Temporal Trends in Cardiovascular Disease Prevalence Among Asian American Subgroups.

BACKGROUND: Asian and multiracial individuals represent the 2 fastest growing racial and ethnic groups in the United States, yet most prior studies report Asian American and Native Hawaiian or Other Pacific Islander as a single racial group, with limited data on cardiovascular disease (CVD) prevalence among subgroups. We sought to evaluate temporal trends in CVD burden among disaggregated Asian subgroups. METHODS AND RESULTS: Patients with CVD based on International Classification of Diseases, Ninth Revision and Tenth Revision (ICD-9 and ICD-10) coding who received care from a mixed-payer health care organization in California between 2008 and 2018 were classified into self-identified racial and ethnic subgroups (non-Hispanic White [NHW], Asian Indian, Chinese, Filipino, Japanese, Korean, Native Hawaiian or Other Pacific Islander, and multiracial groups). Adjusted trends in CVD prevalence over time by subgroup were compared using logistic regression. Among 3 494 071 patient-years, prevalence of CVD increased faster among all subgroups except Japanese and Native Hawaiian or Other Pacific Islander patients (P<0.01 for each, reference: NHW). Filipino patients had the highest overall CVD prevalence, which increased from 34.3% to 45.1% over 11 years (increase from 17.3%-21.9%, P<0.0001, reference: NHW). Asian Indian patients had the fastest increase in CVD prevalence over time (16.9%-23.7%, P<0.0001, reference: NHW). Among subcategories of disease, hypertension increased faster among Asian Indian, Chinese, Filipino, Korean, and multiracial groups (P<0.01 for all, reference: NHW), and coronary artery disease increased faster among Asian Indian, Chinese, Filipino, and Japanese groups (P<0.05 for each, reference: NHW). CONCLUSIONS: The increasing prevalence of CVD among disaggregated Asian, Native Hawaiian or Other Pacific Islander, and multiracial subgroups over time highlights the importance of tailored approaches to addressing CVD in these diverse subpopulations.

Contemporary attitudes and beliefs on coronary artery calcium from social media using artificial intelligence.

Coronary artery calcium (CAC) is a powerful tool to refine atherosclerotic cardiovascular disease (ASCVD) risk assessment. Despite its growing interest, contemporary public attitudes around CAC are not well-described in literature and have important implications for shared decision-making around cardiovascular prevention. We used an artificial intelligence (AI) pipeline consisting of a semi-supervised natural language processing model and unsupervised machine learning techniques to analyze 5,606 CAC-related discussions on Reddit. A total of 91 discussion topics were identified and were classified into 14 overarching thematic groups. These included the strong impact of CAC on therapeutic decision-making, ongoing non-evidence-based use of CAC testing, and the patient perceived downsides of CAC testing (e.g., radiation risk). Sentiment analysis also revealed that most discussions had a neutral (49.5%) or negative (48.4%) sentiment. The results of this study demonstrate the potential of an AI-based approach to analyze large, publicly available social media data to generate insights into public perceptions about CAC, which may help guide strategies to improve shared decision-making around ASCVD management and public health interventions.

Association of Coronary Artery Calcium Detected by Routine Ungated CT Imaging With Cardiovascular Outcomes.

BACKGROUND: Coronary artery calcium (CAC) is a strong predictor of cardiovascular events across all racial and ethnic groups. CAC can be quantified on nonelectrocardiography (ECG)-gated computed tomography (CT) performed for other reasons, allowing for opportunistic screening for subclinical atherosclerosis. OBJECTIVES: The authors investigated whether incidental CAC quantified on routine non-ECG-gated CTs using a deep-learning (DL) algorithm provided cardiovascular risk stratification beyond traditional risk prediction methods. METHODS: Incidental CAC was quantified using a DL algorithm (DL-CAC) on non-ECG-gated chest CTs performed for routine care in all settings at a large academic medical center from 2014 to 2019. We measured the association between DL-CAC (0, 1-99, or ≥100) with all-cause death (primary outcome), and the secondary composite outcomes of death/myocardial infarction (MI)/stroke and death/MI/stroke/revascularization using Cox regression. We adjusted for age, sex, race, ethnicity, comorbidities, systolic blood pressure, lipid levels, smoking status, and antihypertensive use. Ten-year atherosclerotic cardiovascular disease risk was calculated using the pooled cohort equations. RESULTS: Of 5,678 adults without ASCVD (51% women, 18% Asian, 13% Hispanic/Latinx), 52% had DL-CAC >0. Those with DL-CAC ≥100 had an average 10-year ASCVD risk of 24%; yet, only 26% were on statins. After adjustment, patients with DL-CAC ≥100 had increased risk of death (HR: 1.51; 95% CI: 1.28-1.79), death/MI/stroke (HR: 1.57; 95% CI: 1.33-1.84), and death/MI/stroke/revascularization (HR: 1.69; 95% CI: 1.45-1.98) compared with DL-CAC = 0. CONCLUSIONS: Incidental CAC ≥100 was associated with an increased risk of all-cause death and adverse cardiovascular outcomes, beyond traditional risk factors. DL-CAC from routine non-ECG-gated CTs identifies patients at increased cardiovascular risk and holds promise as a tool for opportunistic screening to facilitate earlier intervention.

Dissociable effects of oxycodone on behavior, calcium transient activity, and excitability of dorsolateral striatal neurons.

Opioids are the most common medications for moderate to severe pain. Unfortunately, they also have addictive properties that have precipitated opioid misuse and the opioid epidemic. In the present study, we examined the effects of acute administration of oxycodone, a µ-opioid receptor (MOR) agonist, on Ca2+ transient activity of medium-sized spiny neurons (MSNs) in freely moving animals. Ca2+ imaging of MSNs in dopamine D1-Cre mice (expressing Cre predominantly in the direct pathway) or adenosine A2A-Cre mice (expressing Cre predominantly in the indirect pathway) was obtained with the aid of miniaturized microscopes (Miniscopes) and a genetically encoded Cre-dependent Ca2+ indicator (GCaMP6f). Systemic injections of oxycodone (3 mg/kg) increased locomotor activity yet, paradoxically, reduced concomitantly the number of active MSNs. The frequency of Ca2+ transients was significantly reduced in MSNs from A2A-Cre mice but not in those from D1-Cre mice. For comparative purposes, a separate group of mice was injected with a non-Cre dependent Ca2+ indicator in the cerebral cortex and the effects of the opioid also were tested. In contrast to MSNs, the frequency of Ca2+ transients in cortical pyramidal neurons was significantly increased by oxycodone administration. Additional electrophysiological studies in brain slices confirmed generalized inhibitory effects of oxycodone on MSNs, including membrane hyperpolarization, reduced excitability, and decreased frequency of spontaneous excitatory and inhibitory postsynaptic currents. These results demonstrate a dissociation between locomotion and striatal MSN activity after acute administration of oxycodone.

Calcium imaging: A versatile tool to examine Huntington's disease mechanisms and progression.

Huntington's disease (HD) is a fatal, hereditary neurodegenerative disorder that causes chorea, cognitive deficits, and psychiatric symptoms. It is characterized by accumulation of mutant Htt protein, which primarily impacts striatal medium-sized spiny neurons (MSNs), as well as cortical pyramidal neurons (CPNs), causing synapse loss and eventually cell death. Perturbed Ca2+ homeostasis is believed to play a major role in HD, as altered Ca2+ homeostasis often precedes striatal dysfunction and manifestation of HD symptoms. In addition, dysregulation of Ca2+ can cause morphological and functional changes in MSNs and CPNs. Therefore, Ca2+ imaging techniques have the potential of visualizing changes in Ca2+ dynamics and neuronal activity in HD animal models. This minireview focuses on studies using diverse Ca2+ imaging techniques, including two-photon microscopy, fiber photometry, and miniscopes, in combination of Ca2+ indicators to monitor activity of neurons in HD models as the disease progresses. We then discuss the future applications of Ca2+ imaging to visualize disease mechanisms and alterations associated with HD, as well as studies showing how, as a proof-of-concept, Ca2+imaging using miniscopes in freely-behaving animals can help elucidate the differential role of direct and indirect pathway MSNs in HD symptoms.

Coronary artery calcium scores indicating secondary prevention level risk: Findings from the CAC consortium and FOURIER trial.

BACKGROUND AND AIMS: Coronary artery calcium (CAC) burden displays a stepwise association with atherosclerotic cardiovascular disease (ASCVD) risk. Among primary prevention patients, we sought to determine the CAC scores equivalent to ASCVD mortality rates observed in the FOURIER trial, a modern secondary prevention cohort. METHODS AND RESULTS: For the main analysis, we included participants from the CAC Consortium ≥50 years old with a 10-year ASCVD risk ≥7.5% (n = 20,207). Poisson regression was used to define the relationship between CAC and annual ASCVD mortality. Equations generated from the regression models were then used to derive CAC scores associated with equivalent annual ASCVD mortality as observed in FOURIER placebo participants from the overall trial and in key trial subgroups. The CAC Consortium participants had a similar age (65.5 versus 62.5 years) and sex (22% versus 24% female) distribution as FOURIER. The annualized ASCVD mortality rate in FOURIER participants (0.766 per 100 person-years) corresponded to a CAC score of 781 (418-1467). A CAC score of 255 (162-394) corresponded to an ASCVD mortality rate equivalent to the lowest risk FOURIER subgroup (presence of myocardial infarction >2 years prior to trial enrollment). No CAC score produced a risk equivalent to high-risk FOURIER subgroups, particularly those with symptomatic peripheral arterial disease and/or multivessel coronary heart disease. CONCLUSIONS: Primary prevention individuals with increased CAC burden may have annualized ASCVD mortality rates equivalent to persons with stable secondary prevention-level risk. These findings argue for a risk continuum between higher risk primary prevention and stable secondary prevention patients, as their ASCVD risks may overlap.

Very High Coronary Artery Calcium (≥1000) and Association With Cardiovascular Disease Events, Non-Cardiovascular Disease Outcomes, and Mortality: Results From MESA.

BACKGROUND: There are limited data on the unique cardiovascular disease (CVD), non-CVD, and mortality risks of primary prevention individuals with very high coronary artery calcium (CAC; ≥1000), especially compared with rates observed in secondary prevention populations. METHODS: Our study population consisted of 6814 ethnically diverse individuals 45 to 84 years of age who were free of known CVD from MESA (Multi-Ethnic Study of Atherosclerosis), a prospective, observational, community-based cohort. Mean follow-up time was 13.6±4.4 years. Hazard ratios of CAC ≥1000 were compared with both CAC 0 and CAC 400 to 999 for CVD, non-CVD, and mortality outcomes with the use of Cox proportional hazards regression adjusted for age, sex, and traditional risk factors. Using a sex-adjusted logarithmic model, we calculated event rates in MESA as a function of CAC and compared them with those observed in the placebo group of stable secondary prevention patients in the FOURIER clinical trial (Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk). RESULTS: Compared with CAC 400 to 999, those with CAC ≥1000 (n=257) had a greater mean number of coronary vessels with CAC (3.4±0.5), greater total area of CAC (586.5±275.2 mm2), similar CAC density, and more extensive extracoronary calcification. After full adjustment, CAC ≥1000 demonstrated a 4.71- (3.63-6.11), 7.57- (5.50-10.42), 4.86-(3.32-7.11), and 1.94-fold (1.57-2.41) increased risk for all CVD events, all coronary heart disease events, hard coronary heart disease events, and all-cause mortality, respectively, compared with CAC 0 and a 1.65- (1.25-2.16), 1.66- (1.22-2.25), 1.51- (1.03-2.23), and 1.34-fold (1.05-1.71) increased risk compared with CAC 400 to 999. With increasing CAC, hazard ratios increased for all event types, with no apparent upper CAC threshold. CAC ≥1000 was associated with a 1.95- (1.57-2.41) and 1.43-fold (1.12-1.83) increased risk for a first non-CVD event compared with CAC 0 and CAC 400 to 999, respectively. CAC 1000 corresponded to an annualized 3-point major adverse cardiovascular event rate of 3.4 per 100 person-years, similar to that of the total FOURIER population (3.3) and higher than those of the lower-risk FOURIER subgroups. CONCLUSIONS: Individuals with very high CAC (≥1000) are a unique population at substantially higher risk for CVD events, non-CVD outcomes, and mortality than those with lower CAC, with 3-point major adverse cardiovascular event rates similar to those of a stable treated secondary prevention population. Future guidelines should consider a less distinct stratification algorithm between primary and secondary prevention patients in guiding aggressive preventive pharmacotherapy.

Long-Term All-Cause and Cause-Specific Mortality in Asymptomatic Patients With CAC ≥1,000: Results From the CAC Consortium.

OBJECTIVES: This study thoroughly explored the demographic and imaging characteristics, as well as the all-cause and cause-specific mortality risks of patients with a coronary artery calcium (CAC) score ≥1,000 in the largest dataset of this population to date. BACKGROUND: CAC is commonly used to quantify cardiovascular risk. Current guidelines classify a CAC score of >300 or 400 as the highest risk group, yet little is known about the potentially unique imaging characteristics and mortality risk in individuals with a CAC score ≥1,000. METHODS: A total of 66,636 asymptomatic adults were included from the CAC consortium, a large retrospective multicenter clinical cohort. Mean patient follow-up was 12.3 ± 3.9 years for patients with cardiovascular disease (CVD), coronary heart disease (CHD), cancer, and all-cause mortality. Multivariate Cox proportional hazards regression models adjusted for age, sex, and conventional risk factors were used to assess the relative mortality hazard of individuals with CAC ≥1,000 compared with, first, a CAC reference of 0, and second, with patients with a CAC score of 400 to 999. RESULTS: There were 2,869 patients with CAC ≥1,000 (86.3% male, mean 66.3 ± 9.7 years of age). Most patients with CAC ≥1,000 had 4-vessel CAC (mean: 3.5 ± 0.6 vessels) and had greater total CAC area, higher mean CAC density, and more extracoronary calcium (79% with thoracic artery calcium, 46% with aortic valve calcium, and 21% with mitral valve calcium) than those with CAC scores of 400 to 999. After full adjustment, those with CAC ≥1,000 had a 5.04- (95% confidence interval [CI]: 3.92 to 6.48), 6.79- (95% CI: 4.74 to 9.73), 1.55- (95% CI:1.23 to 1.95), and 2.89-fold (95% CI: 2.53 to 3.31) risk of CVD, CHD, cancer, and all-cause mortality, respectively, compared to those with CAC score of 0. The CAC ≥1,000 group had a 1.71- (95% CI: 1.41 to 2.08), 1.84- (95% CI: 1.43 to 2.36), 1.36- (95% CI:1.07 to 1.73), and 1.51-fold (95% CI: 1.33 to 1.70) increased risk of CVD, CHD, cancer, and all-cause mortality compared to those with CAC scores 400 to 999. Graphic analysis of CAC ≥1,000 patients revealed continued logarithmic increase in risk, with no clear evidence of a risk plateau. CONCLUSIONS: Patients with extensive CAC (CAC ≥1,000) represent a unique very high-risk phenotype with mortality outcomes commensurate with high-risk secondary prevention patients. Future guidelines should consider CAC ≥1,000 patients to be a distinct risk group who may benefit from the most aggressive preventive therapy.

Effects of the DASH Diet and Sodium Intake on Bloating: Results From the DASH-Sodium Trial.

INTRODUCTION: Bloating is one of the most common gastrointestinal complaints. Evidence has linked fiber and sodium to bloating; however, randomized trials examining these diet components are lacking. Here, we used a randomized trial to examine the effects of the high-fiber DASH diet and dietary sodium intake on abdominal bloating. We hypothesized that both the high-fiber DASH diet and higher sodium intake would increase bloating. METHODS: The DASH-Sodium trial (1998-1999) randomized healthy adults to a high-fiber (32 g/d) DASH or low-fiber (11 g/d) Western diet (control). On their assigned diet, participants ate 3 sodium levels (50, 100, and 150 mmol/d at 2100 kcal) in 30-day periods in random order, with 5-day breaks between each period. The participants reported the presence of bloating at baseline and after each feeding period. Statistical analyses included log-binomial models to evaluate the risk of bloating. RESULTS: Of 412 participants (mean age 48 years; 57% women; 57% black), 36.7% reported bloating at baseline. Regardless of the diet, high sodium intake increased the risk of bloating (risk ratio = 1.27; 95% confidence interval: 1.06-1.52; P = 0.01). The high-fiber DASH diet also increased the risk of bloating over all sodium levels (risk ratio = 1.41; 95% confidence interval: 1.22-1.64; P < 0.001). The effect of high-fiber DASH on bloating was greater in men than in women (P for interaction = 0.001). DISCUSSION: Higher dietary sodium increased bloating, as did the high-fiber DASH diet. Although healthful high-fiber diets may increase bloating, these effects may be partially mitigated by decreasing dietary sodium intake. Future research is needed to explore mechanisms by which sodium intake and diet can influence bloating.

Effects of sodium intake on postural lightheadedness: Results from the DASH-sodium trial.

Lightheadedness after standing contributes to adverse clinical events, including falls. Recommendations for higher sodium intake to treat postural lightheadedness have not been evaluated in a trial setting. The Dietary Approaches to Stop Hypertension (DASH)-Sodium trial (1998-1999) tested the effects of the DASH diet and sodium reduction on blood pressure (BP). Participants were randomly assigned to DASH or a typical Western diet (control). During either diet, participants ate three sodium levels (50, 100, 150 meq/d at 2100 kcal) in random order for 30-days, separated by 5-day breaks. Participants reported the presence and severity of postural lightheadedness at baseline and after each feeding period. There were 412 participants (mean age 48 years; 57% women; 57% black). Mean baseline SBP/DBP was 135/86 mm Hg; 9.5% reported baseline lightheadedness. Among those consuming the DASH diet, high vs low sodium increased lightheadedness (OR 1.71; 95% CI: 1.01, 2.90; P = 0.047) and severity of lightheadedness (P = 0.02), but did not affect lightheadedness in those consuming the control diet (OR 0.77; 95% CI: 0.46, 1.29; P = 0.32). Among those consuming high vs low sodium in the context of the DASH diet, adults <60 vs ≥60 years old experienced more lightheadedness (P-interaction = 0.04), along with obese vs non-obese adults (P-interaction = 0.01). In the context of the DASH diet, higher sodium intake was associated with more frequent and severe lightheadedness. These findings challenge traditional recommendations to increase sodium intake to prevent lightheadedness.

Correction to: Coronary Artery Calcium: Recommendations for Risk Assessment in Cardiovascular Prevention Guidelines.

In the recently published review "Coronary Artery Calcium: Recommendations for Risk Assessment in Cardiovascular Prevention Guidelines," the following author name was inadvertently misspelled as Alison Peng. The correct spelling of the author's name is: Allison Peng as shown above.

Coronary Artery Calcium: Recommendations for Risk Assessment in Cardiovascular Prevention Guidelines.

PURPOSE OF REVIEW: In this review, we evaluate the coronary artery calcium (CAC) score as a biomarker for advanced atherosclerotic cardiovascular disease (ASCVD) risk assessment. RECENT FINDINGS: We summarize the evidence from multiple epidemiological studies, which show a clear advantage of CAC compared to traditional and non-traditional cardiovascular risk factors. We then compare the recommendations included in the 2013 American College of Cardiology/American Heart Association (ACC/AHA) and in the 2017 Society of Cardiovascular Computed Tomography (SCCT) guidelines for the use of CAC in ASCVD risk assessment, and examine the recent 2018 US Preventive Services Task Force (USPSTF) document. Finally, based on the currently available evidence, we provide constructive input for the upcoming ACC/AHA guidelines, regarding the population in whom CAC is most likely to be informative, the level of evidence that we believe should be assigned to CAC as an advanced ASCVD risk assessment tool, and the special populations in whom CAC might be beneficial for further risk assessment. We support a pragmatic approach that combines the pooled cohort equations (PCE) for initial ASCVD risk stratification, followed by CAC for refining ASCVD risk assessment among a broad range of intermediate risk patients and other special groups.

Impact of prolonged dialysis prior to renal transplantation.

INTRODUCTION: The new kidney allocation system (KAS) prioritizes patients based on date of dialysis initiation or waitlisting, whichever is earlier. We hypothesized that this change would increase transplant rates for patients with prolonged pretransplant dialysis times (DT) and aimed to assess the impact of prolonged DT on post-transplant outcomes. METHODS: We used United Network for Organ Sharing registry data to assess outcomes for patients added to the renal transplant waitlist from January 1, 1998 to December 31, 2010 and patients transplanted from January 1, 1998 to December 3, 2012. RESULTS: Compared with patients transplanted pre-emptively, patients with <5 years, 5-9 years, and ≥10 years DT had progressively decreased graft and patient survival (P < .001). The rates of short-term complications including delayed graft function, graft loss within 30 days, and patient death within 30 days were significantly higher in cohorts with ≥10 years DT than in cohorts with less DT (P < .001). CONCLUSIONS: Patients with pretransplant DT of ≥10 years had worse outcomes than patients pre-emptively transplanted or transplanted with shorter DT. Durations of dialysis dependence beyond 10 years were associated with further deterioration in short-term but not long-term post-transplant outcomes.

Same policy, different impact: Center-level effects of share 35 liver allocation.

Early studies of national data suggest that the Share 35 allocation policy increased liver transplants without compromising posttransplant outcomes. Changes in center-specific volumes and practice patterns in response to the national policy change are not well characterized. Understanding center-level responses to Share 35 is crucial for optimizing the policy and constructing effective future policy revisions. Data from the United Network for Organ Sharing were analyzed to compare center-level volumes of allocation-Model for End-Stage Liver Disease (aMELD) ≥ 35 transplants before and after policy implementation. There was significant center-level variation in the number and proportion of aMELD ≥ 35 transplants performed from the pre- to post-Share 35 period; 8 centers accounted for 33.7% of the total national increase in aMELD ≥ 35 transplants performed in the 2.5-year post-Share 35 period, whereas 25 centers accounted for 65.0% of the national increase. This trend correlated with increased listing at these centers of patients with Model for End-Stage Liver Disease (MELD) ≥ 35 at the time of initial listing. These centers did not overrepresent the total national volume of liver transplants. Comparison of post-Share 35 aMELD to calculated time-of-transplant (TOT) laboratory MELD scores showed that only 69.6% of patients transplanted with aMELD ≥ 35 maintained a calculated laboratory MELD ≥ 35 at the TOT. In conclusion, Share 35 increased transplantation of aMELD ≥ 35 recipients on a national level, but the policy asymmetrically impacted practice patterns and volumes of a subset of centers. Longer-term data are necessary to assess outcomes at centers with markedly increased volumes of high-MELD transplants after Share 35. Liver Transplantation 23 741-750 2017 AASLD.