Abstract
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Inflammatory markers and the risk of coronary heart disease in men and women
Few studies have simultaneously investigated the role of soluble tumour necrosis factor α (TNF-α) receptors types 1 and 2 (sTNF-R1 and sTNF-R2), C-reactive protein, and interleukin-6 as predictors of cardiovascular events. The value of these inflammatory markers as independent predictors remains controversial.
The authors examined plasma levels of sTNF-R1, sTNF-R2, interleukin-6, and C-reactive protein as markers of risk for coronary heart disease among women participating in the Nurses’ Health Study and men participating in the Health Professionals Follow-up Study in nested case–control analyses. Among participants who provided a blood sample and who were free of cardiovascular disease at baseline, 239 women and 265 men had a non-fatal myocardial infarction or fatal coronary heart disease during 8 and 6 years of follow-up, respectively.
After adjustment for matching factors, high levels of interleukin-6 and C-reactive protein were significantly related to an increased risk of coronary heart disease in both sexes, whereas high levels of soluble TNF-α receptors were significant only among women. Further adjustment for lipid and non-lipid factors attenuated all associations; only C-reactive protein levels remained significant. The relative risk among all participants was 1.79 for those with C-reactive protein levels of at least 3.0 mg/l, as compared with those with levels of less than 1.0 mg/l (95% confidence interval, 1.27–2.51; P for trend < 0.001). Additional adjustment for the presence or absence of diabetes and hypertension moderately attenuated the relative risk to 1.68 (95% confidence interval, 1.18–2.38; P for trend = 0.008).
In conclusion, elevated levels of inflammatory markers, particularly C-reactive protein, indicate an increased risk of coronary heart disease. Although plasma lipid levels were more strongly associated with an increased risk than were inflammatory markers, the level of C-reactive protein remained a significant contributor to the prediction of coronary heart disease.
Pai JK, et al. Inflammatory markers and the risk of coronary heart disease in men and women. N Engl J Med 2004;
C-Reactive protein levels and outcomes after statin therapy
Statins lower the levels of low-density lipoprotein (LDL) cholesterol and C-reactive protein (CRP). Whether this latter property affects clinical outcomes is unknown.
The authors evaluated relationships between the LDL cholesterol and CRP levels achieved after treatment with 80 mg of atorvastatin or 40 mg of pravastatin per day and the risk of recurrent myocardial infarction or death from coronary causes among 3745 patients – with acute coronary syndromes.
Patients in whom statin therapy resulted in LDL cholesterol levels of less than 70 mg/dl (1.8 mmol/l) had lower event rates than those with higher levels (2.7 versus 4.0 events per 100 person-years, P = 0.008). However, a virtually identical difference was observed between those who had CRP levels of less than 2 mg/l after statin therapy and those who had higher levels (2.8 versus 3.9 events per 100 person-years, P = 0.006), an effect present at all levels of LDL cholesterol achieved. For patients with post-treatment LDL cholesterol levels of more than 70 mg/dl, the rates of recurrent events were 4.6 per 100 person-years among those with CRP levels of more than 2 mg/l and 3.2 events per 100 person-years among those with CRP levels of less than 2 mg/l; the respective rates among those with LDL cholesterol levels of less than 70 mg/dl were 3.1 and 2.4 events per 100 person-years (P < 0.001). Although atorvastatin was more likely than pravastatin to result in low levels of LDL cholesterol and CRP, meeting these targets was more important in determining the outcomes than was the specific choice of therapy. Patients who had LDL cholesterol levels of less than 70 mg/dl and CRP levels of less than 1mg/l after statin therapy had the lowest rate of recurrent events (1.9 per 100 person-years).
In conclusion, patients who have low CRP levels after statin therapy have better clinical outcomes than those with higher CRP levels, regardless of the resultant level of LDL cholesterol. Strategies to lower cardiovascular risk with statins should include monitoring CRP as well as cholesterol.
Ridker PM, et al. C-Reactive protein levels and outcomes after statin therapy. N Engl J Med 2005;
Statin therapy, LDL cholesterol, C-reactive protein, and coronary artery disease
Recent trials have demonstrated better outcomes with intensive than with moderate statin treatment. Intensive treatment produced greater reductions in both low-density lipoprotein (LDL) cholesterol and C-reactive protein (CRP), suggesting a relationship between these two biomarkers and disease progression.
The authors performed intravascular ultrasonography in 502 patients with angiographically documented coronary disease. Patients were randomly assigned to receive moderate treatment (40 mg of pravastatin orally per day) or intensive treatment (80 mg of atorvastatin orally per day). Ultrasonography was repeated after 18 months to measure the progression of atherosclerosis. Lipoprotein and CRP levels were measured at baseline and follow-up.
In the group as a whole, the mean LDL cholesterol level was reduced from 150.2 mg/dl (3.88 mmol/l) at baseline to 94.5 mg/dl (2.44 mmol/l) at 18 months (P < 0.00l), and the geometric mean CRP level decreased from 2.9–2.3 mg/l (P < 0.00l). The correlation between the reduction in LDL cholesterol levels and that in CRP levels was weak but significant in the group as a whole (r = 0.13, P = 0.005), but not in either treatment group alone. In univariate analyses, the percent change in the levels of LDL cholesterol, CRP, apolipoprotein B-100, and non-high-density lipoprotein cholesterol were related to the rate of progression of atherosclerosis. After adjustment for the reduction in these lipid levels, the decrease in CRP levels was independently and significantly correlated with the rate of progression. Patients with reductions in both LDL cholesterol and CRP that were greater than the median had significantly slower rates of progression than patients with reductions in both biomarkers that were less than the median (P = 0.00l).
In conclusion, for patients with coronary artery disease, the reduced rate of progression of atherosclerosis associated with intensive statin treatment, as compared with moderate statin treatment, is significantly related to greater reductions in the levels of both atherogenic lipoproteins and CRP.
Nissen SE, et al. Statin therapy, LDL cholesterol, C-reactive protein, and coronary artery disease. N Engl J Med 2005;
Amiodarone or an implantable cardioverter-defibrillator for congestive heart failure
Sudden death from cardiac causes remains a leading cause of death among patients with congestive heart failure (CHF). Treatment with amiodarone or an implantable cardioverter-defibrillator (ICD) has been proposed to improve the prognosis in such patients.
A total of 2521 patients with New York Heart Association (NYHA) class II or III CHF and a left ventricular ejection fraction (LVEF) of 35% or less were randomly assigned to conventional therapy for CHF plus placebo (847 patients), conventional therapy plus amiodarone (845 patients), or conventional therapy plus a conservatively programmed, shock-only, single-lead ICD (829 patients). Placebo and amiodarone were administered in a double-blind fashion. The primary end-point was death from any cause.
The median LVEF in patients was 25%; 70% were in NYHA class II, and 30% were in class III CHF. The cause of CHF was ischaemic in 52% and non-ischaemic in 48%. The median follow-up was 45.5 months. There were 244 deaths (29%) in the placebo group, 240 (28%) in the amiodarone group, and 182 (22%) in the ICD group. As compared with placebo, amiodarone was associated with a similar risk of death (hazard ratio, 1.06; 97.5% confidence interval, 0.86–1.30; P = 0.53) and ICD therapy was associated with a decreased risk of death of 23% (0.77; 97.5% confidence interval, 0.62–0.96; P = 0.007) and an absolute decrease in mortality of 7.2% after 5 years in the overall population. Results did not vary according to either ischaemic or non-ischaemic causes of CHF, but they did vary according to the NYHA class.
Therefore, in patients with NYHA class II or III CHF and LVEF of 35% or less, amiodarone has no favourable effect on survival, whereas single-lead, shock-only ICD therapy reduces overall mortality by 23%.
Bardy GH, et al. Amiodarone or an implantable cardioverter-defibrillator for congestive heart failure. N Engl J Med 2005;
Air pollution and coagulation
Air pollution has been associated with cardiovascular disease. Similarly, people exposed to air pollution, such as professional drivers also have increased risk. The mechanisms, however, are not well known. In an experimental study researchers from the University of Edinburgh found that pollution carried in the air, especially particulate matter, could induce thrombosis by creating a pro-inflammatory and pro-coagulant environment in the lungs and circulatory system. They tested the inflammatory, pro-thrombotic, and fibrinolytic responses of cells from the human immune system, umbilical cord, and lungs at 6 and 24 h after pulmonary environmental particles exposure. Culture media exposed to environmental particles from macrophages showed enhanced clotting ability. Tissue factor expression was elevated in macrophages exposed to environmental particles, but, conversely, tissue factor and tissue plasminogen activator gene and protein expression in umbilical cord endothelial vein cells were inhibited. They concluded that pollutant particles and other insults such as oxidative stress might generate a pro-coagulant environment within the lungs. The pro-coagulant effects of environmental particles on macrophages might be relevant to thrombosis on atherosclerotic plaques. Similarities to some of the effects of smoking spring to mind.
Wilmour PS, et al. The procoagulant potential of environmental particles. Occup Environ Med 2005;
Nurse-led CHD secondary prevention is cost-effective
A study that aimed to establish the cost effectiveness of nurse-led secondary prevention clinics for coronary heart disease in a randomized controlled trial was conducted in 19 general practices in north-east Scotland. A total of 1343 patients aged under 80 years with a diagnosis of coronary heart disease were randomized, either to nurse-led clinics to promote medical and lifestyle components of secondary prevention, or to standard care. The follow-up lasted 4 years. The cost of the intervention (clinics and drugs) was higher in the intervention group, but the difference in other costs, although lower for the intervention group, was not statistically significant. Overall, 28 fewer deaths occurred in the intervention group [100 (14.5%) versus 128 (19.1%); P = 0.04] leading to a gain in mean life years per patient. The authors concluded that nurse-led clinics for the secondary prevention of coronary heart disease in primary care seem to be cost effective compared with most interventions in health care, with the main gains in life years saved.
Raftery JP, et al. Cost-effectiveness of nurse-led secondary prevention clinics for coronary heart disease in primary care: follow-up of a randomized controlled trial. BMJ 2005 Feb 16; [Epub ahead of print].
Migraine linked to cardiovascular risk factors
Migraine has been linked to elevated risk of ischaemic stroke, particularly at younger ages. The reason for this is not quite clear. In a study from the Genetic Epidemiology of Migraine (GEM) study, a population-based study in the Netherlands, cardiovascular disease (CVD) risk factors were compared in 620 patients with migraine and 5135 controls. People with migraine were found have a higher prevalence of smoking, and a family history of CVD. Patients with migraine with an aura more often had unfavourable cholesterol levels, elevated blood pressure, and they also more often reported a history of heart disease or stroke. These intriguing findings raise additional questions concerning other vasospastic conditions, for instance coronary vasospasm with angina.
Scher AI, et al. Cardiovascular risk factors and migraine: The GEM population-based study. Neurology 2005;