Chronic Inflammatory Disorders and Risk of Type 2 Diabetes Mellitus, Coronary Heart Disease, and Stroke

Dregan, Alexandru; Charlton, Judith Lynne; Chowienczyk, Phil; Gulliford, Martin

doi:10.1161/circulationaha.114.009990

Cited by 257 publications

(252 citation statements)

References 50 publications

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“…70 In the general population, high-sensitivity (hs) CRP and fibrinogen both provide additive predictive ability for cardiovascular disease although the incremental addition beyond clinical risk factors is relatively modest. In subjects without known cardiovascular disease, markers of cardiac injury and stress, such as hs-cardiac troponin (cTn) I, ST2, GDF-15, and N-terminal-proBNP (NT-proBNP; Table 3) are associated with an increased risk of death and adverse cardiovascular events, particularly heart failure, with a lesser effect on the risk of coronary heart disease events.…”

Section: Inflammationmentioning

confidence: 99%

“…70 In the general population, high-sensitivity (hs) CRP and fibrinogen both provide additive predictive ability for cardiovascular disease although the incremental addition beyond clinical risk factors is relatively modest. 71,72 More recent, but less clearly established, emerging predictors of coronary artery disease in the general population include TNFRII, 73 EN-RAGE, 74 and soluble CD14.…”

Section: Inflammationmentioning

confidence: 99%

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Novel Risk Markers and Risk Assessments for Cardiovascular Disease

Thomas

Lip

2017

Circulation Research

115

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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...

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Section: Inflammationmentioning

confidence: 99%

“…70 In the general population, high-sensitivity (hs) CRP and fibrinogen both provide additive predictive ability for cardiovascular disease although the incremental addition beyond clinical risk factors is relatively modest. 71,72 More recent, but less clearly established, emerging predictors of coronary artery disease in the general population include TNFRII, 73 EN-RAGE, 74 and soluble CD14.…”

Section: Inflammationmentioning

confidence: 99%

Novel Risk Markers and Risk Assessments for Cardiovascular Disease

Thomas

Lip

2017

Circulation Research

115

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“…34 A recent study of a large primary care database (UK Clinical Practice Research Datalink), including participants with psoriasis and related disorders, bullous skin disorders, ulcerative colitis, Crohn disease, inflammatory arthritis, systemic autoimmune diseases, and systemic vasculitis, showed an increased risk of CVD with chronic inflammatory disease, calling for the importance of clinical management of such conditions to reduce cardiovascular risk. 35 Chronic inflammation may also be involved in the development of atherosclerosis in persons without rheumatologic disorders. In the JUPITER (Justification for the Use of Statins in Primary Prevention: An Intervention Trial Evaluating Rosuvastatin) trial of apparently healthy persons without hyperlipidemia but with elevated C-reactive protein levels (a marker of inflammation), rosuvastatin significantly reduced the incidence of major cardiovascular events including stroke.…”

Section: Bang Et Al Nontraditional Risk Factors For Ischemic Stroke 3573mentioning

confidence: 99%

Nontraditional Risk Factors for Ischemic Stroke

Bang

Ovbiagele

Kim

2015

Stroke

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A lthough it is encouraging that during the past decade there has been a notable decline in the incidence of stroke in several countries around the world, 1-6 further reductions in stroke occurrence will require even better treatment of conventional risk factors, as well as the identification and treatment of nontraditional risk factors. 7 Hypertension, diabetes mellitus, hypercholesterolemia, cigarette smoking, atrial fibrillation, and carotid stenosis are definite causal risk factors because randomized controlled trials showed that treating them reduced the incidence of ischemic stroke/transient ischemic attack (TIA) or because epidemiological studies have shown that they are prospectively and independently associated with incident risk of stroke.8 Several risk models and risk calculators are available for stroke. However, they include only a few traditional risk factors, and not all ischemic strokes are explained by these factors. About 60% to 80% of all ischemic strokes can be attributed to these factors.8 Adding more factors may improve the predictive values of the risk models for stroke, and controlling nontraditional risk factors may further reduce stroke risks. The INTERSTROKE study, which examined 10 factors including less traditional factors such as obesity, psychosocial stress and depression, and ratio of apolipoprotein B to A1, found that these conditions were linked to 90% of the risk of stroke. 9The carotid substudy of Northern Manhattan studies showed that traditional risk factors explain only a minority of the variability in carotid plaque, suggesting a possible role for unaccounted nontraditional risk factors in the development of atherosclerotic plaque. 10,11 The Reasons for Geographic and Racial Differences in Stroke (REGARDS) study confirmed the existence of a stroke belt in the southeastern United States, where the rates of stroke mortality were higher (>40%) than those of other regions.12 However, in this study, only modest differences were found in 9 known risk factors common to stroke screening (the Framingham Stroke Risk Score) between the stroke belt and the stroke buckle compared with the rest of the United States. Similarly, a stroke belt with high stroke incidence was found in north and west China. 13Of note, a high prevalence of obesity was reported in stroke belts of both United States and China (Figure). These findings indirectly suggest a role for nontraditional risk factors to predict and prevent stroke. Search Strategy and Selection CriteriaIn this review, we defined traditional risk factors as those used in the Framingham study (ie, age, sex, hypertension, diabetes mellitus, cigarette smoking, cardiovascular disease [CVD], atrial fibrillation, and left ventricular hypertrophy) 15 and hypercholesterolemia. Others are defined as nontraditional risk factors if the association between the factors and the occurrence of stroke was demonstrated with plausible biological explanation. We identified references for this review by searching PubMed and ClinicalTrials.gov published in En...

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“…Two inception cohorts using the Clinical Practice Research Datalink have provided opposing results; Parisi et al [25] found no increased risk of major cardiovascular events while Degran et al [26] reported an increased risk for severe psoriasis patients.…”

Section: Introductionmentioning

confidence: 99%