A comparison of the efficacy and duration of action of candesartan cilexetil and losartan as assessed by clinic and ambulatory blood pressure after a missed dose, in truly hypertensive patients : A placebo-controlled, forced titration study

The purpose of this double-blind, forced titration study was to compare the antihypertensive effect duration of candesartan cilexetil, which has a long-lasting binding to the human AT₁-receptor, to that of losartan on ambulatory BP (ABP) not only during the 24-h dosing interval but also during the day of a missed dose intake. After a 4-week placebo lead-in period, 268 patients with sitting diastolic BP 95 to 110 mm Hg and mean awake ambulatory DBP ≥85 mm Hg were randomized to receive either 8 mg of candesartan, 50 mg of losartan, or placebo for a 4-week period. Thereafter, the doses were doubled in all patients for an additional 4-week period. Ambulatory BP monitoring was performed for 36 h after dosing and clinic BP measured 48 h after dosing.

Candesartan cilexetil (16 mg) reduced ABP to a significantly greater extent than 100 mg of losartan, particularly for systolic ABP during daytime (P < .05), nighttime (P < .05), and 24-h (P < .01) periods, systolic (P < .01) and diastolic (P < .05) ABP between 0 and 36 h, and both systolic (P < .001) and diastolic (P < 0.001) ABP during the day of a missed dose. Clinic BP at 48 h after dosing was significantly reduced exclusively with 16 mg of candesartan. The differences in BP reduction between 8 mg of candesartan and 50 mg of losartan were statistically significant for systolic ABP during daytime (P < .01), nighttime (P < .05), 24-h (P < .01), 0 to 36 h (P < .05) and during the day of missed dose (P < .05). Moreover, although losartan did not significantly reduce ambulatory BP in a dose-related manner, ambulatory systolic and diastolic BP reductions with 16 mg of candesartan were significantly greater (P < .01 and < .001) than those seen with 8 mg of candesartan during every period at the ABP supporting a dose–response relationship.

In conclusion, this forced titration study in ambulatory hypertensive patients demonstrates that candesartan cilexetil provides significant dose-dependent reduction in both clinic and ambulatory BP in doses ranging from 8 to 16 mg once daily. Furthermore, candesartan cilexetil is superior to losartan in reducing systolic ABP and in controlling both systolic and diastolic ABP on the day of a missed dose. The differences observed between both agents are most likely attributable to a tighter binding to, and a slower dissociation from, the receptor binding site with candesartan cilexetil.     

Prognostic value of lipoprotein fractions in essential hypertension

Background: To evaluate distribution and prognostic value of total cholesterol and lipoprotein fractions in essential hypertension. Methods: In a prospective cohort study, 2649 initially untreated subjects with essential hypertension (aged 51, 46.5% women) were investigated at entry and followed for a mean of 5.6 years (range: 1-16). Results: At entry, subjects with total cholesterol (TC) ≥240 mg/dl (≥6.22 mmol/l) or high-density lipoprotein (HDL) cholesterol (HDL-C) 6 were 47.7%. TC, HDL-C, LDL-C and triglycerides (TG) did not show any association with office or 24-h ambulatory blood pressure (BP). During follow-up there were 167 first cardiac events and 122 first cerebrovascular events. TC, HDL-C, LDL-C and TC/HDL-C ratio showed an association with cardiac events, but not with cerebrovascular events. TG did not show any association with cardiac or cerebrovascular events. After adjustment for age, sex, diabetes, smoking, left ventricular (LV) hypertrophy and 24-h pulse pressure, the hazard ratio for cardiac events was 1.83 (95% CI 1.23-2.71) in association with a TC ≥6.22 mmol/l, 2.23 with a HDL-C 6.0 (95% CI 2.23-6.81). When forced in the same model, HDL-C and LDL-C showed an independent association with cardiac events. Conclusions: Abnormalities of TC and lipoproteins are common in essential hypertension. HDL-C and LDL-C independently predict the risk of cardiac, but not cerebrovascular, events. Their predictive value is independent of several confounding factors including LV hypertrophy and ambulatory BP.     

Decreasing population blood pressure: 15 years of follow-up in the Copenhagen City Heart Study (CCHS)

Objective: Population blood pressure (BP) levels from a longitudinal study were analysed for trends during a period of 15 years. Trends from unadjusted data are reported as well as trends adjusted for major cardiovascular (CV) risk factors and use of antihypertensive therapy, thus allowing assessment of independent BP trends. Design: The Copenhagen City Heart Study is a longitudinal epidemiological study of CV risk in a random population sample of both genders aged 20 and above. Three cross-sectional population surveys were performed: 1976-78 (n = 14000), 1981-83 (n = 12675) and 1991-94 (n = 9661). Methods: BP was measured by a London School of Hygiene Sphygmomanometer. Weight and height were measured and body mass index (BMI) calculated. Non-fasting plasma cholesterol was determined. A questionnaire concerning smoking status and diabetes was completed. Measurement methods were strictly standardized and unchanged in the three cross-sectional surveys. Results: Unadjusted systolic BP (SBP) levels decreased during 15 years of follow-up, and unadjusted diastolic BP (DBP) levels increased. An investigation of the effect of major CV risk factors, both singly and jointly on BP levels, revealed a pattern of correlations contributing to BP variability. Adjustments for BMI, cholesterol, diabetes, use of antihypertensive therapy and smoking status were made in the final analyses of BP trend. The adjusted trend model demonstrated that SBP levels remained lower than SBP levels in the first survey. DBP levels increased slightly. Conclusions: The results demonstrate a decrease in population SBP. The decrease is independent of major CV risk factors. Possible contributing factors are discussed.     

Central and peripheral hemodynamic effects of losartan and in combination with hydrochlorothiazide in mild to moderate essential hypertension

Background: Angiotensin II antagonists have proved to be effective antihypertensive agents with organoprotective properties. We aimed to clarify the effects of losartan and its combination with hydrochlorothiazide on 24-h blood pressures (BPs), central hemodynamics and microcirculation in essential hypertension (EH). Methods: Forty patients with mild to moderate EH were randomly allocated to receive losartan 50 mg (group I) or losartan 50 mg in combination with hydrochlorothiazide, 12.5 mg (group II). At baseline, week 2 and 8, ambulatory BP monitoring (ABPM), central hemodynamics monitoring and microcirculation investigation were performed. Results: In both groups, 24-h, daytime and night-time systolic (SBP) and diastolic (SBP) significantly decreased at week 8. DBP decreased more than SBP. Both drug regimens led to significant decrease in total peripheral vascular resistance; stroke and cardiac indexes remained unchanged. Losartan and its combination with hydrochlorothiazide improved main parameters of microcirculation. The index of microcirculation increased, as did the amplitude of cardiodependent and low frequency waves. Conclusions: Losartan monotherapy and losartan in combination with hydrochlorothiazide are effective antihypertensive agents. The BP-lowering effect is realized through reduction of total peripheral vascular resistance. Moreover, both drug regimens significantly improve parameters of microcirculation.     

The Use of a Single-Pill Calcium Channel Blocker/Statin Combination in the Management of Hypertension and Dyslipidemia: A Randomized, Placebo-Controlled, Multicenter Study

Poor control of hypertension or dyslipidemia may at least in part be due to these risk factors being treated in isolation. The Caduet in Untreated Subjects Population (CUSP) trial was an 8-week, randomized, double-blind, placebo-controlled trial evaluating the efficacy/safety of the combination of a calcium channel blocker (amlodipine besylate) and a statin (atorvastatin calcium) in a single-pill form (5/20 mg) plus therapeutic lifestyle changes (TLC) compared with placebo plus TLC in patients with comorbid hypertension and dyslipidemia without evidence of cardiovascular disease. At week 4, additional antihypertensive/lipid-lowering medication was permitted. The primary end point was the proportion of patients in whom the dual goal of blood pressure (<140/90 mm Hg) and low-density lipoprotein cholesterol control (<100 mg/dL) was met at week 4. This dual goal attainment was significantly greater with amlodipine/atorvastatin plus TLC compared with placebo plus TLC at week 4 (47.6% vs 1.7%; P <.001), with further improvements at week 8. Most adverse events were mild to moderate. Therapy with single-pill amlodipine/atorvastatin plus TLC in these patients significantly increased dual blood pressure/low-density lipoprotein cholesterol goal attainment compared with placebo plus TLC.     

Effect of combination therapy of benidipine hydrochloride and candesartan cilexetil on serum lipid metabolism and blood pressure in elderly hypertensive patients with type 2 diabetes mellitus

The effects of combination therapy of angiotensin II receptor blockers (ARBs) and a calcium antagonist, benidipine hydrochloride, on glucose and lipid metabolism and pulse pressure were studied in elderly hypertensive patients with type 2 diabetes mellitus. Twenty-five hypertensive diabetic patients aged 65 years or older, who had been receiving candesartan cilexetil, were administered benidipine hydrochloride (4 mg/day) and followed for 4 months. After 4 months, systolic and diastolic blood pressure decreased significantly from 154/91 mmHg to 139/78 mmHg (p<0.01 versus before benidipine hydrochloride administration). Body mass index (BMI) and glycosylated hemoglobin (HbA1c) were apparently reduced but the changes were not statistically significant. The serum lipid profile showed no significant changes in serum total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C). Serum lipoprotein lipase mass levels (preheparin LPL mass) increased significantly from 51 to 59 ng/dl (p<0.01 versus before benidipine hydrochloride administration), and the LDL/HDL motility ratio calculated from PAG disc electrophoresis decreased significantly (p<0.05 versus before benidipine hydrochloride administration). When patients were divided into a systolic hypertension group (systolic blood pressure > or =140 mmHg and diastolic blood pressure <90 mmHg) and non-systolic hypertension group (others), preheparin LPL mass was significantly lower in the systolic hypertension group, and the decrease in pulse pressure and increase in preheparin LPL mass were significantly greater in the systolic hypertension group. Stepwise regression analysis showed that low preheparin LPL mass at baseline was associated with a decrease in pulse pressure. Add-on benidipine hydrochloride therapy in elderly hypertensive patients with type 2 diabetes mellitus significantly decreases the LDL/HDL motility ratio and pulse pressure, and significantly increases preheparin LPL mass, in addition to improving blood pressure control. These findings suggest that combination therapy with benidipine hydrochloride and candesartan cilexetil may contribute to the suppression of arteriosclerosis and may be useful for elderly hypertensive patients with diabetes mellitus.     

Regression of left ventricular hypertrophy by AT1 receptor blockade in renal transplant recipients

AT₁ receptor antagonists control blood pressure (BP) effectively and reduce left ventricular hypertrophy in patients with essential hypertension. Because left ventricular hypertrophy is very common in renal transplant recipients, we examined the cardiovascular effects and the safety profile of the AT₁ receptor antagonist losartan in hypertensive renal transplant recipients. In 20 renal transplant recipients with stable renal graft function 50 mg of losartan was added to the preexisting antihypertensive treatment (no angiotensin-converting enzyme inhibitors) at least 6 months after renal transplantation. Twenty-four–hour ambulatory BP, two-dimensional-guided M-mode echocardiography, and duplex sonography, as well as renal function, red blood cell count, cyclosporine A and FK 506 levels, erythropoetin, and angiotensin II concentration were determined at baseline and after 6 months of therapy. With 24-h ambulatory BP measurement, systolic blood pressure (SBP) was reduced by 7.5 ± 2.4 mm Hg and diastolic blood pressure (DBP) by 4.5 ± 1.8 mm Hg (P < .01 and P < .05, respectively). Posterior, septal, and relative wall thickness decreased by 0.95 ± 0.2 mm, 0.91 ± 0.2 mm and 0.04 ± 0.01 mm, respectively (all P < .001). Left ventricular mass index decreased by 18.1 ± 4.7 g/m² (P < .01). Ejection fraction and midwall fractional fiber shortening as systolic parameters and the relation of passive-to-active diastolic filling of the left ventricle were unaltered. Serum creatinine and cyclosporine A concentration remained stable in all patients. Hemoglobin and hematocrit decreased by 1.0 ± 0.3 g/dL and 3.6% ± 0.9%, respectively (P < .002 and P < .001) without a change in serum erythropoetin level. In renal transplant recipients the AT₁ receptor antagonist losartan reduces left ventricular hypertrophy without altering systolic or diastolic function. It is safe with regard to renal function and immunosuppression, but slightly decreases hemoglobin level.     

The effects of terazosin and methyclothiazide on blood pressure and serum lipids

This study compared the antihypertensive efficacy and the effects on serum lipids of terazosin, a new selective alpha 1-adrenergic antagonist, of methyclothiazide (MCTZ), and of the two drugs used as combination therapy. Adult patients with supine diastolic blood pressure ranging from 95 to 120 mm Hg were eligible to enter this double-blind, randomized, parallel-group study. Analyses of the blood pressure data from the 194 evaluable patients revealed that all three treatments produced significant (p less than 0.001) reductions in supine and standing systolic and diastolic blood pressures from baseline values. Moreover, combination therapy resulted in significantly greater mean blood pressure reductions than were observed with either drug used as monotherapy. In the group receiving terazosin monotherapy, the total serum cholesterol level, low-density lipoprotein plus very-low-density lipoprotein cholesterol fraction, and triglyceride level fell significantly (median changes of 3.7%, 5.0%, and 16.3%, respectively, p less than 0.05). However, in the group receiving MCTZ monotherapy, the total serum cholesterol level, low-density lipoprotein plus very-low-density lipoprotein cholesterol fraction, and triglyceride level increased significantly (4.7%, 7.1%, and 12.5%, respectively, p less than 0.001). In contrast, no significant changes from baseline values were observed for any lipid variable in the group receiving terazosin/MCTZ combination therapy. We conclude that terazosin is effective antihypertensive therapy that has a potentially beneficial effect on the serum lipid profile when used as monotherapy and that it counteracts the negative impact of MCTZ monotherapy on the serum lipid profile when used concurrently with this thiazide diuretic.     

Relationship between alcohol consumption, ambulatory blood pressure recordings and left ventricular mass

The relationship between alcohol consumption, blood pressure and left ventricular mass remains uncertain. A detailed alcohol intake history, clinic blood pressure measurements, 24-h ambulatory blood pressure recordings and measurements of left ventricular mass using magnetic resonance imaging (MRI) were performed in 98 males aged 47.9 ± 9.7 years, 20 of whom were receiving antihypertensive monotherapy. Alcohol consumption (median intake 315 g/week, range 0-2050) was significantly related to supine systolic clinic blood pressures (β = 0.20, p = 0.05) but not to clinic supine diastolic blood pressures (β = 0.12, p = 0.25), 24-h blood pressures (systolic: β = -0.03, p = 0.75; diastolic β = -0.05, p = 0.60), awake blood pressures or sleeping blood pressures. Alcohol consumption was not related to left ventricular mass index (β = -0.05, p = 0.59). Left ventricular mass was strongly related to mean 24-h systolic blood pressures (β = 0.28, p = 0.01), mean awake and sleeping systolic blood pressures, and less strongly to clinic systolic blood pressures (β = 0.23, p = 0.03). These results were not significantly altered by adjusting for age, smoking, body mass index or alcohol intake, or by excluding the 20 men who were receiving antihypertensive therapy. The results of this study suggest that alcohol consumption at levels commonly encountered in the community is not an important predictor of left ventricular mass index in men, either via direct effects or by indirect effects on blood pressure.     

Comparison of the efficacy and safety of azilsartan with that of candesartan cilexetil in Japanese patients with grade I-II essential hypertension: a randomized, double-blind clinical study

Azilsartan is a novel angiotensin receptor blocker being developed for hypertension treatment. This 16-week, multicenter, randomized, double-blind study compared the efficacy and safety of azilsartan (20-40 mg once daily by forced titration) and its ability to provide 24-h blood pressure (BP) control, with that of candesartan cilexetil (candesartan; 8-12 mg once daily by forced titration) in 622 Japanese patients with grade I-II essential hypertension. Efficacy was evaluated by clinic-measured sitting BP, and by ambulatory BP monitoring (ABPM) at week 14. Participants (mean age: 57 years, 61% males) had a mean baseline sitting BP of 159.8/100.4 mm Hg. The mean change from baseline in sitting diastolic BP at week 16 (primary endpoint) was -12.4 mm Hg in the azilsartan group and -9.8 mm Hg in the candesartan group, demonstrating a statistically significant greater reduction with azilsartan vs. candesartan (difference: -2.6 mm Hg, 95% confidence interval (CI): -4.08 to -1.22 mm Hg, P=0.0003). The week 16 (secondary endpoint) mean change from baseline in sitting systolic BP was -21.8 mm Hg and -17.5 mm Hg, respectively, a significant decrease with azilsartan vs. candesartan (difference: -4.4 mm Hg, 95% CI: -6.53 to -2.20 mm Hg, P<0.0001). On ABPM, the week 14 mean changes from baseline in diastolic and systolic BP were also significantly greater with azilsartan over a 24-h period, and during the daytime, night-time and early morning. Safety and tolerability were similar among the two groups. These data demonstrate that once-daily azilsartan provides a more potent 24-h sustained antihypertensive effect than that of candesartan but with equivalent safety.     

Comparative effects of candesartan cilexetil and amlodipine in patients with mild systemic hypertension. Comparison of Candesartan and Amlodipine for Safety, Tolerability and Efficacy (CASTLE) Study Investigators

The comparative antihypertensive efficacy and tolerability of the angiotensin II receptor blocker candesartan cilexetil and the calcium channel blocker amlodipine were evaluated in an 8-week, multicenter, double-blind, randomized, parallel-group, forced-titration study in 251 adult patients (45% women, 16% black) with mild hypertension (stage 1). Following a 4- to 5-week placebo run-in period, patients with sitting diastolic blood pressure (BP) of 90 to 99 mm Hg received candesartan cilexetil 16 mg (n = 123) or amlodipine 5 mg (n = 128) once daily. After 4 weeks of double-blind treatment, patients were uptitrated to candesartan cilexetil 32 mg or amlodipine 10 mg once daily. There were no significant differences between the candesartan cilexetil and amlodipine regimens for reducing BP; mean systolic BP/diastolic BP reductions were -15.2/-10.2 mm Hg versus -15.4/-11.3 mm Hg, respectively (p = 0.88/0.25). Overall, 79% of patients on candesartan cilexetil and 87% of those on amlodipine were controlled (diastolic BP <90 mm Hg). A total of 3.3% of patients on candesartan cilexetil discontinued treatment, compared with 9.4% of patients on amlodipine, including 2.4% versus 4.7% for adverse events and 0% versus 1.6% for peripheral edema, respectively. Peripheral edema, the prespecified primary tolerability end point, occurred with significantly greater frequency in patients on amlodipine (22.1%; mild 8.7%, moderate 11.8%, severe 1.6%) versus patients on candesartan cilexetil (8.9%; mild 8.1%, moderate 0.8%) (p = 0.005). Candesartan cilexetil and amlodipine are both highly effective in controlling BP in patients with mild hypertension. Candesartan cilexetil offers a significant tolerability advantage with respect to less risk of developing peripheral edema.     

Cardiovascular events in elderly patients with isolated systolic hypertension. A subgroup analysis of treatment strategies in STOP-Hypertension-2

Objective: To perform a subgroup analysis on those patients in STOP-Hypertension-2 who had isolated systolic hypertension. Design and methods: The STOP-Hypertension-2 study evaluated cardiovascular mortality and morbidity in elderly hypertensives comparing treatment with conventional drugs (diuretics, beta-blockers) with that of newer ones [angiotensin-converting enzyme (ACE) inhibitors, calcium antagonists]. In all, 6614 elderly patients with hypertension (mean age 76.0 years, range 70-84 years at baseline) were included in STOP-Hypertension-2. In the present subgroup analysis of STOP-Hypertension-2, isolated systolic hypertension was defined as systolic blood pressure at least 160 mmHg and diastolic blood pressure below 95 mmHg, in accordance with the Syst-Eur and Syst-China study criteria. In total, 2280 patients in STOP-Hypertension-2 met these criteria. In the study, patients were randomized to one of three treatment groups: “conventional” antihypertensive therapy with beta-blockers or diuretics (atenolol 50 mg, metoprolol 100 mg, pindolol 5 mg, or fixed-ratio hydrochlorothiazide 25 mg plus amiloride 2.5 mg daily); ACE inhibitors (enalapril 10 mg or lisinopril 10 mg daily); or calcium antagonists (felodipine 2.5 mg or isradipine 2.5 mg daily). Analysis was by intention to treat. Results: The blood pressure lowering effect in patients with systolic hypertension was similar with all three therapeutic regimens: 35/13 mmHg in the conventional group (n = 717), 34/12 mmHg in the ACE inhibitor group (n = 724), and 35/13 mmHg in the calcium antagonist group (n = 708). Prevention of cardiovascular mortality, the primary endpoint of the study, did not differ between the three treatment groups. All stroke events, i.e. fatal and non-fatal stroke together, were significantly reduced by 25% in the newer-drugs group compared with the conventional group (95% CI 0.58-0.97; p = 0.027). This difference was attributable to reduction of non-fatal stroke while fatal stroke events did not differ between groups. New cases of atrial fibrillation were significantly increased by 43% (95% CI 1.02-1.99; p = 0.037) on “newer” drugs compared with “conventional” therapy, mainly attributable to the calcium antagonists. There were no significant differences between the three treatment groups with respect to the risks of myocardial infarction, sudden death or congestive heart failure. Conclusions: The analysis demonstrated that “newer” therapy (ACE inhibitors/calcium antagonists) was significantly better (25%) than “conventional” (diuretics/beta-blockers) in preventing all stroke in elderly patients with isolated systolic hypertension.     

Accuracy of a new wrist cuff oscillometric blood pressure device: Comparisons with intraarterial and mercury manometer measurements

Accurate measurement of arterial blood pressure is of great importance for the diagnosis and treatment of hypertension. Because of the chronic nature of antihypertensive drug therapy, the involvement of the patient in blood pressure control is desirable. Such an involvement, however, is only feasible if simple, user-friendly, and precise blood pressure measurement devices are available.

In this study we tested a new wrist cuff oscillometric blood pressure measurement device in 100 consecutive patients undergoing cardiac catheterization. Blood pressures were simultaneously taken intraarterially (axillary artery) and with a mercury manometer and stethoscope or noninvasive measurement device (OMRON R3). Intraarterial measurements were directly compared with two measurements taken in random order with either an arm cuff mercury manometer or the wrist cuff device.

Systolic and diastolic blood pressure as assessed with the mercury manometer was higher, especially when compared with the intraarterial and the wrist cuff values, which were comparable. Correlations of blood pressure values with intraarterial measurement were 0.86 systolic and 0.75 diastolic (P < .01) for the wrist cuff and 0.84 systolic (P < .01) and 0.59 diastolic (P < .05) for the mercury manometer measurements. Reproducibility of both measurements was good for the wrist cuff device ([systolic/diastolic]: r = 0.94/0.92; P < .01) and the mercury manometer (r = 0.97/0.88; P < .01). Both methods overestimated high diastolic values, whereas only the wrist cuff underestimated high systolic values.

Thus, the new oscillometric wrist cuff blood pressure measurement device measures arterial blood pressure with great accuracy and reproducibility. As compared with intraarterial values, the wrist cuff device overestimated high diastolic and underestimated high systolic blood pressure values. Blood pressure values as measured by the mercury manometer were higher than intraarterial values and those of the wrist cuff. Both noninvasive devices overestimated high diastolic values.     

Relationship of change in traditional cardiometabolic risk factors to change in coronary artery calcification among individuals with detectable subclinical atherosclerosis: The multi-ethnic study of atherosclerosis

Background/Objectives

Data describing relationships between change in risk factors and coronary artery calcification (CAC) are lacking and could inform optimal cardiovascular disease prevention and treatment strategies. This study aimed to examine how change in traditional cardiometabolic risk factors related to change in CAC among individuals with detectable subclinical atherosclerosis.

Methods

Latent growth modeling was used to examine change in cardiometabolic risk factors (waist circumference, body mass index, systolic and diastolic blood pressure, high- and low-density lipoprotein cholesterol, triglycerides, and glucose) related to change in CAC up to an average 4.9-year follow-up in a multi-ethnic cohort of 3398 asymptomatic individuals (57.8% men) who had detectable CAC (score > 0) at baseline, adjusting for baseline risk factor levels and CAC values, age, gender, race/ethnicity, smoking, family history of CVD, income, and use of antihypertensive, lipid-lowering, and glucose-lowering medications.

Results

Greater declines in blood pressure (systolic and diastolic) and low-density lipoprotein cholesterol at follow-up were each associated with greater CAC progression. The observed inverse associations were attributable to greater CAC progression in participants taking antihypertensive and lipid-lowering drugs who, as expected, had declines in blood pressure and lipid levels, respectively. These inverse associations did not emerge in participants not taking these medications.

Conclusions

Among individuals with subclinical atherosclerosis, the unexpected inverse associations observed between change in blood pressure and lipid levels with CAC progression emphasize the importance of considering medication use, and, when feasible, the severity and duration of disease, in exploring associations between risk factors and CAC change.     

Findings and implications of the Study on COgnition and Prognosis in the Elderly (SCOPE) - a review

The Study on Cognition and Prognosis in the Elderly (SCOPE) assessed the effect of candesartan on cardiovascular and cognitive outcomes in elderly patients (aged 70-89 years) with mild to moderate hypertension. Patients were randomized to treatment with candesartan 8-16 mg daily (n = 2477) or placebo (n = 2460) and followed for 3.7 years on average. In agreement with the study protocol, other antihypertensive drugs were added if blood pressure remained ≥160 mHg systolic and/or ≥90 mmHg diastolic. Due to extensive add-on therapy, particularly in patients randomized to placebo, the between-treatment difference in blood pressure was only 3.2/1.6 mmHg. Nevertheless, the main analysis showed that non-fatal stroke was reduced by 28% (p = 0.04) in the candesartan group compared with the control group, and there was a non-significant 11% reduction in the primary endpoint, major cardiovascular events (p = 0.19). This review article presents different predefined and post hoc analyses made so far. Of particular interest are significant risk reductions with candesartan in major cardiovascular events (32%, p = 0.013), cardiovascular mortality (29%, p = 0.049) and total mortality (27%, p = 0.018) in patients who did not receive add-on therapy after randomization, and in whom the difference in blood pressure was 4.7/2.6 mmHg. Other analyses suggest positive effects of candesartan-based treatment on cognitive function, quality of life and new-onset diabetes. In conclusion, SCOPE strongly suggests that candesartan treatment reduces cardiovascular morbidity and mortality in old and very old patients with mild to moderate hypertension. Candesartan-based antihypertensive treatment may also have positive effects on cognitive function and quality of life.     

The predictive power of low-density lipoprotein cholesterol for coronary calcification

Background: Chronic elevation of low-density lipoprotein cholesterol is a major risk factor for developing atherosclerosis. The purpose of this study was to examine the correlation and predictive power of low-density lipoprotein cholesterol for calcified atheromatous disease as measured by electron beam computed tomography. Methods: Six-thousand and ninety-three subjects underwent electron beam computed tomography of their coronary arteries, serum lipid testing, body fat determination and assessment of health status by questionnaire. Predictive power of low-density lipoprotein cholesterol for calcified atherosclerotic plaque was determined by correlations and multivariate logistic regression. Results: The correlation between low-density lipoprotein cholesterol and calcified plaque score was very modest (r=0.055, P<0.001). There was a trend toward increasing calcified plaque with increasing levels of low-density lipoprotein cholesterol. Multivariate logistic regression revealed that low-density lipoprotein cholesterol is a modest but significant predictor of calcified coronary plaque. After adjusting for age, gender and high-density lipoprotein cholesterol, the risk of having any calcified plaque was 1.05-times higher for each 10 mg/dl increase in low-density lipoprotein cholesterol (P<0.001). Individuals with a low-density lipoprotein cholesterol level above 160 mg/dl had a 62% increase in odds for the presence of calcified plaque. Conclusions: Low-density lipoprotein cholesterol is weakly correlated with and predictive of calcified atherosclerotic plaque burden as measured by electron beam computed tomography. Higher levels of low-density lipoprotein cholesterol are associated with increased risk for the presence of calcified atheromas.     

Indapamide. Effects on apoprotein, lipoprotein, and glucoregulation in ambulatory diabetic patients

We evaluated the long-term effects of indapamide, a non-thiazide diuretic, on blood pressure, glucoregulation, free insulin and C-peptide levels, and lipoprotein and apoprotein metabolism in 13 hypertensive diabetic patients for 24 weeks. Indapamide significantly reduced both systolic and diastolic blood pressure by 15% and 17%, respectively. Both mean fasting serum glucose and integrated glucose responses after oral glucose load (75 g) were significantly higher during indapamide therapy than at week 0. The mean fasting and stimulated C-peptide responses were significantly increased despite worsening glucose control. At the end of 24 weeks, mean glycosylated hemoglobin level had increased significantly. Indapamide caused a slight but insignificant rise in the total triglyceride, cholesterol, and low-density lipoprotein cholesterol levels, while the high-density lipoprotein cholesterol level decreased. In addition, the apoprotein A-1 concentrations remained unchanged while the apoprotein B-100 level decreased. Apart from hypokalemia (less than 3.5 mEq/L [less than 3.5 mmol/L]) in three patients that required oral potassium supplementation, biochemical changes were of no clinical consequence.     

Single- or double-blind treatment With Balsamodendron mukul and nifedipine in hypertensive patients

This study assessed and compared the effects of Balsamodendron mukul (an extract of the gum of a small tree) and nifedipine (a calcium-channel-blocking reference drug) on blood pressure, lipids, lipoproteins, and phospholipids in randomly selected patients with essential hypertension. Fifty-seven newly diagnosed hypertensive patients were randomly divided into three groups. They received either single-blind B. mukul (1.5 g/d) or single-blind nifedipine (10 mg/d) double-blind therapy with nifedipine (10 mg/d) and B. mukul (1.5 g/d) for 6 weeks. These groups were compared with control subjects. On treatment with B. mukul, levels of systolic blood pressure, diastolic blood pressure, plasma total cholesterol, low-density lipoprotein cholesterol, very low-density lipoprotein cholesterol, triglycerides, free fatty acids, and phospholipid levels were significantly reduced, and high-density lipoprotein cholesterol levels were significantly elevated, as compared with untreated hypertensive patients. Combined therapy with B. mukul and nifedipine was more beneficial than the treatment with B. mukul alone. Our study suggests that B. mukul may be an effective antihypertensive and hypolipidemic agent.     

Characteristics and lipid distribution of a large, high-risk, hypertensive population: the lipid-lowering component of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT)

The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) consisted of 42,418 participants randomized to one of four antihypertensive treatment groups: chlorthalidone, amlodipine, lisinopril, or doxazosin. A subset of these participants with fasting low-density lipoprotein cholesterol levels 100–189 mg/dL were randomized into a lipid-lowering component: 5170 to receive pravastatin (40 mg daily) and 5185 to receive usual care. This report describes the characteristics and lipid distribution of these participants. There were no important differences between the randomized treatment groups. Women had higher total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol than men. There was a similar finding for black participants compared with whites, except blacks had lower triglycerides. Diabetics had lower high-density lipoprotein cholesterol and higher triglycerides than nondiabetics, and patients with body mass index <25 kg/m² had higher high-density lipoprotein cholesterol but lower low-density lipoprotein cholesterol and triglycerides than patients with higher body mass index. The success of the randomization of this large, diverse population and the differences in the lipid distributions among its subgroups will allow further understanding of optimal lipid-lowering treatment.