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This special issue focuses on key areas in preventive cardiology. Although clinicians commonly refer to primary and secondary prevention of coronary heart disease (CHD), it is probably more useful to [...]

The beneficial effect of β-hydroxy-β-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) in primary prevention of coronary artery disease in those with hypercholesterolaemia and in secondary prevention in those with established coronary vascular disease are now well known. A growing body of evidence suggests that statins also possess important additional clinical benefits, such as stroke risk reduction. In this article we review the evidence that statins may be neuroprotective, especially in the brain parenchyma during stroke. We also review the observational data that statins may prevent the onset of dementia.

Hypercholesterolemia has not traditionally been considered an important risk factor in the pathogenesis of stroke. However, recent studies show that statin therapy significantly reduces ischemic stroke for patients with established coronary artery disease. Statin therapy may reduce stroke through amelioration of precerebral atherosclerosis in the carotid artery and the aorta. Anti-atherosclerotic, anti-inflammatory, and antithrombotic actions of statins occur within the blood and in plaque. Statins may also protect against cerebral ischemia through beneficial modulation of the brain endothelial nitric oxide system. Ongoing studies are exploring the role of statin therapy in the primary prevention of stroke and in the prevention of cognitive decline and multi-infarct cerebrovascular disease.

Recent molecular genetic investigations of primary cardiac tumors (myxomas, lipomas, rhabdomyomas, and fibromas) have provided insight into fundamental mechanisms of cardiac cell growth. Myxomas are the most common adult cardiac tumor, and familial cardiac myxomas are now appreciated to be caused by mutations in the PRKAR1gene that encodes a regulatory subunit of protein kinase A. Cytogenetic studies have targeted candidate chromosomal loci that may be perturbed during cardiac lipoma pathogenesis. Rhabdomyomas, the most common pediatric cardiac neoplasm, are frequently associated with tuberous sclerosis, caused by mutations in the TSC-1and TSC-2genes. The study of Gorlin syndrome has shed light on the etiology of cardiac fibromas. This disorder is caused by mutation of the PTCgene, which regulates cell growth, commitment and differentiation. In the future, manipulation of PRKAR1-, TSC-,and PTC-dependent pathways may foster new strategies to regenerate myocardium in the ischemic or myopathic heart.

Septation defects and patent ductus arteriosus are the most common human cardiovascular malformations (CVMs). Genetic factors play a major part in the origin of these malformations. Recent molecular analyses have shed light on several mendelian forms. In the autosomal dominant Holt-Oram syndrome, both atrial and ventricular septal defects are inherited in association with limb deformity as a result of mutations in the gene encoding the TBX5 transcription factor. Mutations in the NKX2.5 transcription factor gene cause autosomal dominant familial atrial septal defects in association with progressive atrioventricular block as well as complex congenital heart disease. Common atrial syndromes in autosomal dominant Ellis–van Creveld syndrome arise in the context of axial skeletal and limb malformation as a result of mutations in the EVC gene, whose function is unknown. Patent ductus arteriosis occurs in several syndromic forms of congenital heart disease, including Holt-Oram syndrome. Recent analyses of autosomal dominant Char syndrome, which includes, with variable penetrance, patent ductus arteriosus as well as craniofacial and hand malformations, have shown that the syndrome is caused by mutations in the TFAP2B transcription factor gene. Ongoing analyses are poised to determine the contribution of these genes as well as others yet to be identified to common, sporadic forms of congenital heart disease. Am. J. Med. Genet. (Semin. Med. Genet.) 97:304–309, 2000. © 2001 Wiley-Liss, Inc.

Significant advances in the management of cardiovascular disease have been made possible by the development of 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitors—“statins.” Initial studies explored the impact of statin therapy on coronary artery disease (CAD) progression and regression. Although the angiographic changes were small, associated clinical responses appeared significant. Subsequent large prospective placebo-controlled clinical trials with statins demonstrated benefit in the secondary and primary prevention of CAD in subjects with elevated cholesterol levels. More recently, the efficacy of statins has been extended to the primary prevention of CAD in subjects with average cholesterol levels. Recent studies also suggest that statins have benefits beyond the coronary vascular bed and are capable of reducing ischemic stroke risk by approximately one-third in patients with evidence of vascular disease. In addition to lowering low-density lipoprotein (LDL) cholesterol, statin therapy appears to exhibit pleiotropic effects on many components of atherosclerosis including plaque thrombogenicity, cellular migration, endothelial function and thrombotic tendency. Growing clinical and experimental evidence indicates that the beneficial actions of statins occur rapidly and yield potentially clinically important anti- ischemic effects as early as one month after commencement of therapy. Future investigations are warranted to determine threshold LDL values in primary prevention studies, and to elucidate effects of statins other than LDL lowering. Finally, given the rapid and protean effects of statins on determinants of platelet reactivity, coagulation, and endothelial function, further research may establish a role for statin therapy in acute coronary syndromes.

Seizures are commonly encountered in patients who do not have epilepsy. Factors that may provoke such seizures include organ failure, electrolyte imbalance, medication and medication withdrawal, and hypersensitive encephalopathy. There is usually one underlying cause, which may be reversible in some patients. A full assessment should be done to rule out primary neurological disease. Treatment of seizures in medically ill patients is aimed at correction of the underlying cause with appropriate short-term anticonvulsant medication. Phenytoin is ineffective in the management of seizures secondary to alcohol withdrawal, and in those due to theophylline or isoniazid toxicity. Control of blood pressure is important in patients with renal failure and seizures. Non-convulsive status epilepticus should be considered in any patient with confusion or coma of unclear cause, and electroencephalography should be done at the earliest opportunity. Most ill patients with secondary seizures do not have epilepsy, and this should be explained to patients and their families. Only those patients with recurrent seizures and uncorrectable predisposing factors need long-term treatment with anticonvulsant medication.