Cardiovascular disease therapeutic interventions

Cardiovascular diseases are known to be accompanied by activation of lipid peroxidation processes in blood. The evidence that oxidative modification of LDL may play an important causative role in atherosclerosis has been increasing rapidly over the past several years. One of the important challenges that remains in this field of research is to go beyond the risk-factor concept to a comprehensive understanding of the biochemical mechanisms responsible for initiation and progression of lesions, and in particular to identity factors essential for atheroma development that might be susceptible to therapeutic intervention. 

Cardiovascular disease (CVD) remains the most important cause of morbidity and mortality in people with diabetes [1], This high-risk population is more likely to suffer a fatal event as the first manifestation of myocardial infarction (MI) or stroke, making primary prevention a priority. The pathogenesis of atherosclerosis-related disease is multifactorial but dyslipidaemia is a common and important risk predictor and is open to therapeutic intervention. Pharmacological intervention is supported by major randomised, controlled clinical trials (RCTs) of primary and secondary CVD prevention. RCTs with statin drugs have demonstrated unequivocal benefit in reducing major coronary events and stroke. 

Cardiovascular disease (CVD) continues to take a heavy toll on people in the productive period of life, especially in industrialized countries. Although its incidence has fallen in the last decade, CVD is still the main cause of death in industrialized countries. In the United States and many other countries, it is the number one chronic condition requiring hospitalization, and is also the most prevalent disease condition in the elderly. Despite intensive research, the etiology and the pathogenesis of arteriosclerosis and its consequences are not completely understood. An important causative factor is hypercholesterolemia, and cUnical intervention studies have demonstrated the therapeutic value of correcting it. However, at any given level of hypercholesterolemia, even in combination with all other classical risk factors such as hypertension or smoking, there is considerable variation in the expression of the disease. 

The central role played by ACE in cardiovascular pathologies such as hypertension and cardiac hypertrophy is well established. The action of ACE as the major mechanism in the biosynthesis of angiotensin II (Angll) has made it an excellent target for therapeutic intervention in the treatment of cardiovascular diseases [4]. While a number of ACE inhibitors have been developed and used effectively... 

Nitric oxide (NO) displays potent activities in the cardiovascular system as well as in the central and peripheral nervous systems. NO and its co-product L-citruUine are produced by the oxidation of L-arginine (28) by nitric oxide synthase (NOS) (Scheme 13.4). Selective modulation of NO biosynthesis offers the opportunity for therapeutic intervention of neurodegenerative diseases, among others. Based on the mechanism proposed for NO biosynthesis, two boronic acid analogues (29 and 30, Figure 13.7) of... 

By far, the most important therapeutic intervention in any patient with LEAD and CAD is smoking cessation. Smoking is the strongest risk factor for arterial disease progression, cardiovascular morbidity, and mortality from Ml, thrombotic stroke, and cardiovascular death. Smok-... 

The adversary relationship between prostacyclin (PGI2) and thromboxane-A2 (TXA2), which modulates coronary blood vessel caliber [112] and platelet aggregation [113], presents opportunities for therapeutic intervention in cardiovascular diseases. Substances that inhibit TXA2 synthetase or interfere at the TXA2 receptor... 

It is also evident that inhaled particles and irritants, such as ozone and SO2, can cause perturbations in both the lungs and the cardiovascular system that can potentially contribute to the increased morbidity and mortality observed with increasing levels of these pollutants. There is httle doubt that these neural responses to inhaled irritants and antigen are increased in persons with hypersensitive airways, pulmonary congestion, and heart disease. Clearly, the roles of these irritants and allergens on these vital pulmonary and cardiovascular functions as well as the mechanisms whereby they defend the body or compromise its function need further delineation. This will help provide the needed mechanistic links between inhaled irritants and increased morbidity and mortality. In addition, it will lead to the identification of target sites for prophylactic and therapeutic intervention. 

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