Phase Of Atherosclerosis Research Articles

Influence of Cigarette Smoking in the Rate Pressure Product among Young Adults:A Case Control Study from Manipal, India

Background Cigarette smoking is an important cause of mortality across the world, resulting in death of nearly six million people. Nearly 40% of the deaths are caused by cardiovascular disease and 20% are due to lung cancer. Cigarette smoking is said to increase the susceptibility towards vascular injuries by impacting phases of atherosclerosis, and altering blood pressure (BP), heart rate (HR) and elevating plasma catecholamine levels. The objective of this study was to assess if cigarette smoking increases the rate pressure product (RPP) at rest and after standing in young adult light smokers compared to non-smokers. Methods 30 young adult smokers and 30 non-smokers (19 - 24 years) were enrolled in this case control study. The smoking pack-years was calculated. Blood pressure (BP) was measured and RPP was calculated. The mean values between both groups were compared using the univariate analysis of variance adjusted for confounding variables. Results The smoking pack-years was 1.6±1.0 (0.2-4.5). RPP in smokers was 88.8±8.0, 96.2±10.2 at rest and after standing respectively. RPP in non-smokers at rest was 81.6±8.1 and 89.5±10.3 after standing. RPP was statistically significant in between both groups at rest. Conclusion Smoking increases the RPP significantly in young adult light smokers due to an increased HR when compared to non-smokers, at rest. This study reinforces that young adults who are light smokers have an increased workload on the heart, which affects their cardiac performance.

Adventitial Vasa Vasorum

To the Editor: I reviewed the article Quantification of adventitial vasa vasorum (VV) vascularization in double-injury restenotic arteries by Meng et al.[1] with great interest, which described their experiment about adventitial VV and postangioplasty restenosis. Percutaneous transluminal angioplasty is now widely used for the treatment of atherosclerotic lesions in various arteries. Restenosis is a major concern following angioplasty, and yet with no good solutions. Previous experimental studies suggested that there is an association between VV and atherosclerotic plaque formation and intimal hyperplasia. As occlusion of VV correlates well with neointima formation, but inhibition of VV neovascularization correlates with reduced plaque growth,[2] VV may play several different roles in different phases of atherosclerosis or postangioplasty restenosis. The causative mechanism is still unclear.

Abstract 55: Histological And Rheological Evaluation At Coronary Artery Lesions In Patients With Kawasaki Disease Within 2 Years From Onset

Background: Some paper reported that intravascular ultrasound (IVUS)- virtual histology (VH) showed atherogenesis in the evolution of coronary artery lesions (CAL) in young adults long after Kawasaki disease(KD). However, there is no report about those findings during early phase of KD. Purpose: We perform coronary intimal histologic evaluation by IVUS-VH for KD patients with CAL within two years from onset. Furthermore, we calculate shear stress in the target site and examine whether rheological potential affects to vascular histological change after KD. Subjects and Methods: IVUS-VH was performed in 12 Japanese KD patients (median age, 5.1 years) during 2 years after onset of KD (median, 10.2months) . All these patients had giant aneurysm in another branches. We investigated 20 coronary branches including 10 sites of small aneurysm (s-AN), 10 sites of regressed s-AN, and 20 sites of normal segment. Each of the 4 plaque components was assigned a respective color and defined as follows: fibrous area (green); fibro-fatty area (yellow) ; necrotic core area (red); and dense calcium area (white). Moreover, we measured average coronary peak flow velocity by Flow wire and calculated shear stress in the each sites. Results: 10 sites of s-AN showed prominent endothelial hypertrophy with fibrous and/or fibro-fatty plaques. In 7 sites of these 10 sites, dense calcium and necrotic core localized which indicates early phase of atherosclerosis. 10 sites of regressed s-AN had circumferential endothelial hypertrophy occupying mainly fibrous and/or fibro-fatty plaques composition. In 8 sites of these regressed 10 sites, dense calcium and necrotic core locally existed. On the other hand, normal segment in 20 sites had no plaque in 19 sites and trivial plaque in 1 site. Moreover, shear stress in all evaluated VH sites were within normal limit, which shows rheological potential doesn’t affect to vascular remodeling in such coronary artery lesions. Conclusions: IVUS-VH study revealed that initial atherosclerotic findings locally existed not only at small aneurysm site but also at regressed site. Therefore, careful further investigation to vascular remodeling in KD patients with CAL including regressed s-AN will be need.

Endothelial dysfunction and coronary artery disease: assessment, prognosis, and treatment.

Progress in the modification of conventional coronary risk factors and lifestyle behavior has reduced the incidence of atherosclerotic coronary artery disease; nonetheless, it continues to be the leading cause of mortality in the world. This might be attributed to the defective risk stratifying and prevention strategy for coronary artery disease. In the current clinical setting, atherosclerotic coronary artery disease risk is estimated on the basis of identifying and quantifying only traditional risk factors; it does not take into consideration nontraditional risk factors. In addition, most of the prevailing therapies for atherosclerosis are targeted toward traditional risk factors rather than atherosclerosis itself. It is desirable to develop a method that can directly assess the activity of atherogenesis at every moment. Endothelial function is an integrated index of all atherogenic and atheroprotective factors present in an individual including nontraditional factors and heretofore unknown factors, and it is reported to have additional predictive value for future cardiovascular events to traditional risk factors. Moreover, endothelial function has a pivotal role in all phases of atherosclerosis, from initiation to atherothrombotic complication, and is reversible at every phase, indicating that endothelial function-guided therapies might be effective and feasible in cardiovascular practice. Thus, the introduction of endothelial function testing into clinical practice might enable us to innovate individualized cardiovascular medicine. In this review, we summarize the current knowledge on the contribution of endothelial dysfunction to atherogenesis and review the methods that assess endothelial function. Finally, we focus on the effects of major antiatherosclerotic disease therapies on endothelial function and argue the possibility of noninvasive assessment of endothelial function aiming at individualized cardiovascular medicine.

Cardiovascular risk prevention in children

Cardiovascular disease (CVD) is the major cause of mortality in industrialized countries. Atherosclerosis is characterized by a long lag time between onset and clinical manifestations. There is evidence that CVD initiate before birth by developmental changes in utero. Genetic and environmental factors may interact in specific periods of life (prenatal, perinatal, early childhood), giving rise to altered developmental plasticity and epigenetic modifications with abnormal phenotypic expression of genetic information without altering DNA sequence. Nutritional imbalances and other environmental clues may cause intrauterine growth delay, decreased gestational age, low birth weight and postnatal catch-up growth. Fetal exposure to maternal hypercholesterolemia has been associated with increased risk and progression of atherosclerosis. Oxidative stress seems to play a major role in the atherosclerotic process by activating both platelets and monocytes forming proinflammatory and proaterogenic substances, resulting in endothelial dysfunction, decreased flow-mediated dilation, and increased carotid intima-media thickness [1,2]. CVD primary prevention should be implemented early. High risk, apparently healthy [3] subjects should be identified , and treated early by healthy eating, physical activity encouragement, healthy lifestyle, the possible addition of nutraceuticals [4] and adding drugs if risk profile is not decreased. Restoration of endothelial function in the reversible phase of atherosclerosis is an essential step. Epigenetics might provide novel and early markers to identify those at risk, thereby developing innovative therapies.

Human sLZIP promotes atherosclerosis via MMP-9 transcription and vascular smooth muscle cell migration.

Atherosclerosis is a chronic inflammatory response of the vascular wall, and immune responses are involved in every phase of atherosclerosis, from initiation, to progression, and finally to plaque rupture. Cytokines are the major atherogenic mediators that promote plaque formation and progression by activation of inflammatory cells. They induce expressions of matrix metalloproteinases (MMPs), leading to vascular smooth muscle cell (VSMC) migration in atherosclerotic lesions. Although chronic inflammatory mediators, including tumor necrosis factor α (TNF-α) and MMPs, exacerbate atherosclerosis, the molecular mechanism of atherogenesis remains unclear. In this study we investigated the role of a novel transcription factor the human small leucine zipper protein (sLZIP) in TNF-α-induced MMP expression, VSMC migration, and atherosclerosis progression. The proinflammatory cytokine TNF-α enhanced sLZIP expression by 3-fold via activation of NF-κB signaling. sLZIP induced MMP-9 transcription and the proteolytic activity of MMP-9 by 2.8- and 3.2-fold (P< 0.05), respectively, in macrophages, leading to enhancement of VSMC migration by 2.7-fold (P<0.005). sLZIP(OE/+) (sLZIP transgenic); LDLR(-/-) mice fed a high-cholesterol diet exhibited enhanced arterial plaque formation and increased VSMC migration from the media into the intima by 2.8- and 2.6-fold (P<0.01), respectively, compared with atherosclerosis-prone LDLR(-/-) mice. These results indicate that human sLZIP plays a critical role in development of atherosclerosis and can be used as a therapeutic target molecule for treatment of atherosclerosis.

Human bioengineered artery models for in vitro atherosclerosis research: fact or fiction?

Human bioengineered artery equivalents may represent a first step toward the future replacement of the animal models used for studying the initial phases of atherosclerosis

Abstract P353: Serum Levels of Monocyte Chemoattractant Protein-1 and All-cause and Cardiovascular Mortality among Patients with Coronary Artery Disease

Background: Monocyte chemoattractant protein-1 (MCP-1) is an important chemokine at multiple phases of atherosclerosis in animal studies, but results of human studies are inconsistent. Objective: To investigate the association of serum MCP-1with all-cause and CVD mortality among CAD patients and determine whether the novel biomarker can add secondary prognostic value to standard risk predictors. Methods: MCP-1 was measured at baseline in 1411 CAD patients who were 40-85 years of age in the Guangdong Coronary Artery Disease Cohort. Cox proportional hazards regression models were used to estimate the association of different levels of serum MCP-1with risk of mortality. Results: During a median follow-up of 3.3 years, 117 deaths were recorded, 88 of which were due to CVD. The multivariable-adjusted (age, sex, education, occupation, marriage, leisure-time physical activity, smoking, alcohol drinking, body mass index, systolic blood pressure, fasting plasma glucose, low-density lipoprotein cholesterol, glomerular filtration rate, type, severity, duration, and treatment of CAD, history of heart failure, and use of antihypertensive, anti-diabetic, cholesterol-lowering, and anti-platelet drugs) hazard ratios across tertiles of MCP-1 were 1.52 (95% CI 0.90-2.57), 1.00, and 1.93 (95% CI 1.20-3.10) for all-cause mortality, and 1.38 (95% CI 0.75-2.55), 1.00, and 1.93 (95% CI 1.12-3.34) for CVD mortality. Further adjusting for C-reactive protein, all the hazard ratios remained similar. The addition of MCP-1 increased the C-statistic of the fully adjusted all-cause mortality model from 0.811 to 0.820 (p&lt;0.0001) and the CVD mortality model from 0.827 to 0.835 (p&lt;0.0001). After stratifying CAD type, age, gender, body mass index and C-reactive protein levels, the associations became stronger in acute coronary syndrome, males, normal-weight, and elevated C-reactive protein subgroups, while the hazard ratios turned insignificant in stable performance, females, obese, and normal C-reactive protein subgroups. Conclusions: Elevated MCP-1 level is associated with an increased risk of all-cause and CVD mortality among CAD patients. MCP-1 can add prognostic value to standard risk predictors and merits further study.

Cardiovascular Risk, Inflammation and Physical Activity in Rheumatoid Arthritis

Individuals with Rheumatoid Arthritis (RA) have increased mortality when compared with the general population. Much of this increased mortality can be attributed to cardiovascular causes. The exact cause for this increased risk has not been fully determined, although some potential mechanisms have been postulated. This overview aims to outline and discuss some of the potential factors which relate to this increased cardiovascular disease risk in the RA population. Inflammation is one such potential factor as inflammation has been shown to play a central role in all phases of atherosclerosis. Therefore, assessment of inflammatory markers may help identify those at high risk of future cardiovascular events. This paper aims to provide a deeper understanding of the links between inflammation and atherosclerosis and cardiovascular disease. Physical activity is associated with improvements in cardiovascular health in many populations. A link between inflammatory marker levels and physical activity has been determined and the literature specifically assessing this link is analysed in this overview. Although the literature is scarce regarding the RA population, two studies which investigate the relationship in this population are presented and discussed. Keywords: Atherosclerosis, Cardiovascular, Inflammation, Inflammatory Markers, Physical Activity, Rheumatoid Arthritis.

Regulation of Gene Expression in Atherosclerosis: Insights from Microarray Studies in Monocytes/Macrophages

Atherosclerosis is a pathological phenomenon in which the walls of large arteries thicken and lose elasticity as a result of the growth of atheromatous lesions. It is a complex, multifactorial disease that involves several cell types and various pathobiological processes. Its genetic basis has not yet been deciphered, but it is related to complex multigene patterns influenced by environmental interactions. In this review, we focus specifically on the application of microarrays to atherosclerosis research using monocytes and monocyte-derived macrophages, as these are key cells in all phases of atherosclerosis, from the formation of foam cells to the destabilization and rupture of the atherosclerotic plaque. These studies have provided relevant information on genes involved in atherosclerosis development, contributing to our understanding of the molecular mechanisms that underlie this complex disease.

Inflammation, Atherosclerosis, and Psoriasis

Increasing evidence supports an important role for inflammation in all phases of atherosclerosis, from initiation of the fatty streak to final culmination in acute coronary syndromes. Numerous inflammatory biomarkers including cell adhesion molecules, cytokines, chemokines, and acute-phase reactants such as fibrinogen, serum amyloid A, and C-reactive protein (CRP) have been shown to predict cardiovascular (CVD) events. Several prospective studies have shown a consistent and robust relationship between levels of high-sensitivity CRP and the risk of future CVD events. Toll-like receptors are pattern recognition receptors and members of the innate immune system that contribute to inflammation and appear to play key roles in atherosclerosis. Lipoprotein-associated phospholipase A2 may also be an independent CVD risk factor. Psoriasis has been associated with an increasing risk for atherosclerosis, including coronary artery disease and stroke. Patients with psoriasis have a 5-year shorter life expectancy, most frequently due to CVD. Psoriasis is associated with a chronic inflammatory state and with elevated levels of CRP and other inflammatory cytokines and these may play a causative role in the increased risk of psoriatic patients for CVD. Patients with psoriasis may represent an emerging risk population and patients with moderate to severe psoriasis should be screened and aggressively treated for CVD risk factors.

CRP and gender differences in patients with acute myocardial infarction

Objective. Inflammation appears to be pivotal in all phases of atherosclerosis from the endothelial dysfunction to acute coronary syndromes. An important marker of inflammation is C-reactive protein (CRP). The sex hormones estrogen and testosterone have been shown to modify the inflammatory response by influencing cytokine expression in human macrophage cells. Method. Our retrospective study included 147 patients (73 patients with STEMI, 44 with NSTEMI) and 30 controls. Information about demographic characteristics, CRP values (at admission) we collected using clinical files. All results were carrying out using Student T test and binary logistic regression. P values =<0.05 were considered statistically significant. Results. CRP difference in 117 patients with acute myocardial infarction (73 patients with STEMI and 44 patients with NSTEMI) and 30 healthy individuals (controls) is statistically significant (p=0.001). CRP difference between male and female is statistically significant in patient with STEMI (25,14 ± 29,23 versus 13,16 ± 17,05, p =0,038), but not in NSTEMI patients. Observing CRP, gender and age in binary logistic regression, only CRP increases risk for acute myocardial infarction, OR=1,952. Conclusion. CRP value is higher in patients with acute myocardial infarction and shows gender difference, higher values are in women with STEMI.

Vascular cell dysfunctions: a possible atheroprotective role of melatonin

Atherosclerosis is a chronic disease of the arterial wall and a leading cause of death and loss of productive life years worldwide. It is considered a chronic inflammatory vascular disease characterized of monocyte extravasation into the arterial wall (Libby et al., 2011). Researches into the disease have led to many compelling hypotheses about the pathophysiology of atherosclerotic lesion formation and of complications such as myocardial infarction and stroke (Ross, 1999). The last several decades have witnessed aburgeoning growth of understanding of the molecular pathways involved in atherogenesis, atherosclerotic lesion progression and the pathogenetic mechanisms involved. In this study was evaluated the role of cyclophilin A (CyPA) in early phase of atherosclerosis, the beneficial effects of melatonin in vascular remodelling due to its ability to modulate rolling of mononuclear cells and its acting on vascular smooth muscle cell proliferation and neointima formation. In particular, in this study APOE null mice at 6 and 15 weeks of age were used; they were treated with melatonin at dose of 0.1mg/kg/day and 10mg/kg/day. We evaluated both CyPA expression and its signaling pathways in atherosclerosis development. CyPA expression increased in mononuclear cells and, in turn, stimulated vascular cell adhesion and interleukin-6 increase in the endothelial cells and vascular smooth muscle cells in a time-dependent manner. Melatonin treatment at the dose of 10mg/ kg/day completely improved vascular injury inhibiting the increase of CyPA. In summary, these findings suggest that CyPA induces the early step of atherosclerosis and indicate that the antioxidant effects of melatonin are both on antioxidant enzymes and other proteins, such as CyPA. Moreover, CyPA will be considered the bridge between inflammation and atherosclerosis. Thus, melatonin use could be a safe strategy of improving the development and progression of atherosclerosis.

Anti-inflammatory Treatment of Acute Coronary Syndromes

The past decade has seen a steady growth in the treatment options available for Acute Coronary Syndromes (ACS), as a consequence of our better understanding of ACS pathophysiology. Administration of fibrinolytics in ST-elevation myocardial infarction, and of potent antiplatelet and anticoagulant drugs in all ACS, has allowed us to considerably improve their outcome. Yet, the rate of adverse cardiac events at early follow-up ranges from 15% to 20%. Thus, to further improve the outcome of ACS or to prevent their occurrence, it is important to identify new therapeutic target. A number of experimental and clinical studies have highlighted the key role of inflammation in all phases of atherosclerosis, from fatty streaks to disrupted plaques and raised levels of inflammatory markers have been associated to a poor outcome despite optimal treatment, including myocardial revascularization. In this review, we will focus on inflammation as a possible new therapeutic target of ACS, discussing the anti-inflammatory treatments in four sections: 1) non specific anti-inflammatory drugs; 2) specific antagonists of key cytokines; 3) immunomodulatory therapies; 4) immunization as promising therapeutic modality against atherosclerosis.

Is Atherosclerosis an Allergic Disease?

### IgE Stimulates Human and Mouse Arterial Cell Apoptosis and Cytokine Expression and Promotes Atherogenesis in Apoe –/– Mice Wang et al J Clin Invest . 2011;121:3564–3577. A new report in the Journal of Clinical Investigation adds to the ever-increasing evidence that immunological mechanisms play an important role in atherogenesis. These new observations suggest involvement of IgE and its FcϵR1α receptor in the promotion of atherosclerosis, and specifically in plaque instability and clinical events. Evidence continues to accumulate supporting an important role for immunological mechanisms in all phases of atherosclerosis.1–3 Previous studies have supported an important modulating role for disease-specific IgG and IgM and for Fcγ receptors in modulating atherogenesis.4–9 In a recent report, Wang et al contribute to this growing body of literature by presenting novel observations supporting a proatherogenic role for IgE and its high-affinity receptor FcϵR1α.10 The authors compared the extent of atherosclerosis in wild-type apoE –/– mice fed a Western diet with apoE –/– / FcϵR1 α–/– mice and observed a profound reduction in lesion formation. Although nearly all the cell types known to be involved in atherogenesis express FcϵR1α receptors in vivo, the authors focused primarily on the potential role of this receptor in macrophage biology and demonstrated that IgE mediates a variety of proinflammatory effects in macrophages, such as release of interleukin-6 and monocyte chemoattractant protein-1, as well as proteases …

Blood Pressure and Vascular Alterations with Growth in Childhood

The long preclinical phase of atherosclerosis involves the interaction of genetic and environmental factors that modulate the progression of disease from early life. A variety of noninvasive tests have been used to study the arterial phenotype of childhood, allowing identification of arterial alterations long before clinical symptoms of cardiovascular (CV) disease become apparent. These techniques have improved our understanding of the evolution of atherosclerosis, indentifying three major developmental factors which influence the future risk of CV disease in childhood: prenatal growth, early postnatal growth and childhood obesity. Specific changes in arterial properties and increased values of blood pressure are detectable in children with low birth weight, suggesting that intrauterine growth retardation could programme the future risk of CV disease. However, an accelerated growth rate in infancy and early childhood is often associated with low birth weight and with specific vascular alterations, making it difficult to distinguish the contribution of prenatal and postnatal growth patterns to later cardiovascular disease risk. Relationships between growth patterns and CV disease risk are further complicated by the link between rapid postnatal growth and later development of childhood overweight and obesity, conditions associated with early changes in vascular physiology and that potentially affect future CV outcome. This article aims to provide an overview of evidence in support of fetal programming and growth acceleration hypotheses for adult CV disease. Specific attention is given to obesity-related vascular alterations and their effects on future CV disease risk. We also summarise current non-invasive approaches to investigate the precursors and early development of CV disease, emphasising their potential applications in childhood.

Effect of orange juice and beverage with phytosterols on cytokines and PAI-1 activity

Inflammation is pivotal in all phases of atherosclerosis. Dietary options which lower inflammatory biomarkers would be an attractive strategy to reduce risk from cardiovascular diseases and cancer. Indeed, fruit and vegetable intake or fruit juice consumption is associated with health and wellness. However, there is a paucity of data examining the effect of orange juice on biomarkers of inflammation in healthy volunteers. We have previously conducted the first placebo-controlled randomized studies examining the effect of sterol fortified orange juice or sterol fortified reduced calorie orange juice beverage supplementation (2g sterols/day) compared to Placebo OJ or Placebo OJBev, and showed significant benefits on the lipid profile as well as significant reduction in hsCRP, the prototypic marker of inflammation and a cardiovascular risk marker. The aim of this study was to examine the effect of orange juice (OJ) or OJ beverage (Bev) alone and fortified with plant sterols (1g/240ml juice or beverage twice a day) on pro-inflammatory cytokines and PAI-1, a marker of impaired fibrinolysis in healthy human volunteers. In the first study, 72 healthy human volunteers received Placebo OJ or Sterol OJ and in the second study, 72 volunteers received OJBev or Sterol OJBev for 8 weeks and blood was drawn at baseline and following supplementation for 8 weeks. Biomarkers of Inflammation (IL-1b, IL-6, TNF, IL-8, IL-10) were assessed in serum using the BD Human Inflammatory Cytokine Cytometric Bead Array and PAI-1 activity was assessed in citrated plasma. OJ or OJBev alone failed to result in any significant effects on circulating cytokine levels or PAI-1 activity. There was a significant reduction in IL-1b with sterol fortified OJ (p<0.05) compared to baseline. In addition, both sterol fortified OJ as well as sterol fortified OJBev resulted in significant reductions in serum IL-6 levels (p<0.01). Thus, sterol fortified OJ and OJ Beverage are able to effectively lower biomarkers of inflammation in healthy human volunteers in addition to providing lipid profile benefits and may thus contribute to decreasing cardiovascular risk.

Status of lipids and the frequency diseases of cardiovascular origin in smokers according to the length period of smoking and a number of cigarettes smoked daily

Cigarette smoking affects all phases of atherosclerosis from endothelial dysfunction to acute occlusive clinical events. The problem is, whether the length of the period of cigarette smoking has a more reflection to the status of lipids and illnesses of cardiovascular system or the bigger number of smoked cigarettes in a shorter time-period? The observed sample has constituted of two groups of smokers, both gender, age 25-64 years old. The first group consisted of 210 examinees divided in 7 subgroups according to a number of years they have been smoking. The second group consisted of 150 examinees, which was divided in 5 subgroups, according to average number of cigarettes smoked daily. The average values of serum cholesterol (6.98 vs. 6.13 mmol/L), triglycerides (3.15 vs. 3.13 mmol/L) and LDL-cholesterol (3.80 vs. 3.64 mmol/L) were always higher in a group of smokers according to a number of daily smoked cigarettes. Average value of smoking consumption period was higher in a group of smokers according to the length of smoking consumption period than in a group of smokers according to a number of cigarettes smoked daily (20.34 y vs. 13.55 y.). Hypertension (72% vs. 30.9%), angina pectoris (44.6% vs. 20.4%), CHD (30.6% vs. 22.8%) and myocardial infarction (16% vs. 11.4%) appeared much more in the group of smokers according to a number of cigarettes smoked daily. More reflection to the status of lipids and illnesses of cardiovascular system has the bigger number of smoked cigarettes daily than the length of the period of cigarette smoking.

Rosuvastatin, inflammation, C-reactive protein, JUPITER, and primary prevention of cardiovascular disease--a perspective.

The major public health concern worldwide is coronary heart disease, with dyslipidemia as a major risk factor. Statin drugs are recommended by several guidelines for both primary and secondary prevention. Rosuvastatin has been widely accepted because of its efficacy, potency, and superior safety profile. Inflammation is involved in all phases of atherosclerosis, with the process beginning in early youth and advancing relentlessly for decades throughout life. C-reactive protein (CRP) is a well-studied, nonspecific marker of inflammation which may reflect general health risk. Considerable evidence suggests CRP is an independent predictor of future cardiovascular events, but direct involvement in atherosclerosis remains controversial. Rosuvastatin is a synthetic, hydrophilic statin with unique stereochemistry. A large proportion of patients achieve evidence-based lipid targets while using the drug, and it slows progression and induces regression of atherosclerotic coronary lesions. Rosuvastatin lowers CRP levels significantly. The Justification for Use of statins in Prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER) trial was designed after the observation that when both low density lipoprotein and CRP were reduced, patients fared better than when only LDL was lowered. Advocates and critics alike acknowledge that the benefits of rosuvastatin in JUPITER were real. After a review, the US Food and Drug Administration extended the indications for rosuvastatin to include asymptomatic JUPITER-eligible individuals with one additional risk factor. The American Heart Association and Centers of Disease Control and Prevention had previously recognized the use of CRP in persons with “intermediate risk” as defined by global risk scores. The Canadian Cardiovascular Society guidelines went further and recommended use of statins in persons with low LDL and high CRP levels at intermediate risk. The JUPITER study focused attention on ostensibly healthy individuals with “normal” lipid profiles and high CRP values who benefited from statin therapy. The backdrop to JUPITER during this period was an increasing awareness of a rising cardiovascular risk burden and imperfect methods of risk evaluation, so that a significant number of individuals were being denied beneficial therapies. Other concerns have been a high level of residual risk in those who are treated, poor patient adherence, a need to follow guidelines more closely, a dual global epidemic of obesity and diabetes, and a progressively deteriorating level of physical activity in the population. Calls for new and more effective means of reducing risk for coronary heart disease are intensifying. In view of compelling evidence supporting earlier and aggressive therapy in people with high risk burdens, JUPITER simply offers another choice for stratification and earlier risk reduction in primary prevention patients. When indicated, and in individuals unwilling or unable to change their diet and lifestyles sufficiently, the benefits of statins greatly exceed the risks. Two side effects of interest are myotoxicity and an increase in the incidence of diabetes.

Atherosclerosis Update: Development, Prevention/Stabilization, and Risk

Inflammation plays a critical role in all phases of atherosclerosis, and it is triggered in part by lipid entry and retention and subsequent oxidation in the vessel walls. Most of the factors that contribute to plaque instability are related to lipid accumulation and subsequent inflammatory pathway activation. Changing the phenotype of the atherosclerotic lesions could increase plaque stability and reduce clinical events. This article discusses several interventions to reduce inflammation, as well as selected studies regarding the reduction of risk factors.