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Biomedical subjects

Gervasio A Lamas

Publications and source records attributed to Gervasio A Lamas.

At least 37 records · Page 2Linked to original sources

Impact of diabetes on mortality in patients with myocardial infarction and left ventricular dysfunction.

BACKGROUND: Diabetes is a major risk factor for developing coronary heart disease. In patients with diabetes who survived myocardial infarction (MI), less is known about subsequent morbidity and mortality. We evaluated the effects of diabetes in post-MI patients with left ventricular dysfunction on cardiovascular events and death. METHODS: The Survival and Ventricular Enlargement, a randomized, double-blind, placebo-controlled multicenter trial, evaluated the efficacy of captopril vs placebo in 2231 patients following acute MI with left ventricular dysfunction defined as an ejection fraction less than or equal to 40%. Patients were randomly assigned to captopril or placebo 3 to 16 days following MI and were followed up for 2 to 5 years (mean, 3.5 years). RESULTS: Among the 2231, 496 (22.2%) were patients with a history of diabetes, of which 168 (33.9%) were treated with insulin. Patients with diabetes were significantly older; more likely to be women; have a history of prior MI or hypertension; be obese or manifest Killip class II or greater; and have higher systolic blood pressure, pulse pressure, and heart rate, as well as lower ejection fraction. During follow-up, 31.3% of patients with diabetes and 20.1% of nondiabetic patients died (P<.001). Furthermore, 50% of the patients with diabetes had at least 1 major cardiovascular event compared with 32.3% among the nondiabetic patients (P<.001). In multivariate analysis that adjusted for all significant differences in baseline characteristics, patients with diabetes had a 39% higher total mortality (P = .001) and 49% more cardiovascular events (P = .001). Among the patients with diabetes, baseline insulin treatment was associated with a greater risk of death (41.1% vs 26.2%; P = .001) and cardiovascular events (58.3% vs 45.7%; P = .008). CONCLUSIONS: In patients who survived MI with left ventricular dysfunction, diabetes increased risk of death from all causes even after controlling for differences in other risk factors. Patients with diabetes treated with insulin have a particularly higher mortality risk. Patients with diabetes who survived MI with left ventricular dysfunction, in particular those receiving insulin, are at high risk of subsequent mortality and cardiovascular events and thus require intensive risk factor modification, as well as evaluation for novel therapies.

Aged↗

The national cholesterol education program diet vs a diet lower in carbohydrates and higher in protein and monounsaturated fat: a randomized trial.

BACKGROUND: In the United States, obesity is a major clinical and public health problem causing diabetes, dyslipidemia, and hypertension, as well as increasing cardiovascular and total mortality. Dietary restrictions of calories and saturated fat are beneficial. However, it remains unclear whether replacement of saturated fat with carbohydrates (as in the US National Cholesterol Education Program [NCEP] diet) or protein and monounsaturated fat (as in our isocaloric modified low-carbohydrate [MLC] diet, which is lower in total carbohydrates but higher in protein, monounsaturated fat, and complex carbohydrates) is optimal. METHODS: We randomized 60 participants (29 women and 31 men) to the NCEP or the MLC diet and evaluated them every 2 weeks for 12 weeks. They were aged 28 to 71 years (mean age, 44 years in the NCEP and 46 years in the MLC group). A total of 36% of participants from the NCEP group and 35% from the MLC group had a body mass index (calculated as weight in kilograms divided by the square of height in meters) greater than 27. The primary end point was weight loss, and secondary end points were blood lipid levels and waist-to-hip ratio. RESULTS: Weight loss was significantly greater in the MLC (13.6 lb) than in the NCEP group (7.5 lb), a difference of 6.1 lb (P = .02). There were no significant differences between the groups for total, low density, and high-density lipoprotein cholesterol, triglycerides, or the proportion of small, dense low-density lipoprotein particles. There were significantly favorable changes in all lipid levels within the MLC but not within the NCEP group. Waist-to-hip ratio was not significantly reduced between the groups (P = .27), but it significantly decreased within the MLC group (P = .009). CONCLUSIONS: Compared with the NCEP diet, the MLC diet, which is lower in total carbohydrates but higher in complex carbohydrates, protein, and monounsaturated fat, caused significantly greater weight loss over 12 weeks. There were no significant differences between the groups in blood lipid levels, but favorable changes were observed within the MLC diet group.

Adult↗

Randomized trials of vitamin E in the treatment and prevention of cardiovascular disease.

BACKGROUND: Observational epidemiological studies consistently show that individuals who choose to take high amounts of vitamin E through diet or supplements experience cardiovascular benefits, for which basic research provides plausible mechanisms. However, because the size of the postulated benefit is small to moderate, the confounding inherent in observational studies is as great as the effect size. Before the availability of randomized evidence, about 1 in 4 adults was taking vitamin E supplements in the United States. METHODS: We conducted a computerized search of the English-language literature from 1990 to the present and found 7 large-scale randomized trials of the effectiveness vitamin E in the treatment and prevention of cardiovascular disease. Data were available on myocardial infarction, stroke, or cardiovascular death. RESULTS: Six of the 7 trials showed no significant effect of vitamin E on cardiovascular disease. In an overview, vitamin E had neither a statistically significant nor a clinically important effect on any important cardiovascular event (odds ratio [OR], 0.98; 95% confidence interval [CI], 0.94-1.03) or its components: nonfatal myocardial infarction (OR, 1.00; 95% CI, 0.92-1.09), nonfatal stroke (OR, 1.03; 95% CI, 0.93-1.14), or cardiovascular death (OR, 1.00; 95% CI, 0.94-1.05). CONCLUSIONS: The ORs and CIs provide strong support for a lack of statistically significant or clinically important effects of vitamin E on cardiovascular disease. The use of agents of proven lack of benefit, especially those easily available over the counter, may contribute to underuse of agents of proven benefit and failure to adopt healthy lifestyles.

Adult↗

Effect of antecedent systemic hypertension on subsequent left ventricular dilation after acute myocardial infarction (from the Survival and Ventricular Enlargement trial).

Whether antecedent systemic hypertension influences the risk of subsequent left ventricular (LV) dilation in patients after an acute myocardial infarction with LV systolic dysfunction is unclear. We assessed echocardiographic evidence of ventricular remodeling from baseline (mean +/- SD 11 +/- 3 days) to 2 years after an acute myocardial infarction in 122 hypertensive (defined as a history of treated hypertension, baseline systolic blood pressure > or =140 or baseline diastolic blood pressure > or =90 mm Hg) and 334 nonhypertensive patients in the Survival and Ventricular Enlargement echocardiographic substudy. Compared with nonhypertensives, baseline heart size, defined as the sum of the average short- and long-axis LV cavity areas, was similar (70.1 +/- 11.9 vs 68.8 +/- 11.2 cm(2), p = 0.33 at end-diastole; 50.1 +/- 11.3 vs 48.8 +/- 10.8 cm(2), p = 0.31 at end-systole), but short-axis LV myocardial area (24.7 +/- 4.3 vs 25.7 +/- 5.0 cm(2), p = 0.043) and wall thickness (1.15 +/- 0.16 vs 1.21 +/- 0.17 cm, p = 0.004) at end-diastole were greater among hypertensives. The myocardial infarct segment lengths were similar in the 2 groups (p = 0.22). Although LV cavity areas increased significantly in the 2 groups from baseline to 2 years (p < or =0.001), the increase was significantly greater in hypertensives than in nonhypertensives (+5.6 +/- 11.5 vs +2.2 +/- 10.7 cm(2), p = 0.005 at end-diastole; +6.23 +/- 12.75 vs +2.94 +/- 11.4 cm(2), p = 0.012 at end-systole). There was no concomitant difference in the change in LV myocardial area or LV wall thickness between the 2 groups (p >0.30). After adjusting for known confounders, antecedent hypertension was associated with a doubling of the risk of LV dilation (50.8% vs 37.7%, odds ratio 2.09, 95% confidence interval 1.27 to 3.45, p = 0.004). This association was not modified by diabetes mellitus, myocardial infarct segment length, or captopril use (all p values for interaction >0.10). We conclude that antecedent hypertension is associated with subsequent LV dilation in patients after acute myocardial infarction with LV systolic dysfunction.

Antihypertensive Agents↗

High incidence of pacemaker syndrome in patients with sinus node dysfunction treated with ventricular-based pacing in the Mode Selection Trial (MOST).

OBJECTIVES: We evaluated the incidence, predictors, and treatment of pacemaker syndrome in patients with sinus node dysfunction treated with ventricular-based (VVIR) pacing in the Mode Selection Trial (MOST). BACKGROUND: Pacemaker syndrome, or intolerance to VVIR pacing, consists of cardiovascular signs and symptoms induced by VVIR pacing. METHODS: The definition of pacemaker syndrome required that a patient with single-chamber VVIR pacing develop either congestive signs and symptoms associated with retrograde conduction during VVIR pacing or a >or=20 mm Hg reduction of systolic blood pressure during VVIR pacing, associated with reproducible symptoms of weakness, lightheadedness, or syncope. RESULTS: Of 996 patients randomized to VVIR pacing, 182 (18.3%) met criteria for pacemaker syndrome in follow-up. Pacemaker syndrome occurred early in most patients (13.8% at 6 months, 16.0% at 1 year, increasing to 19.7% at 4 years). Baseline univariate predictors of pacemaker syndrome included a lower sinus rate and higher programmed pacemaker rate. Previous heart failure, ejection fraction, and drop in systolic blood pressure with VVIR pacing at implantation did not predict the development of pacemaker syndrome. Post-implantation predictors of pacemaker syndrome were a higher percentage of paced beats, higher programmed low rate, and slower underlying spontaneous sinus rate. Quality of life decreased at the time of diagnosis of pacemaker syndrome and improved with reprogramming to atrial-based pacing. CONCLUSIONS: Severe pacemaker syndrome developed in nearly 20% of VVIR-paced patients and improved with reprogramming to the dual-chamber pacing mode. Because prediction of pacemaker syndrome is difficult, the only way to prevent pacemaker syndrome is to implant atrial-based pacemakers in all patients.

Aged↗

Alcohol consumption and prognosis in patients with left ventricular systolic dysfunction after a myocardial infarction.

OBJECTIVES: We assessed the influence of alcohol intake on the development of symptomatic heart failure (HF) in patients with left ventricular (LV) dysfunction after a myocardial infarction (MI). BACKGROUND: In contrast to protection from coronary heart disease, alcohol consumption has been linked to cardiodepressant effects and has been considered contraindicated in patients with HF. METHODS: The Survival And Ventricular Enlargement (SAVE) trial randomized 2231 patients with a LV ejection fraction (EF) <40% following MI to an angiotensin-converting enzyme inhibitor or placebo. Patients were classified as nondrinkers, light-to-moderate drinkers (1 to 10 drinks/week), or heavy drinkers (>10 drinks/week) based on alcohol consumption reported at baseline. The primary outcome was hospitalization for HF or need for an open-label angiotensin-converting enzyme inhibitor. Analyses were repeated using alcohol consumption reported three months after MI. RESULTS: Nondrinkers were older and had more comorbidities than light-to-moderate and heavy drinkers. In univariate analyses, baseline light-to-moderate alcohol intake was associated with a lower incidence of HF compared with nondrinkers (hazard ratio [HR] 0.71; 95% confidence interval [CI] 0.57 to 0.87), whereas heavy drinking was not (HR 0.91; 95% CI 0.67 to 1.23). After adjustment for baseline differences, light-to-moderate baseline alcohol consumption no longer significantly influenced the development of HF (light-to-moderate drinkers HR 0.93; 95% CI 0.75 to 1.17; heavy drinkers HR 1.25; 95% CI 0.91 to 1.72). Alcohol consumption reported three months after the MI similarly did not modify the risk of adverse outcome. CONCLUSIONS: In patients with LV dysfunction after an MI, light-to-moderate alcohol intake either at baseline or following MI did not alter the risk for the development of HF requiring hospitalization or an open-label angiotensin-converting enzyme inhibitor.

Alcohol Drinking↗

Prolonged QTc interval and risks of total and cardiovascular mortality and sudden death in the general population: a review and qualitative overview of the prospective cohort studies.

BACKGROUND: In certain subgroups of patients, prolongation of the QTc interval may increase total and cardiovascular mortality due to life-threatening ventricular arrhythmias and sudden death. Nonetheless, whether modest prolongation of the QTc interval in the general population has clinical importance remains unclear. METHODS: We conducted a literature search from 1990 forward to identify all published prospective cohort studies evaluating the association between prolonged QTc interval and risks of total and cardiovascular mortality as well as sudden death. We reviewed each of the studies individually and then conducted a qualitative overview. RESULTS: The 7 prospective cohort studies identified included 36 031 individuals. There were 2677 (8.7%) individuals with prolonged QTc interval, defined as 440 milliseconds or greater. Whereas 1 study reported no association between prolonged QTc interval and mortality (relative risk, 1.02; 95% confidence interval, 0.70-1.49), the other 6 reported inconsistent associations overall as well as across subgroups defined by various characteristics including age, sex, and comorbidities. The reported associations for both cardiovascular mortality and sudden death were also inconsistent. In the overview, the only consistent findings were for the subgroup of patients with prior cardiovascular disease, in which relative risks ranged from 1.1 to 3.8 for total mortality, from 1.2 to 8.0 for cardiovascular mortality, and from 1.0 to 2.1 for sudden death. Further, in individuals without prior cardiovascular disease, associations were either absent or greatly attenuated; specifically, relative risks ranged from 0.9 to 1.6 for total mortality, from 1.2 to 1.7 for cardiovascular mortality, and from 1.3 to 2.4 for sudden death. CONCLUSIONS: There was no consistent evidence for increased risks of total or cardiovascular mortality or of sudden death, except perhaps for patients with prior cardiovascular disease. In the general population, if QTc interval prolongation is associated with any increase in mortality, that risk is likely to be small and difficult to detect reliably.

Cardiovascular Diseases↗

Predictors of stroke in patients paced for sick sinus syndrome.

OBJECTIVES: This study was an analysis of factors associated with stroke in a population of patients paced for sinus node dysfunction in a large prospective clinical trial (Mode Selection Trial [MOST]). BACKGROUND: The effects of dual-chamber versus single-chamber ventricular pacing on subsequent stroke in patients with sinus node dysfunction are not known. METHODS: A total of 2,010 patients with sinus node dysfunction were randomized to ventricular or dual-chamber pacing and followed for a median of 33.1 months. RESULTS: The median participant age was 74 years. During 5,664 patient-years of follow-up, 90 strokes (11 hemorrhagic) occurred. By life-table analysis, the rate of stroke was 2.2% (95% confidence interval [CI] 1.6 to 2.9) at one year and 5.8% (95% CI 4.5 to 7.1) at four years. The incidence of stroke was not significantly different in dual-chamber (4%) as compared with ventricular-paced patients (4.9%) (hazard ratio [HR] 0.82, 95% CI 0.54 to 1.25, p = 0.36). Multivariable analysis demonstrated that significant predictors of stroke included prior stroke or transient ischemic attack, Caucasian race, hypertension, prior systemic embolism, and New York Heart Association functional class III or IV (p < 0.05); pacing mode remained non-significant after adjustment for these factors (p = 0.37). Clinically reported atrial fibrillation after implantation was a risk factor for stroke in this cohort after adjustment for other predictors of stroke (p = 0.042, HR 1.68 [95% CI 1.02 to 2.76]). CONCLUSIONS: Clinical characteristics, but not mode of pacing, were associated with subsequent stroke in patients paced for sinus node dysfunction.

Age Factors↗

Homocysteine and cardiovascular disease: biological mechanisms, observational epidemiology, and the need for randomized trials.

Basic research indicates that homocysteine causes endothelial dysfunction and damage, accelerates thrombin formation, inhibits native thrombolysis, promotes lipid peroxidation through free radical formation, and induces vascular smooth muscle proliferation and monocyte chemotaxis. Most, but not all, observational epidemiological studies indicate that individuals with higher homocysteine levels have increased risks of cardiovascular disease. The magnitude ranges from approximately 20% in prospective studies to approximately 80% in retrospective case-control studies. In all observational epidemiological studies, however, the amount of uncontrolled and uncontrollable confounding is as large as the postulated small to moderate effect size. Thus, the totality of evidence should include randomized trials of sufficient sample size and duration with clinical end points. Folic acid reduces levels of homocysteine, but at present, despite several plausible biological mechanisms and a large body of observational epidemiological data, it is unclear whether supplementation will reduce risks of cardiovascular disease. It is also unclear whether any benefit of folic acid is attributable to lowering homocysteine levels. The current evidence is necessary, but not sufficient to judge causality. Such judgments await the availability of data from large-scale randomized trials. The availability of such data would permit rational clinical decision-making for individual patients and policy decisions for the health of the general public.

Cardiovascular Diseases↗

Antecedent hypertension and the effect of captopril on the risk of adverse cardiovascular outcomes after acute myocardial infarction with left ventricular systolic dysfunction: Insights from the Survival and Ventricular Enlargement Trial.

BACKGROUND: Hypertension is a well-established risk factor for myocardial infarction (MI), but its prognostic importance in survivors of an acute MI is less clear. METHODS: We used Cox proportional hazards models to examine the risk of any major cardiovascular event (cardiovascular death, heart failure, recurrent MI, or stroke)-combined or individual components-and all-cause death and evaluate the efficacy of captopril in 906 patients with hypertension and 1325 patients without hypertension in the Survival and Ventricular Enlargement (SAVE) clinical trial. All patients had survived an acute MI with resultant left ventricular (LV) systolic dysfunction, but without overt heart failure, and were randomized within 3 to 16 days after the index MI to receive either captopril or placebo. The mean (+/- SD) follow-up period was 42 +/- 10 months. RESULTS: After adjustment for known risk factors, medication use at enrollment, and baseline systolic blood pressure, patients with hypertension had a significant increase in the risk of experiencing a combined cardiovascular event (47.7% vs 31.3%; hazard ratio [HR], 1.49; 95% CI, 1.28-1.74), cardiovascular death (23.4% vs 15.9%; HR, 1.40; 95% CI, 1.12-1.74), heart failure (27.7% vs 15.5%; HR, 1.64; 95% CI, 1.34-2.02), and all-cause death (27.4 vs 19.3%; HR, 1.25; 95% CI, 1.02-1.53), and a similar but statistically non-significant increase in the risk of non-fatal or fatal recurrent MI (17.4% vs 10.9%; HR, 1.27; 95% CI, 0.98-1.65), and non-fatal or fatal stroke (5.0% vs 3.6%; HR, 1.31; 95% CI, 0.81-2.09). Captopril resulted in similar benefits for both patients with and patients without hypertension. The number of combined cardiovascular events prevented for every 100 patients treated with captopril was 7.0 (95% CI, 0.5-13.5) in patients with hypertension and 7.5 (95% CI, 2.6-12.5) in patients without hypertension. CONCLUSIONS: In survivors of an acute MI with LV systolic dysfunction, antecedent hypertension was associated with a greater risk of subsequent adverse cardiovascular events, not directly explained by elevated blood pressure levels. Captopril use was beneficial in both patients with and patients without hypertension.

Adult↗

Prospective randomized study of mode switching in a clinical trial of pacemaker therapy for sinus node dysfunction.

INTRODUCTION: Atrial fibrillation (AF) is common in pacemaker patients with sinus node dysfunction (SND) and may result in rapid ventricular pacing (RVP) in the DDDR mode. Mode switching (MS) reduces RVP, but its clinical benefit in patients with SND is unknown. METHODS AND RESULTS: Two hundred two patients in the Mode Selection Trial (MOST; 2,010-patient, 6-year trial of DDDR vs VVIR pacing in SND) randomized to DDDR pacemakers with atrial high-rate episode (AHRE) storage capabilities were subrandomized to MS ON (N = 96) or MS OFF (N = 106). Cardiovascular symptoms, quality of life (QOL), reprogramming due to RVP, death, stroke, and heart failure hospitalization (HFH) were compared between groups. The treatment groups were similar with regard to AF history (59% MS ON vs 57% MS OFF). AHREs occurred in 49% patients during median follow-up of 2.2 years. Median AHRE duration (in min; MS ON 116 vs MS OFF 58, P = 0.29), frequency AHREs/week (MS ON 3.5 vs MS OFF 6.4, P = 0.23), and time spent in AHRE (min/week) (MS ON 450, MS OFF 268) were similar. Reprogramming due to any RVP during AHREs occurred more in MS OFF vs MS ON (13.2% vs 3.1%, P = 0.011) and marginally more for symptomatic RVP (8.5% vs 2.1%, P = 0.062). Cardiovascular symptoms occurred in 93.6% MS ON vs 90.2% MS OFF (P = 0.38). Median number of symptoms reported per visit was similar (MS ON 1.3 vs MS OFF 1.5, P = 0.62). Median symptom frequency/severity, summed and averaged over visits, was similar (MS ON 4.3 vs MS OFF 4.5, P = 0.74). QOL was not different between groups. Death, stroke, and HFH were not different between groups. CONCLUSION: MS reduces pacemaker reprogramming due to RVP during AHREs in a small number of patients but does not improve QOL or cardiovascular symptoms overall among patients with SND.

Aged↗

An update on clinical trials in pacing: is dual chamber pacing better?

PURPOSE OF REVIEW: As pacemaker technology has increased in complexity and now offers a variety of additional capabilities, there is uncertainty as to which pacing mode offers more benefit-dual-chamber or single-chamber. RECENT FINDINGS: Two large-scale randomized trials, the Canadian Trial of Physiologic Pacing and the Mode Selection Trial, demonstrated that dual-chamber pacing does not reduce the incidence of stroke or improve survival when compared with ventricular pacing. However, dual-chamber pacing does reduce the incidence of atrial fibrillation and in patients with sinus node dysfunction, reduces heart failure symptoms when compared with ventricular pacing. The modest results of these trials were unexpected when viewed in the context of the very favorable retrospective studies. SUMMARY: A rethinking of the physiology of cardiac pacing has led to the concept that although atrioventricular synchrony supports an improvement in cardiac output and ventricular pressures, these favorable hemodynamics may be attenuated by ventricular dyssynchrony from right ventricular apical pacing. In patients with a reduced ejection fraction, this dyssynchrony may be especially detrimental. Two trials (DANPACE and SAVE-PACE) are currently underway that will clarify the clinical significance of reducing forced ventricular desynchronization. The results of these trials may direct pacemaker physicians away from the right ventricular apical lead toward a new imperative of atrioventricular and right ventricular-left ventricular synchrony.

Arrhythmia, Sinus↗

AT1 receptor blockade for the prevention of cardiovascular events after myocardial infarction.

Myocardial infarction is associated with high morbidity and mortality. Multiple therapeutic modalities have been shown to be effective in reducing adverse postmyocardial infarction outcomes. The most prominent drugs that have been used in this group of patients are those that oppose the effects of the renin-angiotensin-aldosterone system. These drugs include beta-blockers, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers and aldosterone blockers. Following initial success with angiotensin-converting enzyme inhibitors in reducing mortality and cardiac remodeling in postmyocardial infarction patients, recent focus has been on adjunctive or alternative use of angiotensin II-receptor antagonists. Multiple large-scale, randomized trials have been conducted in order to compare angiotensin II-receptor antagonists with a combination of angiotensin II-receptor antagonists and angiotensin-converting enzyme inhibitors, and with angiotensin-converting enzyme inhibitors alone in postmyocardial infarction patients and also in heart failure. Although some results are conflicting, the weight of evidence is towards equivalency of these two groups of medicines, provided that the maximum effective dose of the angiotensin II-receptor antagonists is used. The combination of an angiotensin-converting enzyme inhibitor and an angiotensin II-receptor antagonist may have additional benefits for some, but not all, patients; for example, reducing morbidity and mortality in patients with chronic heart failure but not in postmyocardial infarction patients. Indeed, in the postmyocardial infarction setting, the combination appears simply to increase the side effects, without conferring additional benefits. Use of aldosterone antagonists as adjunctive therapy in postmyocardial infarction patients is associated with added benefits in terms of mortality reduction and will become the standard of care in this group of patients.

Adrenergic beta-Antagonists↗