Secondary prevention of arteriosclerosis

Secondary prevention of arteriosclerosis tries to inhibit progression of the atherosclerotic process. Therapeutic measures focus on modification of cardiovascular risk factors and antithrombotic treatment. Hypercholesterolemia is the main risk factor for coronary artery disease. The risk of a coronary event is correlated to the plasma cholesterol level. Lowering plasma cholesterol results in reduction of vascular morbidity and mortality. Cigarette smoking is the predominant risk factor for peripheral arterial occlusive disease (PAOD). Smoking cessation reduces progression of PAOD and lowers cardiovascular morbidity and mortality. The preventive effect of antihypertensive therapy in hypertensive patients is most pronounced for cerebrovascular events. Antihypertensive measures improve prognosis after stroke and myocardial infarction. The increased cardiovascular risk in diabetics is in part explained by hyperglycemia and hyperinsulinemia, but also depends on coexisting dyslipidemia and hypertension. Intensive treatment of elevated blood glucose levels, dyslipidemia and hypertension are important preventive measures. Aspirin is highly effective in secondary prevention of vascular events. For the coronary arteries, low-dose aspirin is well established. Whether low-dose aspirin is equally effective for reducing progression of arteriosclerosis in the cerebrovascular and in the peripheral vessels is questionable. Ticlopidine serves as an alternative to aspirin; however, neutropenia may occur, which requires supervision of the patient.     

Risk factor, natural history and prognosis of the patients with arteriosclerosis obliterans

A sufficient understanding of the risk factor and the natural history of arteriosclerosis obliterans, ASO, is essential for selecting the optimal treatment for this condition. Hypercholesterolemia, hypertension and cigarette smoking have been identified as independent major risk factors of ASO, and diabetics, obesity, hypertrigriceridemia, low HDL-cholesterol level, aging, gender, etc, as minor factors. The patients with ASO often have multiple risk factors, synergistically accelerating the disease progression. Recent objective studies on natural history of claudicants have demonstrated a more morbid prognosis, especially in the patients with disabling claudication, than that outlined by previous historical studies. Mortality rates for ASO patients in long-term follow-up have revealed to be significantly higher than those observed in control groups. The causes of death are mostly arteriosclerotic vascular disease, particularly coronary artery and cerebrovascular diseases, which indicate the significance of the systemic evaluation in treating patients with ASO.     

Non-pharmacological modification of cardiac risk factors: Part 1

Many factors influence whether a person will develop coronary heart disease. Genetic predisposition, gender and advanced age are recognized risk factors for the development of coronary heart disease over which we have little control. On the other hand, high serum cholesterol, cigarette smoking, high blood pressure, excessive body weight and long-term physical inactivity are key risk factors over which we have considerable control. In many cases cardiac risk factors can be modified without resorting to pharmacological intervention. Current evidence suggests that individuals who follow a diet which is low in saturated fats and cholesterol, lose weight, stop cigarette smoking and take regular aerobic exercise will significantly reduce their risk of developing coronary heart disease. In addition, patients who already have evidence of coronary heart disease may improve their symptoms and prognosis by similar life-style changes. In the first of two parts, we review the role of exercise in modifying cardiac risk factors.     

Worldwide experience with the Finetech-Brindley sacral anterior root stimulator

BACKGROUND: Serum creatinine has been reported in previous studies to be a prognostic indicator for overall mortality, in particular in a hypertensive population. METHODS: The Program on the Surgical Control of the Hyperlipidemias (POSCH) was a randomized, controlled clinical trial. All patients had survived a single myocardial infarction, were normotensive, were not obese, were not having heart failure, and were free of diabetes mellitus and renal disease at entry into the study. POSCH had followed its control group patients (N = 417) for a minimum of 7.0 years. In this group, a prospective post hoc analysis of the relationship of baseline serum creatinine with subsequent overall and atherosclerotic coronary heart disease mortality was performed. RESULTS: The baseline serum creatinine values in the control group patients ranged from 0.7 to 1.9 mg/dL (60 to 170 mumol/L), and were found to be independent predictors (P < .01) of both overall mortality and atherosclerotic coronary heart disease mortality. Each 0.1 mg/dL (9 mumol/L) increment in the baseline serum creatinine increased the relative risk for subsequent overall mortality by 36% and the relative risk for subsequent atherosclerotic coronary heart disease mortality by 47%. CONCLUSIONS: These results demonstrate that a serum creatinine value, obtained in normotensive, nonobese, normoglycemic survivors of a myocardial infarction without preexistent renal disease or heart failure, provides independent prognostic information regarding subsequent overall and atherosclerotic coronary heart disease mortality.     

Treatment of severe, drug resistant obsessive compulsive disorder with the 5HT1D agonist sumatriptan

Many risk factors operate in both coronary heart disease and stroke, especially ischaemic stroke--age, sex, social class, blood pressure, pre-existing vascular disease (angina, myocardial infarction, cardiac failure, diabetes and peripheral vascular disease, transient ischaemic attack and stroke), atrial fibrillation and fibrinogen, smoking, alcohol and height. Total cholesterol has also recently been recruited to this list. The various mechanisms involved in stroke and its subtypes and the epidemiological problems in evaluating aetiological factors in stroke make the comparison with coronary heart disease more difficult. The recent discrepancy between much of the epidemiology and the clinical trials evaluating the role of lipids in stroke has spurred the systematic review (meta-analysis) of major prospective observational studies. These will provide a clearer assessment about the quantitative comparison of some of the more important risk factors for stroke and coronary heart disease in the near future.     

Association between white blood cell count and risk factors of coronary artery disease

BACKGROUND: Epidemiologic studies have shown a correlation between white blood cell (WBC) count and risk of developing myocardial infarction. Aim of this study is to assess the association between WBC and the other risk factors of coronary heart disease in a southern Italian population. METHODS: Baseline data for the 1091 subjects (522 males and 569 females) enrolled in the "Montecorvino Rovella Project" were used to study factors associated with leukocytes. RESULTS: WBC count was significantly higher in smokers (8711.1 +/- 1892 cells/dl) than in ex-smokers (6720 +/- 1608 cells/dl) and in those who never smoked (6674 +/- 1608 cells/dl). By multiple linear regression analysis, WBC count showed a positive association with triglycerides (p < 0.01), cholesterol (p < 0.05) fasting glucose levels (p < 0.01) and diastolic blood pressure (p < 0.05). CONCLUSIONS: In this southern Italian population, elevated WBC count has been associated with other risk factors of coronary artery disease, particularly smoking, and has identified a high risk atherogenic profile. Even if the independency of the role of WBC is still under investigation, WBC count should be taken into account in establishing the coronary risk of apparently healthy people.     

A study of the association between the aortic pulse wave velocity and atherosclerotic risk factors among Japanese Americans in Seattle, U.S.A

Cardiovascular disease prevention screening was conducted among 1389 Japanese Americans in Seattle, Washington, U.S.A. from 1989 to 1994. The association between atherosclerotic risk factors and the aortic pulse wave velocity (PWV), an indicator of atherosclerosis, was examined by using multiple logistic regression method. Based on a study in 1996 by Suzuki et al. on the association between PWV and atherosclerotic indicators, abnormally high PWV was defined as 8.0 m/sec. and over for those less than 60 years of age and 9.0 m/sec. and over for those 60 years of age and older Significant odds ratios to estimate the risk for the presence of abnormally high PWV were found in age >or= 60 years (4.31, p < 0.001), hypertension (2.00, p < 0.001), diabetes (5.65, p < 0.001), current drinker (0.44, p < 0.001), ex-drinker (0.49, p < 0.05), and ex-smoker (1.82, p < 0.01) among men. Women showed a similar association: age > or = 60 years (3.03, p < 0.001), hypertension (1.94, p < 0.01), diabetes (2.47, p < 0.05), TC/HDL-C >or= 4.5 (1.98, p < 0.001), current drinker (0.47, p < 0.001), and ex-drinker (0.45, p < 0.05). Our findings are almost identical to those from other studies showing the association between coronary heart disease and its risk factors. The question of whether PWV can be a predictor of atherosclerotic diseases, particularly coronary heart disease, remains to be answered by additional studies. However, PWV may serve as a simple and valuable indicator to estimate the extent and severity of asymptomatic atherosclerosis in the large artery.     

Gout and atherosclerosis

Recently atherosclerotic diseases, such as coronary heart disease and cerebrovascular disease have been considered as an important complication of hyperuricemia and gout. However, it is still controversial whether or not hyperuricemia is an independent risk factor of atherosclerotic diseases. On the other hand, several risk factors for coronary heart disease, for example hyperlipidemia and hypertension, are frequently observed in the patients with gout. Atherosclerosis in relation to hyperuricemia was discussed in view of definite and probable risk factors.     

Preventive trials and the "diet-heart" question: wait for results or act now

Is the relationship between coronary heart disease risk factors and the risk of disease causal? Direct evidence would have to come, of necessity, from preventive trials. However, the difficult nature of such trials carries the inherent danger of false negative results; even positive results may be open to challenge. With regard to demonstrating specifically a preventive effect of lowering serum lipid levels through nutritional changes alone, this evidence may never be forthcoming since ongoing trials intervene simultaneously on multiple factors; against this disadvantage, the strengths of such trials are reviewed. The view is stated and discussed that preventive action in the community is justified now, without waiting for the results of preventive trials, however important they will be eventually to help the development of optimally effective programs.     

Insulin resistance implications for type II diabetes mellitus and coronary heart disease

PURPOSE: To review information on the implications of insulin resistance for type II diabetes mellitus (non-insulin-dependent diabetes mellitus) and coronary heart disease, and to derive guidance from this information for the management of these conditions. DATA SOURCES: A MEDLINE search of English-language articles published between 1985 and July 1996, and review of the bibliographies of articles obtained through the MEDLINE search and textbooks. STUDY SELECTION: Primary research articles, reviews and perspectives on the epidemiology of diabetes and cardiovascular diseases and on intervention outcomes in these diseases. DATA EXTRACTION: Study design and quality were assessed, with particular attention to methods, study population size and other characteristics. Conclusions of review articles and perspectives were analyzed critically. DATA SYNTHESIS: Type II diabetes is associated with a two- to fourfold excess of coronary heart disease, compared to nondiabetic populations. In most studies, glycemia and duration of clinical diabetes were found to be only weak risk factors for coronary heart disease. Conventional coronary heart disease risk factors such as dyslipidemia and hypertension have been associated with coronary heart disease in type II diabetes subjects. Hyperinsulinemia and insulin resistance have been predictive of the development of type II diabetes and, in some studies, of coronary heart disease. CONCLUSION: Strategies to prevent the development of coronary heart disease in diabetic and possibly prediabetic subjects should emphasize a multifactorial approach, including: a) improved glycemic control; b) aggressive treatment of risk factors for coronary heart disease, including insulin resistance; c) primary prevention of NIDDM; and d) use of glucose lowering agents that improve insulin sensitivity and cardiovascular risk factors.     

Cardiac allograft arteriopathy: an ischemic burden of a different sort

As heart transplant recipients live longer, an accelerated and distinct form of coronary artery disease develops that adversely affects survival. Indeed, cardiac allograft arteriopathy may be detected in as many as 90% of heart transplant recipients after 5 years. The precise incidence is not easily determined because the disease can be difficult to recognize when noninvasive tests are used; even angiography has substantive limitations. The distinct characteristics of this type of coronary artery disease result in a different form of chronic ischemic syndrome. The angiographic hallmark of allograft arteriopathy is an extensive, diffuse, obliterative process that primarily involves distal, small, subendocardial arteries. Endothelial injury seems to trigger the disease process. The arteriopathy is likely immunologically mediated and promoted or exacerbated by traditional atherosclerotic disease risk factors. Viral infection may be involved as well. To gain a better understanding of allograft arteriopathy, it is worthwhile to review its incidence, pathophysiology, prognosis, prevention, and treatment.     

Risk factors of arteriosclerosis in patients with severe bradycardia arrhythmias]

The frequency and distribution of risk factors of arteriosclerosis were determined in 405 patients with implanted cardiac pacemakers and compared with the corresponding results of patients with cardiac infarction. The most frequent risk factors were smoking (43,5%), hypertension (35,2%), and diabetes (34,3%) in males, hypertension (52,3%) and diabetes (49,7%) in females. The frequency of cardiac infarction was in average 19,5%. In the infarction group diabetes was lower in both sexes (23,5% and 35,8%), respectively), hyperlipoproteinemia and smoking were more frequent. From the different distribution of risk factors it is suggested, that coronary arteriosclerosis is not the most important etiologic factor in the development of bradycardic dysrhythmias. The higher percentage of diabetes in the pacemaker group could point to metabolic disturbances or specific diabetic vascular disease as harmful factors to the conduction system.     

Dietary and lifestyle correlates of passive smoking in Hong Kong, Japan, Sweden, and the U.S.A

From epidemiologic studies in several countries, passive smoking has been associated with increased risk for lung cancer, respiratory diseases, and coronary heart disease. Since the relative risks derived from those studies are weak, i.e. relative risk less than two, we investigated whether poorer diets and less healthy lifestyles might act as confounders and be correlated with having a smoking husband on a cross-cultural basis. Characteristics of never-smoked wives with or without smoking husbands were compared between 530 women from Hong Kong, 13,047 from Japan, 87 from Sweden, and 144 from the U.S. In all four sites, wives with smoking husbands generally ate less healthy diets. They had a tendency to eat more fried food but less fruit than wives with nonsmoking husbands. Other healthy traits, e.g. avoiding obesity, dietary cholesterol and alcohol, or taking vitamins and participating in preventive screening were also less prevalent among wives with smoking husbands. These patterns suggest that never-smoked wives with smoking husbands tend to share the same less healthy dietary traits characteristic of smokers, and to have dietary habits associated with increased risk for lung cancer and heart disease in their societies. These results emphasize the need to take into account the potential confounding effects of diet and lifestyle in studies evaluating the health effects of passive smoking, especially since it is known that the current prevalence rates of smoking among men is indirectly associated with social class and education in affluent urban societies.     

The effect of sodium nitrite on the realization of defensive and inhibitory conditioned reflexes

In recent years there has been a strong emphasis from both medical and nonmedical communities to improve overall cardiovascular health. Continued attention has been focused on finding improved treatment regimens, and, encouragingly, increased attention is being directed toward prevention strategies for coronary heart disease. Emphasis on heart-healthy diets, fitness, and the now commonplace free blood pressure and cholesterol screenings have become part of our daily life. Multiple studies have demonstrated that atherosclerosis begins in childhood, and increasingly, the need for prevention to begin during childhood is being highlighted. Preventive cardiology in children, however, has long relied on adult data for definitions of risk factors, study protocols, and norms. Gradually, the pediatric data is becoming available. Elevated cholesterol levels, hypertension, obesity, and other risk factors defined in adults are all areas of intense interest in the pediatric population. This brief review of preventive cardiology in children provides a look at the risk factors for adult coronary heart disease as they relate to children, the current recommendations (and associated controversies), and a summary of some of the most recent clinical trials.     

Genetic factors in the development of atherosclerosis]

Atherosclerosis is a complex multifactorial disease of the arterial wall, dependent on genetic disposition and multiple other risk factors. There are probably several candidate genes, that determine the individual susceptibility of the vessel wall to develop atherosclerosis. In recent years, a growing number of gene polymorphisms, associated with an elevated risk of myocardial infarction, has been identified. These genes and gene clusters play a crucial role in lipid metabolism, regulation of blood pressure and clotting. In contrast to rare monogenetic diseases with severe clinical signs and symptoms (e.g. familial hypercholesterolemia), genetic polymorphisms are relatively frequent. Due to their frequency, there is a high probability that one individual carries several alleles predisposing to coronary heart disease. Genetic polymorphisms become clinically important by interacting with lifestyle, environmental factors or endogenous metabolic disorders. We have recently established an animal model of rabbits, which may prove useful in the search for new genes predisposing to or protecting from atherosclerosis. Rabbits with high atherosclerotic response (HAR) show more than 70% atherosclerotic involvement of the aorta when fed a high cholesterol diet. In contrast, rabbits with low atherosclerotic response (LAR) show less than 20% atherosclerosis in spite of comparably high plasma cholesterol levels. Preliminary studies indicate that macrophages of LAR rabbits have a high scavenger receptor activity and high apolipoprotein E expression and thus appear to be very efficient in uptake and elimination of modified lipoproteins. This may result in a more efficient removal of cholesterol from the arterial wall and thus protect the animals from developing atherosclerosis. Today we are only at the beginning of understanding the complexity of gene interaction in atherosclerosis. Further identification of genetic factors of atherosclerosis will no doubt lead to a more efficient and economic prevention of coronary heart disease in the future.     

Isolated sectioning of the medial and posteromedial capsular ligaments in the posterior cruciate ligament-deficient knee. Influence on posterior tibial translation

OBJECTIVES: This study examined whether heightened cardiovascular reactivity and low socioeconomic status had synergistic effects on the progression of carotid atherosclerosis in a population of eastern Finnish men. METHODS: Data from the Kuopio Ischemic Heart Disease Risk Factor Study were used to measure 4-year progression of intima-media thickness in 882 men according to cardiovascular reactivity and socioeconomic status. Associations were examined in relation to risk factors and were stratified by baseline levels of atherosclerosis and prevalent ischemic heart disease. RESULTS: The effect of reactivity on atherosclerotic progression depended on socioeconomic status. Men who had heightened cardiovascular responsiveness to stress and were born into poor families, received little education, or had low incomes had the greatest atherosclerotic progression. CONCLUSIONS: An understanding of associations between individual risk factors and disease should be based on etiologic hypotheses that are conceived at the population level and involve fundamental social and economic causes of disease. This study demonstrates how examining the interaction of an individual biological predisposition will low socioeconomic status over the life course is etiologically informative for understanding the progression of atherosclerotic vascular disease.     

Hyperinsulinemia and the risk of stroke in healthy middle-aged men: the 22-year follow-up results of the Helsinki Policemen Study

BACKGROUND AND PURPOSE: Several studies have shown that hyperinsulinemia is associated with the risk of coronary heart disease, but information on the association of hyperinsulinemia with the risk of stroke is limited. We investigated the association of hyperinsulinemia with the risk of stroke during a 22-year follow-up of the Helsinki Policemen Study population. METHODS: The study was based on a cohort of 970 men aged 34 to 64 years who were free of cerebrovascular disease, other cardiovascular disease, or diabetes. Risk factor measurements at baseline examination included an oral glucose tolerance test with blood glucose and plasma insulin measurements at 0, 1, and 2 hours. Area under the insulin response curve during oral glucose tolerance test was used as a composite variable reflecting plasma insulin levels. RESULTS: During the 22-year follow-up, 70 men had a fatal or nonfatal stroke. Hyperinsulinemia (highest area under the insulin response curve quintile compared with the combined 4 lower quintiles) was associated with the risk of stroke (age-adjusted hazard ratio, 2.12; 95% CI, 1.28 to 3.49), but not independently of other risk factors (multiple-adjusted hazard ratio, 1.54; 95% CI, 0.90 to 2.62), which was mainly due to the impact of obesity, particularly upper body obesity, with subscapular skinfold thickness used as an index. Of other risk factors, upper body obesity, blood pressure, and smoking were independent predictors of the risk of stroke. CONCLUSIONS: Hyperinsulinemia was associated with the risk of stroke in Helsinki policemen during the 22-year follow-up, but not independently of other risk factors, particularly upper body obesity.     

Management of risk factors after coronary heart disease in European countries

BACKGROUND: Despite clinical and epidemiological evidence of benefits from sustained management of vascular risk factors following coronary heart disease, the implication of physicians in secondary prevention remains limited. In 1994, several European scientific societies published jointly guidelines for the prevention of coronary heart disease in clinical practice, ranking as the highest priority the reduction of risk factors in coronary patients. METHODS: The European Society of Cardiology launched at the same period a study on the prevalence and management of vascular risk factors of coronary patients in Europe, the EUROASPIRE project. Six months after a coronary event 3,569 patients, from a total population of 4,863 affected individuals recruited in hospitals of 9 European countries, were interviewed and examined to estimate the levels and management of their vascular risk factors. RESULTS: At least six months after discharge, one patient out of five kept on smoking, one out of four was still obese, one out of two had high blood pressure levels and 44% total cholesterolemia over 5.5 mmol/L. More than 8 smoking patients out of 10 attempted to stop smoking and 8 obese patients out of 10 attempted to lose weight. More than 40% of patients, treated or not for hypertension, had systolic blood pressure levels over 140 mm Hg, and almost one patient out of two, treated or not treated for dyslipemia, a total cholesterolemia over 5.5 mmol/L. CONCLUSIONS: Given the high prevalence of vascular risk factors in coronary patients, efficient secondary prevention aiming at the reduction of the levels of these risk factors, may have a major impact on the decrease of morbidity and mortality of these patients. Thus, joined European efforts to elaborate, diffuse and evaluate secondary prevention strategies towards physicians and patients should be rapidly developed to facilitate the achievement of such benefits for coronary patient health.     

Heart, brain and hypertension

Hypertension is one of the most important cardiovascular risk factors. Without therapy hypertension leads to stroke, coronary heart disease with angina pectoris and myocardial infarction, kidney failure and/or peripheral vascular disease. The association between blood pressure and these cardiovascular complications can be demonstrated over the entire blood pressure range. The risk of stroke, myocardial infarction, renal failure or peripheral vascular disease increases with increasing blood pressure. Additional cardiovascular risk factors such as hyperlipidemia, smoking and diabetes involve a further increase in risk. Today hypertension can be effectively treated. To that end, diuretics, betablockers, ACE-inhibitors or calcium antagonists can be used. Alpha receptor antagonists and angiotensin AT1 receptor antagonists are also of value. The antihypertensive effectiveness of these drugs is comparable but may vary in individual patients. During antihypertensive therapy, a reduction in cerebrovascular and cardiac complications has been demonstrated for alpha methyldopa, diuretics and betablockers. In these studies, fatal and non-fatal strokes were reduced by 42%, while the reduction in cardiac events was less pronounced (14%). The reasons for this greater efficacy of antihypertensive therapy in the cerebral circulation are not clear. Other risk factors may be particularly important in the pathogenesis of coronary artery disease (e.g. genetic factors, hyperlipidemia and others) or hypertensive vascular changes in the coronary circulation may not be as reversible as they are in the cerebral circulation. The well documented correlation between stroke, myocardial infarction and hypertension, as well as the proven efficacy of antihypertensive therapy in preventing cardiovascular events, underscores the importance of effective and sustained blood pressure control in these patients.     

Fletcher Challenge-University of Auckland Heart & Health Study: design and baseline findings

AIMS: The aims of this prospective observational study are to determine the relationship of sociodemographic factors, psychological factors and several factors measured in blood, with the risk of coronary heart disease (CHD) in a New Zealand population. METHODS: Participants were recruited from two sources: employees of the Fletcher Challenge Group and individuals listed on the general electoral roll for the Auckland region. Baseline and follow up risk factor data were obtained from a questionnaire, blood samples and a simple physical examination. Outcome data on deaths and hospitalisations due to coronary heart disease will be obtained primarily through linkage of participant identifiers to data collected nationally by the New Zealand Health Information Service. RESULTS: A total of 10,529 individuals agreed to participate (8011 from Fletcher Challenge and 2518 from the electoral roll), representing a response rate of 74%. Within the study population, there was a broad distribution of sociodemographic characteristics including ethnicity-10% of participants were Maori and 5% were of Pacific Islands origin. There was also wide heterogeneity of coronary heart disease risk as judged from the distributions of established risk factors at baseline-5% of participants had evidence of existing coronary heart disease, a quarter were current smokers, a sixth were nondrinkers, almost a half were overweight, a fifth had blood pressure > or = 150/95 mmHg or were receiving antihypertensive treatment and a sixth had cholesterol levels > or = 6.5 mmol/L. CONCLUSIONS: This is the first, large scale prospective observational study of the determinants of coronary heart disease in a New Zealand population. The study participants represent a broad cross section of society, with wide variation in sociodemographic characteristics and coronary heart disease risk. Initial results concerning the relationships of primary interest should be available within 5 years when sufficient coronary heart disease events have been documented to allow reliable analyses.