differences were present for DSST, Stroop Test, AWMV, or GM-CBFV. CONCLUSION: Cumulative LDL-C was associated with small differences in memory, as assessed by RAVLT scores, but not other cognitive or brain MRI measures over 25 years of follow-up.

Temporal trends in heart failure mortality in an integrated healthcare delivery system, California, and the US, 2001-2017.

BACKGROUND: In recent years, decreases in mortality rates attributable to cardiovascular diseases have slowed but mortality attributable to heart failure (HF) has increased. METHODS: Between 2001-2017, trends in age-adjusted mortality with HF as an underlying cause for Kaiser Permanente Southern California (KPSC) members were derived through linkage with state death files and compared with trends among California residents and the US. Average annual percent change (AAPC) and 95% confidence intervals (CI) were calculated using Joinpoint regression. Analyses were repeated examining HF as a contributing cause of death. RESULTS: In KPSC, the age-adjusted HF mortality rates were comparable to California but lower than the US, increasing from 23.9 per 100,000 person-years (PY) in 2001 to 44.7 per 100,000 PY in 2017, representing an AAPC of 1.3% (95% CI 0.0%, 2.6%). HF mortality also increased in California from 33.9 to 46.5 per 100,000 PY (AAPC 1.5%, 95% CI 0.3%, 2.7%), while remaining unchanged in the US at 57.9 per 100,000 PY in 2001 and 2017 (AAPC 0.0%, 95% CI - 0.5%, 0.5%). Trends among KPSC members ≥ 65 years old were similar to the overall population, while trends among members 45-64 years old were flat between 2001-2017. Small changes in mortality with HF as a contributing cause were observed in KPSC members between 2001 and 2017, which differed from California and the US. CONCLUSION: Lower rates of HF mortality were observed in KPSC compared to the US. Given the aging of the US population and increasing prevalence of HF, it will be important to examine individual and care-related factors driving susceptibility to HF mortality.

Assembling and validating a heart failure-free cohort from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study.

BACKGROUND: Studies examining incident heart failure (HF) have been limited to select populations. To examine incident HF with broader generalizability, there is need to assemble a HF-free cohort using a geographically-diverse sample. We aimed to develop and validate a simple medication-based strategy for assembling a HF-free cohort from the REasons for Geographic And Racial Differences in Stroke (REGARDS) study. METHODS: We examined REGARDS participants with ≥6 months of Medicare inpatient and outpatient claims data at the time of the baseline in-home study examination. To assemble a HF-free cohort, we identified and excluded participants taking HF-specific medications. To validate this approach, we evaluated event rates among this cohort and assessed diagnostic performance using Medicare claims-based definitions of HF as the referent standard. RESULTS: Among 28,884 eligible participants, 3125 were excluded from the proposed HF-free cohort, leaving a total of 25,759 (89%) participants. Depending on the Medicare definition used as the referent, the negative predictive value of this approach ranged from 95.0-99.2%. Negative predictive value was stable across age, sex, and race strata. CONCLUSIONS: The approach to assemble a HF-free cohort in REGARDS can serve as the basis for future studies to examine incident HF in REGARDS and similar studies.

PCSK9 loss-of-function variants and Lp(a) phenotypes among black US adults.

The pharmacologic inhibition of proprotein convertase subtilisin-kexin type 9 (PCSK9) lowers lipoprotein (a) [Lp(a)] concentrations. However, the impact of genetic PCSK9 loss-of-function variants (LOFVs) on Lp(a) is uncertain. We determined the association of PCSK9 LOFVs with Lp(a) measures among black adults. Genotyping for PCSK9 LOFVs was conducted in 10,196 black Reasons for Geographic and Racial Differences in Stroke study participants. Among 241 participants with and 723 randomly selected participants without PCSK9 LOFVs, Lp(a) concentations, apo(a) kringle IV (KIV) repeats (a proxy for isoform size), and oxidized phospholipid (OxPL) apoB levels were measured using validated methods. Median Lp(a) concentrations among participants with and without PCSK9 LOFVs were 63.2 and 80.4 nmol/l, respectively (P = 0.016). After adjusting for age, sex, estimated glomerular filtration rate, LDL cholesterol, and statin use, participants with versus without a PCSK9 LOFV had a lower median Lp(a) concentration [Δ = -18.8 nmol/l (95% CI: -34.2, -3.3)]. Median apo(a) isoform sizes were 24 and 23 KIV repeats (P = 0.12) among participants with and without PCSK9 LOFVs, respectively [Δ = 1.1 (95% CI: 0.2, 2.0) after adjustment]. Median OxPL-apoB levels among participants with and without PCSK9 LOFVs were 3.4 and 4.1 nM (P = 0.20), respectively [Δ = -1.2 nM (95% CI -2.4, -0.04) after adjustment]. Among black adults, PCSK9 LOFVs were associated with lower Lp(a) concentration and OxPL-apoB levels.

PCSK9 Variants, Low-Density Lipoprotein Cholesterol, and Neurocognitive Impairment: Reasons for Geographic and Racial Differences in Stroke Study (REGARDS).

BACKGROUND: Despite concerns about adverse neurocognitive events raised by prior trials, pharmacological PCSK9 (proprotein convertase subtilisin/kexin type-9) inhibition was not associated with neurocognitive effects in a recent phase 3 randomized trial. PCSK9 loss-of-function (LOF) variants that result in lifelong exposure to lower levels of low-density lipoprotein cholesterol can provide information on the potential long-term effects of lower low-density lipoprotein cholesterol on neurocognitive impairment and decline. METHODS: We investigated the association between PCSK9 LOF variants and neurocognitive impairment and decline among black REGARDS study (Reasons for Geographic and Racial Differences in Stroke) participants with (n=241) and without (n=10 454) C697X or Y142X LOF variants. Neurocognitive tests included the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) battery (Word List Learning, World List Delayed Recall, Semantic Animal Fluency) and Six-Item Screener (SIS) assessments, administered longitudinally during follow-up. Neurocognitive impairment was defined as a score ≥1.5 SD below age, sex, and education-based stratum-specific means on 2 or 3 CERAD assessments or, separately, a score <5 on any SIS assessment at baseline or during follow-up. Neurocognitive decline was assessed using standardized continuous scores on individual neurocognitive tests. RESULTS: The mean sample age was 64 years (SD, 9), 62% were women, and the prevalence of neurocognitive impairment at any assessment was 6.3% by CERAD and 15.4% by SIS definitions. Adjusted odds ratios for neurocognitive impairment for participants with versus without PCSK9 LOF variants were 1.11 (95% confidence interval [CI], 0.58-2.13) using the CERAD battery and 0.89 (95% CI, 0.61-1.30) using the SIS assessment. Standardized average differences in individual neurocognitive assessment scores over the 5.6-year (range, 0.1-9.1) study period ranged between 0.07 (95% CI, -0.06 to 0.20) and -0.07 (95% CI, -0.18 to 0.05) among participants with versus without PCSK9 LOF variants. Patterns of neurocognitive decline were similar between participants with and without PCSK9 LOF variants (all P>0.10). Odds ratios for neurocognitive impairment per 20 mg/dL low-density lipoprotein cholesterol decrements were 1.02 (95% CI, 0.96-1.08) and 0.99 (95% CI, 0.95-1.02) for the CERAD and SIS definitions of impairment, respectively. CONCLUSIONS: These results suggest that lifelong exposure to low PCSK9 levels and cumulative exposure to lower levels of low-density lipoprotein cholesterol are not associated with neurocognitive effects in blacks.

Changes in Glomerular Filtration Rate After Switching From Tenofovir Disoproxil Fumarate to Tenofovir Alafenamide Fumarate for Human Immunodeficiency Virus Preexposure Prophylaxis.

Background: Tenofovir alafenamide fumarate (TAF) was promoted as a safer alternative to tenofovir disoproxil fumarate (TDF) for human immunodeficiency virus oral preexposure prophylaxis (PrEP). It is unknown if switching from TDF to TAF translates to improved renal function. We used electronic health record (EHR) data to assess changes in creatinine-estimated glomerular filtration rate (eGFR) after switching from TDF to TAF. Methods: We conducted a retrospective cohort study using EHR data from Kaiser Permanente Southern California. We identified individuals who switched from TDF to TAF between October 2019 and May 2022 and used time-varying propensity score matching to identify controls who were on TDF ("nonswitchers"). We then used Bayesian longitudinal modeling to compare differences in eGFR between switching and nonswitching scenarios. Results: Among 5246 eligible individuals, we included 118 TDF to TAF switchers and 114 nonswitchers. Compared to nonswitchers, switchers had older age of starting TDF but similar body weights at index date. A higher proportion of switchers were White, on Medicare or Medicaid, and had dyslipidemia at index date. Switching to TAF was associated with a higher eGFR compared to staying on TDF in 3-15 months post-switch, but the differences were not statistically significant (eg, month 9 difference: 1.27 [95% credible interval, -1.35 to 3.89]). While most of the estimated changes showed eGFR increase associated with switching, most were <2 eGFR units. Sensitivity analyses to address missingness or nonadherence showed similar results. Conclusions: Switching from TDF to TAF for PrEP was associated with a nonsignificant increase in eGFR. Findings need to be confirmed using larger cohorts.

Antihypertensive medication persistence and adherence among non-Hispanic Asian US patients with hypertension and fee-for-service Medicare health insurance.

BACKGROUND: Less than 50% of non-Hispanic Asian adults taking antihypertensive medication have controlled blood pressure. METHODS: We compared non-persistence and low adherence to antihypertensive medication between non-Hispanic Asian and other race/ethnicity groups among US adults ≥66 years who initiated antihypertensive medication between 2011 and 2018 using a 5% random sample of Medicare beneficiaries (non-Hispanic Asian, n = 2,260; non-Hispanic White, n = 56,000; non-Hispanic Black, n = 5,792; Hispanic, n = 4,212; and Other, n = 1,423). Non-persistence was defined as not having antihypertensive medication available to take in the last 90 of 365 days following treatment initiation. Low adherence was defined as having antihypertensive medication available to take on <80% of the 365 days following initiation. RESULTS: In 2011-2012, 2013-2014, 2015-2016 and 2017-2018, the proportion of non-Hispanic Asian Medicare beneficiaries with non-persistence was 29.1%, 25.6%, 25.4% and 26.7% (p-trend = 0.381), respectively, and the proportion with low adherence was 58.1%, 54.2%, 53.4% and 51.6%, respectively (p-trend = 0.020). In 2017-2018, compared with non-Hispanic Asian beneficiaries, non-persistence was less common among non-Hispanic White beneficiaries (risk ratio 0.74 [95%CI, 0.64-0.85]), non-Hispanic Black beneficiaries (0.80 [95%CI 0.68-0.94]) and those reporting Other race/ethnicity (0.68 [95%CI, 0.54-0.85]) but not among Hispanic beneficiaries (1.04 [95%CI, 0.88-1.23]). Compared to non-Hispanic Asian beneficiaries, non-Hispanic White beneficiaries and beneficiaries reporting Other race/ethnicity were less likely to have low adherence to antihypertensive medication (relative risk 0.78 [95%CI 0.72-0.84] and 0.84 [95%CI 0.74-0.95], respectively); there was no association for non-Hispanic Black or Hispanic beneficiaries. CONCLUSIONS: Non-persistence and low adherence to antihypertensive medication were more common among older non-Hispanic Asian than non-Hispanic White adults.

Use of Tenofovir Alafenamide Fumarate for HIV Pre-Exposure Prophylaxis and Incidence of Hypertension and Initiation of Statins.

Importance: Pre-exposure prophylaxis (PrEP) is an important tool for preventing HIV infection. However, PrEP's impact on cardiometabolic health is understudied. Objective: To examine the risk of incident hypertension and statin initiation among adult (age ≥18 years) health plan members starting PrEP with tenofovir alafenamide fumarate (TAF) compared with propensity score-matched adults taking tenofovir disoproxil fumarate (TDF). Design, Setting, and Participants: This retrospective cohort study used electronic health records (EHRs) from Kaiser Permanente Southern California. Adult members starting PrEP in Kaiser Permanente Southern California between October 2019 and May 2022 were included. Propensity score matching with multiple imputation (50 matched data sets) was conducted to generate 1 TAF:4 TDF matched data sets with balanced baseline covariates. Exposures: PrEP initiation with either TAF or TDF during the study period. Main Outcomes and Measures: Incident hypertension and statin initiation within 2 years of PrEP initiation were ascertained through blood pressure and outpatient pharmacy records, respectively. Risk differences and odds ratios (ORs) were estimated using logistic regression and g-computation. Results: A total of 6824 eligible individuals were identified (mean [SD] age, 33.9 [10.3] years; 6618 [97%] male). This pool was used to generate 2 cohorts without baseline hypertension or statin use for matching (hypertension: n = 5523; statin: n = 6149) In both cohorts, those starting PrEP with TAF were older and were more likely to be non-Hispanic White compared with those starting with TDF. In matched analysis adjusting for baseline covariates, TAF use was associated with elevated risk of incident hypertension (TAF: n = 371; risk difference, 0.81 [95% CI, 0.12-1.50]; OR, 1.64 [95% CI, 1.05-2.56]). TAF use was also associated with elevated risk of statin initiation (TAF: n = 382; risk difference, 0.85 [95% CI, 0.37-1.33]; OR, 2.33 [95% CI, 1.41-3.85]). Subgroup analyses restricted to individuals 40 years and older at PrEP initiation showed similar results with larger risk difference in statin initiation (risk difference, 4.24 [95% CI, 1.82-6.26]; OR, 3.05 [95% CI, 1.64-5.67]). Conclusions and Relevance: In this study of people taking PrEP, TAF use was found to be associated with higher incident hypertension and statin initiation compared with TDF use, especially in those 40 years or older. Continued monitoring of blood pressure and lipids for TAF users is warranted.

Incidence of Diabetes Among Youth Before and During the COVID-19 Pandemic.

Importance: Prior research found increases in diabetes among youth during the COVID-19 pandemic, but few studies examined variation across sociodemographics. Objective: To examine diabetes incidence rates among a diverse population of youth in the US before and during the COVID-19 pandemic. Design, Setting, and Participants: This cohort study included data from Kaiser Permanente Southern California (KPSC) between January 1, 2016, and December 31, 2021. KPSC members aged from birth to 19 years with no history of diabetes were included. Individuals were followed up using electronic health records for diabetes incidence defined using diagnoses, laboratory values, and medications. Analyses were conducted between November 2022 and January 2023. Main Outcome and Measures: Age- and sex-standardized annual and quarterly incidence rates per 100 000 person-years (PYs) were calculated for type 1 diabetes and type 2 diabetes between 2016 and 2021. Rates were calculated within strata of age (<10 and 10-19 years), sex, and race and ethnicity (Asian/Pacific Islander, Hispanic, non-Hispanic Black, non-Hispanic White, and other/multiple/unknown). Using Poisson regression with robust error variances, incidence rate ratios (IRR) comparing 2020 to 2021 with 2016 to 2019 were calculated by diabetes type and within age, sex, and race and ethnicity strata and adjusting for health care utilization. Results: Between 2016 to 2021, there were 1200, 1100, and 63 patients with type 1 diabetes (mean [SD] age, 11.0 [4.5] years; 687 [57.3%] male), type 2 diabetes (mean [SD] age, 15.7 [2.7] years; 516 [46.9%] male), and other diabetes, respectively. Incidence of type 1 diabetes increased from 18.5 per 100 000 PYs in 2016 to 2019 to 22.4 per 100 000 PYs from 2020 to 2021 with increased IRRs among individuals aged 10 to 19 years, male individuals, and Hispanic individuals. Incidence of type 2 diabetes increased from 14.8 per 100 000 PYs from 2016 to 2019 to 24.7 per 100 000 PYs from 2020 to 2021 with increased IRRs among individuals aged 10 to 19 years, male and female individuals, and those with Black, Hispanic, and other/unknown race and ethnicity. Conclusions and Relevance: In this cohort study of youth in KPSC, incidence of diabetes increased during the COVID-19 pandemic and was more pronounced in specific racial and ethnic groups. Future research to understand differential impacts of physiologic and behavioral risk factors is warranted.

Hypertension-Related Cardiovascular Mortality in Asian American Subgroups.

INTRODUCTION: Asian American subgroups experience heterogeneity in cardiovascular disease, but differences in hypertension-related cardiovascular disease mortality between Asian American subgroups is not known. METHODS: Among 1,194,648 deaths in the United States in 2018-2021 with cardiovascular disease as an underlying cause and hypertension-related diseases as contributing cause, sex-specific age-standardized mortality rates, proportional mortality, and proportional mortality ratios for non-Hispanic Asian and Asian subgroups, Hispanic, and non-Hispanic Black individuals were compared with non-Hispanic White individuals. The analysis was conducted in August 2022. RESULTS: There were 37,746; 95,404; 193,899; and 867,599 hypertension-related cardiovascular disease deaths in non-Hispanic Asian; Hispanic; non-Hispanic Black; and non-Hispanic White groups, respectively. Among non-Hispanic Asian females, mortality rates ranged from 41.6 (95% CI 40.0-43.3) per 100,000 population in Japanese to 52.6 (51.0-54.2) per 100,000 in Filipina individuals. Among non-Hispanic Asian males, mortality rates ranged from 45.8 (43.3-48.2) per 100,000 in Korean to 81.0 (78.5-83.5) per 100,000 in Filipino individuals. Proportional mortality was higher for all Asian American subgroups compared to non-Hispanic White individuals. Proportional mortality ratios ranged from 1.11 (in Korean males, proportional mortality was 10.2% [95% CI 9.7-10.8] of all deaths) to 1.38 (in Filipino males, proportional mortality was 12.7% [12.4-13.1] of all deaths; in Chinese females, proportional mortality was 11.9% [11.6-12.3]; and in Filipina females, proportional mortality was 11.9% [12.3-13.0]). CONCLUSIONS: There was up to two-fold variation in hypertension-related cardiovascular disease mortality among Asian American subgroups. All subgroups experienced higher proportional mortality for hypertension-related cardiovascular disease compared with non-Hispanic White individuals.

Safety Net Program to Improve Statin Initiation Among Adults With High Low-Density Lipoprotein Cholesterol.

INTRODUCTION: Despite their effectiveness in reducing low-density lipoprotein cholesterol and cardiovascular disease risk, high-intensity statins are underutilized among adults with low-density lipoprotein cholesterol ≥190 mg/dL. This study determined whether a safety net program (SureNet) facilitating medication and laboratory test orders improved statin initiation and laboratory test completions after (SureNet period: April 2019-September 2021) and before implementation (pre-SureNet period: January 2016-September 2018). METHODS: Kaiser Permanente Southern California members aged 20-60 years with low-density lipoprotein cholesterol ≥190 mg/dL and no statin use in previous 2-6 months were included in this retrospective cohort study. Statin orders within 14 days and statin fills, laboratory test completions, and improved low-density lipoprotein cholesterol within 180 days of the high low-density lipoprotein cholesterol (pre-SureNet) or outreach (SureNet period) were compared. Analyses were conducted in 2022. RESULTS: Overall, 3,534 and 3,555 adults were eligible for statin initiation during the pre-SureNet and SureNet periods, respectively. Overall, 759 (21.5%) and 976 (27.5%) had a statin approved by their physician during pre-SureNet and SureNet periods, respectively (p<0.001). After multivariable adjustment for demographics and clinical characteristics, adults during the SureNet period had a higher likelihood of receiving a statin order (prevalence ratio=1.36, 95% CI=1.25, 1.48), filling their statin (prevalence ratio=1.32, 95% CI=1.26, 1.38), completing their laboratories (prevalence ratio=1.41, 95% CI=1.26, 1.58), and improving low-density lipoprotein cholesterol (prevalence ratio=1.21, 95% CI=1.07, 1.37) than in pre-Surenet period. CONCLUSIONS: The SureNet program was able to improve prescription orders, fills, laboratory test completions, and lower low-density lipoprotein cholesterol. Optimizing both physician adherence to treatment guidelines; and patient adherence to the program may improve low-density lipoprotein cholesterol lowering.

Prevalence, Progression, and Modifiable Risk Factors for Diabetic Retinopathy in Youth and Young Adults With Youth-Onset Type 1 and Type 2 Diabetes: The SEARCH for Diabetes in Youth Study.

OBJECTIVE: To determine the prevalence, progression, and modifiable risk factors associated with the development of diabetic retinopathy (DR) in a population-based cohort of youth-onset diabetes. RESEARCH DESIGN AND METHODS: We conducted a multicenter, population-based prospective cohort study (2002-2019) of youth and young adults with youth-onset type 1 diabetes (n = 2,519) and type 2 diabetes (n = 447). Modifiable factors included baseline and change from baseline to follow-up in BMI z score, waist/height ratio, systolic and diastolic blood pressure z score, and A1C. DR included evidence of mild or moderate nonproliferative DR or proliferative retinopathy. Prevalence estimates were standardized to estimate the burden of DR, and inverse probability weighting for censoring was applied for estimating risk factors for DR at two points of follow-up. RESULTS: DR in youth-onset type 1 and type 2 diabetes is highly prevalent, with 52% of those with type 1 diabetes and 56% of those with type 2 diabetes demonstrating retinal changes at follow-up (mean [SD] 12.5 [2.2] years from diagnosis). Higher baseline A1C, increase in A1C across follow-up, and increase in diastolic and systolic blood pressure were associated with the observation of DR at follow-up for both diabetes types. Increase in A1C across follow-up was associated with retinopathy progression. BMI z score and waist/height ratio were inconsistently associated, with both positive and inverse associations noted. CONCLUSIONS: Extrapolated to all youth-onset diabetes in the U.S., we estimate 110,051 cases of DR developing within ∼12 years postdiagnosis. Tight glucose and blood pressure management may offer the opportunity to mitigate development and progression of DR in youth-onset diabetes.

Representativeness of the GALACTIC-HF Clinical Trial in Patients Having Heart Failure With Reduced Ejection Fraction.

Background Randomized clinical trials in populations with heart failure with reduced ejection fraction may not be reflective of the general population with heart failure with reduced ejection fraction. Our study assessed the representativeness of the GALACTIC-HF (Global Approach to Lowering Adverse Cardiac Outcomes Through Improving Contractility in Heart Failure) patient population in Kaiser Permanente Southern California. Methods and Results We identified 9770 patients with a diagnosis of heart failure with reduced ejection fraction from 2014 to 2018 using electronic health records. Four mutually exclusive cohorts were created, including GALACTIC-HF-ineligible cohorts: (1) not taking guideline-directed medical therapy (GDMT) and (2) taking GDMT; and GALACTIC-HF-eligible cohorts with: (3) ejection fraction (EF) ≤28% and (4) EF 29% to 35%. Patients were followed for 30-day and 1-year mortality and 30-day, 180-day, and 1-year hospitalization. Overall, 3626 (37.1%) met GALACTIC-HF inclusion criteria with EF ≤35%, and 2367 (65.3%) of those individuals had EF ≤28%. The risk of 1-year mortality was lower among all cohorts versus the GALACTIC-HF-ineligible cohort not taking GDMT (hazard ratio, 0.80 [95% CI, 0.70-0.91], 0.84 [95% CI, 0.72-0.98], and 0.62 [95% CI, 0.51-0.75] for the GALACTIC-HF-ineligible cohort taking GDMT and GALACTIC-HF-eligible cohorts with EF ≤28% and 29%-35%, respectively). Compared with the GALACTIC-HF-ineligible cohort not taking GDMT, the short-term hospitalization risk at 30 and 180 days were similar for both GALACTIC-HF-eligible cohorts and the hospitalization risk at 1 year was similar for the GALACTIC-HF-eligible cohort with EF ≤28%. Conclusions A large portion of patients with heart failure with reduced ejection fraction with low EF met inclusion criteria for the GALACTIC-HF trial and, despite being on GDMT, had hospitalization rates similar to those not taking GDMT, suggesting potential benefits from other innovative treatments.

Association of the 2020 US Presidential Election With Hospitalizations for Acute Cardiovascular Conditions.

Importance: Prior studies found a higher risk of acute cardiovascular disease (CVD) around population-wide psychosocial or environmental stressors. Less is known about acute CVD risk in relation to political events. Objective: To examine acute CVD hospitalizations following the 2020 presidential election. Design, Setting, and Participants: This retrospective cohort study examined acute CVD hospitalizations following the 2020 presidential election. Participants were adult members aged 18 years or older at Kaiser Permanente Southern California and Kaiser Permanente Northern California, 2 large, integrated health care delivery systems. Statistical analysis was performed from March to July 2021. Exposure: 2020 US presidential election. Main Outcomes and Measures: Hospitalizations for acute CVD around the 2020 presidential election were examined. CVD was defined as hospitalizations for acute myocardial infarction (AMI), heart failure (HF), or stroke. Rate ratios (RR) and 95% CIs were calculated comparing rates of CVD hospitalization in the 5 days following the 2020 election with the same 5-day period 2 weeks prior. Results: Among 6 396 830 adults (3 970 077 [62.1%] aged 18 to 54 years; 3 422 479 [53.5%] female; 1 083 128 [16.9%] Asian/Pacific Islander, 2 101 367 [32.9%] Hispanic, and 2 641 897 [41.3%] White), rates of hospitalization for CVD following the election (666 hospitalizations; rate = 760.5 per 100 000 person-years [PY]) were 1.17 times higher (95% CI, 1.05-1.31) compared with the same 5-day period 2 weeks prior (569 hospitalizations; rate = 648.0 per 100 000 PY). Rates of AMI were significantly higher following the election (RR, 1.42; 95% CI, 1.13-1.79). No significant difference was found for stroke (RR, 1.02; 95% CI, 0.86-1.21) or HF (RR, 1.18; 95% CI, 0.98-1.42). Conclusions and Relevance: Higher rates of acute CVD hospitalization were observed following the 2020 presidential election. Awareness of the heightened risk of CVD and strategies to mitigate risk during notable political events are needed.

Multimorbidity Burden and Incident Heart Failure Among People With and Without HIV: The HIV-HEART Study.

Objective: To examine the association between multimorbidity burden and incident heart failure (HF) among people with HIV (PWH) and people without HIV (PWoH). Patients and Methods: The HIV-HEART study is a retrospective cohort study that included adult PWH and PWoH aged 21 years or older at Kaiser Permanente between 2000 and 2016. Multimorbidity burden was defined by the baseline prevalence of 22 chronic conditions and was categorized as 0-1, 2-3, and 4 or more comorbidities on the basis of distribution of the overall population. People with HIV and PWoH were followed for a first HF event, all-cause death, or up to the end of follow-up on December 31, 2016. Using Cox proportional hazard regression, hazard ratios and 95% CIs were calculated to examine the association between multimorbidity burden and incident HF among PWH and PWoH, separately. Results: The prevalences of 0-1, 2-3, and 4 or more comorbidities were 83.3%, 13.0%, and 3.7% in PWH (n=38,868), and 82.2%, 14.3%, and 3.5% in PWoH (n=386,586), respectively. After multivariable adjustment, compared with people with 0-1 comorbidities, the hazard ratios of incident HF associated with 2-3 and 4 or more comorbidities were 1.33 (95% CI, 1.04-1.71) and 2.41 (95% CI, 1.78-3.25) in PWH and 2.10 (95% CI, 1.92-2.29) and 4.09 (95% CI, 3.64-4.61) in PWoH, respectively. Conclusion: Multimorbidity was associated with a higher risk of incident HF among PWH and PWoH, with more prominent associations in PWoH and certain patient subgroups. The identification of specific multimorbidity patterns that contribute to higher HF risk in PWH may lead to future preventative strategies.

Risk of hospitalization and mortality associated with uncontrolled blood pressure in patients with hypertension and COVID-19.

OBJECTIVE: The role of uncontrolled blood pressure (BP) in COVID-19 severity among patients with hypertension is unclear. We evaluated the association between uncontrolled BP and the risk of hospitalization and/or mortality in patients with hypertension from a large US integrated healthcare system. METHODS: We identified patients with hypertension and a positive RT-PCR test result or a diagnosis of COVID-19 between March 1 - September 1, 2020 from Kaiser Permanente Southern California. BP categories was defined using the most recent outpatient BP measurement during 12 months prior to COVID-19 infection. The primary outcome of interest was all-cause hospitalization or mortality within 30 days from COVID-19 infection. RESULTS: Among 12,548 patients with hypertension and COVID-19 (mean age = 60 years, 47% male), 63% had uncontrolled BP (≥130/80 mm Hg) prior to COVID-19. Twenty-one percent were hospitalized or died within 30 days of COVID-19 infection. Uncontrolled BP was not associated with higher hospitalization or mortality (adjusted rate ratios for BP ≥ 160/100 mm Hg vs < 130/80 mm Hg = 1.00 [95% CI: 0.87, 1.14]; BP 140-159/90-99 mm Hg vs < 130/80 mm Hg = 1.02 [95% CI: 0.93, 1.11]). These findings were consistent across different age groups, treatment for antihypertensive medications, as well as atherosclerotic cardiovascular disease risk. CONCLUSION: Among patients with hypertension, uncontrolled BP prior to COVID-19 infection did not appear to be an important risk factor for 30-day mortality or hospitalization.