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The inclusion of coronary heart disease (CHD) risk equivalents in the highest CHD risk category, in addition to the lowest low-density lipoprotein cholesterol (LDL-C) targets, has dramatically increased the number of persons eligible for highly effective risk reduction and lipid-lowering treatment. Two such high-risk groups are persons with diabetes and those with metabolic syndrome. These patients typically have a number of lipid and nonlipid risk factors that require aggressive intervention. In patients with diabetes, treatment with 3-hydroxy-3-methyglutaryl coenzyme A reductase inhibitors ("statins") to lower LDL-C levels and improve other lipid measures has been shown to produce protective benefits at least equal to those observed in nondiabetic patients. Although metabolic syndrome is not yet recognized as a CHD risk equivalent and use of Framingham risk scoring may not place some patients with the syndrome in the highest risk category, there is accumulating evidence that these patients are at very elevated risk and should be treated aggressively. Particular problems in risk assessment arise in immigrant groups such as South Asians, in whom traditional risk assessment may be inaccurate. In this article, Dr Deedwania examines the clinical evidence regarding cardiovascular risk associated with diabetes and metabolic syndrome and discusses current therapeutic options. Two case reports are presented, followed by roundtable discussions among the contributors to this Special Report.

Aim: To study the efficacy and tolerability of beta-blockade in elderly patients with heart failure in the MERIT-HF study., Methods and Results: Cox proportional hazards model was used to calculate hazard ratios (HR) with 95% confidence intervals (CI). Risk reduction was defined as (1-HR). In patients > or = 65 years total mortality was reduced by 37% (95% CI 17% to 52%; p=0.0008), sudden death by 43% (95% CI 17% to 61%; p=0.0032), and death from worsening heart failure by 61% (95% CI 32% to 77%; p=0.0005). Hospitalisations for worsening heart failure was reduced by 36% (p=0.0006). Elderly patients with severe heart failure (NYHA class III/IV with ejection fraction < 0.25; n=425, and patients above 75 years (n=490) showed similar risk reductions. Metoprolol CR/XL was safe and well tolerated both during initiating therapy and during long-term follow-up., Conclusions: Metoprolol CR/XL was easily instituted, safe and well tolerated in elderly patients with systolic heart failure. The data suggest that these are the patients in whom treatment will have the greatest impact as shown by number of lives saved and number of hospitalisations avoided. The time has come to overcome the barriers that physicians perceive to beta-blocker treatment, and to provide it to the large number of elderly patients with heart failure in need of this therapy.

The objective of the study was to determine trends in age-specific blood pressure (BP) distribution and hypertension prevalence in an urban Indian population. In successive hypertension epidemiological studies (1995 and 2002), randomly selected 2212 subjects (1412 men, 797 women) in the first and 1123 subjects (550 men, 573 women) in the second study were evaluated. BP was measured using World Health Organization guidelines and hypertension diagnosed using the American Joint National Committee-VI report. Age-specific BP levels in the first and the second study were determined and compared. The mean values of systolic and diastolic BP were not significantly different in various age groups in the first and the second studies. There was an increased variance in the second study as denoted by the significant increase in standard deviations and coefficients of variation in systolic as well as diastolic BP levels at age groups > or =50 years in men and > or =40 years in women (P<0.05). The age-adjusted prevalence of hypertension (known or BP > or =140/> or =90 mmHg) in the first study was 29.5% (men) and 33.5% (women), and in the second study was 30.0% (men) and 30.3% (women) (P=NS). In the second as compared to the first study, there was decrease in age-adjusted prevalence of stage I hypertension (men 16.8 vs 24.9%, women 15.4 vs 27.5%), and increase in stage II hypertension (men 11.7 vs 2.8%, women 18.8 vs 3.1%), and combined stage II and III hypertension (men 13.5 vs 4.7%, women 16.7 vs 6.0%) (P<0.01). This change was associated with greater prevalence of obesity in the second study. In conclusion, increased systolic and diastolic BP dispersion over a 7-year period in this urban population is associated with unchanged hypertension prevalence, decline in stage I hypertension and upsurge in more severe grades. Increasing environmental factors, particularly obesity, appear important.

Cardiovascular disease is a leading cause of death and disability in patients with diabetes or metabolic syndrome (MS). The available data suggest that many patients with diabetes or MS already have vascular abnormalities by the time they are diagnosed with their metabolic disorder. Endothelial dysfunction (ED), which is one of the initial steps in the process of vascular disease, is often present in patients with diabetes or MS. Although the precise mechanism(s) by which diabetes or MS causes ED remains to be elucidated, several possibilities exist. Hyperglycemia, hyperinsulinemia, increased oxidative stress, and diabetic dyslipidemia can all contribute to ED individually or in concert with one another. ED in the setting of diabetes or MS can subsequently result in the activation of a variety of pathways that alter vascular function and participate in the process of vascular remodeling and atherosclerosis. Because insulin resistance is the predominant mechanism responsible for various perturbations seen in MS or diabetes, it is essential to develop a therapeutic strategy that can improve insulin sensitivity with the hope that such interventions would reduce the risk of future cardiovascular events.

Congestive heart failure is a progressive hemodynamic disorder associated with significant morbidity and mortality. Concomitant renal dysfunction is frequently seen in patients with heart failure, and can compromise fluid regulation, leading to acute decompensation, and increased morbidity and mortality. Diuretic therapy has been the mainstay for treatment of congestive symptoms, despite documented mortality benefits. Misuse or overuse of diuretics can have negative consequences in heart failure, and optimizing diuretic efficiency may improve outcomes. In addition, new agents targeting elevated neuropeptides may prove to be beneficial in regulating fluid status and optimizing renal function.

Heart failure is a significant problem among the elderly. Although many nonpharmacologic interventions, such as dietary sodium restriction, and drug therapy with digoxin and angiotensin-converting enzymes are considered to be the standard of care, ss-blockers have recently been shown to improve survival and reduce morbidity when added to the standard regimen. Although studies have demonstrated a significant benefit of ss-blockers, the drugs remain underutilized, partly from concerns about tolerability. Adapting a "start low, go slow" approach and titrating dosage upward can lessen tolerability issues and improve usage among the elderly.

Background: The objective of this pilot study was to evaluate the comparative efficacy of alternate-day dosing of atorvastatin compared with the standard once-daily dose based on mean low-density lipoprotein (LDL) reduction from baseline at 6 and 12 weeks of treatment., Methods: In a double-blind, placebo-controlled design, 35 eligible patients who met the National Cholesterol Education Program (NCEP) Adult Treatment Panel II (ATP II) guidelines for drug therapy, depending on their risk factors, were randomly assigned to receive 10 mg of atorvastatin as an initial dose every day or every other day. Patients were assessed at 6 and 12 weeks as to whether they met the LDL-C goal, and the dose was doubled if the goal was not reached., Results: LDL-C decreased by 27% and 38%, in the every-other-day (n = 15) and every-day (n = 15) groups, respectively, at 6 weeks. At 12 weeks, the LDL-C was reduced by 35% and 38% in the every-other-day and every-day groups, respectively (P =.49). The mean dose was 18 mg (9 mg/d) in the alternate-day group (n = 14) and 12 mg/d in the every-day group (n = 12) at the end of the 12 weeks (P =.001)., Conclusions: Although higher doses of atorvastatin were used on alternate days, these results suggest that the alternate-day administration of atorvastatin can produce a reduction in LDL-C comparable to that of daily administration in patients with hypercholesterolemia, and yet provide some cost savings.

A large proportion of heart failure patients suffer from atrial arrhythmias, prime amongst them being atrial fibrillation (AF). Ventricular dysfunction and the syndrome of heart failure can also be a concomitant pathology in up to 50% of patients with AF. However this association is more than just due to shared risk factors, research from animal and human studies suggest a causal relationship between AF and heart failure. There are numerous reports of tachycardia-induced heart failure where uncontrolled ventricular rate in AF results in heart failure, which is reversible with cardioversion to sinus rhythm or ventricular rate control. However the relationship extends beyond tachycardia-induced cardiomyopathy. Optimal treatment of AF may delay progressive ventricular dysfunction and the onset of heart failure whilst improved management of heart failure can prevent AF or improve ventricular rate control. Prevention and treatment of atrial arrhythmias, and in particular atrial fibrillation, is therefore an important aspect of the management of patients with heart failure. This review describes the incidence and possible predictors of AF and other atrial arrhythmias in patients with heart failure and discusses the feasibility of primary prevention. The evidence for the management of atrial fibrillation in heart failure is systematically reviewed and the strategies of rate versus rhythm control discussed in light of the prevailing evidence.

The coexistence of hypertension and diabetes synergistically increases the risk of cardiovascular and renal diseases. Although aggressive blood pressure reduction can decrease the rate of cardiovascular events in general, blockade of the renin-aldosterone-angiotensin system is a particularly effective target for antihypertensive treatment that may provide additional benefits for patients with diabetes. This article details evidence for blood pressure targets and antihypertensive drug choice in hypertensive patients with diabetes.

Congestive heart failure is a complex clinical hemodynamic disorder characterized by chronic and progressive pump failure and fluid accumulation. Although the overall impact of diuretic therapy on congestive heart failure mortality remains unknown, diuretics remain a vital component of symptomatic congestive heart failure management. Over time, sodium and water excretion are equalized before adequate fluid elimination occurs. This phenomenon is thought to occur in one out of three patients with congestive heart failure on diuretic therapy and is termed diuretic resistance. In congestive heart failure, both pharmacokinetic and pharmacodynamic alterations are thought to be responsible for diuretic resistance. Due to disease chronicity, symptomatic management is vital to improved quality of life and enhancing diuretic response is therefore pivotal.

Although diabetes mellitus is predominantly a metabolic disorder, recent data suggest that it is as much a vascular disorder. Cardiovascular complications are the leading cause of death and disability in patients with diabetes mellitus. A number of recent reports have emphasized that many patients already have atherosclerosis in progression by the time they are diagnosed with clinical evidence of diabetes mellitus. The increased risk of atherosclerosis and cardiovascular complications in diabetic patients is related to the frequently associated dyslipidemia, hypertension, hyperglycemia, hyperinsulinemia, and endothelial dysfunction. The evolving knowledge regarding the variety of metabolic, hormonal, and hemodynamic abnormalities in patients with diabetes mellitus has led to efforts designed for early identification of individuals at risk of subsequent disease. It has been suggested that insulin resistance, the key abnormality in type II diabetes, often precedes clinical features of diabetes by 5-6 years. Careful attention to the criteria described for the cardiovascular dysmetabolic syndrome should help identify those at risk at an early stage. The application of nonpharmacologic as well as newer emerging pharmacologic therapies can have beneficial effects in individuals with cardiovascular dysmetabolic syndrome and/or diabetes mellitus by improving insulin sensitivity and related abnormalities. Early identification and implementation of appropriate therapeutic strategies would be necessary to contain the emerging new epidemic of cardiovascular disease related to diabetes.

The co-existence of hypertension and diabetes dramatically and synergistically increases the risk of microvascular and macrovascular complications. Overwhelming evidence supports aggressive treatment of hypertension in diabetic patients. However, only a small percentage of diabetic hypertensive patients reach their treatment goal of blood pressure (BP) < 130/80 mmHg. Tight BP control is not only cost-effective but also more rewarding than glycaemic control. The optimal goal of BP control in diabetics should be 130/80 mmHg. In subjects with diabetes and renal insufficiency, the BP should be lowered to 125/75 mmHg to delay the progression of renal failure. The choice of an antihypertensive agent should be based on proven effects on morbidity and mortality rather than on surrogate parameters such as lipid or glucose. Limited data suggests that an angiotensin converting enzyme inhibitor (ACEI) is the agent of choice, especially in those with proteinuria or renal insufficiency. beta-blockers (betaBs) can be the first-line agent in diabetics with coronary heart disease, while thiazide diuretics (TD) and calcium-channel blockers (CCBs) are the second-line drugs. Angiotensin II-receptor blockers (ARBs) may be proven to be as effective as ACEIs in diabetics with hypertension. alpha-adrenergic antagonists (AAAs) should be avoided. Most hypertensive patients require more than one agent to control their BP. There is no evidence to support one combination regimen over others; nevertheless, a combination of an ACEI with a TD or a betaB may be the most cost-effective regimens compared to other combinations.

Background: Both angiotensin-converting enzyme inhibitors (ACE-I(s)) and angiotensin receptor blockers (ARB(s)) provide vascular protection. This study was designed to compare ACE-I(s) with widely differing tissue affinity (captopril and quinapril) and an ARB (losartan) on vascular protection against the adverse effects of high cholesterol., Methods and Results: Forty-two New Zealand rabbits on a 0.5% cholesterol diet were randomized into control, captopril (10 mg/kg/d), quinapril (0.3 mg/kg/d), and losartan (8 mg/kg/d) groups for 14 weeks. Captopril, quinapril, and losartan significantly attenuated aortic lipid lesions (P=0.001). Captopril and quinapril were more effective than losartan in preserving vascular relaxation., Conclusions: Captopril, quinapril, and losartan had similar protective effects against atherogenesis. Captopril and quinapril were more effective than losartan in preserving vascular function. Increased bradykinin by ACE inhibition may be responsible for this improved vascular endothelial function.

Atrial fibrillation is a common arrhythmia in patients with heart failure. The presence of atrial fibrillation deteriorates cardiac function and increases the risk of thromboembolic events. The management of patients with atrial fibrillation in association with heart failure should consist of ventricular rate control, prevention of thromboembolic events, and conversion to normal sinus rhythm. Traditionally, digoxin has been widely used in patients with heart failure and atrial fibrillation; however, it does very little to restore sinus rhythm and requires the addition of another rate-limiting agent to control ventricular rate. The likelihood of successful cardioversion is dependent on the duration of heart failure and the degree of neurohormonal activation. The initiation of antiarrhythmic drug therapy in patients with heart failure should be guided by safety issues as well as consideration of potential benefits vs. risks associated with therapy. Amiodarone has been evaluated in numerous clinical trials and appears to be safe and effective when used in low dosage. Treatment with dofetilide is another option. Comparative studies with oral dofetilide vs. amiodarone are needed to evaluate their efficacy in restoration and maintenance of sinus rhythm in patients with heart failure. Such trials will clearly define the role of dofetilide in the treatment of atrial fibrillation. Routine prophylactic use of antiarrhythmic drug therapy for chronic atrial fibrillation in the setting of heart failure is not recommended due to a low efficacy rate and high proarrhythmic risk. Anticoagulation with warfarin and rate control remain the standard therapy. (c)2001 by CHF, Inc.

Aims: To compare the role of early invasive vs conservative management strategies in treating patients with non-Q wave myocardial infarction with or without a prior myocardial infarction., Background: In patients recovering from non-Q wave myocardial infarction, the prognosis among patients with a first non-Q wave myocardial infarction is significantly better than in patients with a prior myocardial infarction, yet physicians often adopt an early invasive strategy to treat patients with a first non-Q wave myocardial infarction., Methods: Non-Q wave myocardial infarction patients enrolled in the VANQWISH trial with a history of prior myocardial infarction were compared to those with a first non-Q wave myocardial infarction, for the trial primary end-point of death or myocardial infarction at 1 and 12 months, as well as for the initial randomized treatment strategy., Results: Of the 920 non-Q wave myocardial infarction patients, 396 had a history of prior myocardial infarction and 524 did not. Patients with a history of prior myocardial infarction were older and had a higher incidence of multiple high-risk baseline characteristics than those with a first non-Q wave myocardial infarction. Compared to the group with a first myocardial infarction, the prior myocardial infarction group suffered more events at both 1 month (11% vs 6%, P=0.007) and at 12 months (29% vs 16%, P<0.001). This difference in outcome remained significant even after adjusting for confounding variables (P<0.0001 at 12 months). Among the non-Q wave myocardial infarction patients with a prior myocardial infarction, the frequency of death or recurrent myocardial infarction was similar in both invasive and conservative groups during the first year of follow-up. Among the first non-Q wave myocardial infarction group, those assigned to the conservative strategy had significantly fewer events (3% vs 9%, P=0.009 at 1 month; 12% vs 20%, P=0.016 at 12 months) and mortality (1% vs 5%, P=0.012 at one month; 5% vs 11%, P=0.009 at 12 months) than those assigned to early invasive strategy., Conclusion: A history of prior myocardial infarction identifies a moderately high-risk subset of non-Q wave myocardial infarction patients who display similar long-term outcomes regardless of the strategy assignment; however, patients with a first non-Q wave myocardial infarction may fare better with a conservative or ischaemia-guided approach during the first post infarction year., (Copyright 2000 The European Society of Cardiology.)

A deadly quartet of risk factors places diabetics at a particularly high risk for adverse cardiovascular events; these factors are hypertension, hyperlipidemia, hyperglycemia and hyperinsulinemia. A number of metabolic abnormalities are common to diabetes. Many of them, including dyslipidemia, have been linked to both insulin resistance and endothelial dysfunction. Several lines of evidence have led to the hypothesis that insulin resistance may be a key pathophysiological mechanism leading to endothelial dysfunction and atherosclerosis in patients with diabetes and possibly other illnesses. In both diabetic and nondiabetic populations, the common risk factors for coronary artery disease events are dyslipidemia, insulin resistance, obesity and high blood pressure. A number of strategies are recommended to prevent the potentially deadly consequences of these factors.

Coronary artery disease (CAD) is a leading cause of death and disability in the elderly. Several recent studies have shown that silent myocardial ischaemia (SMI) is a common manifestation of CAD, especially in the elderly. As many as 40% of elderly patients with no prior history of CAD may have underlying asymptomatic disease and up to 50% of elderly patients with known CAD might have evidence of SMI. The results of studies in elderly patients with CAD have also shown that SMI might exist despite antianginal therapy that is considered adequate for symptom control. In order to diagnose such residual SMI, the clinician would need to perform 24- to 48-hour Holter monitoring in the ambulatory setting while the patient is performing routine daily activities. Although a number of anti-ischaemic drugs have been evaluated for the treatment of SMI, available data suggest that beta-blocker given alone or in combination with a nitrate compound or calcium antagonist provides the best therapeutic choice. The long term benefit of SMI suppression in elderly patients has not been established. Future studies need to evaluate the clinical benefits of therapy given for SMI in the elderly.

Heart failure (HF) is a disease which is prevalent in the elderly. Concomitant rheumatological diseases are also prevalent in this population which require treatment with NSAIDs. Aspirin is also routinely used for the primary and secondary prevention of coronary artery disease (CAD) which is a common cause of HF. ACE inhibitors are the cornerstone of drug therapy in managing patients with HF. Elderly patients with HF are frequently encountered with multiple drug therapy, such as nonsteroidal antiinflammatory drugs (NSAIDs) including aspirin and ACE inhibitors. In recent years there has been a concern of negative interaction between these two common drug therapies in patients with HF which may subsequently attenuate the beneficial effects of ACE inhibitors. Whereas some studies have shown that the coadministration of NSAIDs including aspirin with ACE inhibitors might diminish the degree of improvement in cardiovascular hemodynamics and adversely affect renal functions, other studies have failed to substantiate this. Furthermore, although potential opposing effects of NSAIDs and ACE inhibitors on prostaglandin synthesis has been cited as the mechanism responsible for the negative interactions, more work is needed in this area to better define the precise reasons responsible for it. However, based on the available data thus far, it is prudent to be aware of such negative interaction and especially in case of aspirin to avoid it by using relatively lower dosage. (c)1999 by CHF, Inc.

Secondhand smoke (SHS) and hypercholesterolemia increase cardiovascular risk. We hypothesized that L-arginine, the precursor of nitric oxide (NO), might protect against atherogenesis and endothelial dysfunction caused by SHS. The effects of L-arginine supplementation (2.25% solution ad libitum) and SHS (smoking chambers for 10 weeks) were examined in 32 hypercholesterolemic rabbits. Eight normal rabbits served as controls. Acetylcholine- and nitroglycerin-induced vasorelaxation was assessed in aortic rings precontracted with norepinephrine. Hypercholesterolemia increased intimal lesion area (P=0.012), reduced endothelium-dependent relaxation (P=0.009), and reduced basal (P=0.005) and stimulated (P<0.0005) production of NOs. SHS increased intimal lesion area (P=0. 01) norepinephrine-induced contraction (P=0.001) and reduced endothelium-dependent relaxation (P=0.02). SHS-induced increase in norepinephrine contraction was abolished by the inhibition of NO synthase and removal of endothelium. L-Arginine improved endothelium-dependent relaxation (P=0.001) and attenuated SHS-induced endothelial dysfunction (P=0.007) and atherogenesis (P=0. 001). Basal production of nitrogen oxides correlated inversely with intimal lesion area (r=-0.66; P<0.0005) and stimulated production of NOs correlated with endothelium-dependent relaxation (r=-0.66; P<0. 001). SHS causes endothelial dysfunction and increased adrenergic responsiveness and atherogenesis in hypercholesterolemic rabbits. Chronic dietary supplementation with the NO precursor L-arginine mitigates these effects. The adverse vascular consequences of SHS appear to be mediated via deleterious effects on endothelial function.

The antihypertensive efficacy and tolerability of the novel angiotensin-II (A-II) receptor blocker candesartan cilexetil and the prototype A-II receptor blocker, losartan, were compared in an 8-week, multicenter, double-blind, randomized, parallel-group, titration-to-effect study of 332 adults (42% women, 12% black) with systemic hypertension (sitting diastolic blood pressure [DBP] 95-114 mmHg, inclusive). In patients with a mean trough (24 +/- 3 hours after dose) sitting DBP of 90 mmHg or higher after 4 weeks of once daily administration of candesartan 16 mg or losartan 50 mg, dose was titrated up to candesartan 32 mg or losartan 100 mg once daily. The candesartan regimen was significantly more effective than the losartan regimen in reducing trough sitting DBP at week 8 (11.0 mmHg versus 8.9 mmHg). Candesartan also produced numerically greater reductions in secondary blood pressure parameters, including sitting systolic blood pressure (SBP), trough standing DBP and SBP, and peak (6 +/- 2.5 hours after dose) sitting and standing DBP and SBP. Responder rates (sitting DBP < 90 mmHg or reduction in blood pressure of > or = 10 mmHg) and control rates (sitting DBP <90 mmHg) were higher with candesartan (64% versus 54% and 54% versus 43%, respectively). A total of 1.9% of the patients taking candesartan and 6.5% of those taking losartan discontinued prematurely because of adverse events or lack of efficacy.

Ambulatory electrocardiographic monitoring was used to assess the anti-ischemic effects of amlodipine in a subset of 56 patients enrolled in a 14-week withdrawal study; amlodipine therapy resulted in a marked decrease in the overall mean number of ischemic events and the average number of transient ischemic episodes (p <0.005). Amlodipine substantially reduced the number of ischemic events among all patients during the single-blind phase, with further significant reductions recorded among patients who remained on amlodipine during double-blind therapy, but the number of ischemic events increased almost to baseline levels in patients switched to placebo during double-blind therapy (p = 0.01 by analysis of variance).

Background: In a multicenter, double-blind, placebo-controlled study, the long-term effects of amiodarone on morbidity and mortality in patients with congestive heart failure (CHF) and atrial fibrillation (AF) were evaluated during a 4-year period., Methods and Results: Of 667 patients with CHF, 103 (15%) had AF at baseline. Of these, 51 were randomized to amiodarone and 52 to placebo. The group with sinus rhythm and the group in AF were comparable except for a higher proportion of AF in patients with nonischemic versus ischemic cardiomyopathy (41% versus 27%, P<0.005). The mean ventricular response (VR) during AF over 24 hours was reduced by amiodarone at 2 weeks (20%, P=0.001), at 6 months (18%, P=0.001), and at 12 months (16%, P=0.006). Maximal VR was reduced 22% (P=0.001) at 2 weeks, 19% (P=0.001) at 6 months, and 14% (P=0.001) at 12 months. Sixteen of 51 patients on amiodarone and 4 of 52 on placebo converted to sinus rhythm during the study (chi2=9.23, P=0.002). During follow-up, 11 of 268 patients in sinus rhythm on amiodarone at baseline and 22 of the 263 in sinus rhythm on placebo developed AF; the difference was significant (chi2=12.88, P=0.005). Analysis of total mortality during follow-up showed a significantly lower mortality rate (P=0. 04) in patients in AF at baseline who subsequently converted to sinus rhythm on amiodarone than in those who did not convert to sinus rhythm on the drug., Conclusions: In patients with CHF, amiodarone has a significant potential to spontaneously convert patients in AF to sinus rhythm, with patients who convert having a lower mortality rate than those who do not. The drug prevented the development of new-onset AF and significantly reduced the VR in those with persistent AF.

Objectives: We sought to determine the effects of secondhand smoke (SHS) exposure on vascular reactivity in newborn and infant rats., Background: Secondhand smoke exposure increases cardiovascular risk. Secondhand smoke-induced endothelial dysfunction has been demonstrated in older teenagers and young adults. We have previously shown in adult rabbits that SHS induces atherogenesis and endothelial dysfunction. The effects of SHS on vascular function in the offspring of SHS-exposed mothers and in infants are unknown., Methods: In this study the effects of in-utero (21 days) and neonatal (28 days) exposure to SHS were examined in 80 rats, 4 weeks of age, in a 2-by-2 design study. Rats were exposed to sidestream smoke in smoking chambers. Aortic rings were excised and isometric force responses to phenylephrine, acetylcholine, A23187 and nitroglycerin were studied in organ baths., Results: Neonatal SHS exposure reduced animal weight (p=0.009). In-utero exposure increased the sensitivity (decreased the EC50) of aortic rings to phenylephrine (p < 0.0005), as did neonatal exposure (p=0.01). Maximal contraction to phenylephrine was reduced by in-utero exposure (p=0.04). In-utero SHS exposure reduced maximal endothelium-dependent relaxation to acetylcholine (p=0.04) and increased the EC50 (p=0.05), suggesting impaired sensitivity to acetylcholine. In-utero exposure decreased the sensitivity (increased the EC50) to the endothelium-independent vasodilator nitroglycerin (p=0.003)., Conclusions: Secondhand smoke has detrimental effects on vascular smooth muscle function in the newborn.

BACKGROUND: Although angina is a chronic disease, most clinical trials evaluating antianginal therapy are of a few weeks or months in duration. METHODS AND RESULTS: To evaluate the effects of nicardipine, a second-generation dihydro-pyridine calcium channel blocker, as long-term therapy, patients with chronic stable angina were treated for 1 year with open-label nicardipine. Anginal symptoms were controlled with 20 mg tid in 24%, 30 mg tid in 34%, and 40 mg tid in 42%. Of 72 patients completing the 1-year trial, only 14 (19%) had required the addition of long-acting nitrates for control of symptoms. The remaining 57 patients, who had anginal symptoms controlled with nicardipine alone, were continued into the 3-week, double-blind period and were randomized to continue their usual dose of nicardipine or placebo. Throughout the 1-year, open-label treatment period, the number of anginal episodes and exercise parameters of angina were significantly reduced with nicardipine. CONCLUSIONS: During the double-blind period, the patients who continued on nicardipine had significantly greater exercise time and time to onset of angina than patients who were randomized to placebo. The exercise parameters in the patients randomized to placebo were improved over baseline after 1 year of therapy; however, the improvement with nicardipine was significantly greater.

This report describes a 61-year-old patient on chronic hemodialysis with multiple, left-sided, intracardiac masses causing intermittent coronary obstruction. Mitral valve replacement was performed. Massive deposition of calcium pyrophosphate crystals in and around the valve cusps led to the diagnosis of tophaceous pseudogout (tumoral calcinosis) of the mitral valve.

The clinical benefits of lowering elevated serum cholesterol for both primary and secondary prevention of coronary artery disease are now well established. Reduction in clinical events occurs early and appears to be related to stabilization of atherosclerotic plaque. Despite these salutary findings, lipid-lowering therapy, both nondrug and pharmacologic, is still markedly underutilized in patients and high-risk individuals in the asymptomatic population. Recent practical and uncomplicated guidelines present a rational strategy for selection of patients for low-density lipoprotein (LDL) cholesterol reduction and have the potential to yield major clinical benefits if properly implemented. Preventive cardiology measures should be applied by matching the intensity of the intervention to the hazard for clinical events. We support the current guidelines of the expert panels described in this article and propose several extensions for cholesterol lowering in selected, high-risk populations.

Environmental tobacco smoke (ETS) has been shown to impair endothelium-dependent vasodilation in vitro. This study was performed to investigate the effect of ETS on acetylcholine (ACh)-mediated blood pressure changes in vivo. Seventeen New Zealand White rabbits were fed a cholesterol diet (0.3%) for 13 weeks. Ten animals were exposed to ETS for 6 h/day, and seven animals were not exposed to ETS (non-ETS). Four of the ETS and three of the non-ETS-exposed rabbits received an antioxidant vitamin diet before and during their cholesterol diet for 21 weeks. Six rabbits served as healthy controls. To determine endothelium-dependent and independent blood pressure (BP) responses, BP was measured through a Tygon catheter, inserted into the right carotid artery at baseline and after each of three incremental intravenous doses of norepinephrine (NE; 1, 4, and 20 microg/kg), ACh (3.3, 10, and 30 microg/kg), and nitroglycerin (NTG; 1, 10, and 40 microg/kg). After NE, BP increases were significantly attenuated in the ETS group (p = 0.001) but not in animals receiving the antioxidant supplement. At both the middle and high ACh concentrations, ETS (p = 0.03 and p = 0.01, respectively) and hypercholesterolemia (p = 0.03 and p = 0.06, respectively) attenuated ACh-induced reductions in BP. At the highest ACh concentration, vitamins enhanced the reduction in BP (p = 0.002) and blocked the effect of ETS (p = 0.04). Neither ETS nor vitamins influenced NTG-induced decreases in BP. A combined antioxidant-vitamin diet can preserve endothelium-dependent vasodilatation in the hypercholesterolemic rabbit exposed to ETS.

Background: Antioxidant vitamins are hypothesized to help prevent atherosclerosis by blocking lipoprotein oxidation. We investigated the effects of dietary vitamins C and E on atherosclerosis in rabbits., Methods and Results: Forty New Zealand male rabbits were divided into 4 groups: 0.3% cholesterol diet with (LV) and without vitamin (LC), and 0.5% cholesterol diet with (HV) and without vitamins (HC). The treated groups consumed 137 +/- 8 mg/day vitamin C and 80 +/- 4 mg/day vitamin E for 10 weeks. Vitamin treatment did not significantly affect serum lipids. Alpha-tocopherol values were significantly higher in both serum (mg/dl) and omental fat (microg/g) among the treated rabbits (3.9 +/- 0.5 and 31.6 +/- 2.1 for LV, 1.7 +/- 0.2 and 12.1 +/- 1.9 for LC, 5.6 +/- 0.8 and 51.3 +/- 9.3 for HV and 1.9 +/- 0.3 and 8.2 +/- 0.4 for HC; p < 0.001). Vitamin treatment did not affect the percent of surface lesions in the aorta and pulmonary artery (23.8 +/- 5.2 and 20.1 +/- 3.3% for LV, 19.8 +/- 5.6 and 23.2 +/- 3.5% for LC, 28.1 +/- 6.5 and 51.1 +/- 4.2% for HV and 32.4 +/- 5.5 and 43.7 +/- 3.9% for HC, respectively; p = 0.981 and p = 0.562., Conclusions: Although significantly higher values of alpha-tocopherol were found in both serum and omental fat, antioxidant vitamins C and E did not demonstrate a significant protective effect on atherosclerosis in lipid-fed rabbits during the 10-week study period.

Objectives: The Veterans Affairs Non-Q-Wave Infarction Strategies In-Hospital (VANQWISH) trial was designed to compare outcomes of patients with a non-Q wave myocardial infarction (NQMI) who were randomized prospectively to an early "invasive" strategy versus an early "conservative" strategy. The primary objective was to compare early and late outcomes between the two strategies using a combined trial end point (all-cause mortality or nonfatal infarction) during at least 1 year of follow-up., Background: Because of the widely held view that survivors of NQMI are at high risk for subsequent cardiac events, management of these patients has become more aggressive during the last decade. There is a paucity of data from controlled trials to support such an approach, however., Methods: Appropriate patients with a new NQMI were randomized to an early "invasive" strategy (routine coronary angiography followed by myocardial revascularization, if feasible) versus an early "conservative" strategy (noninvasive, predischarge stress testing with planar thallium scintigraphy and radionuclide ventriculography), where the use of coronary angiography and myocardial revascularization was guided by the development of ischemia (clinical course or results of noninvasive tests, or both)., Results: A total of 920 patients were randomized (mean follow-up 23 months, range 12 to 44). The mean patient age was 61 +/- 10 years; 97% were male; 38% had ST segment depression at study entry; 30% had an anterior NQMI; 54% were hypertensive; 26% had diabetes requiring insulin; 43% were current smokers; 43% had a previous acute myocardial infarction; and 45% had antecedent angina within 3 weeks of the index NQMI., Conclusions: Baseline characteristics were compatible with a moderate to high risk group of patients with an NQMI.

Objectives: We sought to assess the effects of second-hand smoke (SHS) and gender on infarct size in young rats exposed in utero or in the neonatal to adolescent period, or both., Background: We previously demonstrated that exposure to SHS increases infarct size in a rat model of ischemia and reperfusion, with a dose-response relation. These results are consistent with epidemiologic studies demonstrating that SHS increases risk of death from heart disease., Methods: Thirty-one pregnant female rats were randomly divided into two groups: those exposed to SHS and a control group (non-SHS). After 3 weeks, each rat had given birth to 10 to 12 rats. One hundred one neonatal rats were divided into four groups according to exposure to SHS in utero (SHSu) and randomized to SHS exposure in the neonatal to adolescent period (SHSna). After 12 weeks, all rats were subjected to 17 min of left coronary artery occlusion and 2 h of reperfusion., Results: Birth mortality was higher in the SHSu group than in the non-SHSu group (11.9% vs. 2.8%, p < 0.001). Body weight of neonatal rats at 3 and 4 weeks in the two SHSu groups was lower than that of rats in the two non-SHSu groups (p < 0.001). Exposure to SHSna increased endothelin-1 levels in plasma (p = 0.001). In all 70 young rats who survived the neonatal period, infarct size (Infarct mass/Risk area x 100%) was greater in the SHSna groups than in the non-SHSna groups (p = 0.005) and in the male groups than in the female groups (p < 0.001)., Conclusions: Exposure to SHS in the neonatal to adolescent period and male gender increased myocardial infarct size in a young rat model of ischemia and reperfusion. These results are consistent with epidemiologic studies demonstrating that SHS increases the health risk to neonates and adolescents.

A number of antianginal drugs and therapeutic strategies are now available for the treatment of patients with coronary artery disease (CAD) and myocardial ischemia. Of the available antianginal drugs, beta blockers appear to be most effective in suppressing myocardial ischemia. The superior anti-ischemic efficacy of beta blockers can be explained by their beneficial actions on hemodynamic parameters, vasomotion, and platelet function. Compared with other anti-ischemic drugs, beta blockers appear to be more efficacious in reducing the magnitude of myocardial ischemia during routine daily activities. In addition, the results of recent studies indicate that treatment with beta blockers not only suppresses myocardial ischemia, but also improves the clinical outcome in patients with CAD. These beneficial effects, along with the well-demonstrated cardioprotective effects of beta blockade in the postinfarction period, clearly suggest that this class of anti-ischemic drugs is an ideal therapeutic choice in most patients with CAD.

BACKGROUND: Sotalol has combined type II and type III antiarrhythmic properties. Although the beta-blocking action of sotalol is thought to contribute to its antiarrhythmic actions, few data are available from direct comparative clinical trials with pure beta-blocking drugs. METHODS AND RESULTS: In this double-blind, randomized, multicenter, placebo-controlled, parallel study, we have compared the antiarrhythmic efficacy and safety of treatment with sotalol vs propranolol in 181 patients with organic heart disease and frequent (>30 ventricular premature complexes [VPCs]/h) repetitive ventricular premature complexes. Eighty-seven were randomized to receive sotalol and 94 received propranolol. The demographic and clinical characteristics of the two groups were identical, and the majority of patients had coronary artery disease or hypertensive heart disease. Most patients had a long-standing history (>5 years) of ventricular arrhythmias and, in a significant proportion, antiarrhythmic therapy with other drugs had failed in the past. After withdrawal of all antiarrhythmic drugs and 1 week of placebo, qualified patients were randomized to sotalol (320 mg/day) or propranolol (120 mg/day). patients not achieving adequate response were given higher doses of sotalol (640 mg/day) or propranolol (240 mg/day)At baseline, both groups had comparable frequency of total VPCs/hour (274/h and 255/h for sotalol and propranolol groups, respectively) which was reduced to 71 VPCs/h and 109/VPCs/h, respectively, at the end of phase 1. At final evaluation there was a significantly greater response to sotalol as demonstrated by 80% reduction in VPCs/hour with sotalol compared with only 50% reduction noted in the propranolol group. Adequate therapeutic response was also achieved in a significantly greater percentage of patients on sotalol compared with propranolol (56% vs 29%, P =.02). Sotalol was also superior to propranolol in suppressing the VT events/day during phase 1 (89% vs 78% reduction in VT events/day, P <.05). Sotalol was more effective than propranolol in all subgroups and in patients with heart rate <75 beats per minute. CONCLUSIONS: Sotalol is more powerful than propranolol in suppressing ventricular arrhythmias documented on Holter recordings. The superiority of sotalol appears to be related to its combined class II and class III antiarrhythmic actions.

Heart failure (HF) still presents a major health problem despite significant understanding of its underlying pathophysiology and recent therapeutic advances. Hypertension is a major risk factor for HF and plays a key role in the evolution of the disease. In an attempt to compensate for the increased peripheral resistance frequently noted in hypertension, the heart may hypertrophy, with the left ventricular enlargement accompanied by fibrosis and resulting in reduced contractility. Ultimately the hypertrophied or fibrosed myocardium is no longer able to maintain normal cardiac output and left ventricular failure occurs. Evidence shows that treating hypertension effectively can have a major beneficial impact on some, but not all, forms of adult cardiovascular disease. For example, the incidence of HF and stroke are clearly reduced; however, until recently, treating hypertension has had relatively little effect on coronary heart disease (CHD) events. The benefits of antihypertensive treatment are, however, clearly underestimated, possibly because many studies are too short and because more subtle benefits of treatment have been overlooked. Also, it must be realized that hypertension is a complex disorder and antihypertensive drugs do indeed differ regarding their effects on associated metabolic derangements often seen in hypertensive patients. Angiotensin converting enzyme (ACE) inhibitors have been shown to be highly efficacious and safe antihypertensive agents, and have additional favorable effects on metabolic parameters, renal functions, and cardiac hypertrophy. ACE inhibitors are now the mainstay of therapy in the patients with heart failure and it is now well recognized that earlier and more aggressive treatment of hypertension may reduce the incidence of HF. ACE inhibitors are an excellent choice as an antihypertensive agent; however, many physicians limit their use of ACE inhibitors due to concern about possible renal side-effects, which accompanied the early use of these agents at very high doses.