Cardiovascular morbidity

It is well accepted that hypertension is a multifactorial disease. Only about 10% of the hypertensive patients have secondary hypertension for which causes, ie, partial coarctation of the renal artery, pheochromacytoma, aldosteronism, hormonal imbalances, etc, are known. The hallmark of hypertension is an abnormally elevated total peripheral resistance. In most patients hypertension produces no serious symptoms particularly in the early phase of the disease. This is why hypertension is called a silent killer. However, prolonged suffering of high arterial blood pressure leads to end organ damage, causing stroke, myocardial infarction, and heart failure, etc. Adequate treatment of hypertension has been proven to decrease the incidence of cardiovascular morbidity and mortaUty and therefore prolong life (176—183). 

Treatment of essential or primary hypertension emphasizes not only the lowering of the elevated blood pressure, but also individualized therapy for each patient, providing each patient with minimized unnecessary side effects. The patient s cardiovascular morbidity and mortaUty should be decreased and end organ damage reversed or reduced (184,185). 

Systolic pressure, or maximum blood pressure, occurs during left ventricular systole. Diastolic pressure, or minimum blood pressure, occurs during ventricular diastole. The difference between systolic and diastolic pressure is the pulse pressure. While diastolic blood pressure has been historically been used as the most relevant clinical blood pressure phenotype, it has now been clearly established that systolic blood pressure is the more important clinical predictor for cardiovascular morbidity and mortality. More recently, additional attention is focussed on the importance of pulse pressure, i.e. the blood pressure amplitude, as a predictive factor for cardiovascular disease. 

P-Blockers and ACE inhibitors are also indicated for post-myocardial infarction for the reduction of cardiovascular morbidity and mortality, as are aldosterone antagonists, in post-myocardial infarction patients with reduced left ventricular systolic function and diabetes or signs and symptoms of heart failure.2,48... 

Patients receiving LT4 therapy who are not maintained in a euthyroid state are at risk for long-term adverse sequelae. In general, overtreatment and a suppressed TSH is more common than undertreatment27 with an elevated TSH. Patients with long-term overtreatment may be at higher risk for atrial fibrillation and other cardiovascular morbidities, depression, and post-menopausal osteoporosis. Patients who are undertreated are at higher risk for hypercholesterolemia and other cardiovascular problems, depression, and obstetric complications. 

Bjorck JE. (1999) Effect of angiotensin-converting-enzyme inhibition compared with conventional therapy on cardiovascular morbidity and mortality in hypertension The Captopril Prevention Project (CAPPP) randomised trial. Lancet 353 611-616. 

Most patients with established hypertension do not make sufficient lifestyle changes, do not take medication or do not take enough medication to achieve control. Even if adequately treated, patients may not lower their risk to that of persons with normal BP. It has to be emphasized that BP rise and high BP are not inevitable consequences of aging. Therefore an effective population-wide strategy to prevent BP rise with age could affect overall cardiovascular morbidity and mortality as much or more than that of treating only those with established hypertension. A population-wide approach has been shown to prevent or delay the expected rise in BP in susceptible... 

Lindhohn LEI, Ibsen El, Dahlof B, Devereux RB, Beev-ers G, de Eaire U et al. Cardiovascular morbidity and mortality in patients with diabetes in the Losartan Intervention For Endpoint reduction in hypertension study (LIFE) a randomised trial against atenolol. Lancet 2002 359(9311) 1004-10. 

Rice EH, Sombrotto LB, Markowitz, et al Cardiovascular morbidity in high-risk patients during ECT. Am J Psychiatry 151 1637-1641, 1994... 

GH synthesis and secretion does not disappear when linear growth is complete. In fact isolation of hGH from cadaver pituitary glands would not have been possible if it did. Physicians caring for adult patients with pituitary disease began to realize that even with optimum replacement of other hormones, patients who acquired GH deficiency in adulthood complained bitterly about diminished quality of life. Studies from Europe also documented increased cardiovascular morbidity and mortality in these patients [13], Because it was no longer necessary to conserve scarce supplies of hGH for use in children, physicians were able to study GH effects in adults with growth hormone deficiency. These studies have shown that GH improves body composition (decreases fat mass and increases lean body mass) and decreases risk factors for cardiovascular disease [14]. 

Atherosclerotic coronary heart disease (CHD) is a significant disease around the globe and is one of the major causes of death and cardiovascular morbidity in humans. Risk factors for CHD include hypertension, diabetes mellitus, male gender, cigarette smoking etc. but the most dominating risk factor is the serum cholesterol. 

New-onset diabetes mellitus in such patients is of particular concern, owing to the associated cardiovascular morbidity and the difficulty in managing diabetes in psychiatric patients. Soon after the first neuroleptic drugs were used, associations with weight gain and diabetes were reported (769,770). Nevertheless, even before antipsychotic drugs appeared, diabetes was observed to be more common in patients with schizophrenia (771). The rate of diabetes in patients with schizophrenia has been estimated at 6.2-8.7% (772) and at 0.8% in the general population in the USA (773). 

Isomaa, B., Almgren, P., Tuomi, T., Forsen, B., Lahti, K., Nissen, M., Taskinen, M. R., and Groop, L. (2001). Cardiovascular morbidity and mortality associated with the metabolic syndrome. Diabetes Care 24, 683-689. 

DHEA may affect the synthesis of cholesterol and other lipids involved in atherogenesis. Many studies have assessed the relationship between endogenous DHEA levels and the risk for developing cardiovascular disease. Both high and low DHEA levels have been associated with increased risk of cardiovascular morbidity in men. In postmenopausal women, cardiovascular morbidity was greater in women with high DHEAS levels. 

Isomaa B, Almgren P, Tuomi T, et al. Cardiovascular morbidity and mortality associated with the metabolic syndrome. Diabetes Care 2001 24 683-689. 

There is emerging evidence that OSA may be a pro-inflammatory disorder with elevated circulating cytokines [60]. Abdominal visceral fat is a major reservoir of cytokines, and obesity is a leading risk factor for the presence of OSA [60], The mechanism(s) whereby pro-inflammatory cytokines are elevated in OSA is not fully elucidated, but may be related to the excessive sympathetic nervous system activation notable in OSA. Tumor necrosis factor (TNF)-a and interleukin (IL)-6 levels are elevated in OSA [61,62] and the circadian rhythm of TNF-a is disrupted in OSA [63]. IL-6 levels are higher again in OSA patients with systemic hypertension compared to normotensive apneics [60], IL-6 levels return to normal in OSA patients treated effectively with CPAP [64]. Other mediators of inflammation elevated in OSA include intercellular adhesion molecule-1 and C-reactive protein, the latter being synthesized primarily in hepatocytes in response to IL-6 [60], The presence of these and other pro-inflammatory cytokines may link to the increased prevalence of cardiovascular morbidity in OSA. 

Losartan appears to be unique among the ARBs because it inhibits the urate anion transport in renal proximal tubuli hence, it increases uric acid excretion and decreases plasma levels of uric acid in hypertensive patients. This effect is not the consequence of AT] receptor blockade. Since high uric acid levels have been associated with cardiovascular morbidity/mortality, losartan may be the best ARB for patients with gout [7,30,31]. Moreover, losartan was found to decrease ocular pressure in normotensive as well as in hypertensive patients [32]. 

The question as to whether the differences in efficacy (a few mmHg) among the ARBs translates to meaningful end-points (e.g., reduced cardiovascular morbidity and mortality) remains to be answered by further clinical pharmacological trials. It is possible, however, that ARBs may have further potential indications in the prevention of cognitive decline. 

Weight gain is often associated with clozapine (SEDA-21, 54). In 42 patients who took clozapine for at least 1 year, men and women gained both weight and body mass, which is more directly related to cardiovascular morbidity (123). Over 10 weeks, leptin concentrations, which correlate with body mass index, increased significantly from baseline in 12 patients taking clozapine (124). 

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