Showing papers in "American Journal of Cardiology in 1998"
TL;DR: In this paper, the authors found that men had a 1.5-fold higher risk of developing atrial fibrillation than women after adjusting for age and other risk factors.
Abstract: Atrial fibrillation (AF) is the most common of the serious cardiac rhythm disturbances and is responsible for substantial morbidity and mortality in the general population. Its prevalence doubles with each advancing decade of age, from 0.5% at age 50-59 years to almost 9% at age 80-89 years. It is also becoming more prevalent, increasing in men aged 65-84 years from 3.2% in 1968-1970 to 9.1% in 1987-1989. This statistically significant increase in men was not explained by an increase in age, valve disease, or myocardial infarctions in the cohort. The incidence of new onset of AF also doubled with each decade of age, independent of the increasing prevalence of known predisposing conditions. Based on 38-year follow-up data from the Framingham Study, men had a 1.5-fold greater risk of developing AF than women after adjustment for age and predisposing conditions. Of the cardiovascular risk factors, only hypertension and diabetes were significant independent predictors of AF, adjusting for age and other predisposing conditions. Cigarette smoking was a significant risk factor in women adjusting only for age (OR = 1.4), but was just short of significance on adjustment for other risk factors. Neither obesity nor alcohol intake was associated with AF incidence in either sex. For men and women, respectively, diabetes conferred a 1.4- and 1.6-fold risk, and hypertension a 1.5- and 1.4-fold risk, after adjusting for other associated conditions. Because of its high prevalence in the population, hypertension was responsible for more AF in the population (14%) than any other risk factor. Intrinsic overt cardiac conditions imposed a substantially higher risk. Adjusting for other relevant conditions, heart failure was associated with a 4.5- and 5.9-fold risk, and valvular heart disease a 1.8- and 3.4-fold risk for AF in men and women, respectively. Myocardial infarction significantly increased the risk factor-adjusted likelihood of AF by 40% in men only. Echocardiographic predictors of nonrheumatic AF include left atrial enlargement (39%/ increase in risk per 5-mm increment), left ventricular fractional shortening (34% per 5% decrement), and left ventricular wall thickness (28% per 4-mm increment). These echocardiographic features offer prognostic information for AF beyond the traditional clinical risk factors. Electrocardiographic left ventricular hypertrophy increased risk of AF 3-4-fold after adjusting only for age, but this risk ratio is decreased to 1.4 after adjustment for the other associated conditions. The chief hazard of AF is stroke, the risk of which is increased 4-5-fold. Because of its high prevalence in advanced age, AF assumes great importance as a risk factor for stroke and by the ninth decade becomes a dominant factor. The attributable risk for stroke associated with AF increases steeply from 1.5% at age 50-59 years to 23.5% at age 80-89 years. AF is associated with a doubling of mortality in both sexes, which is decreased to 1.5-1.9-fold after adjusting for associated cardiovascular conditions. Decreased survival associated with AF occurs across a wide range of ages.
1,831 citations
TL;DR: In this article, the comparative dose efficacy of the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor atorvastatin 10, 20, 40, and 80 mg was evaluated.
Abstract: The objective of this multicenter, randomized, open-label, parallel-group, 8-week study was to evaluate the comparative dose efficacy of the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor atorvastatin 10, 20, 40, and 80 mg compared with simvastatin 10, 20, and 40 mg, pravastatin 10, 20, and 40 mg, lovastatin 20, 40, and 80 mg, and fluvastatin 20 and 40 mg. Investigators enrolled 534 hypercholesterolemic patients (low-density lipoprotein [LDL] cholesterol > or = 160 mg/dl [4.2 mmol/L] and triglycerides < or = 400 mg/dl [4.5 mmol/L]). The efficacy end points were mean percent change in plasma LDL cholesterol (primary), total cholesterol, triglycerides, and high-density lipoprotein cholesterol concentrations from baseline to the end of treatment (week 8). Atorvastatin 10, 20, and 40 mg produced greater (p < or = 0.01) reductions in LDL cholesterol, -38%, -46%, and -51%, respectively, than the milligram equivalent doses of simvastatin, pravastatin, lovastatin, and fluvastatin. Atorvastatin 10 mg produced LDL cholesterol reductions comparable to or greater than (p < or = 0.02) simvastatin 10, 20, and 40 mg, pravastatin 10, 20, and 40 mg, lovastatin 20 and 40 mg, and fluvastatin 20 and 40 mg. Atorvastatin 10, 20, and 40 mg produced greater (p < or = 0.01) reductions in total cholesterol than the milligram equivalent doses of simvastatin, pravastatin, lovastatin, and fluvastatin. All reductase inhibitors studied had similar tolerability. There were no incidences of persistent elevations in serum transaminases or myositis.
1,080 citations
TL;DR: Three recent prospective epidemiologic studies have shown that plasma triglyceride and low-density lipoprotein particle size predict subsequent coronary artery disease in Caucasian populations, demonstrating the importance of triglyceride levels as a risk factor for cardiovascular disease.
Abstract: To determine the relation between plasma triglyceride levels and the risk of incident cardiovascular disease, the semiquantitative techniques of meta-analysis were applied to 17 population-based prospective studies of triglyceride and cardiovascular disease. Sixteen of these studies represented 2,445 events among 46,413 Caucasian men followed for an average period of 8.4 years, and 5 studies represented 439 events among 10,864 Caucasian women followed for an average period of 11.4 years. Univariate relative risk (RR) estimates for incident cardiovascular disease associated with a 1-mmol/L increase in triglyceride was 1.07-1.98 in men, with a summary RR of 1.32 (95% confidence interval [CI]: 1.26-1.39), indicating a 32% increase in disease risk associated with increased triglyceride. In the studies involving women, individual RR estimates for triglyceride were 1.69-2.05, with a summary RR of 1.76 (95% CI: 1.50-2.07), indicating a 76% increase in disease risk associated with increased triglyceride. After adjustment for high-density lipoprotein cholesterol and other risk factors, these risks were decreased to 14% in men and 37% in women but remained statistically significant. Three recent prospective epidemiologic studies have also shown that plasma triglyceride and low-density lipoprotein particle size predict subsequent coronary artery disease in Caucasian populations. Taken together, these studies demonstrate the importance of triglyceride levels as a risk factor for cardiovascular disease.
1,077 citations
TL;DR: The importance of high serum cholesterol, especially a high level of low-density lipoprotein (LDL) cholesterol, as a risk factor for coronary artery disease is well established as discussed by the authors.
Abstract: The importance of high serum cholesterol, especially a high level of low-density lipoprotein (LDL) cholesterol, as a risk factor for coronary artery disease is well established. Likewise, efficacy for decreasing risk for coronary artery disease by LDL-lowering therapy has recently been documented through clinical trials. However, many high-risk patients manifest elevated serum triglyceride levels, and the role of hypertriglyceridemia in causation of coronary artery disease remains to be elucidated. Nonetheless, there is growing evidence that hypertriglyceridemia is a marker for increased risk for coronary artery disease; in fact, it can serve as a marker for several atherogenic factors. These factors include increased concentrations of atherogenic triglyceride-rich lipoproteins; the atherogenic lipoprotein phenotype, or lipid triad; and the metabolic syndrome. The lipid triad consists of elevated serum triglycerides, small LDL particles, and low high-density lipoprotein (HDL) cholesterol. The metabolic syndrome includes the coexistence of the lipid triad, elevated blood pressure, insulin resistance (plus glucose intolerance), and a prothrombotic state. Many previous studies indicate that hypertriglyceridemia is strongly associated with all of these atherogenic factors. The clinical approach to treatment of patients with hypertriglyceridemia thus requires a broad-based strategy that includes reduction of atherogenic triglyceride-rich lipoproteins, reversal of the lipid triad, and favorable modification of the metabolic syndrome. The development of therapeutic regimens to effect these changes poses a challenge for future research on the problem of hypertriglyceridemia.
538 citations
TL;DR: Women lagged after men in the extent of raised lesions in the right coronary artery by about 5 years, but the effects of risk factors in women, except for adiposity, were similar to those in men.
Abstract: A multicenter cooperative study, Pathobiological Determinants of Atherosclerosis in Youth, examined the relation of the risk factors for adult coronary artery disease to atherosclerosis in nearly 3,000 persons, aged 15–34 years, who died from accidents, homicides, and suicides and were autopsied in forensic laboratories. Very-low-density lipoprotein (VLDL) plus low-density lipoprotein (LDL) cholesterol levels were positively, and high-density lipoprotein (HDL) cholesterol levels were negatively, associated with both fatty streaks and raised lesions in the aorta and right coronary artery, particularly after age 25. Elevated glycohemoglobin levels were associated with raised lesions throughout the 15–34-year age span. Body mass index was associated with both fatty streaks and raised lesions of the right coronary artery in men but not in women. Smoking was associated with a 3-fold increase in raised lesions of the abdominal aorta in the 25–34-year age group. Women lagged after men in the extent of raised lesions in the right coronary artery by about 5 years, but the effects of risk factors in women, except for adiposity, were similar to those in men. The risk factors for adult coronary artery disease accelerate atherogenesis in the teenage years and their effects are amplified in young adulthood, 20–30 years before coronary artery disease becomes clinically manifest. Long-range prevention of adult coronary artery disease will require control of the risk factors early in life.
532 citations
TL;DR: The results indicate that the Doppler RV index is a useful predictor of adverse outcome in patients with primary pulmonary hypertension, and only the Doppo RV index and treatment with calcium blockers were independent predictors within the multivariate model.
Abstract: Primary pulmonary hypertension is characterized by elevated pulmonary arterial pressure and vascular resistance, frequently producing right heart failure and death. Therefore, the Doppler right ventricular (RV) index, which is a measure of global RV function, could be a useful predictor of outcome in primary pulmonary hypertension. The Doppler RV index, defined as the sum of isovolumic contraction time and isovolumic relaxation time divided by ejection time, was retrospectively measured in 53 patients (38 women, aged 45 ± 14 years) with primary pulmonary hypertension. Ejection time was measured from the pulmonary outflow velocity signal. The sum of isovolumic contraction time and isovolumic relaxation time was obtained by subtracting ejection time from the duration of tricuspid regurgitation. The Doppler RV index tended to be elevated (median 0.83) compared with normal ranges. Normal Doppler RV index was 0.28 ± 0.04. After a mean follow-up duration of 2.9 years, 4 patients underwent lung transplantation and 30 patients died; the cause was cardiac in 28, noncardiac in 1, and uncertain in 1. Univariately, the Doppler RV index (chi-square 20.7, p <0.0001), severity of tricuspid regurgitation (chi-square 8.2, p = 0.004), treatment with calcium blockers (chi-square 6.6, p = 0.01), heart rate (chi-square 5.1, p = 0.02), and symptom status (chi-square 4.9, p = 0.03) were associated with adverse outcome (cardiac deaths and lung transplantation). However, only the Doppler RV index and treatment with calcium blockers were independent predictors within the multivariate model. Our results indicate that the Doppler RV index is a useful predictor of adverse outcome in patients with primary pulmonary hypertension.
528 citations
TL;DR: A strong correlation was obtained between flow-mediated dilation in the coronary and brachial arteries (r=0.78, p <0.001) so that noninvasive assessment of flow-mediation in theBrachial artery could be used as a surrogate measure for coronary artery endothelial function.
Abstract: Previous studies showed a weak correlation between endothelial function of the coronary arteries as assessed by acetylcholine and brachial artery vasomotion during reactive hyperemia. When the same stimulus was used, we obtained a strong correlation between flow-mediated dilation in the coronary and brachial arteries (r=0.78, p <0.001), so that noninvasive assessment of flow-mediated dilation in the brachial artery could be used as a surrogate measure for coronary artery endothelial function.
486 citations
TL;DR: In patients participating in the Scandinavian Simvastatin Survival Study as mentioned in this paper, cholesterol lowering was shown to reduce carotid bruits and cerebrovascular events as well as new-onset or worsening of angina pectoris and intermittent claudication.
Abstract: In patients participating in the Scandinavian Simvastatin Survival Study, cholesterol lowering with simvastatin reduced the incidence of carotid bruits and cerebrovascular events as well as new-onset or worsening of angina pectoris and intermittent claudication. These effects suggest that simvastatin may have a general antiatherosclerotic effect not limited to the coronary bed.
416 citations
TL;DR: The Doppler index reflects disease severity and has incremental prognostic value in dilated cardiomyopathy and ease of use, nongeometric dependency, excellent separation of clinical groups, and a strong relation to outcome enhance its appeal.
Abstract: This study sought to investigate, in patients with idiopathic-dilated cardiomyopathy, the clinical and prognostic value of a Doppler-derived index of myocardial function that combines systolic and diastolic time intervals of the left heart cycle. The Doppler index was measured in 75 patients (aged 61 +/- 13 years; 45 men and 30 women) in sinus rhythm and 75 age- and sex-matched controls. Ejection time was measured from the left ventricular outflow Doppler signal. The sum of isovolumic times was obtained by subtracting the ejection time from the interval between cessation and onset of mitral inflow measured from the mitral inflow velocity profile. The index was the sum of isovolumic times divided by ejection time. The values of the Doppler index in patients with idiopathic-dilated cardiomyopathy (0.85 +/- 0.32) were significantly higher than values in controls (0.37 +/- 0.08, p < 0.001). During follow-up of 5 years, 1 patient underwent cardiac transplantation and 36 patients died, 29 of cardiac, 5 of noncardiac, and 2 of unknown causes. Univariate analysis demonstrated that the Doppler index (chi-square = 18.3, p < 0.001), ejection fraction (chi-square = 15.2, p <0.001), symptom status (chi-square = 9.2, p = 0.002), and mitral deceleration time (chi-square = 5.2, p = 0.02) were significant predictors of outcome. However, multivariate stepwise analysis of these variables showed that the Doppler index (chi-square = 10.7, p = 0.001) and ejection fraction (chi-square = 6.7, p = 0.01) were the most significant independent predictors of outcome. The Doppler index reflects disease severity and has incremental prognostic value in dilated cardiomyopathy. Ease of use, nongeometric dependency, excellent separation of clinical groups, and a strong relation to outcome enhance its appeal.
398 citations
TL;DR: The more effective the statin is in decreasing LDL cholesterol, the more effective it will also be in decreasing triglyceride levels in patients with hypertriglyceridemia.
Abstract: In 1996, the first 2 studies using 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor ("statin") therapy in hypertriglyceridemic subjects were published. In subjects with isolated triglyceride elevations who were treated with atorvastatin 5, 20, and 80 mg/day, large and dose-related reductions were noted. In subjects with combined hyperlipidemia treated with 10 mg simvastatin, triglyceride reduction similar to that reported for the 5 mg atorvastatin dose was seen. In response to these findings, we conducted comparative assessments to determine whether all statins are effective in lowering triglyceride levels and whether their effect on triglycerides is related to factors such as drug, dose, and baseline triglyceride levels. To standardize these assessments, we devised a ratio that related changes in triglyceride levels to the known predictable response of low-density lipoprotein (LDL) cholesterol to statins. This triglyceride/LDL cholesterol ratio was obtained by dividing the percent change from baseline in the triglyceride level by the percent change from baseline in the LDL cholesterol level. The triglyceride/LDL cholesterol ratio was initially applied to several published studies, and found to be approximately 1.0 and 0.5 in hypertriglyceridemic and nonhypertriglyceridemic populations, respectively. We then assessed the effect of various statins on triglycerides using a pooled laboratory database of 2,689 subjects who had participated in 7 separate studies with similar designs. All of the studies had a placebo run-in followed by a randomized, double-blind, active treatment phase of at least 4 weeks with a statin. Entry into these studies required a triglyceride level of 250 mg/dL, significant and dose-dependent reductions in triglyceride of 22-45% were seen with all statins. When baseline triglyceride was 250 mg/dL, at 0.0+/-0.3, 0.5+/-0.2, and 1.2+/-0.3, respectively. We conclude that all statins are effective in decreasing triglyceride levels, but only in hypertriglyceridemic patients. Due to the relatively constant triglyceride/LDL cholesterol ratio, our analysis indicates that the more effective the statin is in decreasing LDL cholesterol, the more effective it will also be in decreasing triglyceride levels in patients with hypertriglyceridemia.
376 citations
TL;DR: Overall mortality was 24% after a mean follow-up period of 22 +/- 4 months (range 1 to 88) and eight patients who were significantly older (74 +/- 3 vs 63 +/- 3 years; p = 0.05) died < or = 2 months after electrode removal, whereas 25 were alive and asymptomatic.
Abstract: We identified 33 patients with definite pacemaker endocarditis--that is, with direct evidence of infective endocarditis, based on surgery or autopsy histologic findings of or bacteriologic findings (Gram stain or culture) of valvular vegetation or electrode-tip wire vegetation. Most of the patients (75%) were > or = 60 years of age (mean 66 +/- 3; range 21 to 86). Pouch hematoma or inflammation was common (58%), but other predisposing factors for endocarditis were rare. At the time that pacemaker endocarditis was found, the mean number of leads was 2.4 +/- 1.1 (range 1 to 7). The interval from the last procedure to diagnosis of endocarditis was 20 +/- 4 months (range 1 to 72). Endocarditis appeared after pacemaker implantation, early ( or = 3 months) in 23 patients. Fever was the most common symptom, being isolated in 36%, associated with a poor general condition in 24%, and associated with septic shock in 9%. Transthoracic echocardiography showed vegetations in only 2 of 9 patients. Transesophageal echocardiography demonstrated the presence of lead vegetations (n = 20) or tricuspid vegetations (n = 3) in 23 of 24 patients (96%; p <0.0001 compared with transthoracic echocardiography). Pulmonary scintigraphy showed a typical pulmonary embolization in 7 of 17 patients (41%). Pathogens were mainly isolated from blood (82%) and lead (91%) cultures. The major pathogens causing pacemaker endocarditis were Staphylococcus epidermidis (n = 17) and S. aureus (n = 7). S. epidermidis was found more often in early than in late endocarditis (90% vs 50%; p = 0.05). All patients were treated with prolonged antibiotic regimens before and after electrode removal. Electrode removal was achieved by surgery (n = 29) or traction (n = 4). Associated procedures were performed in 9 patients. After the intensive care period, only 17 patients needed a new permanent pacemaker. Overall mortality was 24% after a mean follow-up period of 22 +/- 4 months (range 1 to 88). Eight patients who were significantly older (74 +/- 3 vs 63 +/- 3 years; p = 0.05) died < or = 2 months after electrode removal, whereas 25 were alive and asymptomatic.
TL;DR: This long-term study confirms the earlier short-term findings that Niaspan is safe and effective as monotherapy in plasma lipoprotein regulation and indicates that the decrease in phosphorus is a new finding in niacin therapy.
Abstract: Crystalline nicotinic acid (immediate-release niacin) is effective therapy for lipoprotein regulation and cardiovascular risk reduction. However, inconvenient regimens and unpleasant side effects decrease compliance. Sustained-release formulations designed to circumvent these difficulties increase hepatotoxicity. Niaspan, a new US Food and Drug Administration (FDA)-approved, once-daily, extended-release form, has been found effective and safe in short-term trials. The long-term efficacy and safety of Niaspan lipid monotherapy was studied in 517 patients (aged 21-75 years) for < or =96 weeks in dosages < or =3,000 mg/day. Primary efficacy endpoints were low-density lipoprotein (LDL) cholesterol and apolipoprotein B (apo B) changes from baseline; secondary efficacy endpoints were changes in total cholesterol, triglycerides, high-density lipoprotein (HDL) cholesterol, lipoprotein(a), and total cholesterol/HDL-cholesterol ratio; safety data included adverse events and laboratory values over the 2-year study period. LDL-cholesterol levels decreased significantly: 18% at week 48 and 20% at week 96; apo B reduction was similar (16% decrease at week 48 and 19% at week 96). Large elevations in HDL cholesterol (26%, week 48; 28%, week 96) allowed only modest decreases in total cholesterol (12% and 13%, respectively), whereas total cholesterol/HDL-cholesterol ratio decreased by almost one third. Triglyceride and lipoprotein(a) levels were decreased by 27% and 30%, respectively (week 48), and by 28% and 40%, respectively (week 96). All changes from baseline were significant (p <0.001). Niaspan was generally well tolerated, although flushing was common (75%); however, there was a progressive decrease in flushing with time from 3.3 episodes in the first month to < or = 1 episode by week 48. Aspirin was used by one third of patients before Niaspan dosing to minimize flushing episodes. Although serious adverse events occurred in about 10% of patients, none were considered probably or definitely related to Niaspan. Adverse events in general varied widely, but their true relation to the study drug is difficult to ascertain without a placebo (control) group. No deaths occurred. There were statistically significant changes in hepatic transaminases, alkaline phosphatase, direct bilirubin, phosphorus, glucose, amylase, and uric acid. However, these changes were mostly small and are not likely to be biologically or clinically significant (the decrease in phosphorus is a new finding in niacin therapy). No myopathy was observed. Thus, this long-term study confirms the earlier short-term findings that Niaspan is safe and effective as monotherapy in plasma lipoprotein regulation.
TL;DR: Exercise training increases parasympathetic tone at rest in both the healthy older and young men, which may contribute to the reduction in mortality associated with regular exercise.
Abstract: Heart rate variability (HRV) (SD of the RR interval), an index of parasympathetic tone, was measured at rest and during exercise in 13 healthy older men (age 60 to 82 years) and 11 healthy young men (age 24 to 32 years) before and after 6 months of aerobic exercise training. Before exercise training, the older subjects had a 47% lower HRV at rest compared with the young subjects (31 +/- 5 ms vs 58 +/- 4 ms, p = 0.0002). During peak exercise, the older subjects had less parasympathetic withdrawal than the young subjects (-45% vs -84%, p = 0.0001). Six months of intensive aerobic exercise training increased maximum oxygen consumption by 21% in the older group and 17% in the young group (analysis of variance: overall training effect, p = 0.0001; training effect in young vs old, p = NS). Training decreased the heart rate at rest in both the older (-9 beats/min) and the young groups (-5 beats/min, before vs after, p = 0.0001). Exercise training increased HRV at rest (p = 0.009) by 68% in the older subjects (31 +/- 5 ms to 52 +/- 8 ms) and by 17% in the young subjects (58 +/- 4 ms to 68 +/- 6 ms). Exercise training increases parasympathetic tone at rest in both the healthy older and young men, which may contribute to the reduction in mortality associated with regular exercise.
TL;DR: The hypothesis that a heterogeneous pattern of longitudinal systolic and diastolic velocities exists among individual left ventricular wall segments is tested, and heterogeneity in longitudinal function is consistent with the known spatial distribution of myocardial fibers.
Abstract: We designed the present study (1) to investigate the velocities of longitudinal movement of the human left ventricle by pulsed-wave tissue Doppler (PWTD) imaging; (2) to test the hypothesis that a heterogeneous pattern of longitudinal systolic and diastolic velocities exists among individual left ventricular wall segments; (3) to establish the range of this heterogeneity, and (4) to correlate the function of individual segments with the known orientation of myocardial fibers. PWTD is a novel ultrasound method to quantify myocardial contraction and relaxation velocities. In 27 young normal subjects, PWTD peak values of longitudinal systolic and diastolic velocities were measured for 12 left ventricular segments visualized from the apical window. The PWTD sampling of each myocardial segment resulted in a triphasic velocity curve during each cardiac cycle: a systolic velocity wave (S) directed toward the transducer, and an early diastolic (E) and a late diastolic (A) velocity wave away from the transducer. A heterogeneous pattern of systolic and diastolic myocardial velocities was observed between individual wall segments as well as for the basal and midsegments of each myocardial wall. The difference between the highest and lowest values for S was 38.4% in the basal segments and 56.3% in the midwall segments. The difference between low and high velocities for E was 61.4% in the basal and 38.2% in the midsegments; for A the difference was 29.5% in the basal and 32.6% in the midsegments. In general, lower velocity values were found in the septum with higher basal to midwall difference. The lateral and posterior walls had higher, but more uniform, velocities. PWTD enables the quantitative assessment of regional systolic and diastolic myocardial velocities. Substantial heterogeneity of velocities exists within individual myocardial segments, and must be taken into account in any clinical application. The observed heterogeneity in longitudinal function is consistent with the known spatial distribution of myocardial fibers.
TL;DR: Aortic stiffness in Marfan syndrome, together with mean blood pressure, is reduced by beta-blocker therapy, and MRI is well suited to detect these changes by measuring distensibility and pulse wave velocity.
Abstract: It has been shown that beta-adrenergic blocking agents may reduce the rate of aortic root dilation and the development of aortic complications in patients with the Marfan syndrome. This may be due to beta-blocker-induced changes in aortic stiffness, of which distensibility and pulse wave velocity are in vivo measurable derivatives. We studied changes in distensibility at 4 levels of the aorta and pulse wave velocity along the entire aorta after 2 weeks of beta-blocker therapy in 6 Marfan syndrome patients and in 6 healthy volunteers, using magnetic resonance imaging (MRI) combined with brachial artery blood pressure measurements. In both groups, mean blood pressure decreased significantly (Marfan: 86 +/- 6 vs 78 +/- 5 mm Hg, p <0.05; control: 80 +/- 8 vs 73 +/- 3 mm Hg, p <0.05) (all data expressed as mean +/- 1 SD). At baseline, the Marfan syndrome patients exhibited decreased distensibility at the level of the ascending aorta (2 +/- 1 vs 6 +/- 2 10(-3)mm Hg(-1), p <0.01) and increased pulse wave velocity (6.2 +/- 0.4 vs 3.9 +/- 0.4 ms(-1), p <0.01) compared with control subjects. Only the Marfan syndrome patients had a significant increase in aortic distensibility at multiple levels and a significant decrease in pulse wave velocity after beta-blocker therapy (ascending aorta distensibility: 2 +/- 1 vs 4 +/- 1 10(-3)mm Hg(-1), p <0.05; abdominal aorta distensibility: 5 +/- 2 vs 8 +/- 3 10(-3)mm Hg(-1), p <0.05; pulse wave velocity: 6.2 +/- 0.4 vs 5.0 +/- 1.0 ms(-1), p <0.05). Thus, aortic stiffness in Marfan syndrome, together with mean blood pressure, is reduced by beta-blocker therapy, and MRI is well suited to detect these changes by measuring distensibility and pulse wave velocity.
TL;DR: Automatic analysis of the frequency content of the fibrillatory baseline on the surface electrocardiogram accurately reflects the average rate of AF and predicts the response to administration of ibutilide.
Abstract: This study assesses a technique for quantifying the frequency spectrum of atrial fibrillation (AF) using the surface electrocardiogram. Electrocardiograhic recordings were obtained in 61 patients during AF. After bandpass filtering, the QRST complexes were subtracted using a template-matching algorithm. The resulting fibrillatory baseline signal was subjected to Fourier transformation and displayed as a frequency power spectrum. These frequency spectra were compared to direct measurements from the right atrium and coronary sinus in 35 patients undergoing electrophysiologic study. The clinical use of this technique was explored by correlating fibrillatory frequency with the behavior of the arrhythmia in 26 patients referred for cardioversion. The electrocardiographic frequency spectrum during AF was characterized by a single peak that varied widely between patients (range 228 to 480 beats/min). There was a strong correlation between electrocardiographic peak frequency and that measured in the right atrium and coronary sinus (r = 0.79 to 0.98, p 5 minutes (324 ± 36 vs 402 ± 78 beats/min, p = 0.001). Chronic AF ( 3 months) (336 ± 48 vs 408 ± 60 beats/min, p = 0.012). Fibrillation frequency was an accurate predictor of conversion with ibutilide. Success rate was 100% in patients with peak frequency
TL;DR: As the interventions available to treat obstructive coronary artery disease become increasingly complex, the authors' understanding of the vascular response to these interventions requires greater sophistication, and molecular and cellular biologic tools have now propelled us into another phase of work with vascular devices.
Abstract: As the interventions available to treat obstructive coronary artery disease become increasingly complex, our understanding of the vascular response to these interventions requires greater sophistication. Molecular and cellular biologic tools have now propelled us into another phase of work with vascular devices. Initially, studies of endovascular implants such as stents focused on developing models of vascular injury. With these models, we could then examine the designs of individual stents and connect structure with performance. Now we are entering a third phase in which stent manufacturers are looking to science to dictate stent design.
TL;DR: The long-term safety and efficacy of intensive cholesterol-lowering therapies with low-density lipoprotein (LDL) apheresis in heterozygous familial hypercholesterolemia (FH) patients with premature coronary heart disease (CHD) was described in this paper.
Abstract: Familial hypercholesterolemia (FH) is characterized by severe hypercholesterolemia and premature coronary heart disease (CHD) The lower the plasma cholesterol level, the more likely it is that CHD can be prevented or retarded; aggressive cholesterol-lowering therapies may be indicated for FH patients with CHD This study describes the long-term (6 years) safety and efficacy of intensive cholesterol-lowering therapies with low-density lipoprotein (LDL) apheresis in heterozygous FH patients with CHD One hundred thirty heterozygous FH patients with CHD documented by coronary angiography had been treated by cholesterol-lowering drug therapy alone (n = 87) or LDL apheresis combined with cholesterol-lowering drugs (n = 43) Serum lipid levels and outcomes in each treatment group were compared after approximately 6 years Both treatment groups had significant reductions in serum cholesterol, LDL cholesterol, and high density lipoprotein cholesterol levels LDL apheresis significantly reduced LDL cholesterol levels from 742 ± 173 to 313 ± 080 mmol/L (58%) compared with group taking drug therapy, from 603 ± 132 to 432 ± 153 mmol/L (28%) With Kaplan-Meier analyses of the coronary events including nonfatal myocardial infarction, percutaneous transluminal coronary angioplasty, coronary artery bypass grafting, and death from CHD, the rate of total coronary events was 72% lower in the LDL-apheresis group (10%) than in drug therapy group (36%) (p = 00088) It is concluded that LDL-apheresis is effective as treatment of CHD in FH heterozygotes, and may become the therapy of choice in severe types of FH
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TL;DR: Late results indicated a 24% target lesion revascularization rate, which improved when a true kissing balloon inflation was used to achieve final deployment of both stents, and this culotte technique is highly feasible and provides excellent short-term results.
Abstract: Coronary angioplasty of bifurcation lesions remains a technical challenge. Balloon angioplasty induces recoil and the "snow-plow" effect with a risk of side branch occlusion. The late result is associated with a high rate of reintervention. Randomized studies in nonbifurcated lesions have demonstrated better short- and midterm results after stent placement. We propose the "culotte" technique as a new technique to place intracoronary stents in bifurcation lesions: implantation of 2 similar stents in 2 steps in the main branch and in the side branch with overlapping of the 2 stents in the main branch before bifurcation. We performed this technique in 50 patients (in the left anterior diagonal branch in 33, in the left circumflex obtuse marginal branch in 12, in the right coronary artery in 4, and in the left main coronary artery in 1). The clinical success rate was 94% with 3 non-Q-wave myocardial infarctions. Late results indicated a 24% target lesion revascularization rate, which improved when a true kissing balloon inflation was used to achieve final deployment of both stents. This culotte technique is highly feasible and provides excellent short-term results. Assessment of its midterm benefit requires further study.
TL;DR: At present, measurement of fasting triglyceride levels and triglyceride assessment in conjunction with LDL cholesterol and HDL cholesterol concentrations are the most practical methods of evaluating hypertriglyceridemia in CAD risk, although postprandial lipemia may prove a better indicator of atherogenicity.
Abstract: The data for an independent association between triglyceride concentrations and risk for coronary artery disease (CAD) are equivocal, unlike the data for low-density lipoprotein (LDL) cholesterol and high-density lipoprotein (HDL) cholesterol, which show strong, consistent, and opposing correlations with CAD risk. There is some evidence for triglyceride as an independent risk factor in certain subgroups, for example, women 50-69 years of age (Framingham Heart Study) and in patients with noninsulin-dependent diabetes. However, the evidence is stronger for triglyceride as a synergistic CAD risk factor. For example, patients with the "lipid triad" of high LDL cholesterol, low HDL cholesterol, and high triglyceride accounted for most of the event reduction with lipid-lowering therapy in the Helsinki Heart Study. An important confounder of the correlation between triglyceride and CAD risk is the heterogeneity of triglyceride-rich lipoproteins: the larger triglyceride-rich particles are thought not to be associated with CAD risk, whereas the smaller (and denser) particles are believed to be atherogenic. At present, measurement of fasting triglyceride levels and triglyceride assessment in conjunction with LDL cholesterol and HDL cholesterol concentrations are the most practical methods of evaluating hypertriglyceridemia in CAD risk, although postprandial lipemia may prove a better indicator of atherogenicity. Management of hypertriglyceridemia should initially focus on nonpharmacologic therapy (i.e., diet, exercise, weight control, and alcohol reduction). In diabetic patients, meticulous glycemic control is also important. However, if this approach proves inadequate, there are several pharmacologic options. Fibrates may be effective in decreasing triglyceride and increasing HDL cholesterol. Nicotinic acid (niacin) has been shown to decrease triglyceride, increase HDL cholesterol, lower LDL cholesterol, and decrease lipoprotein(a); it also decreases fibrinogen. The statins appear to be effective in decreasing triglyceride and LDL cholesterol in hypertriglyceridemia; however, they do not normalize metabolism of apolipoprotein B, and HDL cholesterol may remain low. Therefore, combination with a fibrate or niacin may be appropriate. Attention to hypertriglyceridemia with respect to increased CAD risk represents an important step in assessing global risk for CAD development.
TL;DR: After successful angioplasty, different patterns of myocardial perfusion are associated with different ST-segment changes, and analysis of ST- segment changes predicts the degree ofMyocardial reperfusion.
Abstract: The aim of this study was to evaluate the relation between myocardial perfusion and ST-segment changes in patients with acute myocardial infarction treated with successful direct angioplasty. Thirty-seven patients, successfully treated with direct angioplasty, underwent myocardial contrast echocardiography before and after angioplasty. The sum of ST-segment elevation divided by the number of the leads involved (ST-segment elevation index) was calculated at 1, 5, 10, 20, and 30 minutes after restoration of a Thrombolysis In Myocardial Infarction trial grade 3 flow. After recanalization, myocardial reperfusion within the risk area was observed in 26 patients, whereas a no-reflow phenomenon occurred in 11. In patients with myocardial reperfusion, the ST-segment elevation index progressively declined, whereas in patients with no reflow, no significant change was observed. Reduction of > or = 50% in the ST-segment elevation index occurred in 20 of the 26 patients with reflow and in 1 of the 11 with no reflow (p = 0.0002). An additional increase of > or = 30% in the ST-segment elevation index occurred in 3 patients with reflow and in 7 with no reflow (p = 0.003). Sensitivity, specificity, positive and negative predictive values, and accuracy of the reduction in the ST-segment elevation index for predicting microvascular reflow were 77%, 91%, 95%, 62%, and 81%, respectively. The corresponding values of the increase in ST-segment elevation index for predicting no reflow were 64%, 88%, 70%, 85%, and 81%, respectively. In conclusion, after successful angioplasty, different patterns of myocardial perfusion are associated with different ST-segment changes. Analysis of ST-segment changes predicts the degree of myocardial reperfusion.
TL;DR: Increased atrial response to early-stage left ventricular filling impairment is characterized by augmented reservoir and pump functions, according to a Starling mechanism, which becomes hardly effective at end-stage ventricular dysfunction when the limits of the atrial preload reserve are reached.
Abstract: We sought to investigate the changes in atrial reservoir, pump, and conduit functions that are associated with increasing degrees of left ventricular filling impairment. In 13 patients with an impaired relaxation type of filling and in 15 with restrictive patterns, the left atrial volume curve was constructed combining Doppler and 2-dimensional echocardiography. Nine normal subjects served as controls. Left atrial reservoir (defined as [maximum − minimum atrial volume] minus the amount of blood flow reversal in the pulmonary veins with atrial contraction), pump (defined by the volume of blood that enters the ventricle with atrial contraction), and conduit functions (defined as left ventricular filling volume − [left atrial reservoir plus pump volume]) were computed and each expressed as a percentage of ventricular filling volume. The atrial reservoir function was higher in the impaired relaxation group than in normal subjects (49 ± 8% vs 38 ± 8%, p
TL;DR: It is found that experimental group patients were able to avoid revascularization for at least 3 years by making comprehensive lifestyle changes at substantially lower cost without increasing cardiac morbidity and mortality.
Abstract: The Multicenter Lifestyle Demonstration Project was designed to determine if comprehensive lifestyle changes can be a direct alternative to revascularization for selected patients without increasing cardiac events. A total of 333 patients completed this demonstration project (194 in the experimental group and 139 in the control group). We found that experimental group patients were able to avoid revascularization for at least 3 years by making comprehensive lifestyle changes at substantially lower cost without increasing cardiac morbidity and mortality. These patients reported reductions in angina comparable with what can be achieved with revascularization.
TL;DR: Mean wedge pressure and mean right atrial pressure can be estimated in heart transplants with reasonable accuracy using the ratio of E/Ea, and this method can accurately track changes in filling pressures.
Abstract: Current Doppler methods have been unreliable in estimating filling pressures in heart transplants. Tissue Doppler imaging is a technique that permits evaluation of myocardial relaxation; combined with transvalvular E velocity, it could improve estimation of these pressures. To investigate this possibility, we evaluated 50 patients by right-sided cardiac catheterization and Doppler echocardiography simultaneously. Their mean ±SD age was 53 ± 15 years and the mean age of donor hearts was 30 ± 12.5 years. The mitral E velocity was combined with the early myocardial relaxation (Ea) velocity by tissue Doppler at the lateral border of the mitral annulus. Likewise, the tricuspid E velocity was combined with Ea at the lateral corner of the tricuspid annulus. Mean wedge pressure related weakly to mitral inflow variables but strongly to E/Ea [r = 0.8; wedge pressure=2.6+1.46(E/Ea)]. In 25 repeat right-sided cardiac catheterizations, changes in mean wedge pressure were well detected by Doppler, with a mean difference of −0.7 ± 3 mm Hg. Mean right atrial pressure related weakly to routine tricuspid inflow variables but strongly to tricuspid E/Ea [r = 0.79; n = 38; right atrial pressure=1.76(E/Ea)−3.7]. In 18 repeat right-sided cardiac catheterizations, changes in mean right atrial pressure were well detected by Doppler, with a mean difference of 0 ± 3.45 mm Hg. Mean wedge pressure and mean right atrial pressure can be estimated in heart transplants with reasonable accuracy using the ratio of E/Ea. Furthermore, this method can accurately track changes in filling pressures.
TL;DR: Acute intravenous administration of triiodothyronine is well tolerated in patients with advanced heart failure, establishing the basis for further investigation into the safety and potential hemodynamic benefits of longer infusions, combined infusion with inotropic agents, oral triiodothronine replacement therapy, and new triiodoryronine analogs.
Abstract: Most patients with advanced congestive heart failure have altered thyroid hormone metabolism. A low triiodothyronine level is associated with impaired hemodynamics and is an independent predictor of poor survival. This study sought to evaluate safety and hemodynamic effects of short-term intravenous administration of triiodothyronine in patients with advanced heart failure. An intravenous bolus dose of triiodothyronine, with or without a 6- to 12-hour infusion (cumulative dose 0. 1 5 to 2.7 microg/kg), was administered to 23 patients with advanced heart failure (mean left ventricular ejection fraction 0.22 +/- 0.01). Cardiac rhythm and hemodynamic status were monitored for 12 hours, and basal metabolic rate by indirect calorimetry, echocardiographic parameters of systolic function and valvular regurgitation, thyroid hormone, and catecholamine levels were measured at baseline and at 4 to 6 hours. Triiodothyronine was well tolerated without episodes of ischemia or clinical arrhythmia. There was no significant change in heart rate or metabolic rate and there was minimal increase in core temperature. Cardiac output increased with a reduction in systemic vascular resistance in patients receiving the largest dose, consistent with a peripheral vasodilatory effect. Acute intravenous administration of triiodothyronine is well tolerated in patients with advanced heart failure, establishing the basis for further investigation into the safety and potential hemodynamic benefits of longer infusions, combined infusion with inotropic agents, oral triiodothyronine replacement therapy, and new triiodothyronine analogs.
TL;DR: Findings suggest that a considerable portion of the coronary disease risk attributed to LDL may be accounted for by the IDL particles included in standard LDL measurements, which have been more predictive than low-density lipoprotein of atherosclerosis progression as assessed by coronary artery angiography or carotid artery ultrasonography.
Abstract: There is increasing evidence that alterations in metabolism of triglyceride-rich lipoproteins are of importance in the pathogenesis of atherosclerosis and its clinical consequences. Particles with the characteristics of triglyceride-rich lipoprotein remnants have been related to the extent and severity of atherosclerosis in humans and in animal models. These particles can be identified using ultracentrifugal procedures as small, very low-density lipoprotein (VLDL) and intermediate-density lipoprotein (IDL) with Svedberg flotation rates (Sf) of 12-60. Postprandial triglyceride levels also have been related to risk of coronary artery disease, consistent with a pathologic role for remnant lipoproteins. In studies in which measurements of lipoprotein subfractions have been carried out, levels of IDL have been more predictive than low-density lipoprotein (LDL) of atherosclerosis progression as assessed by coronary artery angiography or carotid artery ultrasonography. These findings suggest that a considerable portion of the coronary disease risk attributed to LDL may be accounted for by the IDL particles included in standard LDL measurements. Other metabolic changes associated with increased levels of plasma triglyceride may also adversely affect cardiovascular disease risk. These include reductions in HDL-cholesterol and apoprotein A1, increased levels of small dense LDL particles, redistribution of apoC-III from HDL to apoB-containing lipoproteins, diminished insulin sensitivity, and procoagulant changes, including increased levels of the fibrinolysis inhibitor, plasminogen-activator inhibitor-1 (PAI-1). A predominance of small dense LDL (subclass pattern B) is a discrete marker for this cluster of interrelated abnormalities and is found in 40-50% of patients with coronary artery disease. Therapeutic interventions with favorable effects on components of this dysmetabolic profile appear to be of value in decreasing atherosclerosis risk in a substantial proportion of the population.
TL;DR: The present results demonstrate the marked impact of advancing age on survival after acute myocardial infarction and the need for targeted secondary prevention efforts in elderly patients with AMI.
Abstract: This study examines age-related differences and temporal trends in hospital and long-term survival after acute myocardial infarction (AMI) over a 2-decade-long (1975 to 1995) experience. A total of 8,070 patients with validated AMI hospitalized in all acute care hospitals in the Worcester, Massachusetts, metropolitan area (1990 census population 437,000) were studied over 10 one-year periods between 1975 and 1995. This population included 1,326 patients aged or = 85 years (9.6%). Compared with patients or = 85 years were at 4.2, 7.8, and 10.2 times greater risk of dying, respectively. Similar age disparities in the risk of dying were seen when controlling for additional prognostic factors. Despite the adverse impact of increasing age on hospital survival after AMI, declining in-hospital death rates were seen in each of the age groups under study, with declining magnitude of these trends with advancing age. Among discharged hospital patients, increasing age was related to a significantly poorer long-term prognosis. Trends toward improving long-term prognosis were seen in patients discharged in the mid-1990s compared with those discharged in the mid- to late 1970s for patients aged <85 years. The present results demonstrate the marked impact of advancing age on survival after AMI. Despite the adverse impact of age on prognosis, encouraging trends in prognosis were observed in all age groups, although to a lesser extent in the oldest elderly patients. These findings emphasize the low death rates in middle-aged patients with AMI and the need for targeted secondary prevention efforts in elderly patients with AMI.
TL;DR: Plasma levels of C-reactive protein were measured 72 hours after successful coronary artery stenting in 76 patients with stable angina pectoris and at 12-month follow-up, the cumulative event rate was higher in patients with abnormal levels ofC-re active protein than that observed in patients who were event free.
Abstract: Plasma levels of C-reactive protein were measured 72 hours after successful coronary artery stenting in 76 patients with stable angina pectoris. At 12-month follow-up, the cumulative event rate was higher in patients with abnormal levels of C-reactive protein than that observed in patients with normal C-reactive protein who were event free.
TL;DR: A very simple measurement of non-HDL cholesterol (serum cholesterol minus HDL cholesterol)-has considerable potential as a screening tool for identifying dyslipoproteinemias, for risk assessment, and for assessing the results of hypolipidemic therapy.
Abstract: The plasma level of low-density lipoprotein (LDL) cholesterol is the "gold standard" for estimating the lipoprotein-related risk for complications of atherosclerotic vascular disease. LDL cholesterol concentrations are commonly estimated by the Friedewald formula that requires only the measurement (after overnight fasting) of plasma cholesterol and triglycerides along with high-density lipoprotein (HDL) cholesterol. This value, however, is not in fact a true estimate of LDL cholesterol but rather of LDL cholesterol along with variable, usually smaller, amounts of intermediate-density lipoprotein (IDL) cholesterol and lipoprotein(a). Estimation of LDL cholesterol levels by the Friedewald formula becomes progressively less accurate as plasma triglyceride concentrations increase, and the formula is generally considered inapplicable when triglyceride levels exceed 400 mg/dL. We believe that a very simple measurement-non-HDL cholesterol (serum cholesterol minus HDL cholesterol)-has considerable potential as a screening tool for identifying dyslipoproteinemias, for risk assessment, and for assessing the results of hypolipidemic therapy. Unlike the estimation of LDL cholesterol levels by the Friedewald formula, the estimation of non-HDL cholesterol concentrations requires no assumptions about the relation of very-low-density (VLDL) cholesterol levels to plasma triglyceride concentrations. This method includes all of the cholesterol present in lipoprotein particles now considered to be potentially atherogenic [VLDL, IDL, LDL, and lipoprotein(a)]. This article provides examples of the utility of non-HDL cholesterol concentrations in clinical medicine.