Atherosclerosis, formerly considered a bland lipid storage disease, actually involves an ongoing inflammatory response. Recent advances in basic science have established a fundamental role for inflammation in mediating all stages of this disease from initiation through progression and, ultimately, the thrombotic complications of atherosclerosis. These new findings provide important links between risk factors and the mechanisms of atherogenesis. Clinical studies have shown that this emerging biology of inflammation in atherosclerosis applies directly to human patients. Elevation in markers of inflammation predicts outcomes of patients with acute coronary syndromes, independently of myocardial damage. In addition, low-grade chronic inflammation, as indicated by levels of the inflammatory marker C-reactive protein, prospectively defines risk of atherosclerotic complications, thus adding to prognostic information provided by traditional risk factors. Moreover, certain treatments that reduce coronary risk also limit inflammation. In the case of lipid lowering with statins, this anti-inflammatory effect does not appear to correlate with reduction in low-density lipoprotein levels. These new insights into inflammation in atherosclerosis not only increase our understanding of this disease, but also have practical clinical applications in risk stratification and targeting of therapy for this scourge of growing worldwide importance.

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Inflammation and Atherosclerosis

In 1998, the American Heart Association convened Prevention Conference V to examine strategies for the identification of high-risk patients who need primary prevention. Among the strategies discussed was the measurement of markers of inflammation.1 The Conference concluded that “many of these markers (including inflammatory markers) are not yet considered applicable for routine risk assessment because of: (1) lack of measurement standardization, (2) lack of consistency in epidemiological findings from prospective studies with endpoints, and (3) lack of evidence that the novel marker adds to risk prediction over and above that already achievable through the use of established risk factors.” The National Cholesterol Education Program Adult Treatment Panel III Guidelines identified these markers as emerging risk factors,1a which could be used as an optional risk factor measurement to adjust estimates of absolute risk obtained using standard risk factors. Since these publications, a large number of peer-reviewed scientific reports have been published relating inflammatory markers to cardiovascular disease (CVD). Several commercial assays for inflammatory markers have become available. As a consequence of the expanding research base and availability of assays, the number of inflammatory marker tests ordered by clinicians for CVD risk prediction has grown rapidly. Despite this, there has been no consensus from professional societies or governmental agencies as to how these assays of markers of inflammation should be used in clinical practice.

On March 14 and 15, 2002, a workshop titled “CDC/AHA Workshop on Inflammatory Markers and Cardiovascular Disease: Applications to Clinical and Public Health Practice” was convened in Atlanta, Ga, to address these issues. The goals of this workshop were to determine which of the currently available tests should be used; what results should be used to define high risk; which patients should be tested; and the indications for which the tests would be most useful. These …

Markers of Inflammation and Cardiovascular Disease Application to Clinical and Public Health Practice: A Statement for Healthcare Professionals From the Centers for Disease Control and Prevention and the American Heart Association

Increased levels of the inflammatory biomarker high-sensitivity C-reactive protein predict cardiovascular events. Since statins lower levels of high-sensitivity C-reactive protein as well as cholesterol, we hypothesized that people with elevated high-sensitivity C-reactive protein levels but without hyperlipidemia might benefit from statin treatment. Methods We randomly assigned 17,802 apparently healthy men and women with low-density lipoprotein (LDL) cholesterol levels of less than 130 mg per deciliter (3.4 mmol per liter) and high-sensitivity C-reactive protein levels of 2.0 mg per liter or higher to rosuvastatin, 20 mg daily, or placebo and followed them for the occurrence of the combined primary end point of myocardial infarction, stroke, arterial revascularization, hospitalization for unstable angina, or death from cardiovascular causes. Results The trial was stopped after a median follow-up of 1.9 years (maximum, 5.0). Rosuvastatin reduced LDL cholesterol levels by 50% and high-sensitivity C-reactive protein levels by 37%. The rates of the primary end point were 0.77 and 1.36 per 100 person-years of follow-up in the rosuvastatin and placebo groups, respectively (hazard ratio for rosuvastatin, 0.56; 95% confidence interval [CI], 0.46 to 0.69; P<0.00001), with corresponding rates of 0.17 and 0.37 for myocardial infarction (hazard ratio, 0.46; 95% CI, 0.30 to 0.70; P = 0.0002), 0.18 and 0.34 for stroke (hazard ratio, 0.52; 95% CI, 0.34 to 0.79; P = 0.002), 0.41 and 0.77 for revascularization or unstable angina (hazard ratio, 0.53; 95% CI, 0.40 to 0.70; P<0.00001), 0.45 and 0.85 for the combined end point of myocardial infarction, stroke, or death from cardiovascular causes (hazard ratio, 0.53; 95% CI, 0.40 to 0.69; P<0.00001), and 1.00 and 1.25 for death from any cause (hazard ratio, 0.80; 95% CI, 0.67 to 0.97; P = 0.02). Consistent effects were observed in all subgroups evaluated. The rosuvastatin group did not have a significant increase in myopathy or cancer but did have a higher incidence of physician-reported diabetes. Conclusions

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Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein.

Since 1980, the American College of Cardiology (ACC) and American Heart Association (AHA) have translated scientific evidence into clinical practice guidelines (guidelines) with recommendations to improve cardiovascular health. In 2013, the National Heart, Lung, and Blood Institute (NHLBI) Advisory

http://kidneys.zaslavsky.com.ua/article/download/122220/118980

2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines

Previous studies have shown that statin therapy reduces high-sensitivity C-reactive protein levels as well as cholesterol, but no prospective trials have directly addressed the issue of whether elevated levels of high-sensitivity C-reactive protein are beneficial for apparently healthy perso

Rosuvastatin to Prevent Vascular Events in Men and Women With Elevated C-Reactive Protein

ContextPlasma levels of the inflammatory biomarker C-reactive protein (CRP)
predict cardiovascular risk, and retrospective studies suggest that 3-hydroxy-3-methylglutaryl
coenzyme A reductase inhibitors (statins) may lower CRP in a manner largely
independent of low-density lipoprotein cholesterol (LDL-C). However, prospective
trial data directly evaluating this anti-inflammatory effect of statins are
not available.ObjectiveTo test the hypothesis that pravastatin has anti-inflammatory effects
as evidenced by CRP reduction.Design, Setting, and ParticipantsCommunity-based, prospective, randomized, double-blind trial including
1702 men and women with no prior history of cardiovascular disease (primary
prevention cohort) and open-label study including 1182 patients with known
cardiovascular disease (secondary prevention cohort) who provided at least
baseline and 12-week blood samples. The study was conducted in US office-based
practices from February to December 2000.InterventionsParticipants in the double-blind primary prevention trial were randomly
assigned to receive 40 mg/d of pravastatin (n = 865) or placebo (n = 837)
for 24 weeks. Participants in the secondary prevention cohort received 40
mg/d of open-label pravastatin for 24 weeks.Main Outcome MeasureChange in CRP levels from baseline to 24 weeks.ResultsIn the primary prevention trial, compared with placebo, pravastatin
reduced median CRP levels by 16.9% (P<.001) at
24 weeks, reflecting a decrease of 0.02 mg/dL in the pravastatin group while
no change in CRP levels was observed in the placebo group. This effect was
seen as early as 12 weeks (median reduction in CRP with pravastatin, 14.7%; P<.001) and was present among all prespecified subgroups
according to sex, age, smoking status, body mass index, baseline lipid levels,
presence of diabetes, and use of aspirin or hormone replacement therapy. No
significant association was observed between baseline CRP and baseline LDL-C
levels, end-of-study CRP and end-of-study LDL-C levels, or change in CRP and
change in LDL-C levels over time. In linear regression analyses, the only
significant predictors of change in CRP on a log scale were randomized pravastatin
allocation and baseline CRP levels (P<.001 for
both). Similar reductions in CRP levels were observed at 12 weeks (−14.3%)
and 24 weeks (−13.1%) in the secondary prevention cohort treated with
pravastatin (P<.005 for both).ConclusionsIn this prospective trial, pravastatin reduced CRP levels at both 12
and 24 weeks in a largely LDL-C–independent manner. These data provide
evidence that statins may have anti-inflammatory effects in addition to lipid-lowering
effects.

/pdf/effect-of-statin-therapy-on-c-reactive-protein-levels-the-xiczdrsp28.pdf

Effect of Statin Therapy on C-Reactive Protein Levels: The Pravastatin Inflammation/CRP Evaluation (PRINCE): A Randomized Trial and Cohort Study

Objective. —To test the short-term feasibility and efficacy of seven nonpharmacologic interventions in persons with high normal diastolic blood pressure. Design. —Randomized control multicenter trials. Setting. —Volunteers recruited from the community, treated and followed up at special clinics. Participants. —Of 16821 screenees, 2182 men and women, aged 30 through 54 years, with diastolic blood pressure from 80 through 89 mm Hg were selected. Of these, 50 did not return for follow-up blood pressure measurements. Interventions. —Three life-style change groups (weight reduction, sodium reduction, and stress management) were each compared with unmasked nonintervention controls over 18 months. Four nutritional supplement groups (calcium, magnesium, potassium, and fish oil) were each compared singly, in double-blind fashion, with placebo controls over 6 months. Main Outcome Measures. —Primary: change in diastolic blood pressure from baseline to final follow-up, measured by blinded observers. Secondary: changes in systolic blood pressure and intervention compliance measures. Results. —Weight reduction intervention produced weight loss of 3.9 kg (P .05). Conclusions. —Weight reduction is the most effective of the strategies tested for reducing blood pressure in normotensive persons. Sodium reduction is also effective. The long-term effects of weight reduction and sodium reduction, alone and in combination, require further evaluation. (JAMA. 1992;267:1213-1220)

https://jamanetwork.com/HttpHandlers/ArticlePdfHandler.ashx?journal=JAMA&articleId=395495&pdfFileName=jama_267_9_028.pdf

The Effects of Nonpharmacologic Interventions on Blood Pressure of Persons With High Normal Levels: Results of the Trials of Hypertension Prevention, Phase I

Ellie Danielson

Papers

Effect of Statin Therapy on C-Reactive Protein Levels: The Pravastatin Inflammation/CRP Evaluation (PRINCE): A Randomized Trial and Cohort Study

The Effects of Nonpharmacologic Interventions on Blood Pressure of Persons With High Normal Levels: Results of the Trials of Hypertension Prevention, Phase I

Effect of statin therapy on C-reactive protein levels. The pravastatin inflammation/CRP evaluation (PRINCE): a randomized trial and cohort study☆

A Randomized Trial and Cohort Study (PRINCE): The Pravastatin Inflammation/CRP Evaluation Effect of Statin Therapy on C-Reactive Protein Levels: