Anti-inflammatory effects of statins: clinical evidence and basic mechanisms

Chronic inflammation is a key feature of vascular disease states such as atherosclerosis. Multiple clinical studies have shown that a class of medications termed statins lower cardiovascular morbidity and mortality. Originally developed to lower serum cholesterol, increasing evidence suggests that these medications have potent anti-inflammatory effects that contribute to their beneficial effects in patients. Here, we discuss the clinical and experimental evidence underlying the anti-inflammatory effects of these agents.     

A prospective study of plasma lipid levels and hypertension in women

BACKGROUND: Although dyslipidemia and hypertension occur together more often than can be explained by chance, few studies have carefully explored the nature of the relationship between plasma lipid levels and the risk of developing hypertension. METHODS: We conducted a prospective study of 16 130 middle-aged and older female health professionals in 1992 who provided baseline blood samples and had no history of high cholesterol level (no treatment or diagnosis) or hypertension (no treatment, diagnosis, or elevated blood pressure). Plasma lipid levels were measured, and baseline risk factors were collected. Incident hypertension included a new physician diagnosis, the initiation of antihypertensive treatment, systolic blood pressure of 140 mm Hg or greater, or diastolic blood pressure of 90 mm Hg or greater. RESULTS: During 10.8 years of follow-up, incident hypertension developed in 4593 women. In multivariate-adjusted models, the relative risks of development of hypertension from the lowest (referent) to the highest quintile of baseline total cholesterol level were 1.00, 0.96, 1.02, 1.09, and 1.12 (P = .002 for trend); for low-density lipoprotein cholesterol level, 1.00, 0.97, 1.00, 1.02, and 1.11 (P = .053 for trend); for high-density lipoprotein cholesterol level, 1.00, 0.93, 0.87, 0.87, and 0.81 (P < .001 for trend); for non-high-density lipoprotein cholesterol level, 1.00, 1.06, 1.11, 1.12, and 1.25 (P < .001 for trend); and for the ratio of total to high-density cholesterol, 1.00, 1.10, 1.14, 1.20, and 1.34 (P < .001 for trend). Similar relative risks were noted for Adult Treatment Panel III clinical cut points and after the exclusion of obese or diabetic women. CONCLUSION: In this large prospective cohort, atherogenic dyslipidemias were associated with the subsequent development of hypertension among healthy women.     

Relapsing polychondritis studied by computed tomography

Computed tomographic findings in a patient with relapsing polychondritis are described. Collapse of the cartilage of the nose and calcification in cartilages of the ears were clearly demonstrated. CT scanning was also helpful in evaluating the tracheobronchial tree for airway compromise, which could prove fatal in this condition.     

C-reactive protein in 2005. Interview by Peter C. Block

Acute coronary events strike nearly 1.4 million Americans annually. This includes an estimated 700,000 new coronary events, 500,000 recurrent events, and 175,000 silent first events each year. Adding to the clinical challenge is the fact that while conventional risk factors remain an important means of predicting who is at risk of developing coronary heart disease (CHD), it's unwise to rely on conventional risk factors alone for estimating patient risk. A 2003 evaluation of 122,458 patients enrolled in 14 international trials was meant to underscore that conventional risk factors are still important, yet one in five men with CHD in these trials (n=87,869) had none of the four conventional risk factors analyzed: smoking, hypertension, diabetes, and hyperlipidemia. Another challenge: Despite the overwhelming effectiveness of HMG-CoA reductase inhibitors in lipid lowering, 60% to 70% of cardiovascular events continue to occur despite statin therapy. This is in stark contrast to a 1996 prediction that statin therapy might eliminate heart attacks by the year 2000. It should be noted that in the large review of international trials mentioned above, only 34.1% of men with CHD had hyperlipidemia. If the lipid hypothesis of atherosclerosis is still correct, why do so few CHD patients have hyperlipidemia and why are so many events still occurring in patients on statin therapy? The seemingly anomalous data have led investigators to question whether the accepted target levels for low-density lipoprotein (LDL) cholesterol are low enough. Recent trials, including REVERSAL and PROVE IT/TIMI-22, have shown that lower target LDL levels, particularly in high-risk patients, are effective in further reducing cardiovascular events. (The implications of these studies were discussed in a 2004 update of clinical guidelines.) Yet, even intensive statin therapy is not the complete answer. In the PROVE-IT TIMI-22 study, for example, high-dose statin therapy still was associated with a 25% recurrent event rate at 2.5 years.     

High-sensitivity C-reactive protein: clinical importance

High-sensitivity C-reactive protein (hsCRP) is a marker of inflammation that predicts incident myocardial infarction, stroke, peripheral arterial disease, and sudden cardiac death among healthy individuals with no history of cardiovascular disease, and recurrent events and death in patients with acute or stable coronary syndromes. hsCRP confers additional prognostic value at all levels of cholesterol, Framingham coronary risk score, severity of the metabolic syndrome, and blood pressure, and in those with and without subclinical atherosclerosis. hsCRP levels of less than 1, 1 to 3, and greater than 3 mg/L are associated with lower, moderate, and higher cardiovascular risks, respectively. This article summarizes epidemiologic data on the relation between CRP and atherothrombotic disease and provides clinical guidelines for hsCRP screening in cardiovascular risk assessment.