Novel Risk Markers and Risk Assessments for Cardiovascular Disease

Abstract

Abstract:The use of risk markers has transformed cardiovascular medicine, exemplified by the routine assessment of troponin, for both diagnosis and assessment of prognosis in patients with chest pain. Clinical risk factors form the basis for risk assessment of cardiovascular disease and the addition of biochemical, cellular, and imaging parameters offers further refinement. Identifying novel risk factors may allow greater risk stratification and a steady, but gradual progression toward precision medicine. Indeed, the generation of data in this area of research is explosive and when combined with new technologies and techniques provides the potential for more refined, targeted approaches to cardiovascular medicine. Although discussing the most recent developments in this field, this review article aims to strike a balance between novelty and validity by focusing on recent large samplesize studies that have been validated in a separate cohort in most cases. Risk markers related to atherosclerosis, thrombosis, inflammation, cardiac injury, and fibrosis are introduced in the context of their pathophysiology. Rapidly developing new areas, such as assessment of micro-RNA, are also explored. Subsequently the prognostic ability of these risk markers in coronary artery disease, heart failure, and atrial fibrillation is discussed in detail. ( addition to these roles in the pathogenesis of coronary artery disease, lipid-related molecules have been identified to be markers of inflammation and oxidative stress (Table 1). Thrombosis-Related Risk MarkersAfter atherosclerotic plaque rupture, platelets adhere to exposed subendothelial components, such as collagen and von Willebrand factor, which promotes platelet activation and aggregation. 10 In addition, platelet activation is potentiated by exposure to released soluble agonists, such as thrombin and ADP.10 Activated platelets then further release ADP, which acts on platelet P2Y 12 ADP receptors and has a central role in amplifying the response of platelets to the initial stimulus. 10 Platelet reactivity to various agonists, including ADP, has been studied extensively in the context of acute coronary syndrome (ACS; Table 2). 11 The VerifyNow and Multiplate pointof-care tests allow for the measurement of platelet aggregation in response to stimulation, and it has been shown that high platelet reactivity is associated with adverse cardiovascular events. 26 Platelet microparticles are released on platelet activation, and their role in cardiovascular disease is an area of active investigation (Table 2). 15 Circulating microparticles are released from cells undergoing activation or apoptosis and are a type of small plasma membrane vesicle that retain defined properties from their original cell lineage. 15 Platelet activation and aggregation lead to the activation of the coagulation cascade and the formation of a stable crosslinked fibrin clot. The balance between prothrombotic factors and endogenous fibrinolysis determines whether the thrombus propagates or instead proceeds to dis...

Effects of Repeated Binge Drinking on Blood Pressure Levels and Other Cardiovascular Health Metrics in Young Adults: National Health and Nutrition Examination Survey, 2011‐2014

“…The role of HDL‐c, however, has been brought into question by negative findings from clinical drug trials and negative Mendelian randomization studies 32. In our study binge drinking was associated with higher HDL‐c levels, and in all groups HDL‐c levels were greater than 50 mg/dL.…”

TRPV4 is a regulator inP. gingivalislipopolysaccharide‐induced exacerbation of macrophage foam cell formation

“…; Ruparelia et al. ; Thomas and Lip ). Numerous clinical and experimental studies have shown that infection with various bacterial pathogens including Porphyromonas gingivalis may serve as an additional risk factor in the development and progression of atherosclerosis (Tonetti ; Kebschull et al.…”

Utilizing state‐of‐the‐art “omics” technology and bioinformatics to identify new biological mechanisms and biomarkers for coronary artery disease

“…An example of this advancement in immunophenotyping is CyTOF, a leukocyte phenotyping assay which can be performed on patient‐derived peripheral blood mononuclear cells stained with isotopically pure lanthanide metal‐conjugated antibodies (Table ). This allows up to 40 markers to be examined on 1 run, and subsequently analyzed by mass spectrometry TOF, providing numeration and characterization of circulating leukocyte cell subsets . This generates a leukocyte “signature” in which the number and functional status of each subset indicates past and present inflammation and immune activity.…”

“…39 C, It is the structure and function of HDL rather than its plasma concentration that is more closely associated with cardiovascular risk, likely through its impact on cholesterol efflux capacity and RCT 7 new insights may be gained by rapid technical and bioinformatics advances in immunophenotyping. An example of this advancement in immunophenotyping is CyTOF, a leukocyte phenotyping assay which can be performed on patient-derived peripheral blood mononuclear cells stained with isotopically pure lanthanide metal-conjugated antibodies 29,30 (Table 1). This allows up to 40 markers to be examined on 1 run, and subsequently analyzed by mass spectrometry TOF, providing numeration and characterization of circulating leukocyte cell subsets.…”