Usefulness of Aspirin for Primary Prevention of Atherosclerotic Cardiovascular Disease.

Aspirin use in the prevention of cardiovascular events has been a mainstay of treatment for decades. However, the use of aspirin in primary prevention of atherosclerotic cardiovascular disease has recently come under scrutiny. Several recent studies have evaluated the use of aspirin in primary prevention and the results suggest that in many patients the risks may outweigh the benefits. Closer examination of these trials suggests that the use of aspirin therapy for primary prevention may have a role but likely needs a more tailored approach and that caution is needed in prescribing aspirin for primary prevention. In conclusion, in this article we review the evolving evidence for aspirin in the primary prevention of atherosclerotic cardiovascular disease.

Current Treatment of Familial Hypercholesterolaemia.

Familial hypercholesterolaemia is an autosomal-dominant disorder associated with mutations in the LDL receptor gene resulting in markedly elevated plasma low-density lipoprotein cholesterol levels. FH is significantly underrecognised with as many as 1 in 300 having the heterozygous form and 1 in 1 million having the homozygous form of the disease. Early diagnosis and treatment of FH is paramount to reduce the risk of premature atherosclerotic cardiovascular disease and death. The goal of treatment is to reduce LDL-C by 50 % from baseline levels with lifestyle modification, pharmacologic lipid-lowering therapy, LDL apheresis and in rare cases, liver transplantation. Pharmacologic treatment ranges from statin medications to newer agents such as lomitapide, mipomersin and PCSK9 inhibitors. Combination therapy is frequently required to achieve goal lipoprotein level reductions and prevent complications.

Niacin and statin combination therapy for atherosclerosis regression and prevention of cardiovascular disease events: reconciling the AIM-HIGH (Atherothrombosis Intervention in Metabolic Syndrome With Low HDL/High Triglycerides: Impact on Global Health Outcomes) trial with previous surrogate endpoint trials.

Despite substantial risk reductions targeting low-density lipoprotein cholesterol with statins, there remains significant residual risk as evidenced by incident and recurrent cardiovascular disease (CVD) events among statin-treated patients. Observational studies have shown that low levels of high-density lipoprotein cholesterol (HDL-C) are associated with increased CVD risk. It remains unclear whether strategies aimed at increasing HDL-C in addition to background statin therapy will further reduce risk. The AIM-HIGH (Atherothrombosis Intervention in Metabolic Syndrome With Low HDL/High Triglycerides: Impact on Global Health Outcomes) trial, which compared combined niacin/simvastatin with simvastatin alone, failed to demonstrate an incremental benefit of niacin among patients with atherosclerotic CVD and on-treatment low-density lipoprotein cholesterol values <70 mg/dl, but this study had some limitations. Previously, small randomized, clinical trials of niacin plus statins showed that modest regression of carotid atherosclerosis is possible in individuals with CVD, CVD risk equivalents, or atherosclerosis. This viewpoint summarizes these imaging trials studying niacin and places them in the context of the failure of AIM-HIGH to support the HDL-C-increasing hypothesis.

High-density lipoprotein therapy: is there hope?

OPINION STATEMENT: The treatment of lipid abnormalities generally has focused on low-density lipoprotein cholesterol (LDL-C) reduction based on extensive clinical trials and the National Cholesterol Education Program Adult Treatment Panel III guidelines. Unfortunately, it has become increasingly clear that a significant percentage of patients continue to have cardiovascular events despite being on LDL-C-lowering medications and having LDL-C levels below 100 mg/dL. Numerous epidemiologic studies have associated low high-density lipoprotein cholesterol (HDL-C) levels with increased risk of cardiovascular disease (CVD). Furthermore, recent data show that up to 55% of patients hospitalized for CVD have low HDL-C levels (<40 mg/dL) on admission, suggesting a possible target for further reducing CVD. Low HDL-C also is part of the atherogenic phenotype associated with obesity, glucose intolerance, and hypertension, termed the metabolic syndrome, and often is seen in patients with insulin resistance states. In general, the first line of therapy for increasing HDL-C in patients with levels below 40 mg/dL is lifestyle modification with smoking cessation, exercise, weight loss, and diet modifications. The pharmacologic treatment of isolated low HDL-C in patients without coronary disease is controversial but should be considered in those with a strong family history of CVD. In patients with coronary artery disease and isolated low HDL-C, statins remain the first-line therapy and should be instituted after lifestyle modifications, with the goal of increasing HDL-C above 40 mg/dL. If concomitant hypertriglyceridemia is present, a fibrate or niacin should be considered. Although statins do offer some HDL-C-raising properties, they tend to have modest effects. If treatment goals have not been achieved with either lifestyle changes or statin therapy, then the next agent of choice is niacin. Among the various HDL-C-raising therapies, niacin continues to be the most potent therapeutic option available. There are several novel HDL-C therapies in the research pipeline; however, only one class of medications is relatively close to clinical use, the cholesteryl ester transferase protein (CETP) inhibitors. Although one of the CETP inhibitors, torcetrapib, has received much negative attention from a large randomized trial showing increased mortality associated with its use, the overall class of therapeutic agents may still hold some benefit. Currently, two new CETP inhibitors without the off-target effects of torcetrapib are undergoing clinical research. Overall, the use of HDL-C-modifying agents likely will increase over the next decade.

Class effect of angiotensin-converting enzyme inhibitors on prevention of myocardial infarction.

Angiotensin-converting enzyme (ACE) inhibitors differ in their affinity for tissue-bound ACE. It has been hypothesized that tissue ACE affinity might be responsible for some of the beneficial cardiovascular properties of ACE inhibitors. The present study examined this question and found no correlation between tissue ACE affinity and risk of first nonfatal myocardial infarction in patients who have hypertension.

Comparison of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers in the primary prevention of myocardial infarction in hypertensive patients.

Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers have slightly different mechanisms of action. As such, it has been hypothesized that these 2 classes of medications differ in their ability to prevent myocardial infarction. In the present case-control study, we found no difference between angiotensin-converting enzyme inhibitors and angiotensin receptor blockers in the primary prevention of nonfatal myocardial infarction among patients with hypertension.

Nuclear factor-kappaB activation in endothelium by Chlamydia pneumoniae without active infection.

Causative molecular mechanisms accounting for the potential link between Chlamydia pneumoniae and atherosclerosis are unknown. Formalin and heat-inactivated C. pneumoniae activated the transcription factor nuclear factor (NF)-kappaB in cultured porcine endothelium and up-regulated the expression of E-selectin messenger RNA and protein. This up-regulation was abolished by an IkappaB super-repressor, an NF-kappaB-specific inhibitor. Live bacteria are not necessary for the activation of endothelial NF-kappaB, and C. pneumoniae may contribute to atherogenesis without active infection.