Coronary artery calcium and sudden cardiac death: current evidence and future directions.

PURPOSE OF REVIEW: To provide a summary of the current evidence and highlight future directions regarding coronary artery calcium (CAC) and risk of sudden cardiac death (SCD). RECENT FINDINGS: Although up to 80% of all SCD is attributed to coronary heart disease (CHD), the subclinical atherosclerosis markers that help to improve SCD risk prediction are largely unknown. Recent observational data have demonstrated that, after adjustment for traditional risk factors, there is a stepwise higher risk for SCD across increasing CAC burden such that asymptomatic patients without overt atherosclerotic cardiovascular disease (ASCVD) experience a three-fold to five-fold higher SCD risk beginning at CAC at least 100 when compared with CAC = 0. Although the mechanisms underlying increasing CAC and SCD risk have yet to be fully elucidated, risk for myocardial infarction and scar, and/or exercise-induced ischemia may be potential mediators. SUMMARY: High CAC burden is an important risk factor for SCD in asymptomatic middle-aged adults, suggesting that SCD risk stratification can begin in the early stages of CHD via measurement of calcific plaque on noncontrast computed tomography. Despite the clinical inertia for downstream functional cardiac testing after detecting high CAC, comprehensive ASCVD prevention strategies should be the primary focus for SCD risk reduction.

Racial and Ethnic Disparities in Hypertension: Barriers and Opportunities to Improve Blood Pressure Control.

PURPOSE OF REVIEW: To characterize the barriers and opportunities associated with racial and ethnic disparities in blood pressure (BP) control. RECENT FINDINGS: Blood pressure (BP) control rates in the USA have worsened over the last decade, with significantly lower rates of control among people from racial and ethnic minority groups, with non-Hispanic (NH) Black persons having 10% lower control rates compared to NH White counterparts. Many factors contribute to BP control including key social determinants of health (SDoH) such as health literacy, socioeconomic status, and access to healthcare as well as low awareness rates and dietary habits. Numerous pharmacologic and non-pharmacologic interventions have been developed to reduce racial and ethnic disparities in BP control. Among these, dietary programs designed to help reduce salt intake, faith-based interventions, and community-based programs have found success in achieving better BP control among people from racial and ethnic minority groups. Disparities in the prevalence and management of hypertension persist and remain high, particularly among racial and ethnic minority populations. Ongoing efforts are needed to address SDoH along with the unique genetic, social, economic, and cultural diversity within these groups that contribute to ongoing BP management inequalities.

A cohort study and meta-analysis of isolated diastolic hypertension: searching for a threshold to guide treatment.

AIMS: Whether isolated diastolic hypertension (IDH), as defined by the 2017 American College of Cardiology (ACC)/American Heart Association (AHA) guideline, is associated with cardiovascular disease (CVD) has been disputed. We aimed to further study the associations of IDH with (i) subclinical CVD in the form of coronary artery calcium (CAC), (ii) incident systolic hypertension, and (iii) CVD events. METHODS AND RESULTS: We used multivariable-adjusted logistic and Cox regression to test whether IDH by 2017 ACC/AHA criteria (i.e. systolic blood pressure <130 mmHg and diastolic blood pressure ≥80 mmHg) was associated with the above outcomes in the Multi-Ethnic Study of Atherosclerosis (MESA). In a random-effects meta-analysis of the association between IDH and CVD events, we combined the MESA results with those from seven other previously published cohort studies. Among the 5104 MESA participants studied, 7.5% had IDH by the 2017 ACC/AHA criteria. There was no association between IDH and CAC [e.g. adjusted prevalence odds ratio for CAC >0 of 0.88 (95% CI 0.66, 1.17)]. Similarly, while IDH was associated with incident systolic hypertension, there was no statistically significant associations with incident CVD [hazard ratio 1.19 (95% CI 0.77, 1.84)] or death [hazard ratio 0.94 (95% CI 0.65, 1.36)] over 13 years in MESA. In a stratified meta-analysis of eight cohort studies (10 037 843 participants), the 2017 IDH definition was also not consistently associated with CVD and the relative magnitude of any potential association was noted to be numerically small [e.g. depending on inclusion criteria applied in the stratification, the adjusted hazard ratios ranged from 1.04 (95% CI 0.98, 1.10) to 1.09 (95% 1.03, 1.15)]. CONCLUSION: The lack of consistent excess in CAC or CVD suggests that emphasis on healthy lifestyle rather than drug therapy is sufficient among the millions of middle-aged or older adults who now meet the 2017 ACC/AHA criteria for IDH, though they require follow-up for incident systolic hypertension. These findings may not extrapolate to adults younger than 40 years, motivating further study in this age group.

Decreased public pursuit of cancer-related information during the COVID-19 pandemic in the United States.

BACKGROUND: In response to the prioritization of healthcare resources towards the COVID-19 pandemic, routine cancer screening and diagnostic have been disrupted, potentially explaining the apparent COVID-era decline in cancer cases and mortality. In this study, we identified temporal trends in public interest in cancer-related health information using the nowcasting tool Google Trends. METHODS: We used Google Trends to query search terms related to cancer types for short-term (September 2019-September 2020) and long-term (September 2016-September 2020) trends in the US. We compared average relative search volumes (RSV) for specified time ranges to detect recent and seasonal variation. RESULTS: General search interest declined for all cancer types beginning in March 2020, with changes in search interest for "Breast cancer," "Colorectal cancer," and "Melanoma" of - 30.6%, - 28.2%, and - 26.7%, respectively, and compared with the mean RSV of the two previous months. In the same time range, search interest for "Telemedicine" has increased by + 907.1% and has reached a 4-year peak with a sustained increased level of search interest. Absolute cancer mortality has declined and is presently at a 4-year low; however, search interest in cancer has been recuperating since July 2020. CONCLUSION: We observed a marked decline in searches for cancer-related health information that mirrors the reduction in new cancer diagnoses and cancer mortality during the COVID-19 pandemic. Health professions need to be prepared for the coming demand for cancer-related healthcare, foreshadowed by recovering interest in cancer-related information on Google Trends.

Pseudouridine and N-formylmethionine associate with left ventricular mass index: Metabolome-wide association analysis of cardiac remodeling.

BACKGROUND: Heart failure (HF) is the fastest growing form of cardiovascular disease both nationally and globally, underlining a need to phenotype subclinical HF intermediaries to improve primary prevention. OBJECTIVES: We aimed to identify novel metabolite associations with left ventricular (LV) remodeling, one upstream HF intermediary, among a community-based cohort of individuals. METHODS: We examined 1052 Bogalusa Heart Study participants (34.98% African American, 57.41% female, aged 33.6-57.5 years). Measures of LV mass and relative wall thickness (RWT) were obtained using two-dimensional-guided echocardiographic measurements via validated eqs. LV mass was indexed to height2.7 to calculate left ventricular mass index (LVMI). Untargeted metabolomic analysis of fasting serum samples was conducted. In combined and ethnicity-stratified analyses, multivariable linear and multinomial logistic regression models tested the associations of metabolites with the continuous LVMI and RWT and categorical LV geometry phenotypes, respectively, after adjusting for demographic and traditional cardiovascular disease risk factors. RESULTS: Pseudouridine (B = 1.38; p = 3.20 × 10-5) and N-formylmethionine (B = 1.65; 3.30 × 10-6) were significantly associated with LVMI in the overall sample as well significant in Caucasians, with consistent effect direction and nominal significance (p < .05) in African Americans. Upon exclusion of individuals with self-report myocardial infarction or congestive HF, we similarly observed a 1.33 g/m2.7 and 1.52 g/m2.7 higher LVMI for each standard deviation increase in pseudouridine and N-formylmethionine, respectively. No significant associations were observed for metabolites with RWT or categorical LV remodeling outcomes. CONCLUSIONS: The current analysis identified novel associations of pseudouridine and N-formylmethionine with LVMI, suggesting that mitochondrial-derived metabolites may serve as early biomarkers for LV remodeling and subclinical HF.

Pooled cohort equations heart failure risk score predicts cardiovascular disease and all-cause mortality in a nationally representative sample of US adults.

BACKGROUND: Heart failure (HF) represents an accumulated burden of systemic vascular damage and is the fastest growing form of cardiovascular disease (CVD). Due to increasing HF-attributable mortality rates, we sought to assess the association of the new 2019 Pooled Cohort equations to Prevent Heart Failure (PCP-HF) risk score with CVD and all-cause mortality. METHODS: We linked data for 6333 black and white men and women aged 40-79 years, whom underwent electrocardiographic examination from the Third National Health and Nutrition Exam Survey, to National Death Index record matches. Sex- and race-specific PCP-HF risk scores were calculated using data on age, smoking, body mass index, systolic blood pressure, total cholesterol, HDL-cholesterol, fasting blood glucose, QRS complex duration, and antihypertensive and/or glucose-lowering medications. Cox regression estimated hazard ratios for the association of the PCP-HF risk score with CVD and all-cause mortality. RESULTS: Individuals were on average 54.9 years old (51.7% women, 25.4% black) and the median 10-year HF risk was 1.6% (Q1 = 0.5, Q3 = 4.8). There were 3178 deaths, 1116 from CVD, over a median follow-up time of 22.3 years. Black women had a higher 10-year HF risk compared to white women (2.1% vs. 1.1%; p < 0.01), while no significant difference was observed in predicted HF risk between black men and white men (2.3% vs. 2.1%, p = 0.16). A two-fold higher PCP-HF risk score was associated with a significant 58% (HR = 1.58; 95% CI, 1.48-1.70; p < 0.0001) and 38% (HR = 1.38; 95% CI, 1.32-1.46; p < 0.0001) greater risk of CVD and all-cause mortality, respectively. CONCLUSION: The PCP-HF risk score predicts CVD and all-cause mortality, in addition to the 10-year risk of incident HF among white and black men and women. These results underline the expanded utility of the PCP-HF risk score and suggest that its implementation in the clinical and population health settings may improve primary CVD prevention in the United States.

Impact of Novel Low-Density Lipoprotein-Cholesterol Assessment on the Utility of Secondary Non-High-Density Lipoprotein-C and Apolipoprotein B Targets in Selected Worldwide Dyslipidemia Guidelines.

BACKGROUND: Selected dyslipidemia guidelines recommend non-high-density lipoprotein-cholesterol (non-HDL-C) and apolipoprotein B (apoB) as secondary targets to the primary target of low-density lipoprotein-cholesterol (LDL-C). After considering 2 LDL-C estimates that differ in accuracy, we examined: (1) how frequently non-HDL-C guideline targets could change management; and (2) the utility of apoB targets after meeting LDL-C and non-HDL-C targets. METHODS: We analyzed 2518 adults representative of the US population from the 2011 to 2012 National Health and Nutrition Examination Survey and 126 092 patients from the Very Large Database of Lipids study with apoB. We identified all individuals as well as those with high-risk clinical features, including coronary artery disease, diabetes mellitus, and metabolic syndrome who met very high- and high-risk guideline targets of LDL-C <70 and <100 mg/dL using Friedewald estimation (LDL-CF) and a novel, more accurate method (LDL-CN). Next, we examined those not meeting non-HDL-C (<100, <130 mg/dL) and apoB (<80, <100 mg/dL) guideline targets. In those meeting dual LDL-C and non-HDL-C targets (<70 and <100 mg/dL, respectively, or <100 and <130 mg/dL, respectively), we determined the proportion of individuals who did not meet guideline apoB targets (<80 or <100 mg/dL). RESULTS: A total of 7% to 9% and 31% to 36% of individuals had LDL-C <70 and <100 mg/dL, respectively. Among those with LDL-CF<70 mg/dL, 14% to 15% had non-HDL-C ≥100 mg/dL, and 7% to 8% had apoB ≥80 mg/dL. Among those with LDL-CF<100 mg/dL, 8% to 10% had non-HDL-C ≥130 mg/dL and 2% to 3% had apoB ≥100 mg/dL. In comparison, among those with LDL-CN<70 or 100 mg/dL, only ≈2% and ≈1% of individuals, respectively, had non-HDL-C and apoB values above guideline targets. Similar trends were upheld among those with high-risk clinical features: ≈0% to 3% of individuals with LDL-CN<70 mg/dL had non-HDL-C ≥100 mg/dL or apoB ≥80 mg/dL compared with 13% to 38% and 9% to 25%, respectively, in those with LDL-CF<70 mg/dL. With LDL-CF or LDL-CN<70 mg/dL and non-HDL-C <100 mg/dL, 0% to 1% had apoB ≥80 mg/dL. Among all dual LDL-CF or LDL-CN<100 mg/dL and non-HDL-C <130 mg/dL individuals, 0% to 0.4% had apoB ≥100 mg/dL. These findings were robust to sex, fasting status, and lipid-lowering therapy status. CONCLUSIONS: After more accurately estimating LDL-C, guideline-suggested non-HDL-C targets could alter management in only a small fraction of individuals, including those with coronary artery disease and other high-risk clinical features. Furthermore, current guideline-suggested apoB targets provide modest utility after meeting cholesterol targets. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01698489.

Sex differences in calcified plaque and long-term cardiovascular mortality: observations from the CAC Consortium.

Aims: Pathologic evidence supports unique sex-specific mechanisms as precursors for acute cardiovascular (CV) events. Current evidence on long-term CV risk among women when compared with men based on measures of coronary artery calcium (CAC) remains incomplete. Methods and results: A total of 63 215 asymptomatic women and men were enrolled in the multicentre, CAC Consortium with median follow-up of 12.6 years. Pooled cohort equation (PCE) risk scores and risk factor data were collected with the Agatston score and other CAC measures (number of lesions and vessels, lesion size, volume, and plaque density). Cox proportional hazard models were employed to estimate CV mortality (n = 919). Sex interactions were calculated. Women and men had average PCE risk scores of 5.8% and 9.1% (P < 0.001). Within CAC subgroups, women had fewer calcified lesions (P < 0.0001) and vessels (P = 0.017), greater lesion size (P < 0.0001), and higher plaque density (P = 0.013) when compared with men. For women and men without CAC, long-term CV mortality was similar (P = 0.67), whereas detectable CAC was associated with 1.3-higher hazard for CV death among women when compared with men (P < 0001). Cardiovascular mortality was higher among women with more extensive, numerous, or larger CAC lesions. The relative hazard for cardiovascular disease (CVD) mortality for women and men was 8.2 vs. 5.1 for multivessel CAC, 8.6 vs. 5.9 for ≥5 CAC lesions, and 8.5 vs. 4.4 for a lesion size ≥15 mm3, respectively. Additional explorations revealed that women with larger sized and more numerous CAC lesions had 2.2-fold higher CVD mortality (P < 0.0001) as compared to men. Moreover, CAC density was not predictive of CV mortality in women (P = 0.51) but was for men (P < 0.001), when controlling for CAC volume and cardiac risk factors. Conclusion: Our overall findings support that measures beyond the Agatston score provide important clues to sex differences in atherosclerotic plaque and may further refine risk detection and focus preventive strategies of care.

Fasting or Non-fasting Lipids for Atherosclerotic Cardiovascular Disease Risk Assessment and Treatment?

PURPOSE OF REVIEW: Dyslipidemia is a major modifiable risk factor for atherosclerotic cardiovascular disease (ASCVD); however, lipid testing for risk assessment and treatment surveillance has been underutilized. Several factors likely account for this, including the common practice of measuring lipid levels in the fasting state, which often necessitates that patients return for an additional visit. In this review, we evaluate potential advantages and cautions associated with measuring lipids in the non-fasting state. RECENT FINDINGS: There is similar performance with the use of either fasting or non-fasting total cholesterol and HDL cholesterol in ASCVD risk assessment. Observational studies demonstrate that in comparison to fasting levels, non-fasting triglycerides are approximately 20% higher on average, although the magnitude of difference is subject to substantial inter-patient variability. Higher triglycerides can lead to the under-estimation of low-density lipoprotein cholesterol (LDL-C) by approximately 10 mg/dL or more when calculated using the Friedewald equation. This is especially clinically relevant at low LDL-C levels, although a novel validated algorithm for LDL-C estimation largely overcomes this limitation. Non-fasting lipid assessment is reasonable in many clinical circumstances given that ASCVD risk prediction is similar using fasting or non-fasting lipid values and because LDL-C can be accurately estimated using modern methods. Allowing the option for non-fasting lipid assessment can reduce a barrier to lipid testing and can facilitate a more convenient assessment of ASCVD risk with the ultimate potential effect of reducing the global burden of ASCVD. However, certain patients such as those with severe hypertriglyceridemias or high-risk patients being treated to low LDL-C levels may still need fasting lipid panels performed for precise diagnosis and to standardize therapeutic monitoring.

Kidney Failure and ESRD in the Atherosclerosis Risk in Communities (ARIC) Study: Comparing Ascertainment of Treated and Untreated Kidney Failure in a Cohort Study.

BACKGROUND: Linkage to the US Renal Data System (USRDS) registry commonly is used to identify end-stage renal disease (ESRD) cases, or kidney failure treated with dialysis or transplantation, but it underestimates the total burden of kidney failure. This study validates a kidney failure definition that includes both kidney failure treated and not treated by dialysis or transplantation. It compares kidney failure risk factors and outcomes using this broader definition with USRDS-identified ESRD risk factors and outcomes. STUDY DESIGN: Diagnostic test study with stratified random sampling of hospitalizations for chart review. SETTING & PARTICIPANTS: Atherosclerosis Risk in Communities Study (n=11,530; chart review, n=546). INDEX TEST: USRDS-identified ESRD; treated or untreated kidney failure defined by USRDS-identified ESRD or International Classification of Diseases, Ninth or Tenth Revision, Clinical Modification (ICD-9-CM/ICD-10-CM) code for hospitalization or death. REFERENCE TEST: For ESRD, determination of permanent dialysis therapy or transplantation; for kidney failure, determination of permanent dialysis therapy, transplantation, or estimated glomerular filtration rate < 15 mL/min/1.73 m(2). RESULTS: During 13 years' median follow-up, 508 kidney failure cases were identified, including 173 (34.1%) from the USRDS registry. ESRD and kidney failure incidence were 1.23 and 3.66 cases per 1,000 person-years in the overall population and 1.35 and 6.59 cases per 1,000 person-years among participants older than 70 years, respectively. Other risk-factor associations were similar between ESRD and kidney failure, except diabetes and albuminuria, which were stronger for ESRD. Survivals at 1 and 5 years were 74.0% and 24.0% for ESRD and 59.8% and 31.6% for kidney failure, respectively. Sensitivity and specificity were 88.0% and 97.3% comparing the kidney failure ICD-9-CM/ICD-10-CM code algorithm to chart review; for USRDS-identified ESRD, sensitivity and specificity were 94.9% and 100.0%. LIMITATIONS: Some medical charts were incomplete. CONCLUSIONS: A kidney failure definition including treated and untreated disease identifies more cases than linkage to the USRDS registry alone, particularly among older adults. Future studies might consider reporting both USRDS-identified ESRD and a more inclusive kidney failure definition.

Identification of incident CKD stage 3 in research studies.

BACKGROUND: In epidemiologic research, incident chronic kidney disease (CKD) commonly is determined by laboratory tests performed at planned study visits. Given the morbidity and mortality associated with CKD, persons with incident disease may be less likely to attend scheduled visits, affecting observed associations. The objective of this study was to quantify loss to follow-up by CKD status and determine whether supplementation with diagnostic code data improves capture of incident CKD. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: 11,560 participants in the Atherosclerosis Risk in Communities (ARIC) Study underwent continuous surveillance for hospitalizations and death from baseline visit (1996-1999) to follow-up visit (2011-2013). A subset of hospitalizations in Washington County, MD, was used in diagnostic code validation (n=2,540). PREDICTOR: Baseline demographics and comorbid conditions. OUTCOMES: Incident CKD stage 3 ascertained by follow-up visit (visit-based definition) or hospitalization surveillance (hospitalization-based definition). MEASUREMENTS: Visit-based definition: ≥25% decline from baseline estimated glomerular filtration rate to <60 mL/min/1.73 m2 at follow-up visit; hospitalization-based definition: hospitalization CKD diagnostic code. RESULTS: Of 11,560 participants, 5,951 attended the follow-up visit and 9,264 were hospitalized. Never-hospitalized participants were younger, more often female, and had fewer comorbid conditions; 73.5% attended the follow-up visit. Incident CKD stage 3 occurred in 1,172 participants by the visit-based definition (251 were never hospitalized) and 1,078 participants by the hospitalization-based definition (237 attended the follow-up study visit). Sensitivity of the hospitalization-based CKD definition was 35.5% (95% CI, 31.6%-39.7%); specificity was 95.7% (95% CI, 94.2%-96.8%). Sensitivity was higher with later time period, older participant age, and baseline prevalent diabetes and CKD. LIMITATIONS: A subset of hospitalizations was used for validation; 15-year gap between study visits. CONCLUSIONS: The sensitivity of diagnostic code-identified CKD is low and varies by certain factors; however, supplementing a visit-based definition with hospitalization information can increase disease identification during periods of follow-up without study visits.

Recent advances in cardiovascular risk assessment: The added value of non-invasive anatomic imaging.

In 2022, multiple original research studies were conducted highlighting the utility of coronary artery calcium (CAC) imaging in young individuals and provided further evidence for the role of CAC to improve atherosclerotic cardiovascular disease (ASCVD) risk assessment. Mean calcium density was shown to be a more reliable predictor than peak density in risk assessment. Additionally, in light of the ACC/AHA/Multispecialty Chest Pain Guideline's recent elevation of coronary computed tomography angiography (CCTA) to a Class I (level of evidence A) recommendation as an index diagnostic test for acute or stable chest pain, several studies support the utility of CCTA and guided future directions. This review summarizes recent studies that highlight the role of non-invasive imaging in enhancing ASCVD risk assessment across different populations.

Opportunistic Screening for Coronary Artery Disease: An Untapped Population Health Resource.

BACKGROUND: Coronary artery disease is the leading cause of death in the United States. At-risk asymptomatic adults are eligible for screening with electrocardiogram-gated coronary artery calcium (CAC) CT, which aids in risk stratification and management decision-making. Incidental CAC (iCAC) is easily quantified on chest CT in patients imaged for noncardiac indications; however, radiologists do not routinely report the finding. OBJECTIVE: To determine the clinical significance of CAC identified incidentally on routine chest CT performed for noncardiac indications. DESIGN: An informationist developed search strategies in MEDLINE, Embase, and SCOPUS, and two reviewers independently screened results at both the abstract and full text levels. Data extracted from eligible articles included age, rate of iCAC identification, radiologist reporting frequency, impact on downstream medical management, and association of iCAC with patient outcomes. RESULTS: From 359 unique citations, 83 research publications met inclusion criteria. The percentage of patients with iCAC ranged from 9% to 100%. Thirty-one investigations measured association(s) between iCAC and cardiovascular morbidity and mortality, and 29 identified significant correlations, including nonfatal myocardial infarction, fatal myocardial infarction, major adverse cardiovascular event, cardiovascular death, and all-cause death. iCAC was present in 20% to 100% of the patients in these cohorts, but when present, iCAC was reported by radiologists in only 31% to 44% of cases. Between 18% and 77% of patients with iCAC were not on preventive medications in studies that reported these data. Seven studies measured the effect of reporting on guideline directed medical therapy, and 5 (71%) reported an increase in medication prescriptions after diagnosis of iCAC, with one confirming reductions in low-density lipoprotein levels. Twelve investigations reported good concordance between CAC grade on noncardiac CT and Agatston score on electrocardiogram-gated cardiac CT, and 10 demonstrated that artificial intelligence tools can reliably calculate an Agatston score on noncardiac CT. CONCLUSION: A body of evidence demonstrates that patients with iCAC on routine chest CT are at risk for cardiovascular disease events and death, but they are often undiagnosed. Uniform reporting of iCAC in the chest CT impression represents an opportunity for radiology to contribute to early identification of high-risk individuals and potentially reduce morbidity and mortality. AI tools have been validated to calculate Agatston score on routine chest CT and hold the best potential for facilitating broad adoption.

Nontraditional Risk Markers for Incident Coronary Artery Calcium Among Persons ≥65 Years of Age.

Background: The initiation of coronary artery calcium (CAC) is an important physiologic milestone associated with increased cardiovascular disease risk. However, traditional risk factors (RF) do not perform well for predicting incident CAC among the 54 million older U.S. adults. Objectives: The authors sought to assess the association between nontraditional cardiovascular disease RF and incident CAC in older persons. Methods: There were 815 MESA (Multi-Ethnic Study of Atherosclerosis) participants ≥65 years of age who had CAC = 0 at Visit 1 and a follow-up CAC scan. Multivariable adjusted Cox hazards ratios (aHR) and C-statistics were calculated to examine the association of nontraditional RF with incident CAC. Results: The mean age was 70.2 years and 67% were women. The median follow-up time to repeat CAC scan was 3.6 years (IQR: 2.6-9.2 years) and 45% of participants developed incident CAC. Albuminuria (aHR: 1.50, 95% CI: 1.07-2.09), carotid plaque (aHR: 1.32, 95% CI: 1.04-1.66), and thoracic aortic calcification (TAC) (aHR: 1.38, 95% CI: 1.10-1.75) were significantly associated with incident CAC, while higher levels of nontraditional RF including apolipoprotein-B, lipoprotein(a), high-sensitivity troponin T, and N-terminal pro-brain natriuretic peptide were not. When added to demographics, albuminuria, carotid plaque, and TAC provided a greater C-statistic improvement (+0.047, P = 0.004) vs all traditional RF combined (+0.033, P = 0.05). Conclusions: Among nontraditional RF and measures of subclinical atherosclerosis, only albuminuria, carotid plaque, and TAC were significantly associated with incident CAC in persons ≥65 years of age. Identification of albuminuria or extracoronary atherosclerosis may help guide the timing of repeat CAC scoring in older persons with baseline CAC = 0.

Aspirin use for primary prevention among US adults with and without elevated Lipoprotein(a).

Objective: Lipoprotein(a) [Lp(a)] is an atherogenic and prothrombotic lipoprotein associated with atherosclerotic cardiovascular disease (ASCVD). We assessed the association between regular aspirin use and ASCVD mortality among individuals with versus without elevated Lp(a) in a nationally representative US cohort. Methods: Eligible participants were aged 40-70 years without clinical ASCVD, reported on aspirin use, and had Lp(a) measurements from the Third National Health and Nutrition Examination Survey (NHANES III, 1988-1994), the only cycle of this nationally representative US cohort to measure Lp(a). Regular aspirin use was defined as taking aspirin ≥30 times in the previous month. Using NHANES III linked mortality records and weighted Cox proportional hazards regression, the association between regular aspirin use and ASCVD mortality was observed in those with and without elevated Lp(a) (≥50 versus <50 mg/dL) over a median 26-year follow-up. Results: Among 2,990 persons meeting inclusion criteria (∼73 million US adults), the mean age was 50 years, 86% were non-Hispanic White, 9% were non-Hispanic Black, 53% were female, and 7% reported regular aspirin use. The median Lp(a) was 14 mg/dL and the proportion with elevated Lp(a) was similar among those with versus without regular aspirin use (15.1% versus 21.9%, p = 0.16). Among individuals with elevated Lp(a), the incidence of ASCVD mortality per 1,000 person-years was lower for those with versus without regular aspirin use (1.2, 95% CI: 0.1-2.3 versus 3.9, 95% CI: 2.8-4.9). In multivariable modeling, regular aspirin use was associated with a 52% lower risk of ASCVD mortality among individuals with elevated Lp(a) (HR=0.48, 95% CI: 0.28-0.83), but not for those without elevated Lp(a) (HR=1.01, 95% CI: 0.81-1.25; p-interaction=0.001). Conclusion: Regular aspirin use was associated with significantly lower ASCVD mortality in adults without clinical ASCVD who had elevated Lp(a). These findings may have clinical and public health implications for aspirin utilization in primary prevention.

Overcoming barriers to implementation: Improving incidental coronary calcium reporting on non-EKG gated chest CT scans.

BACKGROUND: Current guidelines recommend the reporting of incidental CAC on non-EKG-gated CT scans of the chest. The finding of incidental moderate or severe CAC on non-cardiac non-contrast chest CT correlates with a CAC score ≥ 100 Agatston units, a guideline-based indication for a clinician-patient discussion regarding the initiation of statin therapy. In contemporary practice, whether the presence and severity of incidental CAC are routinely reported on such CT scans of the chest is unknown. METHODS: At a major university hospital, we collected a one-month convenience sample of 297 patients who had chest CT imaging for indications other than lung cancer screening (OICT) and 42 patients who underwent lung cancer chest CT screening (LSCT). We evaluated reporting patterns of incidental CAC in the body and impression of the reports as compared to the overreading of such studies by a board-certified CT chest radiologist. We hypothesized and demonstrated that there was underreporting of incidental CAC on these scans. We then undertook an initiative to educate reporting radiologists on the importance of reporting CAC and implemented a reporting template change to encourage routine reporting. Then we repeated another one-month sample (n= 363 for the OICT and n= 63 for the LSCT groups) to evaluate reporting patterns following our intervention. RESULTS: The presence of incidental moderate and severe CAC was systematically underreported in the OICT group (0 and 4.8 %) and the severity was never mentioned in the impression of reports. In the LSCT group, the presence of incidental moderate and severe CAC was also underreported (66.7 % and 75 %) and the severity of CAC was mentioned 50 % of the time in the impression of the reports. Following the initiation of an educational program and radiology reporting template change, there was a significant increase in reporting of moderate or severe CAC in the OICT group (0 vs. 80.0 %, p < 0.001) and (4.8 vs. 93.5 %, p < 0.001) respectively and a significant increase in the reporting of the severity of incidental CAC for those with severe CAC in the LSCT group (50 vs. 94.1 %, p=0.006). CONCLUSION: Despite guideline recommendations, Incidental CAC was underreported at a large academic center. We implemented a system that significantly improved reporting patterns of incidental CAC. Failure to report incidental CAC represents a missed opportunity to initiate preventive therapies. Hospital systems interested in improving the quality of their radiology reporting procedures should examine their practices to assure that CAC quantification is routinely performed.

Prevalence of Aortic Valve Calcium and the Long-Term Risk of Incident Severe Aortic Stenosis.

BACKGROUND: Aortic valve calcification (AVC) is a principal mechanism underlying aortic stenosis (AS). OBJECTIVES: This study sought to determine the prevalence of AVC and its association with the long-term risk for severe AS. METHODS: Noncontrast cardiac computed tomography was performed among 6,814 participants free of known cardiovascular disease at MESA (Multi-Ethnic Study of Atherosclerosis) visit 1. AVC was quantified using the Agatston method, and normative age-, sex-, and race/ethnicity-specific AVC percentiles were derived. The adjudication of severe AS was performed via chart review of all hospital visits and supplemented with visit 6 echocardiographic data. The association between AVC and long-term incident severe AS was evaluated using multivariable Cox HRs. RESULTS: AVC was present in 913 participants (13.4%). The probability of AVC >0 and AVC scores increased with age and were generally highest among men and White participants. In general, the probability of AVC >0 among women was equivalent to men of the same race/ethnicity who were approximately 10 years younger. Incident adjudicated severe AS occurred in 84 participants over a median follow-up of 16.7 years. Higher AVC scores were exponentially associated with the absolute risk and relative risk of severe AS with adjusted HRs of 12.9 (95% CI: 5.6-29.7), 76.4 (95% CI: 34.3-170.2), and 380.9 (95% CI: 169.7-855.0) for AVC groups 1 to 99, 100 to 299, and ≥300 compared with AVC = 0. CONCLUSIONS: The probability of AVC >0 varied significantly by age, sex, and race/ethnicity. The risk of severe AS was exponentially higher with higher AVC scores, whereas AVC = 0 was associated with an extremely low long-term risk of severe AS. The measurement of AVC provides clinically relevant information to assess an individual's long-term risk for severe AS.

Identifying People at High Risk for Severe Aortic Stenosis: Aortic Valve Calcium Versus Lipoprotein(a) and Low-Density Lipoprotein Cholesterol.

BACKGROUND: Aortic valve calcification (AVC), Lp(a) [lipoprotein(a)], and low-density lipoprotein cholesterol (LDL-C) are associated with severe aortic stenosis (AS). We aimed to determine which of these risk factors were most strongly associated with the risk of incident severe AS. METHODS: A total of 6792 participants from the MESA study (Multi-Ethnic Study of Atherosclerosis) had computed tomography-quantified AVC, Lp(a), and LDL-C values at MESA visit 1 (2000-2002). We calculated the absolute event rate of incident adjudicated severe AS per 1000 person-years and performed multivariable adjusted Cox proportional hazards regression. RESULTS: The mean age was 62 years old, and 47% were women. Over a median 16.7-year follow-up, the rate of incident severe AS increased exponentially with higher AVC, regardless of Lp(a) or LDL-C values. Participants with AVC=0 had a very low rate of severe AS even with elevated Lp(a) ≥50 mg/dL (<0.1/1000 person-years) or LDL-C ≥130 mg/dL (0.1/1000 person-years). AVC >0 was strongly associated with severe AS when Lp(a) <50 mg/dL hazard ratio (HR) of 33.8 (95% CI, 16.4-70.0) or ≥50 mg/dL HR of 61.5 (95% CI, 7.7-494.2) and when LDL-C <130 mg/dL HR of 31.1 (95% CI, 14.4-67.1) or ≥130 mg/dL HR of 50.2 (95% CI, 13.2-191.9). CONCLUSIONS: AVC better identifies people at high risk for severe AS compared with Lp(a) or LDL-C, and people with AVC=0 have a very low long-term rate of severe AS regardless of Lp(a) or LDL-C level. These results suggest AVC should be the preferred prognostic risk marker to identify patients at high risk for severe AS, which may help inform participant selection for future trials testing novel strategies to prevent severe AS.