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The antiatherogenic role of high-density lipoprotein cholesterol.

Landmark clinical studies in the past 5 years that demonstrated diminished mortality and first coronary events following lowering of low-density lipoprotein (LDL) cholesterol stimulated considerable interest in the medical community. Yet, high-density lipoprotein (HDL) cholesterol, which transports circulating cholesterol to the liver for clearance, clearly also exerts antiatherogenic effects. The Framingham Heart Study produced compelling epidemiologic evidence indicating that a low level of HDL cholesterol was an independent predictor of coronary artery disease (CAD). Emerging experimental and clinical findings are, collectively, now furnishing a solid scientific foundation for this relation. First, the reverse cholesterol transport pathway--including the roles of nascent (pre-beta) HDL, apolipoprotein A-I, lecithin-cholesterol acyltransferase (LCAT), cholesteryl ester transport protein, and hepatic uptake of cholesteryl ester from HDL by liver--is better understood. For example, the identification of a hepatic HDL receptor, SR-BI, suggests a mechanism of delivery of cholesteryl ester to liver that differs from the receptor-mediated uptake of LDL. Second, apolipoprotein A-I, the major protein component of HDL, and 2 enzymes on HDL, paraoxonase and platelet-activating factor acetylhydrolase appear to diminish the formation of the highly atherogenic oxidized LDL. Third, lower levels of HDL cholesterol are associated in a dose-response fashion with the severity and number of angiographically documented atherosclerotic coronary arteries. Fourth, low HDL cholesterol predicts total mortality in patients with CAD and desirable total cholesterol levels (<200 mg/dL). Fifth, low HDL cholesterol concentrations appear to be associated with increased rates of restenosis after percutaneous transluminal coronary angioplasty. In terms of elevating HDL cholesterol, cessation of cigarette smoking, reduction to ideal body weight, and regular aerobic exercise all appear important. Most medications used to treat dyslipidemias will raise HDL cholesterol levels modestly; however, niacin appears to have the greatest potential to do so, and can increase HDL cholesterol up to 30%. Recognizing these data, the most recent report of the National Cholesterol Education Program identified low HDL cholesterol as a CAD risk factor and recommended that all healthy adults be screened for both total cholesterol and HDL cholesterol levels.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗

Mechanistic studies of high-density lipoproteins.

There is increasing evidence that high-density lipoprotein (HDL) and its subfractions are protective against atherosclerotic cardiovascular disease. Physical exercise, weight reduction, smoking cessation, diabetes mellitus control, and specific drugs, including niacin, fibrates, and estrogens, are effective methods to increase HDL levels. Niacin is the oldest and most powerful clinical agent for raising HDL levels. Niaspan, an extended-release niacin formulation, is as potent as immediate-release niacin in increasing levels of HDL cholesterol; subfractions HDL2 and HDL3; apolipoprotein A-I, the major protein of HDL, and its cardioprotective subfraction lipoprotein A-I. Recent research from our laboratory suggests a novel mechanism by which niacin inhibits hepatic removal of HDL-apoprotein A-I without interfering with the removal of cholesterol carried by HDL, thus augmenting reverse cholesterol transport. Other mechanistic studies indicate that fibrates and estrogens stimulate the synthesis and production of HDL-apoprotein A-I. Because niacin decreases HDL-apoprotein A-I removal, and fibrates and estrogens increase HDL-apoprotein A-I production, combinations of niacin with these agents may raise HDL levels more than fibrates or estrogens alone.

Apolipoprotein A-I↗

Secondary prevention in coronary heart disease patients with low HDL: which options do we have?

Low levels of high-density lipoprotein cholesterol (HDL-C) are frequently encountered in patients with coronary artery disease (CAD), most often in combination with elevated triglycerides as part of a dysmetabolic syndrome. Although no large secondary prevention trials with statin therapy with special emphasis on low HDL-C have been performed, some guidance can be extracted from a number of post-hoc analyses on how to treat patients with low levels of HDL-C. In terms of risk reduction, statin therapy appears to be at least as effective in patients with low compared to normal HDL-C levels. Fibrate therapy seems only effective when low HDL-C coincides with a level of low-density lipoprotein cholesterol (LDL-C) in the low-normal range. Before considering combination therapy of statins with fibrates, much emphasis should be put on dietary changes, weight reduction, smoking cessation and regular exercise, since these measures are effective tools to raise HDL-C levels. Moreover, one should be aware of the fact that combination therapy of statins and fibrates is not evidence-based and confers some potential risk of myopathy. Future therapy options may include CETP (cholesterol ester transfer protein) inhibitors, but these agents are still in an experimental phase. As most patients with low HDL-C levels share features of the dysmetabolic syndrome, one could also consider a combination therapy of statins and ACE-inhibitors, since this combination is not only safe, but the individual preventive effects of these compounds appear to be cumulative.

Coronary Disease↗

The challenge of managing multiple cardiovascular risk factors.

Hypertensive patients have an excess of other cardiovascular risk factors. Moreover, traditional therapy based on diuretics and beta-blockers may aggravate these risk factors. Therefore, attention must be given to the identification of all pertinent risk factors and their amelioration by appropriate therapy. Such therapy must include lifestyle changes including cessation of smoking, reduction of obesity, moderation of sodium intake and alcohol consumption, and increased physical activity. When antihypertensive drugs are chosen, consideration should be given to their potential influences, either negative or positive, on other cardiovascular risk factors. In particular, the adverse effects of diuretics and beta-blockers on lipids and insulin sensitivity may preclude their use. alpha-Blockers and ACE inhibitors may have beneficial effects on these metabolic indices. Calcium antagonists are neutral in most regards. Whatever agents are chosen, the use of low doses in combination is being increasingly recognized as a better way to achieve the desired antihypertensive efficacy while minimizing adverse effects. As has been noted in the other papers in this supplement, the combination of an ACE inhibitor and a calcium antagonist is particularly attractive, not only to treat hypertension, but also to ameliorate other cardiovascular risk factors.

Antihypertensive Agents↗

Lung cancer risks from residential radon among smokers and non-smokers.

Primary lung cancer occurs mainly among elderly smokers. Smoking and radon are generally considered to be the main causes of lung cancer. By simply studying the age dependence of all primary lung cancer incidences it seems plausible to suggest that the risk for obtaining lung cancer from domestic radon is low for children. In addition, as there are few non-smoking primary lung cancer cases at older ages, it seems plausible to suggest that most of the radon-induced lung cancer cases are to be found among the smoking population. Reduction of smoking habits would appear to be the most cost effective method to reduce lung cancer cases.

Adult↗

News of risk for early heart disease as a stressful event.

Modern prevention includes efforts to reduce the frequency of coronary heart disease by screening populations for certain risk factors, and then advising persons high in risk on how to alter their vulnerability. But what is the effect of telling persons they are at increased risk for such threatening events as heart attacks? Without such information they may not be motivated to change such behavior as cigarette smoking or to comply with blood pressure reducing regimens. With it, worry about their health status may increase. The present study examined such variables in 575 men with no previous symptoms of heart disease who were informed of increased risk and followed for three years. The men were divided at random into two groups of equal size. A Special Intervention group received repeated reminders of risk and procedures for cessation of smoking, reduction of blood pressure, and dietary alteration to lower serum cholesterol. A contrast group received usual medical care, as they saw fit, in response to the news of risk. At yearly intervals, scores on level of subjective distress, avoidance, and coping were obtained. One-third of the men reported intrusive or avoidance experiences one year after receipt of the news of increased risk. The Special Intervention group, with its more frequent reminders, had significantly higher levels of intrusive ideas and feelings about the news of risk than the Usual Care group, and significantly higher levels of coping experiences.

Adult↗

Evidence-based guide to slowing the progression of early renal insufficiency.

Early renal insufficiency (ERI), defined as a calculated or measured glomerular filtration rate (GFR) between 30 and 60 mL/min per 1.73 m2, is present in more than 10% of the adult Australian population. This pernicious condition is frequently unrecognised, progressive and accompanied by multiple associated comorbidities, including hypertension, renal osteodystrophy, anaemia, sleep apnoea, cardiovascular disease, hyperparathyroidism and malnutrition. Several treatments have been suggested to retard GFR decline in ERI, including blood pressure reduction, angiotensin-converting enzyme inhibition, angiotensin receptor antagonism, calcium channel blockade, cholesterol reduction, smoking cessation, erythropoietin therapy, dietary protein restriction, intensive glycaemic control and early intensive multidisciplinary patient education within a renal unit. In addition, specific interventions have been reported to be renoprotective in atherosclerotic renal artery stenosis, diabetic nephropathy, lupus nephritis and certain forms of primary glomerulonephritis. The present paper reviews the available published randomised controlled clinical trials and meta-analyses supporting (or refuting) a role for each of these therapeutic manoeuvres.

Disease Progression↗

Ventricular premature contractions: a randomized non-drug intervention trial in normal men.

The influence of a 6-week intervention on factors thought to be related to ectopic cardiac rhythms was tested in normal men with frequent ventricular premature contractions (VPCs), using a randomized, controlled and partial crossover design. The VPC intervention trial experimental regimen included total abstinence from caffeine and smoking, reduction of alcohol intake, and a physical conditioning program. Effects were studied in detail among 81 healthy men with persistent VPCs. VPCs were measured during standard states of rest, dynamic and isometric exercise and other stresses, and 24-hour ambulatory monitoring. Adherence to the treatment was excellent. The experimental group achieved more than 80% of activities asked of them, and little "contamination" occurred in the control group. VPCs were analyzed according to VPC/min, VPC/man and VPC/total number of heart beats. Moderate changes in VPC rates occurred in both experimental and control groups but no significant group differences were found at rest or during any induction test. This 6-week, multiple-factor "hygienic" intervention program had no significant influence on the frequency or occurrence of VPCs in apparently normal men with persistent and frequent VPCs. Because the mechanisms and the significance of VPCs are different in patients with ischemic heart disease, our approach and methods may be useful for similar trials among cardiac patients of adjunct or non-drug therapy for ectopic rhythms.

Adult↗

Overview of the risk of respiratory cancer from airborne contaminants.

This overview on defining risk of respiratory cancer from airborne pollutants summarizes broad issues related to a number of the environmental agents that are discussed in the articles that follow. Lung cancer kills more than 100,000 people annually and is the major form of cancer in both sexes in middle age. Cigarette smoking is the major cause of respiratory cancer and must be taken into account in any study of the effect of an environmental agent on the risk of respiratory cancer, particularly at relatively low levels of excess risk (RR greater than 1.0 but less than 2.0). The agents considered in this series all have the potential for widespread community exposures, either because there is widespread long-term exposure (passive smoking), the agents are direct byproducts of energy consumption (organic particles), have ubiquitous production and use patterns (formaldehyde and fibers), or occur widely in natural settings (radon). Several issues--measurement of exposure, latency, confounding factors and bias, extrapolation from animals to humans, population at risk, and attributable risk--must be considered for each agent. A further issue related to exposure estimates is the relationship of exposure to actual dose. Understanding exposure some 25 to 40 years in the past is important because of the prolonged latency period in the development of respiratory cancers. To the degree that these agents act synergistically with smoking, the reduction of smoking or of exposure to these agents may have greater public health consequences than would be anticipated from the directly measured attributable risk of each of these agents separately.

Air Pollutants↗

Wellness education for individuals with chronic mental illness living in the community.

The article reports a wellness education program developed to enhance and promote healthy life-style behaviors for individuals with chronic mental illness living in the community. Theoretical concepts from health promotion, wellness, and social learning were used in the development of this program. The program comprised three components: wellness education sessions, exercise/activity sessions, and a smoking reduction course.

Adult↗

Smoking cessation during pregnancy.

Smoking during pregnancy is associated with maternal, fetal, and infant morbidity and mortality. An office-based protocol that systematically identifies pregnant women who smoke and offers treatment has been proven to increase quit rates. For pregnant women who smoke less than 20 cigarettes per day, the provision of a 5-15 minute, five-step counseling session and pregnancy-specific educational materials increases cessation by 30-70%. This bulletin outlines this office-based intervention and addresses treatment issues pertaining to pregnant women who smoke heavily, smoking reduction, pharmacotherapy, healthcare support systems, and coding.

Adult↗

Non-pharmacological treatment of hypertension.

Weight reduction, alcohol restriction, mild salt restriction, eating a vegetarian diet and increasing aerobic exercise will generally lower the blood pressure in patients with essential hypertension. Eating a diet rich in potassium and reducing caffeine intake may also be helpful in reducing the pressure, but increasing the fiber or calcium intake will generally be ineffective. Reducing fat intake from the usual 40% of total calories to 25-30% may reduce hypertension directly or by weight reduction. Smoking, when combined with excessive caffeine or alcohol intake may have an additive effect on blood pressure. Monotherapy with such behavioral techniques as self-monitoring of blood pressure, biofeedback, meditation, yoga, progressive muscular relaxation or cognitive therapy may reduce the blood pressure to a variable degree, and combinations of these treatments may be even more successful.

Behavior Therapy↗

[Treatment of obstructive sleep apnea syndrome].

Obstructive sleep apnea syndrome (OSAS) is a chronic disorder in which the subject experiences an abnormally large number of episodes of more or less complete and prolonged ventilatory arrest due to pharyngeal obstruction leading to fragmented sleep pattern and reduced arterial oxygen saturation. OSAS produces invalidating daytime symptoms and appears to be associated with cardiovascular complications and overmortality. Diagnosis is based on an exploration of the sleeping pattern with recording of ventilation function, arterial oxygen saturation, heart rate, and electrophysiological characteristics (polysomnography). Prevalence of a high apnea index (more than 5 per hour of sleep) associated with day-time somnolence may be as high as 3% of the population in the 30 to 60 year age range. Current treatment is mainly based on nasal continuous positive airway pressure given via the nasal route during sleep and pharyngeal surgery (uvulopalatopharyngoplasty). Surgery is reserved for subgroups of patients with anatomic abnormalities and free of contraindications for anesthesia. Continuous positive pressure is always effective in case of symptomatic apnea and has a favorable effect on several associated complications. It can be proposed for any patient with OSAS but its use is limited due to incomplete compliance (approximately 70%). It appears that patients with particularly severe disease benefit most. Thus the ANDEM experts recommend treatment for all symptomatic patients with 30 or more episodes of apnea or hypopnea per hour of sleep during night-time exploration. Below this threshold, electrophysiological recordings are required to eliminate another cause of fragmented sleep which could explain the symptomatology despite a moderately elevated apnea index. Once the treatment has been started, regular surveillance is recommended. In addition, general health and nutritional counselling (weight reduction, smoking cessation, interruption of alcohol consumption and use of sedatives) should be proposed but usually have minimal and transitory effect.

Databases, Bibliographic↗

Sudden cardiac death--preventable--reversible.

SCD is defined as unexpected death due to cardiac causes that occurs within 1 hour of acute symptoms. SCD can be reversed with the use of an ICD. These devices now can be implanted by catheter techniques, obviating thoracotomy. SCD is preventable. The incidence of SCD can be significantly reduced by addressing the fundamental pathophysiology of SCD, which primarily is CAD. Our combined and aggressive implementation of preventive regimens to reduce the risk of cardiac events will save lives. These measures include diet, weight reduction, smoking cessation, regular exercise, and therapeutic drugs. Amiodarone, although effective in preventing lethal ventricular arrhythmias, has not matched the long-term results of the ICD in the successful management of SCD.

Death, Sudden, Cardiac↗

Perisurgical smoking cessation and reduction of postoperative complications.

OBJECTIVE: The purpose of this study was to determine if a perisurgical smoking cessation program reduces smoking-related postoperative complications in urogynecologic surgery. STUDY DESIGN: A review of patients that underwent pelvic reconstructive surgery from 1998 to 2003 was performed. All smokers underwent a perisurgical smoking cessation program of their choice for at least 1 month before surgery, and continued for 1 month after surgery. Complications unrelated to smoking (cystotomy, enterotomy, urethral obstruction, etc) were excluded in the smoking-potentiated complications. Problems considered to be potentiated by smoking were: wound, pulmonary, cardiac, and febrile morbidity. RESULTS: Eight hundred eighty-seven patients were included. There were 233 smoker cessation patients (SC) and 654 nonsmokers (NS). The total number of complications in the SC group was 61 (61/233, 26%) compared with 172 (172/654, 29%) in the NS group: (chi-square, P = .97). When looking at smoking-potentiated complications only, there were 34 (34/61, 56%) patients in the SC group and 90 (90/172, 52%) in the NS group (chi-square, P = .75). CONCLUSION: There are no differences in smoking-potentiated complications between nonsmoking patients and patients who undergo a perisurgical smoking cessation program.

Aged↗

Smoking: high hazards in high school.

BACKGROUND: Young people in school are at an impressionable age, peer pressures are intense, and the probability that they will pick up a high-risk behavior, such as smoking, is high. The key to reduction of smoking among adults is to target our prevention efforts at young adults and teens. OBJECTIVE: To study the prevalence and trend of smoking among young adults and teens and to formulate guidelines on smoking reduction to guide those who counsel young people. STUDY DESIGN: The study design is cross sectional. METHODS: This study is based on the data from the Oklahoma Behavioral Risk Factor Surveillance System and the National Youth Risk Behavioral Surveillance System - the two systems that monitor the prevalence of behaviors that most influence health. RESULTS: The prevalence of smoking among young adults (age 18-24) in Oklahoma is high at more than 21%. The disturbing feature is that it is higher among young females than among young males. The prevalence of smoking among young adults is the highest among high school dropouts and is more than 38%. It is lower among high school graduates (about 28%) and lowest among college graduates (about 18%). The percentage of smoking among students who classify themselves as current smokers rises from 23% to 30% as the students progress from grade 9 to 12 and the percentage of frequent smokers increases from 8% to 16%. CONCLUSIONS: Guidelines suggested for counselors are: 1. Along with smoking, look for comorbid behaviors such as alcohol use, drug abuse, and high-risk sexual behavior. 2. Ask whether the student has easy access to free cigarette samples. 3. Check whether the teen is trying to lose weight; suggest appropriate methods for losing weight if smoking is being used for losing weight. 4. Target health education efforts early in a student's school career starting in elementary school, but concentrate especially at the 8th or 9th grade level to have maximum preventive impact.

Adolescent↗

A 50-year projection of lung cancer deaths among Japanese males and potential impact evaluation of anti-smoking measures and screening using a computerized simulation model.

The lung cancer death rate among Japanese males was projected for 50 years to the year 2041 by a computerized simulation model. Long-term effects of anti-smoking measures and mass screening on lung cancer deaths were also evaluated. The simulation showed that the age-adjusted lung cancer death rate would increase and reach a peak of 166 per 100,000 in 1989 and then decrease to 148 per 100,000 in 2003. It then shows an increasing tendency again, up to 255 per 100,000 in 2028. The smoking initiation rates estimated from the observed lung cancer death rates showed that the changes in death rates may be attributed to a lower smoking initiation rate among those born in the 1930's. Promotion of mass screening programs is effective more quickly than anti-smoking measures but the reduction in annual cancer deaths is expected to be only 11%, even if 100% participation is achieved by the year 2000. A reduction in smoking initiation rate, on the other hand, affects lung cancer deaths very slowly. It was predicted that a 1% annual reduction in smoking initiation rate would result in a 20% decrease in the number of lung cancer deaths in 2041. A smoking cessation program is intermediate with regard to promptness. The predicted reductions in lung cancer deaths in 2041 were 13%, 47%, and 66%, respectively, when the annual smoking cessation rate was increased from 0.46% (present status) to 1%, 3%, and 5%. In conclusion, the combined application of all three preventive measures seems essential to realize the most effective reduction in lung cancer deaths.

Age Factors↗

A biochemical prevalence study of smoking in pregnancy for a cross-section of women in Christchurch, New Zealand.

OBJECTIVE: To biochemically measure and compare the prevalence of maternal smoking by trimester in a cross-section of pregnant women residing in Christchurch, New Zealand, during 1997. METHODS: Residual sera from routinely collected blood samples drawn in early and late pregnancy over a 12-month period, 1 January 1997 to 31 December 1997, was accumulated and anonymously assayed. Cotinine levels were measured by an ELISA test with a result greater than 14 ng/mL indicative of active smoking. RESULTS: Analysis was conducted upon 4,178 samples collected from 3,082 women. Adjusted cotinine validated smoking rates in the first, second and third trimesters were 26.8% (95% CI 24.5-29.2%), 25.0% (95% CI 22.3-27.8%) and 23.0% (95% CI 20.8-25.2%), respectively. This represents an absolute reduction in smoking rates of 4.7% (p = 0.02), 6.6% (p = 0.04) and 3.8% (p = 0.04) for the first, second and third trimesters, respectively, among pregnant women in Christchurch since 1994. CONCLUSION: Smoke reduction and cessation programs implemented locally and nationally have been effective in significantly reducing the biochemically measured prevalence of maternal smoking in pregnancy within a three-year period. IMPLICATIONS: Cigarette smoking during pregnancy is an important yet preventable factor affecting rates of prenatal, perinatal and paediatric morbidity and mortality. Reliable and repeated surveys of pregnant women are necessary to accurately measure changes in the maternal smoking prevalence and determine the efficacy of smoke reduction and cessation programs.

Cotinine↗