Management of Dyslipidemia in Patients with Hypertension, Diabetes, and Metabolic Syndrome.

PURPOSE OF REVIEW: The purpose of this review is to discuss dyslipidemia in the various common clinical conditions including hypertension, diabetes mellitus, and metabolic syndrome and review the current therapeutic strategy in these settings. RECENT FINDINGS: Dyslipidemias are common in patients with hypertension, diabetes mellitus, and metabolic syndrome. Epidemiologic studies have shown a strong correlation between serum lipid levels and risk of atherosclerotic cardiovascular disease. Multifactorial intervention strategies aimed at controlling lipids, blood pressure, and blood glucose simultaneously achieve maximal reductions in cardiovascular risk. Dyslipidemia and metabolic abnormalities are strongly associated with atherosclerosis and worse cardiovascular outcomes. While pharmacotherapy with statins has been proven to be beneficial for dyslipidemia, lifestyle modification emphasizing weight loss and regular exercise is an essential component of the interventional strategy. The common thread underlying atherosclerosis and metabolic abnormalities is endothelial dysfunction. Improved understanding of the role of endothelium in health and disease can potentially lead to novel therapies that may preempt development of atherosclerosis and its complications.

A Single Controlled Exposure to Secondhand Smoke May Not Alter Thrombogenesis or Trigger Platelet Activation.

INTRODUCTION: Chronic secondhand smoke (SHS) exposure increases cardiovascular events, particularly acute thrombotic events. There are little human data on acute SHS exposure. The aim of this study was to determine whether a single controlled exposure of humans to SHS increased thrombogenesis. METHODS: After 6-8 hours fast, subjects (n = 50) were exposed to constant dose SHS (particulate level of 500 µg/m(3)) for 120 minutes in a temperature-regulated and ventilated, simulated bar environment. Blood was drawn before and immediately after SHS exposure for thromboelastography (TEG) and flow cytometry. Maximum clot strength (MA) was measured using TEG and platelet leukocyte aggregates (LPA) were measured as an index of platelet activation. Anti-CD 14 antibodies were used as leukocyte markers and anti-CD 41 antibodies as platelet markers for cytometry. Data were analyzed using students' t test for paired samples. RESULTS: There was no effect of acute exposure to SHS on platelet activation or thrombogenesis. Also, intra group (smokers [n = 19] and nonsmokers [n = 31]) comparisons of LPA and TEG parameters did not show changes with SHS exposure. CONCLUSIONS: While there are abundant data showing enhanced thrombogenesis and platelet activation following repeated exposure to SHS, our study suggests that a single exposure does not appear to significantly alter thrombin kinetics nor result in platelet activation. The effects of SHS on thrombogenesis might be nonlinear.

Spontaneous coronary artery dissection after intense weightlifting UCSF Fresno Department of Cardiology.

Spontaneous coronary artery dissection (SCAD) is a rare cause of chest pain and cardiomyopathy. This phenomenon usually occurs during the peripartum period. SCAD associated with exercise and heavy weight lifting is even rarer and has been reported in less than 10 cases in the literature. We describe a case of SCAD associated with heavy weight lifting and exercise in a 29-year-old male who presented with exertional chest pain. The patient subsequently underwent a cardiac catheterization that showed a left ventricular ejection fraction of 40% and a dissection in the left anterior descending (LAD) coronary artery after the first diagonal/septal branch with extension to the distal LAD that wrapped around the apex. He was effectively managed with the combination of medical therapy followed by a few days later with stenting. In summary, diagnosis and treatment of this rare phenomenon is a challenge, but early diagnosis and appropriate management can lead to a successful outcome.

Effects of cigarette smoke exposure on clot dynamics and fibrin structure: an ex vivo investigation.

OBJECTIVE: The purpose of this study was to examine the effect of cigarette smoke exposure (CSE) on clot dynamics and fibrin architecture and to isolate the relative contribution of platelets and fibrinogen to clot dynamics. METHODS AND RESULTS: From young healthy males smokers (n=34) and nonsmokers (n=34) a baseline blood was drawn, and smokers had another blood draw after smoking 2 regular cigarettes. Using thromboelastography (TEG) the degree of platelet-fibrin interaction was measured. In additional experiments, abciximab (20 microg/mL) was added to the smokers samples (n=27) to reduce the effects of platelet function from the TEG parameters. The maximum clot strength (G) obtained with abciximab measured mainly the contribution of fibrinogen to clot strength (GF). By subtracting GF from G, the contribution of platelets to clot strength (GP) was presumed. A significant difference was found for all TEG parameters between nonsmokers versus postsmoking and pre- versus postsmoking samples. Postsmoking both GF and GP were significantly higher as compared to presmoking. On electron microscopy and turbidity analysis, postsmoking fibrin clots were significantly different compared to presmoking and nonsmoking samples. CONCLUSIONS: Acute CSE changes clot dynamics and alters fibrin architecture. Both functional changes in fibrinogen and platelets appear to contribute to heightened thrombogenicity after acute CSE.

Hypertension as a cardiometabolic risk.

Hypertension is a syndrome that extends beyond high blood pressure and often includes obesity, insulin resistance, altered lipid metabolism and other risk factors. The clustering of risk factors can place even a patient with a modestly elevated blood pressure at high risk for cardiovascular morbidity and mortality. Many of these risk factors either cause or are associated with endothelial dysfunction, which is implicated in development of atherosclerosis and vascular remodeling. Thus, when evaluating an individual with high blood pressure, the presence of other cardiometabolic risk factors should be sought and treated appropriately.

Preventing future acute coronary events: is the target the so-called vulnerable plaque or the high-risk or vulnerable patient?

PURPOSE OF REVIEW: Heart disease still remains the leading cause of mortality in the USA in spite of recent reductions in the death rate; complications of coronary artery disease and its sequelae are the most common mechanism of demise. Although there have been great advances in the prevention and treatment of acute myocardial infarction, greater emphasis on prevention will likely be needed to reduce acute coronary complications further. RECENT FINDINGS: The literature is replete with articles on the attempted localization of so-called vulnerable plaques and vulnerable, or high-risk patients. They emphasize the importance of the identification of that high-risk plaque or high-risk individual prior to a subsequent coronary event. This article highlights the breakthroughs into the pathophysiology of acute coronary syndromes in the past few decades and presents a perspective on current treatments, improved risk stratification and potential technological advances that may impact diagnosis and management. SUMMARY: Unfortunately, the search for the so-called vulnerable plaque is hampered by the lack of both natural history studies and proven local or regional therapies for these otherwise asymptomatic plaques. Thus, emphasis on the vulnerable or high-risk patient is appropriate, but identifying these individuals in primary prevention is also fraught with difficulty. No specific recommendations can be made at present, as more data are needed in both areas. However, guidelines for future advances are proposed.

Methamphetamine-associated acute left ventricular dysfunction: a variant of stress-induced cardiomyopathy.

This brief report describes a case of transient left ventricular dysfunction in a 42-year-old woman associated with methamphetamine abuse. Transient (stress-induced) left ventricular dysfunction has been described previously, usually in postmenopausal women following emotional stress and also severe medical illness. This is the first reported case associated with methamphetamine abuse.

A Case of Iatrogenic Aortic Intramural Hematoma.

Iatrogenic aortic dissection during percutaneous coronary intervention is a rare but serious complication. Both conservative and surgical approaches have been proposed as management strategies. We describe a case of an 87-year-old female who presented with an acute coronary syndrome complicated by the development of an ascending aortic dissection during percutaneous intervention, and we provide a brief review of the literature.

Comprehensive risk reduction of cardiovascular risk factors in the diabetic patient: an integrated approach.

Diabetic patients are at increased risk of CV disease morbidity and mortality. In the past,treatment of diabetic patients largely focused on tight glycemic control. A number of studies,however, have shown that aggressive control of blood pressure and hyperlipidemia and the institution of antithrombotic therapy are beneficial in reducing the risk of CV events in the diabetic patient. Although in general these studies have shown a 15% to 30% reduction in the RR of CV events, the absolute risk of CV events remains high in the intervention group, probably because most of these trials have not incorporated a comprehensive risk-reduction strategy. Emerging data suggest that a therapeutic strategy using appropriate therapy to address multiple components of CV risks in diabetic patients is indeed beneficial in reducing the absolute risk of CV events. Although more data are needed to substantiate the benefits, feasibility, and cost effectiveness of such therapy, there is sufficient evidence for the clinician to provide an individualized approach and to consider aggressive intervention to minimize the predictable risk of CV events in the high-risk diabetic patient.

Pathophysiology of coronary thrombus formation and adverse consequences of thrombus during PCI.

Atherosclerosis is a systemic vascular pathology that is preceded by endothelial dysfunction. Vascular inflammation "fuels" atherosclerosis and creates the milieu for episodes of intravascular thromboses. Thrombotic events in the coronary vasculature may lead to asymptomatic progression of atherosclerosis or could manifest as acute coronary syndromes or even sudden cardiac death. Thrombus encountered in the setting of acute coronary syndromes has been correlated with acute complications during percutaneous coronary interventions such as no-reflow, acute coronary occlusion and long term complications such as stent thrombus. This article reviews the pathophysiology of coronary thrombogenesis and explores the complications associated with thrombus during coronary interventions.

Primary and secondary prevention strategy for cardiovascular disease in diabetes mellitus.

The majority of individuals with diabetes die from cardiovascular disease (CVD) and related complications. The risk of CVD is 2 to 4 fold greater in diabetes and largely magnified by co-morbidities that aggregate along with it. Sufficient evidence-based data now exist to support multifactorial risk intervention with specific targets for goal-directed therapy for both primary and secondary prevention. These interventions have shown survival benefit in addition to prevention of vascular complications. Prevention of diabetes and delaying its onset should also be an important aspect in future health care strategy and research to confront the oncoming tsunami of CVD related to diabetes.

Vulnerable plaques and patients: improving prediction of future coronary events.

Heart disease remains the leading cause of mortality in the United States despite recent reductions in the death rate. Complications of coronary artery disease and its sequelae are the most common mechanism of demise. There have been great advances in the prevention and treatment of acute myocardial infarction, and the literature is replete with articles on attempted localization of so-called vulnerable plaques and vulnerable or high-risk patients to find either that high-risk plaque or that individual before the event. Unfortunately, the search for the so-called vulnerable plaque is hampered by the lack of both natural history studies and proven local or regional therapies for these otherwise asymptomatic plaques. Although emphasis on the vulnerable or high-risk patient is appropriate, identifying these individuals in primary prevention is difficult. This article highlights insights into the pathophysiology of vulnerable plaque and presents a perspective on current treatments, improved risk stratification, and potential technologic advances that might affect future diagnosis and management.

Acute cigarette smoke exposure reduces clot lysis--association between altered fibrin architecture and the response to t-PA.

BACKGROUND: Enhanced thrombolysis is a proposed mechanism for reduced mortality in cigarette smokers with STEMI ("smoker's paradox"). The mechanisms remain unclear but studies suggest fibrin architecture (FA) may affect thrombolysis. Our group has previously shown that acute cigarette smoke exposure (CSE) alters FA. This study was done to evaluate the association between FA, thrombolysis and CSE. METHODS AND RESULTS: Otherwise healthy smokers (n=22) were studied before and after smoking two cigarettes. Non-smokers (n=22) served as controls. Two ex-vivo models were used to evaluate clot lysis of venous blood and these data were compared to FA as determined by SEM. In the first model, clot lysis in a glass tube at 60minutes after addition of t-PA was measured. The second model quantified lysis utilizing thromboelastography. With the latter, after a clot reached maximum strength, t-PA was added and clot lysis at 60min was noted. SEM studies were performed on platelet poor plasma mixed with thrombin and FA was examined at 20K. Clot lysis was similar in both groups except that post-smoking, TEG showed a significantly lower lysis compared to pre- and non-smoking clots. SEM analysis showed significantly thinner fibers and denser clots post-smoking. CONCLUSIONS: Venous clots from smokers failed to show an enhanced lysis when exposed to t-PA. In fact, acute CSE was associated with changes in FA and increased resistance to thrombolysis. These findings in part may explain enhanced thrombogenicity but suggest that mechanisms other than enhanced fibrinolysis are likely to be responsible for "smoker's paradox."

Diabetes and vascular disease.

Type 2 diabetes has reached epidemic proportions and is now recognized as a coronary heart disease equivalent. While the most common metabolic abnormality associated with diabetes is hyperglycemia, there are also abnormalities in carbohydrate, fat and protein metabolism. These abnormalities increase oxidative stress and activate the renin-angiotensin system leading to endothelial dysfunction and, thereafter, to systemic atherosclerosis. This systemic atherosclerosis is responsible for the increased cardiovascular morbidity and mortality related to diabetes. In this article, we review the evidence and discuss the rationale for comprehensive risk reduction to prevent and treat vascular disease in individuals with diabetes mellitus. The components of comprehensive risk reduction strategy consist of lifestyle changes, glycemic control, control of dyslipidemia and hypertension.

Management of coronary artery disease in patients with type 2 diabetes mellitus.

Diabetes mellitus is as much a vascular disease as it is a metabolic disorder. The metabolic abnormalities associated with diabetes include hyperglycemia, and abnormal carbohydrate, fat, and protein handling. These abnormalities increase oxidative stress and activate the renin angiotensin system, which subsequently causes endothelial dysfunction and predisposes to atherosclerosis. Type 2 diabetes has reached epidemic proportions and because of its strong association with coronary artery disease (CAD), it is responsible for increasing cardiovascular morbidity and mortality in the United States. In this article we review some of the evidence and the rationale for comprehensive risk reduction to prevent and treat CAD in individuals with diabetes mellitus. The comprehensive risk reduction strategy includes lifestyle changes, glycemic control, and control of dyslipidemia and hypertension. Advances in revascularization techniques, and superior outcomes of coronary artery bypass grafting as an interventional modality over percutaneous coronary intervention, are discussed. We also identify controversies and issues that currently remain unresolved.