Epidural administration of ropivacaine and its effects on the pharmacodynamics of rocuronium: Randomized controlled trial. Interaction between ropivacaine and rocuronium.

BACKGROUND: Potentiation of neuromuscular blocking agents by local anesthetics has been described in various clinical and experimental studies. This study assessed the influence of epidural ropivacaine on pharmacodynamic characteristics of rocuronium. DESIGN: This was a prospective randomized clinical trial at the women's hospital, an university tertiary hospital in Brazil. Sixty-two patients underwent elective abdominal surgeries requiring general anesthesia. INTERVENTION: Patients were distributed into two groups: Group 1 (general anesthesia and epidural anesthesia) and Group 2 (general anesthesia). In Group 1, 0.2% ropivacaine at a dose of 40 mg (20 ml) was associated with 2 mg (2 ml) of morphine in a single epidural injection. The following parameters were assessed: clinical duration (DC25) and time for recovery of the train-of-four (TOF) 0.9 ratio (T4/T1 = 90%) after an initial 0.6 mg/kg dose of rocuronium. The primary outcomes were DC25 and TOF 0.9 ratio (T4/T1 = 90%). Secondary outcomes were total propofol and remifentanil consumption. RESULTS: Values were presented as median and interquartile range. The results for DC25 and TOF 0.9 of rocuronium were, respectively, 41.5 35.0-55.0 (25.0-63.0) in Group 1 and 44.0 37.0-51.0 (20.0-67.0) in Group 2 (P = 0.88); 88.0 67.0-99.0 (43.0-137.0) in Group 1; and 80.0 71.0-86.0 (38.0-155.0) in Group 2 (P = 0.83). There was no significant difference between the groups, in terms of pharmacodynamic characteristics of rocuronium. Propofol consumption did not show any difference between the groups. However, remifentanil consumption was significantly lower in Group 1 (P < 0.01). CONCLUSION: Epidural ropivacaine, in the dose studied, did not prolong the duration of rocuronium-induced neuromuscular blockade. TRIAL REGISTRY NUMBER: ReBEC (ref: RBR-7cyp6t).

Initial combination therapy for rapid and effective control of moderate and severe hypertension.

Moderate (grade 2) and severe (grade 3) hypertension are important public health problems associated with high cardiovascular risk. Blood pressure (BP) control becomes more difficult to achieve as hypertension progresses. Therefore, early and effective treatment is essential to prevent hypertensive urgencies and emergencies and reduce cardiovascular risk. Currently, less than 50% of patients being treated for moderate or severe hypertension in the United States achieve their BP goal as recommended by treatment guidelines. This review examines the cardiovascular risk and physician inertia associated with moderate and severe hypertension, and concludes that increased use of initial combination therapy can overcome many of the barriers to effective BP control. Furthermore, initial combination therapy with a renin-angiotensin system (RAS) inhibitor and diuretic has the potential to rapidly and effectively reduce BP across a range of baseline BPs, with a comparable adverse event profile to monotherapy.

A comparison of the efficacy and safety of irbesartan/HCTZ combination therapy with irbesartan and HCTZ monotherapy in the treatment of moderate hypertension.

This prospective, double-blind, parallel-group study randomized patients with moderate hypertension (seated systolic blood pressure (SeSBP) 160-179 mm Hg when seated diastolic blood pressure (SeDBP) <110 mm Hg; or SeDBP 100-109 mm Hg when SeSBP <180 mm Hg) 3:1:1 to treatment with irbesartan 300 mg/hydrochlorothiazide (HCTZ) 25 mg combination therapy (n=328), irbesartan 300 mg monotherapy (n=106) or HCTZ monotherapy 25 mg (n=104). Treatment was initiated at half dose, with forced titration to full dose after two weeks followed by ten further weeks' treatment. The primary efficacy variable was the mean reduction in SeSBP from baseline to week 8. Baseline characteristics were similar between groups, with mean baseline blood pressure approximately 162/98 mm Hg; the mean age was 55 years. At week 8 there was a reduction in SeSBP of 27.1 mm Hg with irbesartan/HCTZ, compared with 22.1 mm Hg with irbesartan monotherapy (P=0.0016) and 15.7 mm Hg with HCTZ (P<0.0001). Both the rate of decline and the total degree of decline achieved were greatest with irbesartan/HCTZ and least with HCTZ. A significantly greater percentage of patients reached a treatment goal of SeSBP <140 mm Hg and SeDBP <90 mm Hg by week 8 with irbesartan/HCTZ (53.4%), compared with irbesartan (40.6%; P=0.0254) and HCTZ (20.2%; P<0.0001) alone. Treatment was well tolerated in all three-treatment groups with a slight increase in adverse events in the combination therapy group. In conclusion, irbesartan/HCTZ (300/25 mg) is well tolerated and achieves rapid and sustained reductions in both systolic blood pressure and diastolic blood pressure in patients with moderate hypertension.

Should pulse pressure become part of the Framingham risk score?

An increased pulse pressure suggests aortic stiffening. New evidence also suggests that pulse pressure is a more sensitive measure of risk than other indexes of blood pressure in middle-aged and older persons. The objective of the study was to relate pulse pressure to the risk of cardiovascular events in the general population, and to assess whether pulse pressure could improve the Framingham risk prediction. A total of 378 men and 391 women over the age of 50 years (mean 62.7 years) were followed. Sex-specific Framingham cardiovascular risk scores were derived from age, systolic pressure, diastolic pressure, total and HDL cholesterol, smoking status and the presence or absence of diabetes mellitus. The cutoff points used to develop a pulse pressure score were calculated by determining the percentile points corresponding to the blood pressure categories in the Framingham risk score. We calculated relative hazard rates by multiple Cox regression. After a median follow-up of 7.2 years (range: 11 months-15 years), a total of 148 cardiovascular events occurred. In Cox regression analysis, a 10 mmHg higher pulse pressure was associated with 31% (P<0.0001) increase in the risk for cardiovascular events (fatal and nonfatal) after adjustment for sex, age, total and HDL cholesterol, smoking and the presence of diabetes mellitus. After adjustment for the aforementioned risk factors, a one-point increment in the blood pressure and pulse pressure scores was associated with a 40 and 48% (both P<0.0001) increase in the risk of fatal and nonfatal cardiovascular events, respectively. When both the blood pressure and pulse pressure scores were forced into a Cox model, only the pulse pressure score remained statistically significant (P<0.0001) with a relative hazard rate of 1.37 (CI: 1.16-1.69). These prospective data suggest that pulse pressure may improve the Framingham risk prediction among middle-aged and older individuals. Further studies, especially in the Framingham cohort, are warranted.

Pressure amplification explains why pulse pressure is unrelated to risk in young subjects.

Pulse pressure rather than diastolic pressure is the best predictor of coronary heart disease risk in older subjects, but the converse is true in younger subjects. We hypothesized that this disparity results from an age-related difference in pressure amplification from the aorta to brachial artery. Data from 212 subjects age < 50 years and 230 subjects age > or =50 years were abstracted from a community database. All subjects were free from cardiovascular disease, diabetes, and medication. Peripheral blood pressure was assessed by sphygmomanometry. Radial artery waveforms recorded noninvasively by applanation tonometry were used to derive central blood pressure. Pressure amplification (peripheral/central pulse pressure ratio) was linearly related to age (r=0.7; P<0.001). There was an inverse, linear relationship between amplification and diastolic pressure in the younger group (r=0.3; P<0.001) but not in older subjects (r=0.1; P=0.2). There was no relationship in either group when the amplification ratio was calculated with nonaugmented central pressure. Amplification is reduced in older subjects because of enhanced wave reflection. In younger, but not older, subjects, amplification declines as diastolic pressure rises. Therefore, peripheral pulse pressure underestimates the effect that diastolic pressure has on central pulse pressure in younger subjects. This may explain why diastolic pressure is a better predictor of risk in this age group and suggests that assessment of central pressure may improve risk stratification further.

Blood pressure and cardiovascular disease: what remains to be achieved?

Despite dramatic improvements in the management of hypertensive cardiovascular disease, much remains to be accomplished. Arterial stiffness, through its effects on central aortic pressure, is a key determinant of increased cardiovascular risk. Increased pulse pressure is a late manifestation of increased arterial stiffness. What is needed is a simple, reliable, non-invasive method of detecting early disturbances in central artery stiffness at a time when therapeutic intervention can be most beneficial. Currently, intervention studies support initiating antihypertensive therapy in uncomplicated hypertension when systolic blood pressure > or = 160 mmHg, whereas the benefit of treating systolic blood pressure of 140-159 mmHg, the largest subset of persons with hypertension, has yet to be tested in controlled trials. Further studies are needed to determine the optimal target goal for blood pressure reduction in both uncomplicated hypertension and in hypertension complicated by diabetes, coronary heart disease, or renal disease. Angiotensin converting enzyme inhibitors may provide selective cardiac and renal protection beyond their blood pressure-lowering effect in the presence of specific cardiovascular disease and/or diabetes. In contrast, there is as yet no definitive answer as to the relative benefit of blood pressure lowering versus specific drug effects in minimizing cardiovascular events in uncomplicated hypertension. Although there has been a recent increase in hypertension awareness and treatment, only a small percentage of affected individuals are being treated to goal. Hypertensive cardiovascular disease represents a world-wide public health challenge that can be solved only by new innovative measures aimed at both prevention and treatment.

The challenge of controlling systolic blood pressure: data from the National Health and Nutrition Examination Survey (NHANES III), 1988--1994.

Clinicians tend to focus on diastolic blood pressure (DBP), rather than systolic blood pressure (SBP), to identify and treat hypertension. The authors used data from the National Health and Nutrition Examination Survey (NHANES III, 1988--1994) Mobile Examination Center to examine the distributions of SBP and DBP in treated and untreated individuals with hypertension. We identified the percentage of the hypertensive population with SBP controlled to less than 140 mm Hg and the percentage with DBP controlled to less than 90 mm Hg, stratified by treatment status, gender, race, and ethnicity. Individuals were classified as having hypertension if they had SBP of more than 140 mm Hg or DBP of more than 90 mm Hg, or if they were taking medication for hypertension. A weighted analysis was performed to project the results to the entire U.S. population from 1988--1994; these totals were further estimated for the year 2000 by extrapolation. For men, women, whites, African Americans, and Hispanics, SBP control rates were uniformly poorer than DBP control rates. The difference persisted when subgroups were categorized according to treatment status. The disparity in SBP and DBP control rates was especially great for women: only 50% of treated white women with hypertension had SBP control, but 92% had DBP control. The prevalence of isolated systolic hypertension was greater than 50% among all individuals with hypertension in the 55--60-year age group and increased with age thereafter. A greater emphasis on SBP is needed to improve population blood pressure control. (c)2001 Le Jacq Communications, Inc.

Different prognostic impact of 24-hour mean blood pressure and pulse pressure on stroke and coronary artery disease in essential hypertension.

BACKGROUND: We tested the hypothesis that the steady and pulsatile components of blood pressure (BP) exert a different influence on coronary artery disease and stroke in subjects with hypertension. METHODS AND RESULTS: We analyzed data on 2311 subjects with essential hypertension. All subjects (mean age 51 years, 47% women) underwent off-therapy 24-hour ambulatory BP monitoring. Over a follow-up period of up to 14 years (mean 4.7 years), there were 132 major cardiac events (1.20 per 100 person-years) and 105 cerebrovascular events (0.90 per 100 person-years). After adjustment for age, sex, diabetes, serum cholesterol, and cigarette smoking (all P<0.01), for each 10 mm Hg increase in 24-hour pulse pressure (PP), there was an independent 35% increase in the risk of cardiac events (95% CI 17% to 55%). Twenty-four-hour mean BP was not a significant predictor of cardiac events after controlling for PP. After adjustment for age, sex, and diabetes (all P<0.05), for every 10 mm Hg increase in 24-hour mean BP, the risk of cerebrovascular events increased by 42% (95% CI 19% to 69%), and 24-hour PP did not yield significance after controlling for 24-hour mean BP. Twenty-four-hour PP was also an independent predictor of fatal cardiac events, and 24-hour mean BP was an independent predictor of fatal cerebrovascular events. CONCLUSIONS: In subjects with predominantly systolic and diastolic hypertension, ambulatory mean BP and PP exert a different predictive effect on the cardiac and cerebrovascular complications. Although PP is the dominant predictor of cardiac events, mean BP is the major independent predictor of cerebrovascular events.

Predominance of isolated systolic hypertension among middle-aged and elderly US hypertensives: analysis based on National Health and Nutrition Examination Survey (NHANES) III.

The purpose of the present study was to examine patterns of systolic and diastolic hypertension by age in the nationally representative National Health and Nutrition Examination Survey (NHANES) III and to determine when treatment and control efforts should be recommended. Percentage distribution of 3 blood pressure subtypes (isolated systolic hypertension, combined systolic/diastolic hypertension, and isolated diastolic hypertension) was categorized for uncontrolled hypertension (untreated and inadequately treated) in 2 age groups (ages <50 and >/=50 years). Overall, isolated systolic hypertension was the most frequent subtype of uncontrolled hypertension (65%). Most subjects with hypertension (74%) were >/=50 years of age, and of this untreated older group, nearly all (94%) were accurately staged by systolic blood pressure alone, in contrast to subjects in the untreated younger group, who were best staged by diastolic blood pressure. Furthermore, most subjects (80%) in the older untreated and the inadequately treated groups had isolated systolic hypertension and required a greater reduction in systolic blood pressure than in the younger groups (-13.3 and -16.5 mm Hg versus -6.8 and -6.1 mm Hg, respectively; P:=0.0001) to attain a systolic blood pressure treatment goal of <140 mm Hg. Contrary to previous perceptions, isolated systolic hypertension was the majority subtype of uncontrolled hypertension in subjects of ages 50 to 59 years, comprised 87% frequency for subjects in the sixth decade of life, and required greater reduction in systolic blood pressure in these subjects to reach treatment goal compared with subjects in the younger group. Better awareness of this middle-aged and older high-risk group and more aggressive antihypertensive therapy are necessary to address this treatment gap.

Does the relation of blood pressure to coronary heart disease risk change with aging? The Framingham Heart Study.

BACKGROUND: We examined the relative importance of diastolic (DBP), systolic (SBP) and pulse pressure (PP) as predictors of coronary heart disease (CHD) risk in different age groups of Framingham Heart Study participants. METHODS AND RESULTS: We studied 3060 men and 3479 women between 20 and 79 years of age who were free of CHD and were not on antihypertensive drug therapy at baseline. Cox regression adjusted for age, sex, and other risk factors was used to assess the relations of BP indexes to CHD risk over a 20-year follow-up. In the group <50 years of age, DBP was the strongest predictor of CHD risk (hazard ratio [HR] per 10 mm Hg increment, 1.34; 95% CI, 1.18 to 1.51) rather than SBP (HR, 1.14; 95% CI, 1.06 to 1.24) or PP (HR, 1.02; 95% CI, 0.89 to 1.17). In the group 50 to 59 years of age, risks were comparable for all 3 BP indexes. In the older age group, the strongest predictor of CHD risk was PP (HR, 1.24; 95% CI, 1.16 to 1.33). When both SBP and DBP were considered jointly, the former was directly and the latter was inversely related to CHD risk in the oldest age group CONCLUSIONS: With increasing age, there was a gradual shift from DBP to SBP and then to PP as predictors of CHD risk. In patients <50 years of age, DBP was the strongest predictor. Age 50 to 59 years was a transition period when all 3 BP indexes were comparable predictors, and from 60 years of age on, DBP was negatively related to CHD risk so that PP became superior to SBP.

Is there a preferred antihypertensive therapy for isolated systolic hypertension and reduced arterial compliance?

Isolated systolic hypertension (ISH) is the most common type of hypertension and the most difficult type to control with antihypertensive therapy. ISH, by definition, is wide pulse pressure hypertension resulting largely from excessive large artery stiffness and representing an independent risk factor for cardiovascular disease in the older aged population. Two major intervention studies of ISH have shown significant benefit in reducing systolic blood pressure with active drug therapy, including thiazide diuretics and calcium receptor antagonists. The optimal treatment strategy is to maximize reduction in systolic blood pressure and to minimize reduction in diastolic blood pressure, thereby reducing pulse pressure. All classes of antihypertensive drugs reduce pulse pressure by means of lowering peripheral resistance, but certain drugs like nitrates, angiotensin converting enzyme inhibitors, and other drugs affecting the renin-angiotensin system have multiple actions that improve large artery stiffness and early wave reflection and are especially useful in treating ISH in the elderly.

Cardiovascular risks related to increased diastolic, systolic and pulse pressure. An epidemiologist's point of view.

Since the introduction of the sphygmomanometer at the beginning to the 20th century, the significance of diastolic (DBP), Systolic (DBP) and pulse pressure (PP) as hypertensive cardiovascular risk factors has been controversial. These historical controversies are reviewed. Initially, DBP was thought to be the best measure of risk, but more recently both SBP and DBP, which ever is higher, are used in classifying hypertensive cardiovascular risk. There are problems with the present guidelines, in that SBP and DBP represent only two inflection points on the propagated pulse wave that is measured by cuff readings at the peripheral brachial artery. The heart is exposed to the central aortic pressure not to the brachial artery pressure. Moreover, both peripheral vascular resistance and large artery stiffness contribute to hypertensive cardiovascular risk. In middle-aged and elderly, elevated SBP is a better surrogate measurement of resistance than DBP, but SBP underestimates large artery stiffness. PP, the difference between peak SBP and end DBP, is the single best blood pressure surrogate for large artery stiffness. Epidemiological studies over the past decade point to SBP and DBP as the best cardiovascular risk markers for young subjects, whereas PP takes over as the more powerful risk marker for middle-aged and elderly subjects. These findings support the concept that cardiovascular events are more related to the pulsatile stress of large artery stiffness during systole than the steady-state stress of small vessel resistance during diastole. Therefore, at similar elevations of SBP, subjects with isolated systolic hypertension are at greater risk for cardiovascular events than those with combined systolic/diastolic hypertension.

Is pulse pressure useful in predicting risk for coronary heart Disease? The Framingham heart study.

BACKGROUND: Current definitions of hypertension are based on levels of systolic blood pressure (SBP) and diastolic blood pressure (DBP), but not on pulse pressure (PP). We examined whether PP adds useful information for predicting coronary heart disease (CHD) in the population-based Framingham Heart Study. METHODS AND RESULTS: We studied 1924 men and women between 50 and 79 years of age at baseline with no clinical evidence of CHD and not taking antihypertensive drug therapy. Cox regression, adjusted for age, sex, and other risk factors, was used to assess the relations between blood pressure components and CHD risk over a 20-year follow-up. The association with CHD risk was positive for SBP, DBP, and PP, considering each pressure individually; of the 3, PP yielded the largest chi(2) statistic. When SBP and DBP were jointly entered into the multivariable model, the association with CHD risk was positive for SBP (HR, 1.22; 95% CI, 1.15 to 1.30) and negative for DBP (HR, 0. 86; 95% CI, 0.75 to 0.98). Four subgroups were defined according to SBP levels (<120, 120 to 139, 140 to 159, and >/=160 mm Hg). Within each subgroup, the association with CHD risk was negative for DBP and positive for PP. A cross-classification of SBP-DBP levels confirmed these results. CONCLUSIONS: In the middle-aged and elderly, CHD risk increased with lower DBP at any level of SBP>/=120 mm Hg, suggesting that higher PP was an important component of risk. Neither SBP nor DBP was superior to PP in predicting CHD risk.

Ageing and hypertension: the assessment of blood pressure indices in predicting coronary heart disease.

OBJECTIVE: To determine whether pulse pressure (PP), diastolic blood pressure (DBP), systolic blood pressure (SBP), or mean arterial pressure (MAP) is the superior haemodynamic predictor for the risk of coronary heart disease (CHD). METHODS: Age-related changes of blood pressure in normotensive and untreated hypertensive subjects in a population-based cohort from the Framingham Heart Study were characterized. The relationship between these blood pressure indices and risk of CH D over a 20-year follow-up period were then evaluated. RESULTS: There was a parallel linear rise in SBP, DBP and MAP from age 30-49 years, suggesting increased peripheral vascular resistance (PVR) in this age group. After age 50-60 years, DBP declined, PP rose steeply, and MAP levelled off, while SBP continued to show a linear increase, suggesting increasing predominance of large artery stiffness (LAS) in this middle-aged and elderly group. After adjusting for age, sex and other risk factors, MAP and DBP consistently underestimated PVR and risk of CHD. Systolic blood pressure fully represented PVR but frequently underestimated LAS and risk of CHD. Pulse pressure was superior to SBP as a surrogate marker for LAS and predictor of CHD risk in the presence of discordantly low DBP, but PP frequently underestimated PVR. CONCLUSIONS: In middle-aged and older subjects, at any given level of SBP > or = 120 mmHg, the risk of CHD rose with discordantly lower DBP, suggesting that the wider PP was driving the risk for CHD. These results suggest that total haemodynamic load, defined as the sum of pulsatile load (LAS) and steady-state load (PVR), is a major determinant of CHD risk.

The importance of pulsatile components of hypertension in predicting carotid stenosis in older adults.

OBJECTIVE: To evaluate pulsatile components of the blood pressure as risk markers for carotid stenosis in isolated systolic hypertension. DESIGN: Duplex scans with Doppler measures of the blood flow velocity were used to diagnose carotid stenosis in 187 participants in the Systolic Hypertension in the Elderly Program and in 187 normotensive and mildly hypertensive control subjects. METHODS: The systolic blood pressure (SBP), diastolic blood pressure (DBP), pulse pressure, and mean arterial pressure (MAP) were selected as independent variables. A logistic regression model for carotid stenosis was used to adjust for potentially confounding risk factors. Serial models, each containing single or double blood pressure variables, were run to compare risk markers for carotid stenosis. Receiver operating characteristic curves were compared to assess the predictive value of each model. RESULTS: In the multivariate analysis, both the SBP (P = 0.005) and the pulse pressure (P < 0.001) were predictive of carotid stenosis, but the DBP and MAP were not. However, when either the SBP or the pulse pressure was included in the model, the DBP was associated negatively with carotid stenosis (P < 0.001 and P = 0.023, respectively). An increased pulse pressure and a decreased DBP were independent risk markers for carotid stenosis. Comparison of receiver operating characteristic curves indicated that the pulse pressure had superior predictive value to the SBP (P = 0.034). CONCLUSIONS: The pulse pressure is the single best predictor of carotid stenosis. There is a negative correlation between the DBP and carotid stenosis for subjects with isolated systolic hypertension, but this can be demonstrated only after one has stratified for the SBP or for the pulse pressure. Thus, the pulsatile components of the blood pressure, increased pulse pressure and decreased DBP, are the most sensitive risk markers for the diagnoses of carotid stenosis.

Hemodynamic patterns of age-related changes in blood pressure. The Framingham Heart Study.

BACKGROUND: We attempted to characterize age-related changes in blood pressure in both normotensive and untreated hypertensive subjects in a population-based cohort from the original Framingham Heart Study and to infer underlying hemodynamic mechanisms. METHODS AND RESULTS: A total of 2036 participants were divided into four groups according to their systolic blood pressure (SBP) at biennial examination 10, 11, or 12. After excluding subjects receiving antihypertensive drug therapy, up to 30 years of data on normotensive and untreated hypertensive subjects from biennial examinations 2 through 16 were used. Regressions of blood pressure versus age within individual subjects produced slope and curvature estimates that were compared with the use of ANOVA among the four SBP groups. There was a linear rise in SBP from age 30 through 84 years and concurrent increases in diastolic blood pressure (DBP) and mean arterial pressure (MAP); after age 50 to 60 years, DBP declined, pulse pressure (PP) rose steeply, and MAP reached an asymptote. Neither the fall in DBP nor the rise in PP was influenced significantly by removal of subsequent deaths and subjects with nonfatal myocardial infarction or heart failure. Age-related linear increases in SBP, PP, and MAP, as well as the early rise and late fall in DBP, were greatest for subjects with the highest baseline SBP; this represents a divergent rather than parallel tracking pattern. CONCLUSIONS: The late fall in DBP after age 60 years, associated with a continual rise in SBP, cannot be explained by "burned out" diastolic hypertension or by "selective survivorship" but is consistent with increased large artery stiffness. Higher SBP, left untreated, may accelerate large artery stiffness and thus perpetuate a vicious cycle.

Noninvasive tracking of coronary atherosclerosis by electron beam computed tomography: rationale and design of the Felodipine Atherosclerosis Prevention Study (FAPS).

The Felodipine Atherosclerosis Prevention Study is designed to evaluate the efficacy of the calcium antagonist felodipine ER and combined felodipine/simvastatin therapy on retarding the progression of atherosclerosis, estimated by serial changes in coronary calcium evaluated by noninvasive electron beam computed tomography. Subjects include 180 men and women aged 40 to 69 and 50 to 69 years, respectively, with moderate type IIa dyslipidemia, with either cardiovascular disease or risk factors. All subjects receive simvastatin lipid-lowering therapy, and are randomized either to felodipine or placebo for a treatment period of 2 years. Monitoring of blood chemistry, measures of lipids and apolipoproteins, blood pressure, evaluation of symptoms, and interim clinical event monitoring are done at routine follow-up visits. Baseline and 2-year follow-up electron beam computed tomography, measuring changes in total calcium score, area, and mass, evaluate the effects of intervention on the progression of calcified atherosclerosis. The results from the Felodipine Atherosclerosis Prevention Study will provide valuable information about the effect of felodipine alone and in combination with simvastatin on progression of calcified atherosclerosis evaluated noninvasively.