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Allograft coronary artery disease (CAD) is the major determinant of long-term survival following heart transplantation (HTx). In a group of 210 heart transplant recipients, we diagnosed CAD in 54 (27.1%) by coronary angiography, postmortem examination or examination of the transplanted heart at the time of retransplantation. Retrospective analysis of potential risk factors for the development of CAD was performed for both immunological (rejection pattern, immunosuppressive therapy, cytomegalovirus [CMV] infection), and nonimmunological (hyperlipidemia, smoking, hypertension, diabetes mellitus, obesity) risk factors. The total number of rejection episodes correlated significantly with the occurrence of CAD (P less than 0.05), showing that patients who experienced two or more rejection episodes had an incidence of CAD of 40%, as opposed to a 23% incidence in patients who experienced no rejection. A composite rejection score derived from multivariate regression analysis of the severity, frequency, and timing of acute cardiac rejection episodes was found to correlate with the development of CAD (P less than 0.05). Postoperative arterial hypertension also correlated significantly with the onset of CAD (P less than 0.01), with a 92.6% incidence of hypertension in the group with CAD versus 76.3% in the group without CAD. Smoking after transplantation correlated significantly with the occurrence of CAD (P less than 0.05). There was no significant correlation with other analyzed factors in this group of patients. In this review, the development of CAD after heart transplantation correlated with treated allograft rejection. Aggressive treatment of hypertension and cessation of smoking may contribute to alleviation of this serious complication.
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PMID:Risk factors for development of accelerated coronary artery disease in cardiac transplant recipients. 236 Oct 19

The relationship between preinfarction clinical status and short-term outcome was prospectively evaluated in 775 patients hospitalized with acute myocardial infarction after reperfusion therapy. It was anticipated that a history of angina preceding myocardial infarction by more than 7 days would be associated with more extensive underlying coronary artery disease and a more complicated in-hospital course. However, although this group did have a higher risk profile for coronary artery disease (hypertension 53.6% vs 37.2%; diabetes 22.5% vs 12.1%; hyperlipidemia 19.4% vs 9.8%; mean number of risk factors 2.2 vs 1.7, p = 0.0001), a higher incidence of multivessel disease (57.7% vs 39.6%, p less than 0.0001), worse baseline global left ventricular function (left ventricular ejection fraction 48.8% vs 51.3%, p = 0.03), and impaired function of the noninfarct zone (-0.05 vs +0.46 SD/chord, p = 0.002), the in-hospital course was less complicated than in the group without prior angina. Patients without antecedent angina had a higher rate of reocclusion of the infarct-related artery (13.6% vs 8.2%; p = 0.048). Although the difference did not reach statistical significance (7.2% vs 4.6%; p = 0.21), the in-hospital mortality rate was also higher in this group. These findings suggest that a history of prior angina is not necessarily associated with an unfavorable short-term prognosis after reperfusion therapy. This may be related to the greater prior use by this group of beta-adrenergic- and calcium channel-blocking agents (23.1% vs 8.5% and 20.7% vs 3.8%, respectively). It may also be related to the beneficial effects of collateral vessels, myocardial preconditioning, or differences in the native fibrinolytic system.
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PMID:Relationship between antecedent angina pectoris and short-term prognosis after thrombolytic therapy for acute myocardial infarction. Thrombolysis and Angioplasty in Myocardial Infarction (TAMI) Study Group. 240 8

The drug treatment of mild hypertension has been shown to afford protection against fatal and nonfatal strokes, congestive heart failure, progression to more severe levels of hypertension, and all-cause mortality, but not against the complications of coronary artery disease. The lack of benefit against coronary artery disease may result from failure to reduce other risk factors or because the drugs employed increased coronary risk. It can be taken as axiomatic that effective preventive antihypertensive therapy is more likely with drugs with mechanisms and sites of action that are focused on the underlying pathophysiology than with drugs that lower blood pressure by means unrelated to the hypertensive process. Adrenergic predominance plays a major role in the initiation and maintenance of essential hypertension and, consequently, the alpha-adrenergic receptor inhibitors were among the first substances to receive serious consideration as antihypertensive agents. However, since these drugs are nonselective, feedback control of transmitter norepinephrine was lost and, consequently, the clinical expectations of the early alpha-adrenergic receptor inhibitors in the treatment of high blood pressure were not fulfilled. The discovery of selective postjunctional alpha 1-adrenergic-receptor inhibitors, such as prazosin and doxazosin, which preserve feedback control of transmitter norepinephrine release, was the crucially important step in the development of specific drugs to combat the hyperactivity of adrenergic vasoconstrictor nerves in hypertension. These drugs have been shown to normalize hemodynamics in hypertensive patients. They lower blood pressure through a reduction in peripheral resistance at rest and during exercise, independent of changes in heart rate and blood pressure, with minimal reflex activation or tolerance development. Alpha 1-adrenergic-receptor inhibitors, such as prazosin and doxazosin, represent an attractive choice for initial therapy in all grades of hypertension and are especially appropriate in hypertensive patients with congestive heart failure, asthma and chronic obstructive airways disease, renal impairment, diabetes mellitus, hyperlipidemia, benign prostatic hyperplasia, or gout, and in those involved in vigorous work, sports, or exercise. There are no known contraindications to these drugs, except in patients who are sensitive to quinazolines.
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PMID:Pharmacologic basis for the use of doxazosin in the treatment of essential hypertension. 256 23

In any therapeutic situation, the choice of drug therapy depends on an estimation of relative risk and benefit. With respect to moderate hypertension, and with less certainty, mild hypertension, the use of drug therapy has resulted in a decrease in overall mortality, a decrease in the incidence of stroke and renal impairment, but little or no change in the incidence of ischemic heart disease. For several years, the choice of first drug in these situations has rested between thiazide diuretics and beta-adrenoceptor blocking agents. There is probably little to choose between these two groups in terms of efficacy, and equally there is little evidence that patient response to one or other agents can be predicted either on demographic or biochemical evidence. There are, however, several studies both in Africa and America suggesting that black patients have a relatively greater hypotensive response to thiazides than to beta-blockers. The adverse reaction profile of these two groups is quite different. There is currently much debate whether the administration of large doses of thiazide diuretics (for example, 10 mg bendrofluazide per day) may cause a constellation of metabolic side effects (hyperlipemia, hypokalemia, abnormal glucose tolerance, and hyperuricemia) which may result in an increase of the risk of developing coronary artery disease in spite of lowering blood pressure. Further, there is no good evidence that the hypotensive effect of diuretics is dose dependent. On the other hand, the evidence that beta-blockers when used as antihypertensive agents have a primary preventive effect for ischemic heart disease is currently very small.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Angiotensin converting enzyme inhibition in clinical practice. Re-examination of step care: choice of first drug. 258 Jan 63

Observations are reported on 31 patients with coronary artery disease (CAD) from Nigeria (a region where CAD is rare). Hypertension either alone (12 cases), or associated with diabetes mellitus and obesity (4 cases), with diabetes mellitus and heavy cigarette smoking (1 case) was a frequent associated illness. Serum cholesterol measured in 15 cases was high in 13, but nine others without cholesterol assay were in the high socio-economic group, and serum cholesterol was likely to be relatively elevated in them also. Hyper-cholesterolaemia was the one factor that Nigerian patients with CAD had, but which is rare in the Nigerian general population. This observation appears to support the view that other major pre-disposing factors to CAD cause this disease usually when there is a back-ground of hyperlipidaemia.
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PMID:A clinical profile of patients with coronary artery disease in Nigeria. 259 4

Ninety-two patients aged 40 years or less with documented coronary artery disease were studied with special emphasis on risk factors, coronary angiographic patterns and left ventricular function. Tobacco consumption was the most common risk factor (54%) followed by family history of coronary artery disease (40%). Hyperlipidaemia was not a frequent risk factor. Significant single vessel disease was present in 29% of patients. The incidence of double vessel and triple vessel disease was much higher. The left anterior descending artery was the most commonly involved vessel followed by right and circumflex coronary arteries. Left ventricular function as determined by ejection fraction was abnormal in 51% of patients; left ventricular end diastolic pressure was abnormal in 28% of patients. Sixty-eight percent of patients with no risk factors had either zero vessel or single vessel disease indicating a positive relationship between occurrence of risk factors and significant coronary artery disease in the young.
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PMID:Coronary artery disease pattern in the young. 261 37

As is obvious from the previous discussions, obesity is associated with a wide variety of changes in endocrine parameters (Table 1). Some of these changes, such as the reduction in SHBG without change in serum free testosterone levels, reflect merely laboratory abnormalities that may influence interpretation of diagnostic tests but have no important physiologic relevance. Other abnormalities have major clinical impact, such as hyperestrogenemia-endometrial carcinoma and hyperlipidemia-coronary artery disease. In some cases, endocrine changes in obesity are beneficial--that is, hyperestrogenemia leading to lower incidence of osteoporosis. In other cases, such as the profound suppression of growth hormone output in obesity, the physiologic relevance is unknown. Several endocrine changes in obesity, such as the impaired response of many hormones (growth hormone, prolactin, vasopressin, corticotropin) to insulin-induced hypoglycemia and elevated endorphin levels, suggest hypothalamic dysfunction. Furthermore, the failure of all of these abnormalities to be normalized after weight reduction raises the possibility of an underlying disorder leading to both endocrine dysfunction and obesity, rather than the endocrine dysfunction being simply a consequence of the obesity. Successful elucidation of the pathogenesis of obesity, which might then lead to much needed specific treatment modalities, may be advanced if we can solve some of these puzzles.
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PMID:Endocrine aspects of obesity. 264 1

Stroke, caused by either infartion or subarachnoid haemorrhage, can have devastating and debilitating effect on its victims. Traditional therapy has focused on the risk factors of hypertension, hyperlipidemia, atherosclerotic heart disease and diabetes milletus. More recently, the literature has focused on smoking and the short and long term effects of cerebral blood flow. The purpose of this paper will be to review the most recent research literature on both the chronic and acute effects of smoking on the cerebral vascular system. More specifically, there will be an examination of the effect of smoking on the outcome of a carotid endarterectomy, subarachnoid haemorrhage and the progression of atherosclerosis. Smoking is harmful and its cumulative effects, along with additive effects must be recognized. Despite increased risk, people continue to smoke affecting disease progression and treatment. Two models will be discussed--the health belief model and the health decision model. These models can provide a basis for nursing to develop and assess comprehensive smoking cessation programmes.
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PMID:Smoking--the effects on cerebral vascular circulation. A variable in patient decision making. 265 66

Epidemiologic studies have established that elevated low-density lipoprotein (LDL) cholesterol values and decreased levels of high-density lipoprotein (HDL) cholesterol are risk factors for coronary artery disease (CAD). Results from clinical trials indicate that reduction in LDL cholesterol decreases the incidence of and reduces the risk of CAD. The National Cholesterol Education Program recently developed guidelines for the evaluation of plasma cholesterol in adults. Initial classification is categorized and based on the following values: less than 200 mg/dl is "desirable" blood cholesterol; from 200 through 239 mg/dl is classified as "moderate-high" blood cholesterol; and greater than or equal to 240 mg/dl is "high" blood cholesterol. Decision-making regarding therapeutic intervention is influenced by the presence of other lipoprotein risk factors, such as reduced HDL cholesterol and elevated lipoprotein (a), and nonlipid factors, including age, sex, hypertension, obesity, smoking, diabetes mellitus, and family or patient history of CAD. Persons with borderline-high blood cholesterol and established CAD or 2 other risk factors as well as those with high blood cholesterol should undergo lipoprotein analysis. LDL cholesterol is the primary lipoprotein to consider when determining treatment goals. Patients with LDL cholesterol levels greater than 160 mg/dl without CAD or 2 other risk factors and those patients with LDL cholesterol greater than 130 mg/dl with CAD or 2 other risk factors are initially managed with dietary therapy. The goal of treatment of hyperlipidemia is to reduce LDL cholesterol to less than 160 mg/dl or to less than 130 mg/dl in patients with established CAD or with 2 other risk factors.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Clinical significance of plasma lipid levels. 267 28

Endothelial cells can release substances which profoundly affect vascular tone and platelet function. The inhibitory substances include endothelium-derived relaxing factor (EDRF or nitric oxide), prostacyclin and probably an endothelium-derived hyperpolarizing factor. Endothelin is a potent vasoconstrictor peptide released from endothelial cells. Under certain conditions, the endothelium can also produce angiotensin II, thromboxane A2 and a cyclooxygenase-dependent endothelium-derived contracting factor. In normal arteries, the effects of EDRF appear to dominate. In diseased arteries, the release and action of EDRF is impaired and that of endothelium-derived contracting factors is increased. Hyperlipidaemia, atherosclerosis and hypertension reduce endothelium-dependent relaxations. Hypoxia inhibits the release of EDRF and prolonged ischaemia severely impairs the response. Regenerated endothelium at sites of mechanical injury exhibits selective defects in response to aggregating platelets. The more effective release of EDRF in arterial compared with venous bypass grafts further suggests an involvement of the factor in preventing vascular occlusion. Therapeutic interventions with specific drugs and diets can augment the impaired endothelium-dependent relaxation of diseased arteries. Thus, functional changes of the endothelium in coronary artery disease may be an important factor in the development of vasospasm, ischaemia and thrombosis.
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PMID:Endothelium-derived relaxing and contracting factors: potential role in coronary artery disease. 268 Apr 93


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