Atherosclerotic Cardiovascular Disease Event Rates Research Articles

Discordance among apoB, non-high-density lipoprotein cholesterol, and triglycerides: implications for cardiovascular prevention.

Despite growing evidence that apolipoprotein B (apoB) is the most accurate marker of atherosclerotic cardiovascular disease (ASCVD) risk, its adoption in clinical practice has been low. This investigation sought to determine whether low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (HDL-C), and triglycerides are sufficient for routine cardiovascular care. A sample of 293 876 UK Biobank adults (age: 40-73 years, 42% men), free of cardiovascular disease, with a median follow-up for new-onset ASCVD of 11 years was included. Distribution of apoB at pre-specified levels of LDL-C, non-HDL-C, and triglycerides was examined graphically, and 10-year ASCVD event rates were compared for high vs. low apoB. Residuals of apoB were constructed after regressing apoB on LDL-C, non-HDL-C, and log-transformed triglycerides and used as predictors in a proportional hazards regression model for new-onset ASCVD adjusted for standard risk factors, including HDL-C. ApoB was highly correlated with LDL-C and non-HDL-C (Pearson's r = .96, P < .001 for both) but less so with log triglycerides (r = .42, P < .001). However, apoB ranges necessary to capture 95% of all observations at pre-specified levels of LDL-C, non-HDL-C, or triglycerides were wide, spanning 85.8-108.8 md/dL when LDL-C 130 mg/dL, 88.3-112.4 mg/dL when non-HDL-C 160 mg/dL, and 67.8-147.4 md/dL when triglycerides 115 mg/dL. At these levels (±10 mg/dL), 10-year ASCVD rates for apoB above mean + 1 SD vs. below mean - 1 SD were 7.3 vs. 4.0 for LDL-C, 6.4 vs. 4.6 for non-HDL-C, and 7.0 vs. 4.6 for triglycerides (all P < .001). With 19 982 new-onset ASCVD events on follow-up, in the adjusted model, residual apoB remained statistically significant after accounting for LDL-C and HDL-C (hazard ratio 1.06, 95% confidence interval 1.0-1.07), after accounting for non-HDL-C and HDL-C (hazard ratio 1.04, 95% confidence interval 1.03-1.06), and after accounting for triglycerides and HDL-C (hazard ratio 1.13, 95% confidence interval 1.12-1.15). None of the residuals of LDL-C, non-HDL-C, or of log triglycerides remained significant when apoB was included in the model. High variability of apoB at individual levels of LDL-C, non-HDL-C, and triglycerides coupled with meaningful differences in 10-year ASCVD rates and significant residual information contained in apoB for prediction of new-onset ASCVD events demonstrate that LDL-C, non-HDL-C, and triglycerides are not adequate proxies for apoB in clinical care.

Lipoprotein(a) and the pooled cohort equations for ASCVD risk prediction: The Multi-Ethnic Study of Atherosclerosis

Background and aimsLipoprotein(a) [Lp(a)] is an independent risk factor for atherosclerotic cardiovascular disease (ASCVD) but is not included in the Pooled Cohort Equations (PCE). We aimed to assess how well the PCE predict 10-year event rates in individuals with elevated Lp(a), and whether the addition of Lp(a) improves risk prediction. MethodsWe compared observed versus PCE-predicted 10-year ASCVD event rates, stratified by Lp(a) level and ASCVD risk category using Poisson regression, and evaluated the association between Lp(a) > 50 mg/dL and ASCVD risk using Cox proportional hazards models in the Multi-Ethnic Study of Atherosclerosis (MESA). We evaluated the C-index and net reclassification improvement (NRI) with addition of Lp(a) to the PCE. ResultsThe study population included 6639 individuals (20%, n = 1325 with elevated Lp(a)). The PCE accurately predicted 10-year event rates for individuals with elevated Lp(a) with observed event rates falling within predicted limits. Elevated Lp(a) was associated with increased risk of CVD events overall (HR 1.27, 95% CI 1.00–1.60), particularly in low (HR 2.45, 95% CI 1.40–4.31), and high-risk (HR 1.41, 95% CI 1.02–1.96) individuals. Continuous NRI (95% CI) with the addition of Lp(a) to the PCE for CVD was 0.0963 (0.0158–0.1953) overall, and 0.2999 (0.0876, 0.5525) among low-risk individuals. ConclusionsThe PCE performs well for event rate prediction in individuals with elevated Lp(a). However, Lp(a) is associated with increased CVD risk, and the addition of Lp(a) to the PCE improves risk prediction, particularly among low-risk individuals. These results lend support for increasing use of Lp(a) testing for risk assessment.

Rate of Change in 10-Year Atherosclerotic Cardiovascular Disease Risk and Its Implications for Primary Prevention.

Contemporary cardiovascular primary prevention is based on the assessment of the 10-year risk of atherosclerotic cardiovascular disease (ASCVD). However, the clinical implications of temporal change in the 10-year ASCVD risk estimate (∆10-year ASCVD risk/year) are unknown. A total of 211 077 participants without established ASCVD and with repetitive 10-year ASCVD risk assessment at an interval of 4 to 5 years were selected from the Korean National Health Insurance Service data. The primary end point was a composite of myocardial infarction, stroke, coronary revascularization, and all-cause death. ASCVD event rates were proportional to the ∆10-year ASCVD risk/year regardless of the baseline 10-year ASCVD risk. Adjusted hazard ratio for ASCVD events per 1% increase in ∆10-year ASCVD risk/year was 1.53 (95% CI, 1.44-1.63), 1.24 (95% CI, 1.15-1.32), 1.18 (95% CI, 1.13-1.23), and 1.05 (95% CI, 1.00-1.10) in those with a baseline 10-year ASCVD risk of <5%, 5% to 7.5%, 7.5% to 20%, and ≥20%, respectively. Appropriate control of risk factors, including low-density lipoprotein cholesterol, blood pressure, body mass index, exercise habits, and smoking status, was associated with lower ASCVD event rates, whereas failure to control these risk factors resulted in higher ASCVD event rates. The temporal change in 10-year ASCVD risk over a period of 4 to 5 years reflects success or failure in controlling major cardiovascular risk factors and indicates the risk of future ASCVD events. The ∆10-year ASCVD risk/year can be used as an indicator of primary prevention and guide the application of preventive measures.

When Does a Calcium Score Equate to Secondary Prevention?: Insights From the Multinational CONFIRM Registry

BackgroundElevated coronary artery calcium (CAC) scores in subjects without prior atherosclerotic cardiovascular disease (ASCVD) have been shown to be associated with increased cardiovascular risk. ObjectivesThe authors sought to determine at what level individuals with elevated CAC scores who have not had an ASCVD event should be treated as aggressively for cardiovascular risk factors as patients who have already survived an ASCVD event. MethodsThe authors performed a cohort study comparing event rates of patients with established ASVCD to event rates in persons with no history of ASCVD and known calcium scores to ascertain at what level elevated CAC scores equate to risk associated with existing ASCVD. In the multinational CONFIRM (Coronary CT Angiography Evaluation for Clinical Outcomes: An International Multicenter) registry, the authors compared ASCVD event rates in persons without a history of myocardial infarction (MI) or revascularization (as categorized on CAC scores) to event rates in those with established ASCVD. They identified 4,511 individuals without known coronary artery disease (CAC) who were compared to 438 individuals with established ASCVD. CAC was categorized as 0, 1 to 100, 101 to 300, and >300. Cumulative major adverse cardiovascular events (MACE), MACE plus late revascularization, MI, and all-cause mortality incidence was assessed using the Kaplan-Meier method for persons with no ASCVD history by CAC level and persons with established ASCVD. Cox proportional hazards regression analysis was used to calculate HRs with 95% CIs, which were adjusted for traditional cardiovascular risk factors. ResultsThe mean age was 57.6 ± 12.4 years (56% male). In total, 442 of 4,949 (9%) patients experienced MACEs over a median follow-up of 4 years (IQR: 1.7-5.7 years). Incident MACEs increased with higher CAC scores, with the highest rates observed with CAC score >300 and in those with prior ASCVD. All-cause mortality, MACEs, MACE + late revascularization, and MI event rates were not statistically significantly different in those with CAC >300 compared with established ASCVD (all P > 0.05). Persons with a CAC score <300 had substantially lower event rates. ConclusionsPatients with CAC scores >300 are at an equivalent risk of MACE and its components as those treated for established ASCVD. This observation, that those with CAC >300 have event rates comparable to those with established ASCVD, supplies important background for further study related to secondary prevention treatment targets in subjects without prior ASCVD with elevated CAC. Understanding the CAC scores that are associated with ASCVD risk equivalent to stable secondary prevention populations may be important for guiding the intensity of preventive approaches more broadly.

Abstract P451: Coronary Artery Calcium and the Association Between Dietary Fish Intake and Atherosclerotic Cardiovascular Disease Risk

Introduction: Current guidelines recommend ≥2 servings of fish/week for the prevention of atherosclerotic cardiovascular disease (ASCVD). However, a recent large meta-analysis suggested that the benefit may exist only for persons with a prior ASCVD event. Whether coronary artery calcium (CAC) can help to identify individuals who are likely to benefit from habitual fish consumption is unknown. Hypothesis: CAC will stratify persons who may and may not benefit from habitual fish consumption. Methods: There were 4977 participants in the Multi-Ethnic Study of Atherosclerosis who reported their frequency of fish intake and underwent CAC scanning at Visit 1. Adjusted Cox proportional hazards regression models stratified by the presence/absence of CAC assessed the association between fish intake and incident ASCVD over a median follow-up of 15.7 years. Results: The mean age was 61 years old, 53% were women, 26% were Black, and 49% of participants had prevalent CAC. A similar proportion of individuals reported consuming ≥2 servings of fish/week for those with CAC=0 and CAC &gt;0 (35% versus 33%, p=0.12). The absolute ASCVD event rate for those with &lt;2 or ≥2 servings of fish/week was 5.5 vs. 4.2 per 1,000 person-years for CAC=0 and 18.2 vs. 19.0 person-years for CAC &gt;0 (Figure 1). Each additional serving of fish/week was associated with a 9% lower risk of ASCVD for participants with CAC=0 (HR=0.91, 95% CI: 0.83-0.99) whereas there was no significant association for persons with CAC &gt;0 (HR=1.03, 95% CI: 0.99-1.07). Conclusions: A higher amount of fish consumption was associated with a lower risk of incident ASCVD for participants with CAC=0, but not those with CAC &gt;0, although the absolute ASCVD event rate was low for persons with CAC=0 regardless of fish consumption frequency.

Estimated versus observed 10-year atherosclerotic cardiovascular event rates in a rural population-based health initiative: The Heart of New Ulm Project

ObjectiveAssess discrepancy between estimated 10-year atherosclerotic cardiovascular disease (ASCVD) risk and observed 10-year event rates in a rural population participating in cardiovascular health initiative. MethodsThe study included a rural sample of individuals participating in the Heart of New Ulm (HONU), a population-based health initiative aimed at reducing ASCVD risk in a rural community. HONU conducted over 100 baseline screening events with 5221 individuals participating in 2009. For this analysis, we included participants who were aged 40–79 years, free of ASCVD at baseline, and had adequate data to calculate 10-year ASCVD risk. Electronic health record data and state death records were used to determine rates of non-fatal myocardial infarction and stroke, and ASCVD death from 2010–2019. ASCVD event rates were compared to estimated 10-year risks calculated using the Pooled Cohort Equations, stratified by sex and clinically relevant risk categories. ResultsThe sample (n = 2819, mean ± SD age 56.1 ± 9.9 years, 59.6% female) had a low prevalence of tobacco use (8.1% current smokers) and diabetes (6.5%) and a high prevalence of hypertension (44.4%) and hyperlipidemia (56.6%). The median estimated 10-year ASCVD risk for the entire sample was 5.7% (IQR 2.3–13.5%) with an observed 10-year ASCVD event rate of 3.4%. The largest gap between observed and estimated risk was in those at intermediate/high (≥7.5%) ASCVD risk (median 10-year risk 15.8% [IQR 10.4–29.0], observed ASCVD event rate 6.4%). ConclusioIn a sample of rural participants exposed to a multifaceted ASCVD prevention initiative, observed rates of ASCVD were substantially lower compared to estimated ASCVD risk. The potential for significantly lower than predicted ASCVD event rates in certain populations should be included in the clinician-patient risk discussion.

Coronary Artery Calcium Score to Refine the Use of PCSK9i in Asymptomatic Individuals: A Multicohort Study

BackgroundThe value of coronary artery calcium (CAC) in the allocation of PCSK9i (proprotein convertase subtilisin/kexin type 9 inhibitors) among individuals without clinically evident atherosclerotic cardiovascular disease (ASCVD) is unknown for indications that do not require confirmed familial hypercholesterolemia. We aimed to assess the ability of CAC to stratify ASCVD risk under 3 non–familial hypercholesterolemia PCSK9i allocation paradigms.Methods and ResultsWe included participants without clinically evident ASCVD from MESA (Multi‐Ethnic Study of Atherosclerosis), CARDIA (Coronary Artery Risk Development in Young Adults) study, DHS (Dallas Heart Study), and HNR (Heinz Nixdorf Recall) study. Three PCSK9i eligibility scenarios were defined: a broad scenario informed only by high low‐density lipoprotein cholesterol levels (N=567), a restrictive one combining higher low‐density lipoprotein cholesterol levels and presence of ≥2 additional risk factors (N=127), and a high‐risk scenario where individuals with subclinical organ damage or high estimated risk would be treated to achieve low‐density lipoprotein cholesterol <55 mg/dL (N=471). The high‐risk scenario had the highest ASCVD event rates (27.8% at 10 years). CAC=0 was observed in 35% participants in the broad scenario, 25% in the restrictive scenario, and 16% in the high‐risk scenario. In all, CAC=0 was associated with the lowest incident ASCVD rates at 5 and 10 years, and CAC burden was independently associated with ASCVD events adjusting for traditional risk factors.ConclusionsCAC may be used to refine the allocation of PCSK9i, potentially leading to a more conservative use if CAC=0. The value of CAC testing is greater in scenarios that use low‐density lipoprotein cholesterol levels and/or traditional risk factors to define PCSK9i eligibility (CAC=0 present in 1 of 3–4 patients), whereas its prevalence is lower when allocation is informed by presence of noncoronary subclinical organ damage.

Association between REDUCE-IT criteria, coronary artery disease severity, and cardiovascular events: the Western Denmark Heart Registry.

The Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention Trial (REDUCE-IT) trial demonstrated that icosapent ethyl lowered the risk of atherosclerotic cardiovascular disease (ASCVD) among patients with elevated triglycerides. However, how to appropriately implement its use in clinical practice is not well-defined. We aimed to determine whether plaque burden as assessed by coronary artery calcium (CAC) could stratify ASCVD risk among patients eligible for icosapent ethyl. Among 23 759 patients who underwent computed tomography angiography (CTA) in the Western Denmark Heart Registry, we identified eligibility for the REDUCE-IT trial. A total of 2146 participants (9%) met enrolment criteria for REDUCE-IT. During a median of 4.3 years of follow-up, 146 ASCVD events occurred. Overall, there was a stepwise increase in ASCVD event rates per 1000 person-years with increasing CAC (CAC = 0: 10.5, CAC 1-299: 18.7, CAC ≥300: 49.8). REDUCE-IT-eligible patients with CAC ≥300 had a multivariable-adjusted hazard ratio of 3.1 compared with CAC = 0 (95% confidence interval: 1.9-4.9). Coronary artery calcium differentiated risk similarly in patients with and without obstructive coronary artery disease (CAD). Overall, the 5-year estimated number needed to treat to prevent one event with icosapent ethyl was 45 and ranged from 87 in those with CAC = 0 to 17 in those with CAC ≥300. Some patients with non-obstructive CAD had lower estimated number needed to treat than patients with obstructive CAD when their plaque burden was higher. Atherosclerotic plaque burden as assessed by CAC can identify REDUCE-IT-eligible patients who are expected to derive most, and least, absolute benefit from treatment with icosapent ethyl regardless of obstructive versus non-obstructive CAD status.

Coronary Artery Calcium for Risk Assessment in Young Adults.

To review the prognostic significance and clinical utility of coronary artery calcium (CAC) for risk assessment for atherosclerotic cardiovascular disease (ASCVD) in younger adults. Data from over 3000 young adults (mean age of 40.3 ± 3.6 followed for 12.5years) in the CARDIA registry found that in an asymptomatic, community representative sample, there was a low prevalence of CAC (~ 10%) but those with CAC had an exponential increase in CAC over time and significantly higher rates of ASCVD events. Alternatively, data from the CAC consortium analyzed 22,346 asymptomatic individuals undergoing CAC for clinical indications (mean age 43.5 ± 4.5years, followed for 13 ± 4years) and found a much higher prevalence of CAC at 34% with rates of coronary heart disease mortality that varied significantly according to CAC. In younger adults, CAC provides clear prognostic value and can be considered in select individuals with uncertainties about their ASCVD risk or the benefit of preventive therapies.

Abstract 9055: Vascular Age in Patients With Familial Hypercholesterolemia and/or Elevated Lipoprotein(a) Treated With Lipoprotein Apheresis

Introduction: The 2020 ASE guidelines indicate that an average mean carotid intima-media thickness (CIMT) ≥75th percentile for the patient’s age, sex, race/ethnicity is indicative of increased risk of atherosclerotic cardiovascular disease (ASCVD). With each 10 μm/year reduction of CIMT progression there is a relative risk reduction in the ASCVD event rate by 9% (95% confidence interval, 0.87-0.94). Published nomograms of CIMT percentiles determine “vascular age,” defined as the age at which the composite CIMT value for an individual would represent the median value. Hypothesis: Lipid-modifying treatment with lipoprotein apheresis (LA) over the course of 10 years will affect vascular age in patients with baseline elevated CIMT due to severe hypercholesterolemia. Methods: Ten individuals (mean age 60±9 years, 70% female) with familial hypercholesterolemia and/or elevated lipoprotein(a) [Lp(a)] were treated every two weeks with LA (Liposorber, Kaneka, Japan) between 2005 and 2020 (median duration, 12 years). Results: Acute effects of LA included reduction in LDL-C and Lp(a) levels by a median of 72±8% and 75±7%, respectively. The proportion of patients with average mean CIMT ≥75th percentile was 8/10 at the time of apheresis initiation. LA resulted in mean CIMT reduction of –40μm (IQR, –50 to 20). This translated into 70% (7/10) of cases demonstrating composite mean CIMT below their expected vascular age. The follow-up mean CIMT strongly correlated only with the baseline Lp(a) levels. The number of patients with CIMT above their “vascular age” decreased from 80% to 30% over treatment course. The rate of ASCVD was 37.5 per 1000 person-years while on LA. Conclusions: While annual CIMT progression rates average 15 μm/y, an increase in CIMT seen with advanced age and severe hypercholesterolemia was halted with LA with an estimated annual rate of change in mean common CIMT of –4 μm/y and maximum CIMT of –3μm /y. This analysis demonstrates positive impact of LA on vascular age.

Abstract 9969: Determinants of Incident Atherosclerotic Cardiovascular Disease Events Among Individuals with Absent Coronary Artery Calcium: Results from the Multi-Ethnic Study of Atherosclerosis

Introduction: We evaluated whether traditional cardiovascular risk factors are associated with incident atherosclerotic cardiovascular disease (ASCVD) among individuals with absent coronary artery calcium (CAC=0) over long-term follow-up. Methods: We included participants with CAC=0 at baseline from the Multi-Ethnic Study of Atherosclerosis (MESA), a prospective cohort study of individuals free of clinical ASCVD at baseline. After calculating crude event rates, we used multivariable-adjusted Cox proportional hazards models to study the association between cardiovascular risk factors [cigarette smoking, diabetes mellitus, hypertension, preventive medication use (aspirin and statin), family history of premature ASCVD, chronic kidney disease, waist circumference, lipid and inflammatory markers] and adjudicated incident ASCVD events. Results: The study population consisted of 3,416 individuals with CAC=0 (mean (SD) age 58 (9) years; 63% were female, 33% White, 31% Black, 12% Chinese-American, and 24% Hispanic. At a median follow-up of 16 years, there were 189 ASCVD events (101 CHD, 98 stroke). The unadjusted 16-year incidence rates of ASCVD were ≤5 per 1000-person-years among individuals with CAC=0 with the exception of current cigarette smoking (7.30), diabetes mellitus (8.92), hypertension (5.44), and chronic kidney disease (6.75). ASCVD event rates were 6.19 per 1000 person-years among those with estimated baseline ASCVD risk 7.5%–&lt;15% and 5.87 per 1000 person-years among those with estimated ASCVD risk 15%–&lt;20%. After multivariable-adjustment, risk factors that were significantly associated with ASCVD: hazard ratio (HR) 95% confidence interval (CI) included current cigarette smoking: 2.12 (1.32,3.42), diabetes mellitus: 1.68 (1.01,2.80), and hypertension: 1.57 (1.06,2.33). Conclusion: In a middle-age population free of ASCVD at baseline, current cigarette smoking, diabetes mellitus, and hypertension are independently associated with incident ASCVD over 16-year follow-up among those with CAC=0. If considering a long treatment horizon, it may be reasonable to continue to recommend statin therapy in the presence of these risk factors despite the absence of CAC.

Abstract 9891: Are CAC Scores Less Valuable for Patients of Low Socioeconomic Status? A Dallas Heart Study Analysis

Background: Low socioeconomic status (SES) is associated with atherosclerotic cardiovascular disease (ASCVD) and possible underestimation of risk by the pooled cohort equations (PCE). Whether coronary artery calcium (CAC) scores can improve risk discrimination in those with low SES is unknown. Methods: Individuals from the Dallas Heart Study free of ASCVD and with CAC scanning were evaluated. Low SES was defined as an annual income &lt;$16,000 or an educational attainment level ≤11 years. Unadjusted and adjusted analyses assessing the relationships between SES and 1) CAC scores and 2) ASCVD events (fatal or non-fatal MI or stroke) were performed. The incremental predictive value of CAC in those at low and higher SES was assessed using c-statistics (PCE alone vs PCE + CAC). Results: Among 2246 individuals (mean age 44 yrs, 55% women, 45% Black), 115 ASCVD events occurred over a median of 12.5 years. Low SES by income (n=451) was associated with increased risk of ASCVD after adjustment for risk factors (HR 2.16, 95% CI 1.37-3.42), but was not independently associated with CAC. Higher CAC scores (0, 1-99, ≥100) tracked with increased 10-year ASCVD event rates in those at low (5, 10, and 22%) and higher SES (0.002, 4, and 11%), with low SES groups carrying greater ASCVD risk for every stratum of CAC, including with CAC=0. In multivariable models compared with CAC=0, those with CAC 1-99 and ≥100 had a greater risk of ASCVD events for individuals at higher SES [HR 3.40 (1.5-7.8), and 4.8 (1.9-12.6)], but not for those with low SES [HR 1.00 (0.4-2.4), and 1.6 (0.6-4.6)], (p-interaction CAC x SES=0.002). Similar results were found for low SES defined by education. The addition of CAC to PCE improved risk discrimination for individuals at higher SES, but not for individuals at low SES (Table 1). Conclusion: Individuals at low SES have significantly increased risk of ASCVD, however, CAC scores are not independently associated with ASCVD in this population and may be less useful in risk discrimination.

Assessment and management of the heightened risk for atherosclerotic cardiovascular events in patients with lupus erythematosus or dermatomyositis.

For patients with lupus erythematosus (LE) or dermatomyositis (DM), there is an urgent need to address a heightened risk of clinical events, chiefly heart attacks and strokes, caused by atherosclerotic cardiovascular disease (ASCVD). Patients with LE or DM frequently exhibit high levels of conventional risk factors for ASCVD events, particularly dyslipoproteinemia and hypertension; an amplified burden of atherosclerotic plaques; and increased age- and sex-adjusted rates of ASCVD events compared with the general population. The rate of ASCVD events exceeds what would be expected from conventional risk factors, suggesting that disease-specific autoimmune processes exacerbate specific, known pathogenic steps in atherosclerosis. Importantly, despite their heightened risk, patients with LE or DM are often undertreated for known causative agents and exacerbators of ASCVD. Herein, we propose an approach to assess and manage the heightened risk of ASCVD events in patients with LE or DM. Our approach is modeled in large part on established approaches to patients with diabetes mellitus or stage 3 or 4 chronic kidney disease, which are well-studied conditions that also show heightened risk for ASCVD events and have been explicitly incorporated into standard clinical guidelines for ASCVD. Based on the available evidence, we conclude that patients with LE or DM require earlier and more aggressive screening and management of ASCVD. We suggest that physicians consider implementing multipliers of conventional risk calculators to trigger earlier initiation of lifestyle modifications and medical therapies in primary prevention of ASCVD events, employ vascular imaging to quantify the burden of subclinical plaques, and treat to lower lipid targets using statins and newer therapies, such as PCSK9 inhibitors, that decrease ASCVD events in nonautoimmune cohorts. More clinical vigilance is needed regarding surveillance, prevention, risk modification, and treatment of dyslipidemias, hypertension, and smoking in patients with LE or DM. All of these goals are achievable.

Atherosclerotic Cardiovascular Disease Events in Adults With CKD Taking a Moderate- or High-Intensity Statin: The Chronic Renal Insufficiency Cohort (CRIC) Study

Rationale & ObjectiveThe 2018 American Heart Association/American College of Cardiology (AHA/ACC) cholesterol guideline uses risk stratification to guide the decision to initiate nonstatin lipid-lowering medication among adults with atherosclerotic cardiovascular disease (CVD). We determined atherosclerotic CVD (ASCVD) event rates among adults with chronic kidney disease (CKD) taking statin therapy within 2018 AHA/ACC cholesterol guideline risk categories.Study DesignObservational cohort study.Setting & ParticipantsAdults with CKD not on dialysis in the Chronic Renal Insufficiency Cohort (CRIC) study who were taking a moderate/high-intensity statin 1 year after enrollment (baseline for the current analysis, n = 1,753).Exposure2018 AHA/ACC cholesterol guideline risk categories: without a history of ASCVD, a history of 1 major ASCVD event and multiple high-risk conditions, and a history of ≥2 major ASCVD events.OutcomeAdjudicated ASCVD events after the year 1 study visit.Analytical ApproachWe calculated age-sex standardized rates for ASCVD events and age-sex adjusted hazard ratios for ASCVD events accounting for the competing risk of death.ResultsThere were 394 ASCVD events over a median follow-up period of 8 years. The ASCVD event rates (with 95% CI) per 1,000 person-years among participants without a history of ASCVD, with a history of 1 major ASCVD event and multiple high-risk conditions, and with a history of ≥2 major ASCVD events were 21.7 (18.4-25.1), 45.0 (37.8-52.3), and 73.3 (53.3-93.4), respectively. Compared with participants without a history of ASCVD, the HR (95% CI) rates for ASCVD events among those with a history of 1 major ASCVD event and multiple high-risk conditions, and with a history of ≥2 major ASCVD events were 1.89 (1.52-2.36) and 2.50 (1.85-3.39), respectively.LimitationsData on whether participants were taking a maximally tolerated statin dosage were unavailable.ConclusionsThe 2018 AHA/ACC cholesterol guideline identifies adults with CKD who have very high ASCVD risk despite taking a moderate/high-intensity statin.

Atherosclerotic cardiovascular disease events among statin eligible individuals with and without long-term healthy arterial aging

Background and aimsA large proportion of statin eligible candidates have a baseline absence of coronary artery calcium (CAC) and low 10-year atherosclerotic cardiovascular disease (ASCVD) risk. We sought to determine the proportion of statin eligible individuals who had long-term healthy arterial aging (persistent CAC = 0) and their examined 15-year ASCVD outcomes. MethodsWe included 561 statin eligible candidates from the Multi-Ethnic Study of Atherosclerosis who were not on statin therapy with CAC = 0 at Visit 1 (2000-02) and underwent a subsequent CAC scan at Visit 5 (2010-11). Adjusted Cox proportional hazards regression assessed the association between persistent CAC = 0 and ASCVD events over 15.9 years. ResultsParticipants were on average 61.7 years old, 50% were women, and 43% maintained long-term CAC = 0. Individuals with an LDL-C ≥190 mg/dL (54%) and those with an ASCVD risk ≥20% (33%) had the highest and lowest proportion of persistent CAC = 0, respectively. There were 57 ASCVD events, and 15-year ASCVD event rates were low for individuals with and without healthy arterial aging (4.3 versus 8.6 per 1,000 persons-years), but the 10-year number needed to treat to prevent one ASCVD event differed by more than two fold (117 versus 54). In multivariable modeling, persistent CAC = 0 conferred a 51% lower risk of ASCVD compared to those with incident CAC (HR = 0.49, 95% CI: 0.27–0.90, p=0.02). ConclusionsMore than 40% of statin eligible individuals with baseline CAC = 0 had long-term healthy arterial aging. Statin eligible candidates with persistent CAC = 0 had a very low 15-year ASCVD risk, suggesting that statin therapy may be of limited benefit among this group of individuals.

Relation of First and Total Recurrent Atherosclerotic Cardiovascular Disease Events to Increased Lipoprotein(a) Levels Among Statin Treated Adults With Cardiovascular Disease

The relation between elevated lipoprotein(a) and total atherosclerotic cardiovascular disease (ASCVD) residual risk in persons with known cardiovascular disease on statin therapy is not well-established. We examined first and total recurrent ASCVD event risk in statin-treated adults with prior ASCVD. We studied 3,359 adults (mean age 63.6 years, 85.1% male) with prior ASCVD on statin therapy from the AIM-HIGH clinical trial cohort. The first and total ASCVD event rates were calculated by lipoprotein(a) [Lp(a)] categories. Cox regression and Prentice, Williams and Peterson (PWP) models provided hazard ratios (HRs) for ASCVD events over a mean follow-up of 3.3 years, adjusted for age, gender, trial treatment, LDL-C, and other risk factors. A total of 747 events occurred during follow-up, among which 544 were first events. First and total ASCVD event rates were greater with higher Lp(a) levels. Compared with Lp(a)<15 mg/dL, HRs (95% CIs) for subsequent total ASCVD events among Lp(a) levels of 15-<30, 30-<50, 50-<70, and ≥70 mg/dL were 1.04 (0.82 to 1.32), 1.15 (0.88 to 1.49), 1.27 (1.00 to 1.63) and 1.51 (1.25 to 1.84). Moreover, a continuous relation for total events was observed (HR=1.08 [1.04 to 1.12] per 20 mg/dL greater Lp(a). Findings for first ASCVD events and in those with LDL-C ≥70 mg/dL versus <70 mg/dL and with and without diabetes were similar. The risk of first and total ASCVD events is increased with Lp(a) levels of ≥70 mg/dL and ≥50 mg/dL, respectively, among adults with known CVD on statin therapy.

Age-Related Variation in Cardiovascular Risk Associated With Red Cell Distribution Width

We previously showed that routine indicators of immune-hematologic function are strongly associated with all-cause and cardiovascular mortality, especially among older adults, in whom traditional atherosclerotic cardiovascular disease (ASCVD) risk factors predict poorly. The objective of this study was to quantify differences in the relationship between red cell distribution width (RDW) and 5-year risk of ASCVD events (stroke, myocardial infarction or cardiovascular death) as a function of age and the area deprivation index (ADI). We analyzed electronic health records of 76287 Cuyahoga County, Ohio residents who were over age 40 and who visited Cleveland Clinic Health System and/or MetroHealth System in two consecutive years between 2005 and 2015, the latter of which served as the index/baseline. Multivariable Cox regression was used, adjusting for sex, race/ethnicity, diabetes, systolic blood pressure and antihypertensive use. Generally, RDW levels in disadvantaged neighborhoods corresponded to people 15-20 years older from affluent neighborhoods. In a main-effects-only model, we found higher ASCVD event rates associated with age (hazard ratio [95% confidence interval] per 10 year increment: 1.34 [1.32–1.35]), ADI (top vs. bottom quintile: 1.30 [1.24–1.36]) and RDW (>16% vs ≤13%: 2.03 [1.94–2.12]). Age and RDW exhibited a synergistic interaction (χ2 = 17.7 on 2 df, p<0.001), with slightly larger RDW effects associated with increasing age, while evidence of differential RDW effects across ADI quintiles was weak (χ2 = 12.9 on 8 df, p=0.11). We conclude that RDW effects on ASCVD event risk are large, independent from traditional ASCVD risk factors and increase with advancing age.

Can the Absence of Hypertension Refine the Risk Assessment of Older Adults for Future Cardiovascular Events?

We sought to determine if the absence of hypertension in older adults can be used to identify those at lower risk of atherosclerotic cardiovascular disease (ASCVD). We identified participants ≥75 years old free of cardiovascular disease (CVD) in the National Institutes of Health Pooled Cohorts with and without hypertension. We assessed the association between systolic blood pressure (BP), diastolic BP, and cardiovascular events using multivariable modeling. The association between predicted ASCVD risk and observed events was compared. Of 2,667 adults aged ≥75 years, 67.9% had hypertension. Lower systolic BP correlated with lower CVD event rates. ASCVD predicted risk score and systolic BP were both independently associated with ASCVD event rates. Among adults with similar ASCVD predicted risk estimates, those without (vs with) hypertension had lower observed event rates across the predicted risk spectrum. The absence of hypertension may help refine the risk stratification of older adults, particularly those with intermediate predicted risk.

Estimation of Atherosclerotic Cardiovascular Disease Risk Among Patients in the Veterans Affairs Health Care System

Current guidelines recommend statin therapy for millions of US residents for the primary prevention of atherosclerotic cardiovascular disease (ASCVD). It is unclear whether traditional prediction models that do not account for current widespread statin use are sufficient for risk assessment. To examine the performance of the Pooled Cohort Equations (PCE) for 5-year ASCVD risk estimation in a contemporary cohort and to test the hypothesis that inclusion of statin therapy improves model performance. This cohort study included adult patients in the Veterans Affairs health care system without baseline ASCVD. Using national electronic health record data, 3 Cox proportional hazards models were developed to estimate 5-year ASCVD risk, as follows: the variables and published β coefficients from the PCE (model 1), the PCE variables with cohort-derived β coefficients (model 2), and model 2 plus baseline statin use (model 3). Data were collected from January 2002 to December 2012 and analyzed from June 2016 to March 2020. Traditional ASCVD risk factors from the PCE plus baseline statin use. Incident ASCVD and ASCVD mortality. Of 1 672 336 patients in the cohort (mean [SD] baseline age 58.0 [13.8] years, 1 575 163 [94.2%] men, 1 383 993 [82.8%] white), 312 155 (18.7%) were receiving statin therapy at baseline. During 5 years of follow-up, 66 605 (4.0%) experienced an ASCVD event, and 31 878 (1.9%) experienced ASCVD death. Compared with the original PCE, the cohort-derived model did not improve model discrimination in any of the 4 age-sex strata but did improve model calibration. The PCE overestimated ASCVD risk compared with the cohort-derived model; 211 237 of 1 136 161 white men (18.6%), 29 634 of 218 463 black men (13.6%), 1741 of 44 399 white women (3.9%), and 836 of 16 034 black women (5.2%) would be potentially eligible for statin therapy under the PCE but not the cohort-derived model. When added to the cohort-derived model, baseline statin therapy was associated with a 7% (95% CI, 5%-9%) lower relative risk of ASCVD and a 25% (95% CI, 23%-28%) lower relative risk for ASCVD death. In this study, lower than expected rates of incident ASCVD events in a contemporary national cohort were observed. The PCE overestimated ASCVD risk, and more than 15% of patients would be potentially eligible for statin therapy based on the PCE but not on a cohort-derived model. In the statin era, health care professionals and systems should base ASCVD risk assessment on models calibrated to their patient populations.

Atherosclerotic Risk and Statin Use Among Patients With Peripheral Artery Disease

BackgroundPeripheral artery disease (PAD) is associated with increased risk for atherosclerotic cardiovascular disease (ASCVD) events. ObjectivesThe goal of this study was to compare the risk for ASCVD events and the use of statins among patients with PAD versus those with coronary heart disease (CHD) or cerebrovascular disease. MethodsThe authors conducted a retrospective cohort study of adults age ≥19 years with commercial or Medicare health insurance who had a history of PAD, CHD, or cerebrovascular disease on December 31, 2014. Patients were followed for ASCVD events comprising CHD, cerebrovascular disease, and PAD events until December 31, 2017. ResultsAmong 943,232 patients included in the analysis, the age-standardized ASCVD event rate per 1,000 person-years for those with a history of 1, 2, and 3 conditions including PAD, CHD, and cerebrovascular disease was 40.8 (95% confidence interval [CI]: 40.3 to 41.3), 68.9 (95% CI: 67.9 to 70.0), and 119.5 (95% CI: 117.0 to 122.0), respectively. The ASCVD event rate among patients with PAD only, CHD only, and cerebrovascular disease only was 34.7 (95% CI: 33.2 to 36.2), 42.2 (95% CI: 41.5 to 42.8), and 38.9 (95% CI: 37.6 to 40.1), respectively. Among patients with PAD and CHD, with PAD and cerebrovascular disease, and with CHD and cerebrovascular disease, the ASCVD event rate was 72.8 (95% CI: 71.0 to 74.7), 63.9 (95% CI: 60.6 to 67.4), and 67.9 (95% CI: 66.4 to 69.3), respectively. Statin use was lower in patients with PAD only (33.9%) versus those with cerebrovascular disease only (43.0%) or CHD only (51.7%). ConclusionsDespite having high risk for ASCVD events, patients with PAD were less likely to be taking a statin versus those with CHD or cerebrovascular disease. ASCVD risk-reduction interventions including statin therapy in patients with PAD are warranted.