Lipoprotein (a) Testing in Patients With Atherosclerotic Cardiovascular Disease in 5 Large US Health Systems.

BACKGROUND: Lipoprotein (a) is an independent risk factor for atherosclerotic cardiovascular disease. However, lipoprotein (a) testing remains variable and it is unclear what factors influence testing and if testing changes clinical management. METHODS AND RESULTS: A retrospective study using electronic medical record data from 5 health systems identified an atherosclerotic cardiovascular disease cohort divided into those with and without a lipoprotein (a) test between 2019 and 2021. Baseline characteristics and lipid-lowering therapy patterns were assessed. Multivariable regression modeling was used to determine factors associated with lipoprotein (a) testing. Among 595 684 patients with atherosclerotic cardiovascular disease, only 2587 (0.4%) were tested for lipoprotein (a). Those who were older or Black individuals were less likely to have lipoprotein (a) testing, while those with familial hypercholesterolemia, ischemic stroke/transient ischemic attack, peripheral artery disease, prior lipid-lowering therapy, or low-density lipoprotein cholesterol ≥130 mg/dL were more likely to be tested. Those with a lipoprotein (a) test, regardless of the lipoprotein (a) value, were more frequently initiated on any statin therapy (30.3% versus 10.6%, P < 0.001), ezetimibe (7.65% versus 0.8%, P < 0.001), or proprotein convertase substilisin/kexin type 9 inhibitor (6.7% versus 0.3%, P < 0.001) compared with those without a test. Those with an elevated lipoprotein (a) level more frequently initiated ezetimibe (11.5% versus 5.9%, P < 0.001) or proprotein convertase substilisin/kexin type 9 inhibitor (10.9% versus 4.8%, P < 0.001). CONCLUSIONS: Lipoprotein (a) testing in patients with atherosclerotic cardiovascular disease is infrequent, with evidence of disparities among older or Black individuals. Testing for lipoprotein (a), regardless of level, is associated with greater initiation of any lipid-lowering therapy, while elevated lipoprotein (a) is associated with greater initiation of nonstatin lipid-lowering therapy. There is a critical need for multidisciplinary and inclusive approaches to raise awareness for lipoprotein (a) testing, and its implications on management.

Real-World Exploration of LDL-Cholesterol Management in Patients with Atherosclerotic Cardiovascular Disease.

BACKGROUND: Although guidelines recommend low-density lipoprotein cholesterol (LDL-C) to be <70mg/dL in patients with atherosclerotic cardiovascular disease (ASCVD), the rate of achieving this goal remains suboptimal. We sought to understand real world contemporary practice patterns of LDL-C management in patients with ASCVD, and whether LDL-C testing influenced management across US health systems. METHODS: A retrospective cohort study utilizing electronic medical record data from five health systems participating in the CardioHealth Alliance was performed on patients with an LDL-C measurement in 2021 and prior ASCVD. Multivariable regression modeling was used to determine the relationship of clinical factors with achievement of guideline directed LDL-C target. Changes in lipid lowering therapy (LLT) after LDL-C testing were also described. RESULTS: Among 216,074 patients with ASCVD, 129,886 (60.1%) had uncontrolled LDL-C (i.e. ≥70 mg/dL). Compared with participants with controlled LDL-C (<70mg/dL), those with uncontrolled LDL-C were more frequently female (50.9% vs 35.1%), or Black (13.7% vs. 10.3%), and less commonly had coronary artery disease as the form of vascular disease (73.0% vs. 83.5% %), heart failure (21.3% vs. 29.1% %), diabetes (34.1% vs. 48.2%), atrial fibrillation (19.3% vs. 26.1%), or chronic kidney disease (25.1% vs. 32.2%). In multivariable analyses, the factors most strongly associated with failure to achieve LDL-C control were female sex (RR 1.13 [95% CI 1.12-1.14] p <0.001) and Black race (1.15 [1.14-1.17] p <0.001). Among the 53,957 (41.5%) of those with uncontrolled LDL-C ≥70 mg/dL not on lipid lowering therapy (LLT) at baseline, only 21% were initiated on any LLT within 6 months of the uncontrolled LDL-C value. CONCLUSIONS: Within five diverse large health systems in the CardioHealth Alliance, more than half of the patients with ASCVD had uncontrolled LDL-C with significant disparities based on sex and race at baseline. The vast majority were not initiated on any lipid lowering therapy within 6 months of an elevated test result indicating persistent gaps in care that will likely worsen health inequities in outcomes. This highlights the urgent need for implementation efforts to improve equitable care.

Long term association of low-density lipoprotein subtypes with coronary artery calcium score and atherosclerotic cardiovascular disease events: Insights from HeartSCORE study.

INTRODUCTION: Elevated low-density lipoprotein (LDL) cholesterol is associated with risk of atherosclerotic cardiovascular disease (ASCVD). However, the association of midlife LDL subtypes in long-term clinical and subclinical ASCVD remains unknown. OBJECTIVE: We examine LDL pattern associations with subclinical ASCVD. METHODS: LDL subtypes were assessed in the Heart Strategies Concentrating on Risk Evaluation (Heart SCORE) study participants. Baseline coronary artery calcium (CAC) scores were calculated and long-term ASCVD events were assessed. Adjusted odds ratios and hazard ratios (95 % CI) were calculated to estimate the independent association between LDL patterns and CAC and ASCVD events, stratified by sex and race. RESULTS: 1,884 participants (age 59 ± 7.5 years. 66 % women, 44 % Black) were involved in the survival analysis; a subset of 740 (age 60.7 ± 7.3 years, 44 % women and 47 % Black) had their CAC score assessed. Men and Black individuals with LDL pattern AB had higher odds for positive CAC score (ORmen,patternAB = 2.47, 95 % CI [1.11-5.58]). Individuals with LDL patterns B (HR = 1.98, 95 % CI [1.22-3.21]; p-value < 0.05) and AB (HR = 1.54, 95 % CI of [1.00-2.38]; p-value < 0.05) were at a higher risk of ASCVD events. Self-identified Black individuals with type B and AB had higher risk of ASCVD events. CONCLUSIONS: In cohort of Black and White community dwellers, LDL patterns B and AB showed a higher risk of ASCVD events. Pattern AB was associated with positive CAC in men and Black individuals. Further studies investigating LDL patterns in ASCVD risk based on race and sex are needed to drive precise preventive strategies for ASCVD.

Impact of Guideline-Directed Statin Prescriptions on Cardiovascular Outcomes by Race in a Real-World Primary Prevention Cohort.

Background: Data on real-world statin prescription in large, private health care networks and impacts on primary prevention of atherosclerotic cardiovascular disease (ASCVD) outcomes across race are scarce. Objectives: The purpose of this study was to investigate the impact of statin prescription on ASCVD outcomes within and across race in a large, nongovernmental health care system. Methods: Statin prescription in Black and White patients without ASCVD was evaluated (2013-2019). Guideline-directed statin intensity was defined as at least "moderate" for intermediate and high-risk patients. Statin prescription at index and ASCVD outcomes at follow-up (myocardial infarction/revascularization, stroke, mortality) were assessed via electronic health care records using International Classification of Diseases-9 and 10 codes. Cox regression models, adjusted for CVD risk factors, were used to calculate HRs for association between statin prescription and incident ASCVD events across race. Results: Among 270,079 patients, 7.6% (n = 20,477) and 92.4% (n = 249,602) identified as Black and White, respectively. Significantly fewer Black patients were prescribed statin therapy than White patients (13.6% vs 19.0%; P < 0.001). At a mean follow-up of 6 years, patients with "no statin" prescription vs guideline-directed statin intensity showed increased ASCVD in Black patients (HR: 1.40 [95% CI: 1.05-1.86]), and White patients (HR: 1.32 [95% CI: 1.21-1.45]; P < 0.05) and all-cause mortality. Intermediate and high-risk Black patients faced a 17% higher risk of mortality compared to White patients. However, the interaction between race and statin prescription was not a significant predictor of incident ASCVD events. Conclusions: Statins remain underprescribed. Although Black patients received proportionally less statin prescription than White patients, this was not associated with higher risk of mortality in Black patients.

Early Onset Atherosclerotic Cardiovascular Disease.

Recent trends indicate a concerning increase in early-onset atherosclerotic cardiovascular disease (ASCVD) among younger individuals (age < 55 in men and <65 in women). These findings highlight the pathobiology of ASCVD as a disease process that begins early in life and underscores the need for more tailored screening methods and preventive strategies. Increasing attention has been placed on the growing burden of traditional cardiometabolic risk factors in young individuals while also recognizing unique factors that mediate risk of premature atherosclerosis in this demographic such as substance use, socioeconomic disparities, adverse pregnancy outcomes, and chronic inflammatory states that contribute to the increasing incidence of early ASCVD. Additionally, mounting evidence has pointed out significant disparities in the diagnosis and management of early ASCVD and cardiovascular outcomes based on sex and race. Moving toward a more personalized approach, emerging data and technological developments using diverse tools such as polygenic risk scores and coronary artery calcium scans have shown potential in earlier detection of ASCVD risk. Thus, we review current evidence on causal risk factors that drive the increase in early ASCVD and highlight emerging tools to improve ASCVD risk assessment in young individuals.

Sex-based utilization of guideline recommended statin therapy and cardiovascular disease outcomes: Data from a multisite healthcare network primary prevention cohort.

Background: In the US, women have similar cardiovascular death rates as men. However, less is known about sex differences in statin use for primary prevention and associated atherosclerotic cardiovascular disease (ASCVD) outcomes. Methods: Statin prescriptions using electronic health records were examined in patients without ASCVD (myocardial infarction (MI), revascularization or ischemic stroke) between 2013 and 2019. Guideline-directed statin intensity (GDSI) at index (at least moderate intensity, defined per pooled-cohort equation) and follow-up visits were compared between sexes across ASCVD risk groups, defined by the pooled-cohort equation. Cox regression hazard ratios were calculated for statin use and outcomes (myocardial infarction, stroke/transient ischemic attack (TIA), and all-cause mortality) stratified by sex. Interaction terms (statin and sex) were applied. Results: Among 282,298 patients, (mean age ∼ 50 years) 17.1 % women and 19.5 % men were prescribed any statin at index visit. Time to GDSI was similar between sexes, but the proportion of high-risk women on GDSI at follow-up were lower compared to high-risk men (2-years: 27.7 vs 32.0 %, and 5-years: 47.2 vs 55.2 %, p < 0.05). When compared to GDSI, no statin use was associated with higher risk of MI and ischemic stroke/TIA among both sexes. High-risk women on GDSI had a lower risk of mortality (HR=1.39 [1.22-1.59]) vs. men (HR=1.67 [1.50-1.86]) of similar risk (p value interaction=0.004). Conclusion: In a large contemporary healthcare system, there was underutilization of statins across both sexes in primary prevention. High-risk women were less likely to remain on GDSI compared to high-risk men. GDSI significantly improved the survival in both sexes regardless of ASCVD risk group. Future strategies to ensure continued use of GDSI, specifically among women, should be explored.

Statin utilization and cardiovascular outcomes in a real-world primary prevention cohort of older adults.

Background: Statins are a cost-effective therapy for prevention of atherosclerotic cardiovascular disease (ASCVD). Guidelines on statins for primary prevention are unclear for older adults (>75 years). Objective: Investigate statin utility in older adults without ASCVD events, by risk stratifying in a large healthcare network. Methods: We included 8,114 older adults, without CAD, PVD or ischemic stroke. Statin utilization based on ACC/AHA 10-year ASCVD risk calculation, was evaluated in intermediate (7.5%-19.9%) and high-risk patients (≥ 20%); and categorized using low and 'moderate or high' intensity statins with a follow up period of ∼7 years. Cox regression models were used to calculate hazard ratios for incident ASCVD and mortality across risk categories stratified by statin utilization. Data was adjusted for competing risk using Elixhauser Comorbidity Index. Results: Compared with those on moderate or high intensity statins, high-risk older patients not on any statin had a significantly increased risk of MI [HR 1.51 (1.17-1.95); p<0.01], stroke [HR 1.47 (1.14-1.90); p<0.01] and all-cause mortality [HR 1.37 (1.19-1.58); p<0.001] in models adjusted for Elixhauser Comorbidity Index. When comparing the no statin group versus the moderate or high intensity statin group in the intermediate risk cohort, although a trend for increased risk was seen, it did not meet statistical significance thresholds for MI, stroke or all-cause mortality. Conclusion: Lack of statin use was associated with increased cardiovascular events and mortality in high-risk older adults. Given the benefits appreciated, statin use may need to be strongly considered for primary ASCVD prevention among high-risk older adults. Future studies will assess the risk-benefit ratio of statin intervention in older adults.

Apolipoprotein E and Alzheimer's disease pathology in African American older adults.

The apolipoprotein-E4 (APOE*4) and apolipoprotein-E2 (APOE*2) alleles are more common in African American versus non-Hispanic white populations, but relationships of both alleles with Alzheimer's disease (AD) pathology among African American individuals are unclear. We measured APOE allele and ß-amyloid (Aß) and tau using blood samples and positron emission tomography (PET) images, respectively. Individual regression models tested associations of each APOE allele with Aß or tau PET overall, stratified by racialized group, and with a racialized group interaction. We included 358 older adults (42% African American) with Aß PET, 134 (29% African American) of whom had tau PET. APOE*4 was associated with higher Aß in non-Hispanic white (P < 0.0001), but not African American (P = 0.64) participants; racialized group modified the association between APOE*4 and Aß (P < 0.0001). There were no other racialized group differences. These results suggest that the association of APOE*4 and Aß differs between African American and non-Hispanic white populations. Other drivers of AD pathology in African American populations should be identified as potential therapeutic targets.

Sex-Based Utilization of Guideline Recommended Statin Therapy and Cardiovascular Disease Outcomes: A Primary Prevention Healthcare Network Registry.

Background: In the US, women have similar cardiovascular death rates than men. Less is known about sex differences in statin use for primary prevention and associated atherosclerotic cardiovascular disease (ASCVD) outcomes. Methods: Statin prescriptions using electronic health records were examined in patients without ASCVD (myocardial infarction (MI), revascularization or ischemic stroke) between 2013-2019. Guideline-directed statin intensity (GDSI) at index and follow-up visits were compared among sexes across ASCVD risk groups, defined by pooled-cohort equation. Cox regression hazard ratios (HR) [95% CI] were calculated for statin use and outcomes (myocardial infarction, stroke/transient ischemic attack (TIA), and all-cause mortality) stratified by sex. Interaction terms (statin and sex) were applied. Results: Among 282,298 patients, (mean age ∼ 50 years) 17.1% women and 19.5% men were prescribed any statin at index visit. Time to GDSI was similar between sexes, but the proportion of high-risk women on GDSI at follow-ups was lower compared to high-risk men (2-years: 27.7 vs 32.0%, and 5-years: 47.2 vs 55.2%, p<0.05). When compared to GDSI, no statin use was associated with higher risk of MI and ischemic stroke/TIA amongst both sexes. High-risk women on GDSI had a lower risk of mortality (HR=1.39 [1.22-1.59]) versus men (HR=1.67 [1.50-1.86]) of similar risk (p value interaction=0.004). Conclusion: In a large contemporary healthcare system, there was underutilization of statins across both sexes in primary prevention. High-risk women were less likely to be initiated on GDSI compared with high-risk men. GDSI significantly improved the survival in both sexes regardless of ASCVD risk group. Future strategies to ensure continued use of GDSI, specifically among women, should be explored.

Cardiovascular Disease and Alzheimer's Disease: The Heart-Brain Axis.

Cardiovascular disease (CVD) remains one of the leading causes of morbidity and mortality in aging adults across the United States. Prior studies indicate that the presence of atherosclerosis, the pathogenic basis of CVD, is linked with dementias. Alzheimer's disease (AD) and AD-related dementias are a major public health challenge in the United States. Recent studies indicate that ≈3.7 million Americans ≥65 years of age had clinical AD in 2017, with projected increases to 9.3 million by 2060. Treatment options for AD remain limited. Development of disease-modifying therapies are challenging due, in part, to the long preclinical window of AD. The preclinical incubation period of AD starts in midlife, providing a critical window for identification and optimization of AD risk factors. Studies link AD with CVD risk factors such as hypertension, inflammation, and dyslipidemia. Both AD and CVD are progressive diseases with decades-long development periods. CVD can clinically manifest several years earlier than AD, making CVD and its risk factors a potential predictor of future AD. The current review focuses on the state of literature on molecular and metabolic pathways modulating the heart-brain axis underlying the potential association of midlife CVD risk factors and their effect on AD and related dementias. Further, we explore potential CVD/dementia preventive strategies during the window of opportunity in midlife and the future of research in the field in the multiomics and novel biomarker use era.

Impact of Guideline-Directed Statin Intervention for Primary Prevention in Patients With Diabetes.

OBJECTIVE: We examined guideline-directed statin intensity (GDSI) use and atherosclerotic cardiovascular disease (ASCVD) outcomes in patients with diabetes across a contemporary health care system. RESEARCH DESIGN AND METHODS: Patients without preexisting ASCVD were categorized by diabetes status and 10-year ASCVD risk (borderline [5-7.4%], intermediate [7.5-19.9%], high [≥20%]). Mean ±SD time to start of or change to GDSI was calculated. Incident ASCVD and all-cause mortality association, stratified by ASCVD risk, was calculated using Cox regression. RESULTS: Among 282,298 patients, 28,807 (10.2%) had diabetes and 253,491 (89.8%) did not. Only two-thirds of intermediate- and high-risk patients with diabetes were receiving GDSI therapy at 5-year follow-up. In fully adjusted models, patients with diabetes not taking a statin (vs. GDSI) had a significantly higher risk of stroke and mortality in the intermediate- and high-risk groups (hazard ratio for mortality 1.81 [95% CI 1.58-2.07] vs. 1.41 [1.26-1.57]; P for interaction < 0.01). CONCLUSIONS: Significant gaps remain in GDSI use for high-risk patients with diabetes, conferring an increased risk of ASCVD outcomes and all-cause mortality.

Dietary Effects on Monocyte Phenotypes in Subjects With Hypertriglyceridemia and Metabolic Syndrome.

In patients with hypertriglyceridemia, a short-term low-saturated fat vs high-saturated fat diet induced lower plasma lipids and improved monocyte phenotypes. These findings highlight the role of diet fat content and composition for monocyte phenotypes and possibly cardiovascular disease risk in these patients. (Effects of Dietary Interventions on Monocytes in Metabolic Syndrome; NCT03591588).

With Current Safety and Efficacy Data, Should Statins Be Made Available as Nonprescription Over-the-Counter Drugs?

PURPOSE OF REVIEW: Statins inhibit the enzyme 3-hydroxy-3-methylglutaryl-coenzyme A reductase in the liver and reduce atherosclerotic cardiovascular disease (ASCVD) risk by enhancing low-density lipoprotein (LDL) clearance from the circulation. In this review, we discuss their efficacy, safety, and real-world utilization to make a case for reclassifying statins as nonprescription over-the-counter drugs to improve access and availability with the overarching goal of increasing statin utilization in patients most likely to benefit from this class of therapy. RECENT FINDINGS: Statin efficacy for reducing risk in primary and secondary ASCVD prevention populations as well as their safety and tolerability has been thoroughly investigated in large-scale clinical trials over the past 3 decades. Despite the overwhelming scientific evidence, statins are underutilized even among those at the highest ASCVD risk. We propose a nuanced approach to use statins as nonprescription drugs that leverages a multi-disciplinary clinical model. It integrates lessons learned from experiences outside the USA with a proposed Food and Drug Administration rule change that allows nonprescription drug products with an additional condition for nonprescription use.

Racial/Ethnic Disparities and Determinants of Sufficient Physical Activity Levels.

Introduction: Adequate physical activity is an integral requirement for achieving cardiovascular health. Physical inactivity is the fourth leading cause of death worldwide. Hence, it is important to identify racial/ethnic groups that are less likely to achieve sufficient physical activity levels, and to address barriers to meeting physical activity requirements. Methods: Cross-sectional data from the 2006-2015 National Health Interview Survey (NHIS) were used to compare self-reported sufficient physical activity among different racial/ethnic groups: non-Hispanic (NH) Whites, NH Blacks, NH Asians, and Hispanics in the United States. Sufficient physical activity was defined as ≥ 150 minutes per week of moderate-intensity physical activity, ≥ 75 minutes per week of vigorous-intensity physical activity, or ≥ 150 minutes per week of moderate and vigorous physical activity. Results: The study sample consisted of 296,802 individuals, mean age ± standard error age 46.4 ± 0.10 years, 52% women, 70% NH White, 12% NH Black, 5% NH Asian, and 14% Hispanic. The prevalence of sufficient physical activity in the overall population was 46%, while it was 48% among NH Whites, 39% among NH Blacks, 45% among NH Asians, and 40% among Hispanics. In multivariable-adjusted models (odds ratio; 95% confidence interval), NH Blacks (0.79; 0.64,0.97), NH Asians (0.72; 0.62,0.85) and Hispanics (0.71; 0.61,0.82) were significantly less likely to engage in sufficient physical activity compared with NH Whites. Older age, women, and low income were inversely associated with sufficient physical activity, while a college education or higher was associated directly with it. Conclusions: NH Black and Asian Americans and Hispanic adults were less likely to engage in sufficient physical activity levels compared with Whites. It is important to address barriers to meeting physical activity thresholds to help achieve optimal cardiovascular health.

PCSK9 Inhibitors in the Management of Cardiovascular Risk: A Practical Guidance.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors are potent medications in the toolkit for treatment of atherosclerotic cardiovascular disease. These agents have been well studied in clinical trials supporting their efficacy in dramatically reducing low-density lipoprotein cholesterol (LDL-C) and impact on cardiovascular outcomes. Since the approval of commercial use for PCSK9 inhibitors in 2015, we have also gained significant experience in the use of these therapeutics in the real-world setting. In this article, we review current guideline recommendations, clinical trial evidence on efficacy and safety as well as data on cost-effectiveness, prescription and adherence. We focus primarily on the monoclonal antibody class of PCSK9 inhibitors in this review while also touching on other types of therapeutics that are under development.

Lipoprotein(a) and ethnicities.

The initial studies focusing on lipoprotein(a) [Lp(a)] and its role in atherosclerotic cardiovascular disease were conducted exclusively in Whites. Subsequently, multiple large-scale, independent investigations have established clear race/ethnic differences in plasma Lp(a) concentration and population distribution over the last four decades. Blacks have the highest Lp(a) level of all race/ethnic groups studied followed by South Asians, Whites, Hispanics and East Asians. The mechanisms underlying these differences have been sought and genetics plays an important role in providing insights into the observed differences. The association of elevated Lp(a) level with cardiovascular disease risk in different race/ethnic groups has also been studied. These studies show that, in general, elevated Lp(a) level is associated with cardiovascular risk in all groups. However, given race/ethnic differences in Lp(a) level and distribution, finding an appropriate Lp(a) threshold that predicts risk, meaningfully categorizes risk among individuals, and guides preventive therapy use has been challenging. In this review, we discuss the available evidence regarding race/ethnic differences in Lp(a) and the underlying mechanisms. Additionally, the association of Lp(a) with cardiovascular risk in various race/ethnic groups and the nuances of identifying the appropriate Lp(a) threshold are discussed. The key points on Lp(a) and ethnicities are described in Box 1.

Dysbiosis in salivary bacterial diversity of postpartum females and its association with oral health problems and APOs.

The present study investigates the dysbiosis in salivary bacterial diversity by culture-dependent and independent methods. Culturable aerobic and facultative anaerobic bacterial diversity was studied in saliva collected from 267 postpartum and 54 nonpregnant females by using standard microbiological methods. For unculturable bacterial diversity, DNA from saliva samples of four selected females was sequenced by targeting V4 region of 16S rRNA. In postpartum females, S. mutans was significantly more prevalent. Its colonization was also seen significant among females having gingivitis (P < 0.01), dental caries (P < 0.01), and in those giving birth to low weight baby. In postpartum group, 65.16% females were culture positive for Staphylococcus, 12.73% Gram positive rods, 10.48% N. meningitides, 6.36% K. pneumoniae, 5.61% Enterobacter species and 2.62% E. coli. Isolates showed high biofilm forming ability and antibiotic resistance. Upon analysis of unculturable bacterial diversity, a total of 16 phyla and 156 genera were observed. Alpha diversity was decrease in postpartum female having oral health issues with pre-term low weight birth, compared to females with full term birth. Bray-Curtis dissimilarity was highest between female with dental issues and different pregnancy outcomes. Bacterial diversity and abundance altered among females with different oral health conditions and pregnancy outcomes, and also have pathogenic potential.

Cardiovascular Disease Risk-Based Statin Utilization and Associated Outcomes in a Primary Prevention Cohort: Insights From a Large Health Care Network.

BACKGROUND: Current American College of Cardiology/American Heart Association guidelines recommend using the 10-year atherosclerotic cardiovascular disease (ASCVD) risk to guide statin therapy for primary prevention. Real-world data on adherence and consequences of nonadherence to the guidelines in primary are limited. We investigated the guideline-directed statin intensity (GDSI) and associated outcomes in a large health care system, stratified by ASCVD risk. METHODS: Statin prescription in patients without coronary artery disease, peripheral vascular disease, or ischemic stroke were evaluated within a large health care network (2013-2017) using electronic medical health records. Patient categories constructed by the 10-year ASCVD risk were borderline (5%-7.4%), intermediate (7.5%-19.9%), or high (≥20%). The GDSI (before time of first event) was defined as none or any intensity for borderline, and at least moderate for intermediate and high-risk groups. Mean (±SD) time to start/change to GDSI from first interaction in health care and incident rates (per 1000 person-years) for each outcome were calculated. Cox regression models were used to calculate hazard ratios for incident ASCVD and mortality across risk categories stratified by statin utilization. RESULTS: Among 282 298 patients (mean age ≈50 years), 29 134 (10.3%), 63 299 (22.4%), and 26 687 (9.5%) were categorized as borderline, intermediate, and high risk, respectively. Among intermediate and high-risk categories, 27 358 (43%) and 8300 (31%) patients did not receive any statin, respectively. Only 17 519 (65.6%) high-risk patients who were prescribed a statin received GDSI. The mean time to GDSI was ≈2 years among the intermediate and high-risk groups. At a median follow-up of 6 years, there was a graded increase in risk of ASCVD events in intermediate risk (hazard ratio=1.15 [1.07-1.24]) and high risk (hazard ratio=1.27 [1.17-1.37]) when comparing no statin use with GDSI therapy. Similarly, mortality risk among intermediate and high-risk groups was higher in no statin use versus GDSI. CONCLUSIONS: In a real-world primary prevention cohort, over one-third of statin-eligible patients were not prescribed statin therapy. Among those receiving a statin, mean time to GDSI was ≈2 years. The consequences of nonadherence to guidelines are illustrated by greater incident ASCVD and mortality events. Further research can develop and optimize health care system strategies for primary prevention.

Remnant cholesterol predicts cardiovascular disease beyond LDL and ApoB: a primary prevention study.

AIMS: Emerging evidence suggests that remnant cholesterol (RC) promotes atherosclerotic cardiovascular disease (ASCVD). We aimed to estimate RC-related risk beyond low-density lipoprotein cholesterol (LDL-C) and apolipoprotein B (apoB) in patients without known ASCVD. METHODS AND RESULTS: We pooled data from 17 532 ASCVD-free individuals from the Atherosclerosis Risk in Communities study (n = 9748), the Multi-Ethnic Study of Atherosclerosis (n = 3049), and the Coronary Artery Risk Development in Young Adults (n = 4735). RC was calculated as non-high-density lipoprotein cholesterol (non-HDL-C) minus calculated LDL-C. Adjusted Cox models were used to estimate the risk for incident ASCVD associated with log RC levels. We also performed discordance analyses examining relative ASCVD risk in RC vs. LDL-C discordant/concordant groups using difference in percentile units (>10 units) and clinically relevant LDL-C targets. The mean age of participants was 52.3 ± 17.9 years, 56.7% were women and 34% black. There were 2143 ASCVD events over the median follow-up of 18.7 years. After multivariable adjustment including LDL-C and apoB, log RC was associated with higher ASCVD risk [hazard ratio (HR) 1.65, 95% confidence interval (CI) 1.45-1.89]. Moreover, the discordant high RC/low LDL-C group, but not the low RC/high LDL-C group, was associated with increased ASCVD risk compared to the concordant group (HR 1.21, 95% CI 1.08-1.34). Similar results were shown when examining discordance across clinical cutpoints. CONCLUSIONS: In ASCVD-free individuals, elevated RC levels were associated with ASCVD independent of traditional risk factors, LDL-C, and apoB levels. The mechanisms of RC association with ASCVD, surprisingly beyond apoB, and the potential value of targeted RC-lowering in primary prevention need to be further investigated.

Lipoprotein (a): Recent Updates on a Unique Lipoprotein.

PURPOSE OF REVIEW: Genetic, epidemiological, and translational data indicate that Lipoprotein (a) [Lp(a)] is likely in the causal pathway for atherosclerotic cardiovascular diseases as well as calcification of the aortic valves. RECENT FINDINGS: Lp(a) is structurally similar to low-density lipoprotein, but in addition to apolipoprotein B-100, it has a glycoprotein apolipoprotein(a) [apo(a)], which is attached to the apolipoprotein B-100. Several distinctive properties of Lp(a) can be attributed to the presence of apo(a). This review discusses the current state of literature on pathophysiological and clinical aspects of Lp(a). After five decades of research, the understanding of Lp(a) structure, biochemistry, and pathophysiology of its cardiovascular manifestations still remains less than fully understood. Universally, Lp(a) elevation may be the most predominant monogenetic lipid disorder with approximate prevalence of Lp(a)>50 mg/dL among estimated >1.4 billion people. This makes a compelling rationale for diagnosing and managing Lp(a)-mediated risk. In addition to discussing various cardiovascular phenotypes of Lp(a) and associated morbidity, we also outline current and emerging therapies aimed at identifying a definitive treatment for elevated Lp(a) levels.