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Biomedical subjects

S P Glasser

Publications and source records attributed to S P Glasser.

At least 19 recordsLinked to original sources
PubMed2001

Low-density lipoprotein size, pravastatin treatment, and coronary events.

CONTEXT: Small low-density lipoprotein (LDL) particle size has been hypothesized to be a risk factor for coronary heart disease (CHD). Animal models link large LDL to atherosclerosis. However, the strong association between small LDL and other risk factors, particularly triglyceride levels, impedes determining whether LDL size independently predicts CHD in humans. OBJECTIVE: To examine whether LDL size is an independent predictor of recurrent coronary events in patients with known CHD, as opposed to a marker for other lipid abnormalities. DESIGN AND SETTING: Prospective, nested case-control study in the Cholesterol and Recurrent Events (CARE) trial, a randomized placebo-controlled trial of pravastatin conducted in 1989-1996. PARTICIPANTS: Survivors of myocardial infarction with typical LDL concentrations (416 cases and 421 controls). MAIN OUTCOME MEASURE: Subsequent myocardial infarction or coronary death during the 5-year follow-up, analyzed by quintile of LDL particle size and by treatment group. RESULTS: Overall, the mean LDL size was identical in cases and controls (25.6 nm). In patients in the placebo group, large LDL predicted coronary events in models adjusted only for age (relative risk [RR], 1.79; 95% confidence interval [CI], 1.01-3.17) and for age and lipid and nonlipid risk factors (RR, 4.00; 95% CI, 1.81-8.82), comparing those in the highest (mean, 26.6 nm) and lowest (mean, 24.5 nm) quintiles of LDL size. This increased risk was not present in those taking pravastatin (age-adjusted analysis: RR, 0.98; 95% CI, 0.47-2.04; P =.046 for interaction for a difference in the effect of LDL size on coronary events between the placebo and treatment groups; multivariable analysis: RR, 1.33; 95% CI, 0.52-3.38; P =.11 for interaction). CONCLUSIONS: Large LDL size was an independent predictor of coronary events in a typical population with myocardial infarction, but the adverse effect was not present among patients who were treated with pravastatin. Identifying patients on the basis of LDL size may not be useful clinically, since effective treatment for elevated LDL cholesterol concentrations also effectively treats risk associated with large LDL.

Anticholesteremic Agents↗
PubMed2001

Blood pressure and arterial compliance in young adults: the Minnesota Children's Blood Pressure Study.

The aim of this study was to assess the relation between blood pressure (BP) and arterial compliance in a healthy sample of young adults. School children (aged 10 to 14 years at entry) were surveyed in 1977 to 1978, and 1,207 were followed once to twice yearly until age 23 years. Arterial compliance was measured in 179 adults at the last follow-up visit. The sample included individuals in the upper tertile of systolic BP during the last three follow-up visits and race- and sex-matched individuals in the lower two tertiles. We obtained radial artery waveforms using a calibrated tonometer device and characterized waveform morphology to determine large artery (C1) and oscillatory (C2) compliance. Blood pressure was measured using random zero sphygmomanometers. The mean and standard deviation of C1 was 2.13 +/- 0.59 mL/mm Hg and of C2 was 0.083 +/- 0.02 mL/mm Hg. Systolic BP was inversely related to C1 (P < .001) and C2 (P < .01) after adjustment for gender, height, weight, insulin, and HDL and LDL cholesterol. After adjustment, a 1 SD change in systolic BP was associated with a -0.30 mL/mm Hg change in C1 and a -.008 mL/mm Hg change in C2. Data from the Minnesota Children's Blood Pressure Study indicate that systolic BP is inversely related to arterial compliance, particularly C1 (the large artery, or capacitive compliance).

Adolescent↗
PubMed2001

Arterial compliance abnormalities in isolated systolic hypertension.

Arterial compliance measurements using intraarterial pulse contour analysis and a modified Windkessel model were carried out in 19 patients with isolated systolic hypertension (> or = 160/< or = 90 mm Hg) and compared to measurements in 29 patients with essential hypertension (diastolic blood pressure [BP] > or = 95 mm Hg) and 47 normotensive control subjects. Arterial capacitive compliance was significantly lower in isolated systolic hypertension than in essential hypertension (P < .0002) and significantly lower in essential hypertension than in normotensive control subjects (P < .0001). Although the isolated systolic hypertension group was older than the essential hypertension group, the reduction of capacitive compliance in isolated systolic hypertension persisted even when comparison was made with a more nearly age-matched group of essential hypertension. In contrast, oscillatory compliance was reduced similarly in isolated systolic hypertension and essential hypertension compared to normotensive control subjects (P < .0001). Although pulse pressure was greater in isolated systolic hypertension than in essential hypertension, only a weak correlation (r = -0.34) existed between pulse pressure and capacitive compliance. These data indicate that both essential hypertension and isolated systolic hypertension patients exhibit comparably abnormal structure or tone of the small vessels that are the site of oscillations or reflections in the arterial vasculature. In isolated systolic hypertension there is a profound reduction in large artery or capacitive compliance that accounts for the increase in systolic BP and decrease in diastolic BP. This abnormality cannot be accurately assessed by pulse pressure alone.

Aged↗
PubMed2001

Hypertension syndrome and cardiovascular events. High blood pressure is only one risk factor.

It is becoming increasingly clear that high blood pressure is not the sole cause of the high cardiovascular morbidity and mortality rates associated with hypertension. Reduction of blood pressure is of utmost importance, but many other factors contribute significantly to the risk of adverse cardiovascular events and death. In this article, Dr Glasser reviews hypertension as a syndrome, emphasizing therapy to improve blood pressure control, increase arterial compliance, and inhibit or reverse vascular remodeling.

Adolescent↗
PubMed2000

Circadian heart rate response to chronotherapy versus conventional therapy in patients with hypertension and myocardial ischemia.

BACKGROUND: Changes in heart rate (HR) may contribute to the higher incidence of cardiovascular events in the morning. HYPOTHESIS: The objectives of this analysis were to assess HR patterns in two populations (patients with chronic stable angina or stage I to III hypertension) and to compare the effects of various antianginal and antihypertensive treatments on HR. METHODS: This was a retrospective analysis of HR data from two clinical trials evaluating the efficacy of controlled-onset, extended-release (COER)-verapamil. The effects of COER-verapamil were compared with placebo, nifedipine gastrointestinal therapeutic system (GITS), amlodipine, and the combination of amlodipine and atenolol. RESULTS: In patients with angina (n = 498), the change from baseline in HR following 4 weeks of treatment was -6.7 +/- 10.5 beats/min in the COER-verapamil group, -10.8 +/- 10.8 beats/min in the amlodipine/atenolol group, + 2.5 +/- 9.1 beats/ min in the amlodipine monotherapy group, and -1.3 +/- 10.5 beats/min in the placebo group (p<0.001). Data were stratified based on whether patients experienced asymptomatic ischemia during baseline ambulatory electrocardiographic monitoring. The circadian HR pattern was morphologically similar in all groups; however, differences in the magnitude of HR response were evident. In the subset of patients with asymptomatic ischemia (n = 101), treatment with amlodipine monotherapy increased HR compared with placebo. In this same subset of patients, HR reductions were achieved with COER-verapamil and amlodipine/atenolol. In patients with hypertension (n = 557), the change in HR following 10 weeks of treatment was -3.3 beats/min for patients treated with COER-verapamil compared with + 2.0 beats/min for patients treated with nifedipine GITS (p < 0.0001, between-group differences). CONCLUSION: This analysis demonstrates that morphologically similar circadian patterns of HR occur in both hypertensive patients and those with angina. In addition, significant variation exists among antianginal and antihypertensive agents regarding HR effects.

Adrenergic beta-Antagonists↗
PubMed2000

Angiotensin converting enzyme inhibitors: are they preferred first-line therapy?

In patients with hypertension, the primary goal is to reduce elevated blood pressure. All of the currently available and approved antihypertensive therapies are, by and large, equally efficacious. Some patient groups and individual patients may, however, respond differentially, and as a result one therapy may be more optimal than another. Overall, for uncomplicated hypertension and particularly for isolated systolic hypertension, diuretics should be considered for first-line therapy. However, comorbid conditions (which occur in > 50% of hypertensive patients) may prompt the need for a more ideal first-line therapy (eg, hypertension with diabetic nephropathy or with left ventricular dysfunction). Regardless, most patients with hypertension will require multidrug therapy to achieve the blood pressure goal, and an angiotensin converting enzyme (ACE) inhibitor may well be part of that therapy. Many going outcome trials comparing the newer therapies (such as ACE inhibitors) with diuretic-based therapy may redefine or clarify the use of different antihypertensive regimens.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1999

Age-related abnormalities in arterial compliance identified by pressure pulse contour analysis: aging and arterial compliance.

The objective of this study was to evaluate age-related changes in pulsatile arterial function. Aging alters arterial pulsatile function and produces consistent changes in the pressure pulse contour. A reduced systemic arterial compliance that can be derived from analysis of the pulse contour is regarded as the best clinical index of impaired pulsatile arterial function and may mark the presence of early vascular damage. We analyzed intra-arterial brachial artery waveforms in 115 healthy normotensive volunteers (83 men, 32 women) and radial artery waveforms obtained with the use of a calibrated tonometer device in 212 healthy volunteers (147 women, 65 men). A computer-based assessment of the diastolic pressure decay and a modified Windkessel model of the circulation were used to quantify changes in arterial waveform morphology in terms of large artery or capacitive compliance, oscillatory or reflective compliance in the small arteries, inertance, and systemic vascular resistance. Large artery compliance and oscillatory compliance correlated negatively with age for both invasive and noninvasive groups (r=-0.50 and r=-0.55; r=-0.37 and r=-0.66; P<0.001 for all). The slopes of the regression lines for the decline in oscillatory compliance with age were significantly steeper than those recorded for large artery compliance estimates. The change in blood pressure with age independently contributed to the decrease in large artery compliance but not oscillatory compliance in both groups. Consistent age-related changes were found in the pressure pulse contour by analysis of waveforms obtained invasively or noninvasively from the upper limb. The change in the oscillatory or reflective compliance estimate was independent of blood pressure change and may represent a better marker than large artery or capacitive compliance of the degenerative aging process in altering pulsatile arterial function.

Adult↗
PubMed1998

Effect of pravastatin on cardiovascular events in older patients with myocardial infarction and cholesterol levels in the average range. Results of the Cholesterol and Recurrent Events (CARE) trial.

BACKGROUND: A majority of all myocardial infarctions occur in patients who are 65 years of age or older and have average cholesterol levels, but little information is available on whether cholesterol lowering in such patients reduces the rate of recurrent cardiovascular disease. OBJECTIVE: To determine whether pravastatin reduces the rate of recurrent cardiovascular events in older patients. DESIGN: Subset analysis of a randomized, controlled trial. SETTING: 80 hospitals and affiliates in the United States and Canada. PATIENTS: 1283 patients aged 65 to 75 years who had had myocardial infarction and had a plasma total cholesterol level less than 6.2 mmol/L (240 mg/dL) and a low-density lipoprotein cholesterol level of 3.0 to 4.5 mmol/L (115 to 174 mg/dL). INTERVENTION: Pravastatin, 40 mg/d, or placebo. MEASUREMENTS: Five-year event rates of major coronary events (coronary death, nonfatal myocardial infarction, angioplasty, or bypass surgery) and stroke. RESULTS: Major coronary events occurred in 28.1% of placebo recipients and 19.7% of pravastatin recipients (difference, 9.0 percentage points [95% CI, 4 to 13 percentage points]; relative risk reduction, 32%; P < 0.001). Coronary death occurred in 10.3% of the placebo group and in 5.8% of the pravastatin group (difference, 4.6 percentage points [CI, 1.9 to 6.5 percentage points]; relative risk reduction, 45%; P = 0.004). Stroke incidence was 7.3% in the placebo group and 4.5% in the pravastatin group (absolute reduction, 2.9 percentage points [CI, 0.3 to 4.5 percentage points]; relative reduction, 40%; P = 0.03). The numbers of older patients needed to treat for 5 years were 11 (CI, 8 to 24) to prevent a major coronary event and 22 (CI, 15 to 53) to prevent a coronary death. For every 1000 older patients treated, 225 cardiovascular hospitalizations would be prevented compared with 121 hospitalizations in 1000 younger patients. CONCLUSIONS: In older patients with myocardial infarction and cholesterol levels in the average range, pravastatin is associated with a clinically important reduction in risk for major coronary events and stroke. Given the high cardiovascular event rate in older patients, the potential for absolute benefit in this age group is substantial.

Aged↗
PubMed1998

The importance of arterial compliance in cardiovascular drug therapy.

Arterial compliance, defined as a change in dimension in response to a given change in stress, is becoming an increasingly important clinical parameter. Related concepts, such as distensibility, elasticity, and stiffness, and more traditional concepts such as resistance, afterload, and impedance need to be differentiated from compliance, although they are frequently (inappropriately) used interchangably. Many studies cannot differentiate between compliance changes due to a drug's effect on blood pressure and those due to a drug's effect on vessel wall integrity. This differentiation is important because a more physiologic therapy, one that benefits pulsatile and nonpulsatile flow, should be of greater clinical benefit than a therapy that only lowers blood pressure. A number of methods have been used to estimate compliance, but to date there is no generally agreed-on best method. There also are no longitudinal studies that relate abnormal compliance and drug effects to outcome. Nonetheless, patients at risk from a variety of disease states, such as hypertension, diabetes mellitus, and hypercholesterolemia, may benefit from earlier recognition of abnormal compliance. Earlier recognition may lead to interventions that would reduce their risk. This review includes a discussion of compliance and related estimates of blood vessel function and attempts to summarize the data currently available regarding the effects of cardioactive drugs on arterial compliance.

Adrenergic beta-Antagonists↗
PubMed1998

The relevance of T-type calcium antagonists: a profile of mibefradil.

L- and T-type voltage-dependent transmembrane calcium channels are important for normal functioning of the cardiovascular system. T-type channels are a heterogeneous group, and have physiologic and pathophysiologic relevance in a number of organ systems, including the heart and central nervous system. They appear to be involved in the control of blood pressure in patients with essential hypertension and in protection from ischemic damage. Alterations of both L- and T-type calcium channels are involved in the development of hypertension. Pharmacologic modulation of T-type calcium channels appears to reduce membrane calcium flux and ameliorate hypertension. During early ischemic damage, T-type calcium channels appear to remain functional whereas L-type channels are already inactivated. T-type calcium channels also appear to be involved in the development of supraventricular arrhythmias, some forms of arrhythmias in cardiomyopathy, and cardiac hypertrophy. The heterogeneity of T-type calcium channels should make it possible to target drugs to specific subgroups of T-type calcium channels. A new class of calcium antagonist, the benzimidazolyl-substituted tetraline derivatives, has been shown to block both L- and T-type calcium channels. The first member of this class approved for clinical use is mibefradil. Clinical studies have demonstrated the efficacy of mibefradil in lowering blood pressure and as an antianginal and antiischemic agent. At clinically recommended doses, mibefradil has a heart rate lowering effect without a negative inotropic effect, and a favorable side effect profile. Because it is metabolized by the cytochrome P450 pathway, it should be used cautiously with other agents similarly metabolized.

Animals↗
PubMed1998

Hypertension, hypertrophy, hormones, and the heart.

Mild-to-moderate hypertension is common, and its natural history is reasonably well defined. The association of elevated blood pressure with left ventricular hypertrophy, insulin resistance, renal dysfunction, and increased propensity toward atherosclerotic cardiovascular disease and ventricular arrhythmias has been characterized. These associations, however, are not well predicted by the level of blood pressure elevation, suggesting some independence between blood pressure levels and cardiovascular complications. Although the reduction in pressure-related outcomes caused by therapeutic interventions (e.g., stroke) has been demonstrated, a similar reduction in many atherosclerotic outcomes has not been definitively demonstrated. The latter observation may be related to a number of factors but may be partly explained by the lack of direct correlation between blood pressure and cardiovascular outcome. This review attempts to update available information on the intermediating factors mitigating the relation among blood pressure, adverse cardiovascular outcome, and the treatment of hypertension.

Arteriosclerosis↗
PubMed1997

Effect of extended-release isosorbide mononitrate one hour after dosing in patients with stable angina pectoris. IMDUR Study Group.

The effect of extended-release isosorbide mononitrate (ER-ISMN) on exercise tolerance 1 hour after dosing was compared with that of placebo in a multicenter, randomized, double-blind study of 151 patients with stable effort-induced angina. During a 9- to 24-day placebo run-in, patients underwent Bruce protocol baseline exercise tolerance tests, after which they received ER-ISMN or placebo for 5 days. ER-ISMN patients took 60 mg each morning for the first 4 days and 120 mg on the morning of the fifth day. One hour after dosing, ER-ISMN patients had a significantly greater increase in total exercise time (days 1 to 4: 5 +/- 53 seconds; day 5: 53 +/- 58 seconds) than the placebo-treated patients (days 1 to 4: 14 +/- 37 seconds; day 5: 21 +/- 48) (p <0.001). The times to development of angina and 1-mm ST-segment depression were significantly longer in the ER-ISMN group than in the placebo group. The difference between the groups in mean time to onset of angina was 34 seconds after the 60-mg dose (p = 0.004) and 49 seconds after the 120-mg dose (p <0.001). The mean time to development of a 1-mm ST-segment depression was 51 and 61 seconds longer after the 60-mg and 120-mg ER-ISMN doses, respectively, than after placebo (p <0.001). Treatment-related adverse events were reported in 37% (28 of 75) and 7% (5 of 76) of patients in the ER-ISMN and placebo groups, respectively. As expected, headache was more frequent in the ER-ISMN group than in the placebo group (28% and 1%, respectively). The effects of ER-ISMN (60 mg and 120 mg) are clinically evident 1 hour after dosing, resulting in better exercise tolerance in patients with angina pectoris.

Adult↗
PubMed1997

Effects of zatebradine (ULFS 49 CL), a sinus node inhibitor, on heart rate and exercise duration in chronic stable angina pectoris. Zatebradine Investigators.

Zatebridine selectively reduces resting and exercise heart rate without any other myocardial effects. In this study, despite significant reductions in resting and exercise heart rate, there were no clinically significant effects on myocardial ischemia, suggesting that the anti-ischemic effect of heart rate reduction should be reevaluated.

Adult↗
PubMed1997

Safety and efficacy of monotherapy with fantofarone, a novel calcium channel antagonist, in patients with chronic stable angina pectoris. Fantofarone Study Group.

Fantofarone is a calcium channel antagonist of a class (sulfone indolizine) that is structurally different from the existing classes. The primary cardiac action of fantofarone is on the sinus node, although it is also a potent peripheral and coronary vasodilator. This is a multicenter, double-blind, randomized, placebo-controlled, dose-ranging study evaluating the efficacy and safety of fantofarone. Three hundred and thirty patients were included as intent-to-treat, and 299 patients completed the entire protocol. Doses of fantofarone studied were 50, 100, 150, and 200 mg twice daily. The 100- and 150-mg groups demonstrated antianginal activity, prolonging exercise time walking on a treadmill by 38 and 45 seconds to the endpoint of moderate angina, compared with the placebo group. Sinus bradycardia occurred in 23 patients and was somewhat dose-related. Systolic blood pressure at rest and while exercising was not altered by therapy. No deaths occurred in the treated group. Of the 20 patients in the treatment group who did not complete the protocol (compared with 23 in the placebo group) 6 were dropped because of symptomatic bradycardia, 5 because of increased angina, and 9 for miscellaneous reasons. In doses of 100 mg to 150 mg twice daily, monotherapy fantofarone was effective and safe in the treatment of patients with chronic, stable angina pectoris.

Adolescent↗