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Concept: Lipoprotein(a)

231

The accuracy of the 2013 American College of Cardiology/American Heart Association (ACC/AHA) Pooled Cohort Risk Equation for atherosclerotic cardiovascular disease (ASCVD) events in contemporary and ethnically diverse populations is not well understood.

Concepts: Myocardial infarction, Atherosclerosis, Demography, Blood vessel, Cardiovascular disease, Low-density lipoprotein, Cardiovascular diseases, Lipoprotein(a)

27

B-mode ultrasound measurement of the carotid intima-media thickness (CIMT) is a widely used marker for atherosclerosis and is associated with future cardiovascular events. This article provides a review and meta-analysis of the published evidence on the association of CIMT with future cardiovascular events and its additional value to traditional cardiovascular risk prediction models.

Concepts: Atherosclerosis, Blood vessel, Cardiovascular disease, Systematic review, Low-density lipoprotein, Intima-media thickness, Cardiovascular diseases, Lipoprotein(a)

2

Rationale: One measure of protein glycosylation (GlycA) has been reported to predict higher cardiovascular risk by reflecting inflammatory pathways Objective: To assess the role of a comprehensive panel of immunoglobulin (IgG) glycosylation traits on traditional risk factors for cardiovascular disease and on presence of subclinical atherosclerosis in addition to GlycA. Methods and Results: We measured 76 IgG glycosylation traits in 2970 women (age range 40-79 years) from the TwinsUK cohort and correlated it to their estimated 10-year atherosclerotic cardiovascular disease (ASCVD) risk score and their carotid and femoral plaque measured by ultrasound imaging. Eight IgG glycan traits are associated with the 10-year ASCVD risk score after adjusting for multiple tests and for individual risk factors - 5 with increased risk and 3 with decreased risk. These glycans replicated in 967 women from ORCADES cohort, six of them were also associated in 845 men. A linear combination of IgG glycans and GlycA is also associated with presence of carotid (OR[95%CI]=1.55 [1.25;1.93], P=7.5X10-5) and femoral (OR[95%CI]==1.32[1.06;1.64], P=0.01) plaque in a subset of women with atherosclerosis data after adjustment for traditional risk factors. One specific glycosylation trait, GP18 was negatively correlated with VLDL and triglyceride levels in serum and with presence of carotid plaque (OR[95%CI] = 0.60[0.50;0.71], P = 5x10-4). Conclusions: We find molecular pathways linking IgG to arterial lesion formation. Glycosylation traits are independently associated with subclinical atherosclerosis. One specific trait related to the sialylated N-glycan is negatively correlated with CVD risk, VLDL and triglyceride serum levels and presence of carotid plaque.

Concepts: Immune system, Glycoproteins, Myocardial infarction, Atherosclerosis, Blood vessel, Cardiovascular disease, Low-density lipoprotein, Lipoprotein(a)

2

In the Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk (FOURIER) trial,1 treatment with evolocumab resulted in a 15% relative (1.5% absolute) risk reduction of major cardiovascular events in patients with atherosclerotic cardiovascular disease (ASCVD) at a median follow-up of 2.2 years. This trial included patients with LDL-C≥70mg/dL or non-HDL-C ≥100mg/dL on at least moderate-intensity statins. It is not known what proportion of ASCVD patients would qualify for evolocumab based on FOURIER entry criteria and how eligibility would change if maximal doses of evidence-based lipid lowering therapies were required. We assessed the number and proportion of U.S. Veterans with ASCVD who would qualify for evolocumab based on FOURIER trial entry criteria and how these figures would change if high-intensity statins, ezetimibe or the combination of both agents was used.

Concepts: Myocardial infarction, Atherosclerosis, Blood vessel, Cardiovascular disease, Low-density lipoprotein, Statin, Cardiovascular diseases, Lipoprotein(a)

2

The extent to which the relative contributions of traditional cardiovascular risk factors to incident cardiovascular disease (CVD) may have changed over time remains unclear.

Concepts: Epidemiology, Myocardial infarction, Atherosclerosis, Blood vessel, Cardiovascular disease, Low-density lipoprotein, Cardiovascular diseases, Lipoprotein(a)

2

Levels of atherogenic lipoproteins achieved with statin therapy are highly variable, but the consequence of this variability for cardiovascular disease risk is not well-documented.

Concepts: Myocardial infarction, Atherosclerosis, Blood vessel, Cardiovascular disease, Low-density lipoprotein, Statin, Cardiovascular diseases, Lipoprotein(a)

1

Vascular calcification (VC) and atherosclerosis are associated with an increased cardiovascular morbimortality in chronic kidney disease (CKD). Osteoprotegerin (OPG) and osteopontin (OPN) are involved in both VC and CKD. Soluble tumor necrosis factor-like weak inducer of apoptosis (sTWEAK) has been related to cardiovascular disease. We hypothesized that OPG, OPN and sTWEAK levels may be associated with a higher prevalence of cardiovascular outcomes in patients with CKD.

Concepts: Chronic kidney disease, Disease, Myocardial infarction, Atherosclerosis, Blood vessel, Cardiovascular disease, Low-density lipoprotein, Lipoprotein(a)

1

The atherosclerosis cardiovascular disease (ASCVD) Pooled Cohort risk equations have shown different calibration across US populations with varied levels of social deprivation.

Concepts: Myocardial infarction, Atherosclerosis, Demography, Blood vessel, Cardiovascular disease, Low-density lipoprotein, Sociology, Lipoprotein(a)

1

The improvement in discrimination gained by adding nontraditional cardiovascular risk markers cited in the 2013 American College of Cardiology/American Heart Association cholesterol guidelines to the atherosclerotic cardiovascular disease (ASCVD) risk estimator (pooled cohort equation [PCE]) is untested.

Concepts: Myocardial infarction, Atherosclerosis, Blood vessel, Risk, Cardiovascular disease, Low-density lipoprotein, Cardiovascular diseases, Lipoprotein(a)

1

Perceived discrimination is positively related to cardiovascular disease (CVD) risk factors; its relationship with incident CVD is unknown. Using data from the Multi-Ethnic Study of Atherosclerosis, a population-based multiethnic cohort study of 6,508 adults aged 45-84 years who were initially free of clinical CVD, we examined lifetime discrimination (experiences of unfair treatment in 6 life domains) and everyday discrimination (frequency of day-to-day occurrences of perceived unfair treatment) in relation to incident CVD. During a median 10.1 years of follow-up (2000-2011), 604 incident events occurred. Persons reporting lifetime discrimination in ≥2 domains (versus none) had increased CVD risk, after adjustment for race/ethnicity and sociodemographic factors, behaviors, and traditional CVD risk factors (hazard ratio (HR) = 1.36, 95% confidence interval (CI): 1.09, 1.70) and after control for chronic stress and depressive symptoms (HR = 1.28, 95% CI: 1.01, 1.60). Reported discrimination in 1 domain was unrelated to CVD (HR = 1.05, 95% CI: 0.86, 1.30). There were no differences by race/ethnicity, age, or sex. In contrast, everyday discrimination interacted with sex (P = 0.03). Stratified models showed increased risk only among men (for each 1-standard deviation increase in score, adjusted HR = 1.14, 95% CI: 1.03, 1.27); controlling for chronic stress and depressive symptoms slightly reduced this association (HR = 1.11, 95% CI: 0.99, 1.25). This study suggests that perceived discrimination is adversely related to CVD risk in middle-aged and older adults.

Concepts: Epidemiology, Myocardial infarction, Atherosclerosis, Blood vessel, Cardiovascular disease, Low-density lipoprotein, Cardiovascular diseases, Lipoprotein(a)