Olov Wiklund

A number of plasma lipid parameters have been used to estimate cardiovascular risk and to be targets for treatment to reduce risk. Most risk algorithms are based on total cholesterol (T-C) or low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C), and most intervention trials have targeted the LDL-C levels. Emerging measures, which in some cases may be better for risk calculation and as alternative treatment targets, are apolipoprotein B and non-HDL-C. Other lipid measures that may contribute in risk analysis are triglycerides (TG), lipoprotein(a), and lipoprotein-associated phospholipase A₂. The primary treatment target in cardiovascular prevention is LDL-C, and potential alternative targets are apoB and non-HDL-C. In selected individuals at high cardiovascular (CV) risk, TG should be targeted, but HDL-C, Lp(a), and ratios such as LDL-C/HDL-C or apoB/apoAI are not recommended as treatment targets. Lipids should be monitored during titration to targets. Thereafter, lipids should be checked at least once a year or more frequently to improve treatment adherence if indicated. Monitoring of muscle and liver enzymes should be done before the start of treatment. In stable conditions during treatment, the focus should be on clinical symptoms that may alert muscle or liver complications. Routine measurement of CK or ALT is not necessary during treatment with statins.

Neutrophils are activated and infiltrate the myocardium after ischemia and reperfusion. The involvement of neutrophils in irreversible reperfusion injury is suggested by numerous experimental studies. The aim of this study was to investigate markers of neutrophil activation following reperfusion of acute myocardial infarction (AMI) accomplished with percutaneous coronary intervention (PCI) and their relationship to markers of lipid peroxidation, cytokines and highly-sensitive C-reactive protein (hsCRP). Non-consecutive patients with their first myocardial infarction were evaluated. Setting. University hospital as primary referral center, single center. Forty-nine patients with AMI were evaluated. All were treated with primary PCI and infusion of abciximab. Reperfusion was verified by angiography. Blood samples for analyses of myeloperoxidase (MPO), neutrophil gelatinase-associated lipocalin (NGAL), matrix metalloproteinase-9 (MMP-9), malondialdehyde (MDA), 8-isoprostane-prostaglandin F2alpha (Iso-P), interleukin 6 (IL-6), interleukin 8 (IL-8), tumor necrosis factoralpha (TNFalpha), hsCRP, creatine kinase-monobasic fraction (CK-MB) and troponin-T (TnT) were obtained at baseline with the occluded coronary vessel, and subsequently after verified reperfusion at 1.5, 3 and 24 hours. Significant increases in MMP-9, IL-6, IL-8, TNFalpha and hsCRP were observed, and a significant decrease in MPO and MDA was also observed over the same period. No significant changes in Iso-P and NGAL were found. We found a dissociation of the inflammatory reaction after PCI for AMI: a decrease of markers of neutrophil activation and MDA, but an increase in cytokines and hsCRP. An antineutrophil effect of the PCI procedure including treatment with abciximab, an antiplatelet drug and a modulator of inflammation, is conceivable.

Background and Purpose — β-Adrenergic blockade has in several studies been shown to improve survival after myocardial infarction. In animal experiments β-blockers have also shown an antiatherosclerotic effect. The aim of this study was to test the hypothesis that the β-blocker metoprolol succinate controlled release/extended release (CR/XL), when given to patients with hypercholesterolemia on concomitant lipid-lowering therapy, provides an additional antiatherosclerotic effect to that provided by the statins, measured as carotid intima-media thickness (IMT). Methods — We conducted a randomized, double-blind, placebo-controlled, single center trial to compare the effect of metoprolol CR/XL (100 mg once daily) and placebo on the progression of carotid IMT during 36 months of treatment in patients with hypercholesterolemia and signs of early atherosclerosis in the carotid artery. Most patients were prescribed lipid-lowering treatment with statins. Results — A highly significant difference in the progression rate of the composite variable of carotid bulb IMT+common carotid IMT was observed between the metoprolol CR/XL and placebo groups after 1 year of treatment (−0.08 versus −0.01 mm; P =0.004), an effect that was sustained after 3 years of follow-up (−0.06 versus +0.03 mm; P =0.011). The patients had high levels of total cholesterol at randomization: 9.4 mmol/L in the metoprolol CR/XL group and 8.6 mmol/L in the placebo group. During the study the 2 randomization groups were treated with lipid-lowering drugs, mainly statins, to a similar extent, and total cholesterol was reduced to 6.4 mmol/L at end of follow-up in both groups. Conclusions — The results from the present study in patients with hypercholesterolemia under concomitant lipid-lowering therapy are the first clinical data to show an antiatherosclerotic effect of β-blockade as additional therapy to statins. The data indicate that statin treatment and treatment with β-blockers affect different mechanisms in the atherosclerotic process and have additive beneficial effects.