Showing papers in "Circulation in 2001"
TL;DR: An overview of the global burden of atherothrombotic cardiovascular disease is provided and overarching factors influencing variations in CVD by ethnicity and region and the influence of urbanization are described.
Abstract: This two-part article provides an overview of the global burden of atherothrombotic cardiovascular disease. Part I initially discusses the epidemiologic transition which has resulted in a decrease in deaths in childhood due to infections, with a concomitant increase in cardiovascular and other chronic diseases; and then provides estimates of the burden of cardiovascular (CV) diseases with specific focus on the developing countries. Next, we summarize key information on risk factors for cardiovascular disease (CVD) and indicate that their importance may have been underestimated. Then, we describe overarching factors influencing variations in CVD by ethnicity and region and the influence of urbanization. Part II of this article describes the burden of CV disease by specific region or ethnic group, the risk factors of importance, and possible strategies for prevention.
2,779 citations
TL;DR: Data support the concept that oxidative stress may contribute not only to endothelial dysfunction but also to coronary artery disease activity, and predict the risk of cardiovascular events in patients with coronary arteries disease.
Abstract: Background Endothelial function is impaired in coronary artery disease and may contribute to its clinical manifestations. Increased oxidative stress has been linked to impaired endothelial function in atherosclerosis and may play a role in the pathogenesis of cardiovascular events. This study was designed to determine whether endothelial dysfunction and vascular oxidative stress have prognostic impact on cardiovascular event rates in patients with coronary artery disease. Methods and Results Endothelium-dependent and -independent vasodilation was determined in 281 patients with documented coronary artery disease by measuring forearm blood flow responses to acetylcholine and sodium nitroprusside using venous occlusion plethysmography. The effect of the coadministration of vitamin C (24 mg/min) was assessed in a subgroup of 179 patients. Cardiovascular events, including death from cardiovascular causes, myocardial infarction, ischemic stroke, coronary angioplasty, and coronary or peripheral bypass operation...
1,903 citations
TL;DR: In this article, the authors provide revised standards and guidelines for the exercise testing and training of individuals who are free from clinical manifestations of cardiovascular disease and those with known cardiovascular disease, which are intended for physicians, nurses, exercise physiologists, specialists, technologists, and other healthcare professionals involved in exercise testing.
Abstract: The purpose of this report is to provide revised standards and guidelines for the exercise testing and training of individuals who are free from clinical manifestations of cardiovascular disease and those with known cardiovascular disease. These guidelines are intended for physicians, nurses, exercise physiologists, specialists, technologists, and other healthcare professionals involved in exercise testing and training of these populations. This report is in accord with the “Statement on Exercise” published by the American Heart Association (AHA).1
These guidelines are a revision of the 1995 standards of the AHA that addressed the issues of exercise testing and training.2 An update of background, scientific rationale, and selected references is provided, and current issues of practical importance in the clinical use of these standards are considered. These guidelines are in accord with the American College of Cardiology (ACC)/AHA Guidelines for Exercise Testing.3
### The Cardiovascular Response to Exercise
Exercise, a common physiological stress, can elicit cardiovascular abnormalities that are not present at rest, and it can be used to determine the adequacy of cardiac function. Because exercise is only one of many stresses to which humans can be exposed, it is more appropriate to call an exercise test exactly that and not a “stress test.” This is particularly relevant considering the increased use of nonexercise stress tests.
### Types of Exercise
Three types of muscular contraction or exercise can be applied as a stress to the cardiovascular system: isometric (static), isotonic (dynamic or locomotory), and resistance (a combination of isometric and isotonic).4,5 Isotonic exercise, which is defined as a muscular contraction resulting in movement, primarily provides a volume load to the left ventricle, and the response is proportional to the size of the working muscle mass and the intensity of exercise. Isometric exercise is defined as a muscular contraction without movement (eg, handgrip) and imposes greater pressure than volume …
1,697 citations
TL;DR: Life-threatening arrhythmias in LQTS patients tend to occur under specific circumstances in a gene-specific manner, allowing new insights into the mechanisms that relate the electrophysiological consequences of mutations on specific genes to clinical manifestations and offer the possibility of complementing traditional therapy with gene- specific approaches.
Abstract: Background The congenital long-QT syndrome (LQTS) is caused by mutations on several genes, all of which encode cardiac ion channels. The progressive understanding of the electrophysiological consequences of these mutations opens unforeseen possibilities for genotype-phenotype correlation studies. Preliminary observations suggested that the conditions ("triggers") associated with cardiac events may in large part be gene specific. Methods and results We identified 670 LQTS patients of known genotype (LQT1, n=371; LQT2, n=234; LQT3, n=65) who had symptoms (syncope, cardiac arrest, sudden death) and examined whether 3 specific triggers (exercise, emotion, and sleep/rest without arousal) differed according to genotype. LQT1 patients experienced the majority of their events (62%) during exercise, and only 3% occurred during rest/sleep. These percentages were almost reversed among LQT2 and LQT3 patients, who were less likely to have events during exercise (13%) and more likely to have events during rest/sleep (29% and 39%). Lethal and nonlethal events followed the same pattern. Corrected QT interval did not differ among LQT1, LQT2, and LQT3 patients (498, 497, and 506 ms, respectively). The percent of patients who were free of recurrence with ss-blocker therapy was higher and the death rate was lower among LQT1 patients (81% and 4%, respectively) than among LQT2 (59% and 4%, respectively) and LQT3 (50% and 17%, respectively) patients. Conclusions Life-threatening arrhythmias in LQTS patients tend to occur under specific circumstances in a gene-specific manner. These data allow new insights into the mechanisms that relate the electrophysiological consequences of mutations on specific genes to clinical manifestations and offer the possibility of complementing traditional therapy with gene-specific approaches.
1,665 citations
TL;DR: New guidelines for management of supraventricular tachyarrhythmia characterized by uncoordinated atrial activation with consequent deterioration of atrial mechanical function are published.
Abstract: Atrial fibrillation (AF), the most common sustained cardiac rhythm disturbance, is increasing in prevalence as the population ages. Although it is often associated with heart disease, AF occurs in many patients with no detectable disease. Hemodynamic impairment and thromboembolic events result in significant morbidity, mortality, and cost. Accordingly, the American College of Cardiology (ACC), the American Heart Association (AHA), and the European Society of Cardiology (ESC) created a committee of experts to establish guidelines for management of this arrhythmia.
The committee was composed of 8 members representing the ACC and AHA, 4 representing the ESC, 1 from the North American Society of Pacing and Electrophysiology (NASPE), and a representative of the Johns Hopkins University Evidence-Based Practice Center representing the Agency for Healthcare Research and Quality’s report on Atrial Fibrillation in the Elderly. This document was reviewed by 3 official reviewers nominated by the ACC, 3 nominated by the AHA, and 3 nominated by the ESC, as well as by the ACC Clinical Electrophysiology Committee, the AHA ECG and Arrhythmia Committee, NASPE, and 25 reviewers nominated by the writing committee. The document was approved for publication by the governing bodies of the ACC, AHA, and ESC and officially endorsed by NASPE. These guidelines will be reviewed annually by the task force and will be considered current unless the task force revises or withdraws them from distribution.
The committee conducted a comprehensive review of the literature from 1980 to June 2000 relevant to AF using the following databases: PubMed/Medline, EMBASE, the Cochrane Library (including the Cochrane Database of Systematic Reviews and the Cochrane Controlled Trials Registry), and Best Evidence. Searches were limited to English language sources and to human subjects.
### A. Atrial Fibrillation
AF is a supraventricular tachyarrhythmia characterized by uncoordinated atrial activation with consequent deterioration of atrial mechanical function. On the electrocardiogram (ECG), AF …
1,628 citations
TL;DR: Knowledge of the underlying mechanisms has increased substantially since this topic was last reviewed in these pages 6 years ago and the present article provides an update of this rapidly moving field.
Abstract: The last decade has witnessed a major reassessment of our perceptions about the acute coronary syndromes. Today, we recognize that thrombosis underlies most acute complications of atherosclerosis, notably unstable angina and acute myocardial infarction. A consensus has emerged that inflammation plays a decisive role in the pathophysiology of these acute thrombotic events (Figure 1). Knowledge of the underlying mechanisms has increased substantially since this topic was last reviewed in these pages 6 years ago. The present article provides an update of this rapidly moving field.
Figure 1. Initiation, progression, and complication of human coronary atherosclerotic plaque. Top, Longitudinal section of artery depicting “timeline” of human atherogenesis from normal artery (1) to atheroma that caused clinical manifestations by thrombosis or stenosis (5, 6, 7). Bottom, Cross sections of artery during various stages of atheroma evolution. 1, Normal artery. Note that in human arteries, the intimal layer is much better developed than in most other species. The intima of human arteries contains resident smooth muscle cells often as early as first year of life. 2, Lesion initiation occurs when endothelial cells, activated by risk factors such as hyperlipoproteinemia, express adhesion and chemoattractant molecules that recruit inflammatory leukocytes such as monocytes and T lymphocytes. Extracellular lipid begins to accumulate in intima at this stage. 3, Evolution to fibrofatty stage. Monocytes recruited to artery wall become macrophages and express scavenger receptors that bind modified lipoproteins. Macrophages become lipid-laden foam cells by engulfing modified lipoproteins. Leukocytes and resident vascular wall cells can secrete inflammatory cytokines and growth factors that amplify leukocyte recruitment and cause smooth muscle cell migration and proliferation. 4, As lesion progresses, inflammatory mediators cause expression of tissue factor, a potent procoagulant, and of matrix-degrading proteinases that weaken fibrous cap of plaque. 5, If fibrous cap ruptures at point of weakening, coagulation factors …
1,541 citations
TL;DR: Death rates for SCD increased with age and were higher in men than women, although there was no difference at age ≥85 years, and the increase in death rates forSCD among younger women warrants additional investigation.
Abstract: Background Sudden cardiac death (SCD) is a major clinical and public health problem. Methods and Results United States (US) vital statistics mortality data from 1989 to 1998 were analyzed. SCD is defined as deaths occurring out of the hospital or in the emergency room or as “dead on arrival” with an underlying cause of death reported as a cardiac disease (ICD-9 code 390 to 398, 402, or 404 to 429). Death rates were calculated for residents of the US aged ≥35 years and standardized to the 2000 US population. Of 719 456 cardiac deaths among adults aged ≥35 years in 1998, 456 076 (63%) were defined as SCD. Among decedents aged 35 to 44 years, 74% of cardiac deaths were SCD. Of all SCDs in 1998, coronary heart disease (ICD-9 codes 410 to 414) was the underlying cause on 62% of death certificates. Death rates for SCD increased with age and were higher in men than women, although there was no difference at age ≥85 years. The black population had higher death rates for SCD than white, American Indian/Alaska Nati...
1,533 citations
TL;DR: In this paper, a case-crossover approach was used to analyze the data for evidence of triggering, and the risk of acute myocardial infarction onset increased in association with elevated concentrations of fine particles in the previous 2-hour period.
Abstract: Background—Elevated concentrations of ambient particulate air pollution have been associated with increased hospital admissions for cardiovascular disease. Whether high concentrations of ambient particles can trigger the onset of acute myocardial infarction (MI), however, remains unknown. Methods and Results—We interviewed 772 patients with MI in the greater Boston area between January 1995 and May 1996 as part of the Determinants of Myocardial Infarction Onset Study. Hourly concentrations of particle mass <2.5 μm (PM2.5), carbon black, and gaseous air pollutants were measured. A case-crossover approach was used to analyze the data for evidence of triggering. The risk of MI onset increased in association with elevated concentrations of fine particles in the previous 2-hour period. In addition, a delayed response associated with 24-hour average exposure 1 day before the onset of symptoms was observed. Multivariate analyses considering both time windows jointly revealed an estimated odds ratio of 1.48 assoc...
1,418 citations
TL;DR: In this article, high-sensitivity C-reactive protein (HSCRP) was used as a biomarker for predicting future myocardial infarction and stroke among apparently healthy men and women.
Abstract: Inflammation plays a major role in atherothrombosis, and measurement of inflammatory markers such as high-sensitivity C-reactive protein (HSCRP) may provide a novel method for detecting individuals at high risk of plaque rupture. Several large-scale prospective studies demonstrate that HSCRP is a strong independent predictor of future myocardial infarction and stroke among apparently healthy men and women and that the addition of HSCRP to standard lipid screening may improve global risk prediction among those with high as well as low cholesterol levels. Because agents such as aspirin and statins seem to attenuate inflammatory risk, HSCRP may also have utility in targeting proven therapies for primary prevention. Inexpensive commercial assays for HSCRP are now available; they have shown variability and classification accuracy similar to that of cholesterol screening. Risk prediction algorithms using a simple quintile approach to HSCRP evaluation have been developed for outpatient use. Thus, although limitations inherent to inflammatory screening remain, available data suggest that HSCRP has the potential to play an important role as an adjunct for global risk assessment in the primary prevention of cardiovascular disease.
1,395 citations
TL;DR: Age 50 to 59 years was a transition period when all 3 BP indexes were comparable predictors, and from 60 years of age on, DBP was negatively related to CHD risk so that PP became superior to SBP.
Abstract: Background—We examined the relative importance of diastolic (DBP), systolic (SBP) and pulse pressure (PP) as predictors of coronary heart disease (CHD) risk in different age groups of Framingham Heart Study participants. Methods and Results—We studied 3060 men and 3479 women between 20 and 79 years of age who were free of CHD and were not on antihypertensive drug therapy at baseline. Cox regression adjusted for age, sex, and other risk factors was used to assess the relations of BP indexes to CHD risk over a 20-year follow-up. In the group <50 years of age, DBP was the strongest predictor of CHD risk (hazard ratio [HR] per 10 mm Hg increment, 1.34; 95% CI, 1.18 to 1.51) rather than SBP (HR, 1.14; 95% CI, 1.06 to 1.24) or PP (HR, 1.02; 95% CI, 0.89 to 1.17). In the group 50 to 59 years of age, risks were comparable for all 3 BP indexes. In the older age group, the strongest predictor of CHD risk was PP (HR, 1.24; 95% CI, 1.16 to 1.33). When both SBP and DBP were considered jointly, the former was directly ...
1,376 citations
TL;DR: Elevated CRP levels in AF patients may reflect an inflammatory state that promotes the persistence of AF, and is the first to document elevated CRP in non-postoperative arrhythmia patients.
Abstract: Background Atrial fibrillation (AF) may persist due to structural changes in the atria that are promoted by inflammation. C-reactive protein (CRP), a marker of systemic inflammation, predicts cardiovascular events and stroke, a common sequela of AF. We hypothesized that CRP is elevated in patients with atrial arrhythmias. Methods and Results Using a case-control study design, CRP in 131 patients with atrial arrhythmias was compared with CRP in 71 control patients. Among arrhythmia patients, 6 had frequent atrial ectopy or tachycardia, 86 had paroxysmal AF, 39 had persistent AF lasting >30 days, and 70 had lone arrhythmias. CRP was higher in arrhythmia than in control patients (median, 0.21 versus 0.096 mg/dL; P<0.001). Arrhythmia patients in AF within 24 hours before sampling had higher CRP than those in sinus rhythm (0.30 versus 0.15 mg/dL; P<0.001). CRP in controls was not different than in patients with atrial ectopy or tachycardia. Lone arrhythmia patients had a CRP of 0.21 mg/dL, which was not signif...
TL;DR: It is demonstrated that hRyR2 is a gene responsible for catecholaminergic polymorphic ventricular tachycardia, in agreement with the hypothesis that a genetically determined abnormality of intracellular calcium handling might be the substrate of the disease.
Abstract: Background —Catecholaminergic polymorphic ventricular tachycardia is a genetic arrhythmogenic disorder characterized by stress-induced, bidirectional ventricular tachycardia that may degenerate into cardiac arrest and cause sudden death. The electrocardiographic pattern of this ventricular tachycardia closely resembles the arrhythmias associated with calcium overload and the delayed afterdepolarizations observed during digitalis toxicity. We speculated that a genetically determined abnormality of intracellular calcium handling might be the substrate of the disease; therefore, we considered the human cardiac ryanodine receptor gene ( hRyR2 ) a likely candidate for this genetically transmitted arrhythmic disorder. Methods and Results —Twelve patients presenting with typical catecholaminergic polymorphic ventricular tachycardia in the absence of structural heart abnormalities were identified. DNA was extracted from peripheral blood lymphocytes, and single-strand conformation polymorphism analysis was performed on polymerase chain reaction–amplified exons of the hRyR2 gene. Four single nucleotide substitutions leading to missense mutations were identified in 4 probands affected by the disease. Genetic analysis of the asymptomatic parents revealed that 3 probands carried de novo mutations. In 1 case, the identical twin of the proband died suddenly after having suffered syncopal episodes. The fourth mutation was identified in the proband, in 4 clinically affected family members, and in none of 3 nonaffected family members in a kindred with 2 sudden deaths that occurred at 16 and 14 years, respectively, in the sisters of the proband. Conclusions —We demonstrated that, in agreement with our hypothesis, hRyR2 is a gene responsible for catecholaminergic polymorphic ventricular tachycardia.
TL;DR: Patients with previous (>16 days) Q-wave MI by ECG who underwent transthoracic echocardiography found that after 5 years, total mortality and cardiac mortality for patients with IMR were higher than for those without IMR.
Abstract: Background—Myocardial infarction (MI) can directly cause ischemic mitral regurgitation (IMR), which has been touted as an indicator of poor prognosis in acute and early phases after MI However, in the chronic post-MI phase, prognostic implications of IMR presence and degree are poorly defined Methods and Results—We analyzed 303 patients with previous (>16 days) Q-wave MI by ECG who underwent transthoracic echocardiography: 194 with IMR quantitatively assessed in routine practice and 109 without IMR matched for baseline age (71±11 versus 70±9 years, P=020), sex, and ejection fraction (EF, 33±14% versus 34±11%, P=014) In IMR patients, regurgitant volume (RVol) and effective regurgitant orifice (ERO) area were 36±24 mL/beat and 21±12 mm2, respectively After 5 years, total mortality and cardiac mortality for patients with IMR (62±5% and 50±6%, respectively) were higher than for those without IMR (39±6% and 30±5%, respectively) (both P<0001) In multivariate analysis, independently of all baseline chara
TL;DR: Ex vivo expanded EPCs incorporate into foci of myocardial neovascularization and have a favorable impact on the preservation of left ventricular function.
Abstract: Background—We investigated the therapeutic potential of ex vivo expanded endothelial progenitor cells (EPCs) for myocardial neovascularization. Methods and Results—Peripheral blood mononuclear cells obtained from healthy human adults were cultured in EPC medium and harvested 7 days later. Myocardial ischemia was induced by ligating the left anterior descending coronary artery in male Hsd:RH-rnu (athymic nude) rats. A total of 106 EPCs labeled with 1,1′-dioctadecyl-1 to 3,3,3′,3′-tetramethylindocarbocyanine perchlorate were injected intravenously 3 hours after the induction of myocardial ischemia. Seven days later, fluorescence-conjugated Bandeiraea simplicifolia lectin I was administered intravenously, and the rats were immediately killed. Fluorescence microscopy revealed that transplanted EPCs accumulated in the ischemic area and incorporated into foci of myocardial neovascularization. To determine the impact on left ventricular function, 5 rats (EPC group) were injected intravenously with 106 EPCs 3 hou...
TL;DR: The adipocyte-derived plasma protein adiponectin suppressed macrophage-to-foam cell transformation, suggesting that adip onectin may act as a modulator for macrophages- to-foams cell transformation.
Abstract: Background—Excessive lipid accumulation in macrophages plays an important role in the development of atherosclerosis. Recently, we discovered an adipocyte-specific plasma protein, adiponectin, that is decreased in patients with coronary artery disease. We previously demonstrated that adiponectin acts as a modulator for proinflammatory stimuli and inhibits monocyte adhesion to endothelial cells. The present study investigated the effects of adiponectin on lipid accumulation in human monocyte-derived macrophages. Methods and Results—Human monocytes were differentiated into macrophages by incubation in human type AB serum for 7 days, and the effects of adiponectin were investigated at different time intervals. Treatment with physiological concentrations of adiponectin reduced intracellular cholesteryl ester content, as determined using the enzymatic, fluorometric method. The adiponectin-treated macrophages contained fewer lipid droplets stained by oil red O. Adiponectin suppressed the expression of the class...
TL;DR: In the United States, nearly 5 million patients in this country have heart failure, and nearly 500,000 patients are diagnosed with heart failure for the first time each year as mentioned in this paper.
Abstract: References......2112
Heart failure (HF) is a major public health problem in the United States. Nearly 5 million patients in this country have HF, and nearly 500,000 patients are diagnosed with HF for the first time each year. The disorder is the underlying reason for 12 to 15 million office visits
TL;DR: This is the first clinical demonstration showing that lineage-committed EPCs and MNCCD34+, their putative precursors, are mobilized during an acute ischemic event in humans.
Abstract: Background—Endothelial progenitor cells (EPCs) circulate in adult peripheral blood (PB) and contribute to neovascularization. However, little is known regarding whether EPCs and their putative precursor, CD34-positive mononuclear cells (MNCCD34+), are mobilized into PB in acute ischemic events in humans. Methods and Results—Flow cytometry revealed that circulating MNCCD34+ counts significantly increased in patients with acute myocardial infarction (n=16), peaking on day 7 after onset, whereas they were unchanged in control subjects (n=8) who had no evidence of cardiac ischemia. During culture, PB-MNCs formed multiple cell clusters, and EPC-like attaching cells with endothelial cell lineage markers (CD31, vascular endothelial cadherin, and kinase insert domain receptor) sprouted from clusters. In patients with acute myocardial infarction, more cell clusters and EPCs developed from cultured PB-MNCs obtained on day 7 than those on day 1. Plasma levels of vascular endothelial growth factor significantly incre...
TL;DR: A novel mechanism of action of statin treatment in patients with stable CAD is defined: the augmentation of circulating EPCs with enhanced functional activity.
Abstract: Background—Therapeutic neovascularization may constitute an important strategy to salvage tissue from critical ischemia. Circulating bone marrow–derived endothelial progenitor cells (EPCs) were shown to augment the neovascularization of ischemic tissue. In addition to lipid-lowering activity, hydroxymethyl glutaryl coenzyme A reductase inhibitors (statins) reportedly promote the neovascularization of ischemic tissue in normocholesterolemic animals. Methods and Results—Fifteen patients with angiographically documented stable coronary artery disease (CAD) were prospectively treated with 40 mg of atorvastatin per day for 4 weeks. Before and weekly after the initiation of statin therapy, EPCs were isolated from peripheral blood and counted. In addition, the number of hematopoietic precursor cells positive for CD34, CD133, and CD34/kinase insert domain receptor was analyzed. Statin treatment of patients with stable CAD was associated with an ≈1.5-fold increase in the number of circulating EPCs by 1 week after ...
TL;DR: Endothelium-dependent and -independent vasodilation was investigated in 225 never-treated hypertensive patients by intra-arterial infusion of increasing doses of ACh and sodium nitroprusside by finding no significant differences between the groups.
Abstract: Background— Forearm endothelial dysfunction, characterized by an impaired vasodilating response to acetylcholine (ACh), may be associated with several cardiovascular risk factors, including essential hypertension. Although the prognostic value of coronary endothelial dysfunction has been demonstrated, that of forearm endothelial dysfunction is still unknown. Methods and Results— Endothelium-dependent and -independent vasodilation was investigated in 225 never-treated hypertensive patients (age, 35 to 54 years) by intra-arterial infusion of increasing doses of ACh and sodium nitroprusside. Patients were divided into tertiles on the basis of their increase in ACh-stimulated forearm blood flow (FBF) from basal: group 1, from 30% to 184%; group 2, from 185% to 333%; and group 3, from 339% to 760% increase from basal. During a mean follow-up of 31.5 of months (range, 4 to 84 months), there were 29 major adverse events at the cardiac (n=19), cerebrovascular (n=9), or peripheral vascular (n=1) level. Events incl...
TL;DR: In this article, the authors provide an overview of the global burden of atherothrombotic cardiovascular disease with a specific focus on the developing countries and summarize key information on risk factors for cardiovascular disease.
Abstract: This two-part article provides an overview of the global burden of atherothrombotic cardiovascular disease. Part I initially discusses the epidemiological transition which has resulted in a decrease in deaths in childhood due to infections, with a concomitant increase in cardiovascular and other chronic diseases; and then provides estimates of the burden of cardiovascular (CV) diseases with specific focus on the developing countries. Next, we summarize key information on risk factors for cardiovascular disease (CVD) and indicate that their importance may have been underestimated. Then, we describe overarching factors influencing variations in CVD by ethnicity and region and the influence of urbanization. Part II of this article describes the burden of CV disease by specific region or ethnic group, the risk factors of importance, and possible strategies for prevention.
TL;DR: In ESRF patients, the insensitivity of PWV to decreased BP is an independent predictor of mortality and that use of ACE inhibitors has a favorable effect on survival that is independent of BP changes.
Abstract: Background—Aortic pulse wave velocity (PWV) is a predictor of mortality in patients with end-stage renal failure (ESRF). The PWV is partly dependent on blood pressure (BP), and a decrease in BP can attenuate the stiffness. Whether the changes in PWV in response to decreases in BP can predict mortality in ESRF patients has never been investigated. Methods and Results—One hundred fifty ESRF patients (aged 52 616 years) were monitored for 51638 months. From entry until the end of follow-up, the changes of PWV in response to decreased BP were measured ultrasonographically. BP was controlled by adjustment of “dry weight” and, when necessary, with ACE inhibitors, calcium antagonists, and/or b-blockers, in combination if necessary. Fifty-nine deaths occurred, including 40 cardiovascular and 19 noncardiovascular events. Cox analyses demonstrated that independent of BP changes, the predictors of all-cause and cardiovascular mortality were as follows: absence of PWV decrease in response to BP decrease, increased left ventricular mass, age, and preexisting cardiovascular disease. Survival was positively associated with ACE inhibitor use. After adjustment for all confounding factors, the risk ratio for the absence of PWV decrease was 2.59 (95% CI 1.51 to 4.43) for all-cause mortality and 2.35 (95% CI 1.23 to 4.41) for cardiovascular mortality. The risk ratio for ACE inhibitor use was 0.19 (95% CI 0.14 to 0.43) for all-cause mortality and 0.18 (95% CI 0.06 to 0.55) for cardiovascular mortality. Conclusions—These results indicate that in ESRF patients, the insensitivity of PWV to decreased BP is an independent predictor of mortality and that use of ACE inhibitors has a favorable effect on survival that is independent of BP changes. (Circulation. 2001;103:987-992.)
TL;DR: Pravastatin decreased lipids, lipid oxidation, inflammation, MMP-2, and cell death and increased TIMP-1 and collagen content in human carotid plaques, confirming its plaque-stabilizing effect in humans.
Abstract: Background—The clinical benefits of lipid lowering with statins are attributed to changes in plaque composition leading to lesion stability, but supporting clinical data from human studies are lacking. Therefore, we investigated the effect of 3 months of pravastatin treatment on composition of human carotid plaques removed during carotid endarterectomy. Methods and Results—Consecutive patients with symptomatic carotid artery stenosis received 40 mg/d pravastatin (n=11) or no lipid-lowering therapy (n=13; control subjects) for 3 months before scheduled carotid endarterectomy. Carotid plaque composition was assessed with special stains and immunocytochemistry with quantitative image analysis. Plaques from the pravastatin group had less lipid by oil red O staining (8.2±8.4% versus 23.9±21.1% of the plaque area, P<0.05), less oxidized LDL immunoreactivity (13.3±3.6% versus 22.0±6.5%, P<0.001), fewer macrophages (15.0±10.2% versus 25.3±12.5%, P<0.05), fewer T cells (11.2±9.3% versus 24.3±13.4%, P<0.05), less m...
TL;DR: Heterotopic ossification consisting of mature lamellar bone formation and active bone remodeling is a relatively common and unexpected finding in end-stage valvular heart disease and may be associated with repair of pathological microfractures in calcified cardiac valves.
Abstract: Background—For nearly a century, the mechanical failure of calcified heart valves was attributed to a passive degenerative process. Recently, several case reports described bone formation in surgically excised heart valves and suggested an unexpected process of tissue repair. Methods and Results—We studied the prevalence and pathology of heterotopic ossification in 347 surgically excised heart valves (256 aortic, 91 mitral) in 324 consecutive patients (182 men, 142 women; mean age 68 years) who underwent cardiac valve replacement surgery between 1994 and 1998. The valves were examined microscopically to determine the prevalence and features of bone formation and remodeling. Two hundred eighty-eight valves (83%) had dystrophic calcification. Mature lamellar bone with hematopoietic elements and active bone remodeling were present in 36 valves (13%) with dystrophic calcification. Endochondral bone formation, similar to that seen in normal fracture repair, was identified in 4 valves. Microfractures were prese...
TL;DR: BMI may constitute a novel safety strategy for achieving optimal therapeutic angiogenesis by the natural ability of the BM cells to secrete potent angiogenic ligands and cytokines as well as to be incorporated into foci of neovascularization.
Abstract: Background Bone marrow implantation (BMI) was shown to enhance angiogenesis in a rat ischemic heart model. This preclinical study using a swine model was designed to test the safety and therapeutic...
TL;DR: Optimal LDL-C values are <100 mg/dL in both women and men, and LDL- C, HDL-C, TG, and Lp(a), without additional apolipoproteins or lipid subfractions, provide substantial CHD prediction, with much higher RR in women than men.
Abstract: Background— Despite consensus on the need for blood cholesterol reductions to prevent coronary heart disease (CHD), available evidence on optimal cholesterol levels or the added predictive value of additional lipids is sparse. Methods and Results— After 10 years follow-up of 12 339 middle-aged participants free of CHD in the Atherosclerosis Risk in Communities Study (ARIC), 725 CHD events occurred. The lowest incidence was observed in those at the lowest LDL cholesterol (LDL-C) quintile, with medians of 88 mg/dL in women and 95 mg/dL in men, and risk accelerated at higher levels, with relative risks (RRs) for the highest quintile of 2.7 in women and 2.5 in men. LDL-C, HDL-C, lipoprotein(a) [Lp(a)], and in women but not men, triglycerides (TG) were all independent CHD predictors, providing an RR, together with blood pressure, smoking, and diabetes, of 13.5 in women and 4.9 in men. Lp(a) was less significant in blacks than whites. Prediction was not enhanced by HDL-C density subfractions or apolipoproteins ...
TL;DR: In this paper, the authors analyzed circulating levels of cytokines (tumor necrosis factor [TNF] and interleukin-6) and their cognate receptors in 1200 consecutive patients who were enrolled in a multicenter clinical trial of patients with advanced heart failure.
Abstract: Background—Previous reports have shown that elevated circulating levels of cytokines and/or cytokine receptors predict adverse outcomes in patients with heart failure. However, these studies were limited by small numbers of patients and/or they were performed in a single center. In addition, these studies did not have sufficient size to address the influence of age, race, sex, and cause of heart failure on the circulating levels of these inflammatory mediators in patients with heart failure. Methods and Results—We analyzed circulating levels of cytokines (tumor necrosis factor [TNF] and interleukin-6) and their cognate receptors in 1200 consecutive patients who were enrolled in a multicenter clinical trial of patients with advanced heart failure. This analysis constitutes the largest analysis of cytokines and cytokine receptors to date. Analysis of the patients receiving placebo showed that increasing circulating levels of TNF, interleukin-6, and the soluble TNF receptors were associated with increased mo...
TL;DR: Higher carotid IMT in young and middle-aged adults is associated with childhood and current cardiovascular risk factors, as well as risk factor load.
Abstract: Background Higher carotid intimal-medial thickness (IMT) is associated with cardiovascular risk factors and is predictive of coronary artery disease and stroke in older adults. Carotid IMT was measured in young and middle-aged adults to determine its relationship with risk factors measured (1) in childhood, (2) currently, and (3) as a “load” from childhood to adulthood. Methods and Results Carotid ultrasound studies were performed in 346 men and 379 women aged 33 to 42 years who were representative of a cohort followed since childhood and who live in Muscatine, Iowa. The mean of the measurements of maximal carotid IMT at 12 locations was determined for each subject. A medical questionnaire was completed, and measurements of anthropometric characteristics and risk factors were obtained. The mean maximum carotid IMT was 0.79±0.12 mm for men and 0.72±0.10 mm for women. On the basis of multivariable analysis, the significant current predictors of IMT were age and LDL cholesterol in both sexes and diastolic bl...
TL;DR: It is concluded that foam cell formation in human atherogenesis may be caused in part by uptake of CRP-opsonized native LDL, which is mediated by the CRP receptor CD32.
Abstract: Background—LDL and C-reactive protein (CRP) are important cardiovascular risk factors. Both LDL and CRP deposit in the arterial wall during atherogenesis. Stranded LDL is taken up by macrophages, c...
TL;DR: Evidence is provided that silent plaque rupture is a form of wound healing that results in increased percent stenosis and is a frequent finding in men who die suddenly with severe coronary atherosclerosis.
Abstract: Background—Subclinical episodes of plaque disruption followed by healing are considered a mechanism of increased plaque burden. Detailed pathological studies of healed ruptures, however, are lacking. Methods and Results—We identified acute and healed ruptures from 142 men who died of sudden coronary death and performed morphometric measurements of plaque burden, luminal stenosis, and smooth muscle cell phenotype. Healed ruptures were found in 61% of hearts and were associated with healed myocardial infarction, increased heart weight, dyslipidemia, and diabetes. Multiple healed rupture sites with layering were frequently found in segments with acute and healed rupture; the percent area luminal narrowing increased with increased numbers of healed sites of previous rupture. The underlying percent luminal narrowing for acute ruptures (mean 79±15%) exceeded that for healed ruptures (mean 66±14%, P=0.0001), and the area within the internal elastic lamina was significantly less in healed ruptures than in acute r...
TL;DR: By lowering plasma triglyceride levels, pravastatin therapy may favorably influence the development of diabetes, but other explanations, such as the anti-inflammatory properties of this drug in combination with its endothelial effects, cannot be excluded with these analyses.
Abstract: Background—We examined the development of new diabetes mellitus in men aged 45 to 64 years during the West of Scotland Coronary Prevention Study. Methods and Results—Our definition of diabetes mellitus was based on the American Diabetic Association threshold of a blood glucose level of ≥7.0 mmol/L. Subjects who self-reported diabetes at baseline or had a baseline glucose level of ≥7.0 mmol/L were excluded from the analyses. A total of 5974 of the 6595 randomized subjects were included in the analysis, and 139 subjects became diabetic during the study. The baseline predictors of the transition from normal glucose control to diabetes were studied. In the univariate model, body mass index, log triglyceride, log white blood cell count, systolic blood pressure, total and HDL cholesterol, glucose, and randomized treatment assignment to pravastatin were significant predictors. In a multivariate model, body mass index, log triglyceride, glucose, and pravastatin therapy were retained as predictors of diabetes in t...