Blood pressure reduction and renin-angiotensin system inhibition for prevention of congestive heart failure: a meta-analysis.

AIMS: It is unclear whether prevention of congestive heart failure (CHF) by drugs that inhibit the renin-angiotensin system (RAS) occurs over and beyond the reduction in blood pressure (BP) achieved by these drugs. METHODS AND RESULTS: We conducted a meta-analysis of trials comparing angiotensin-converting enzyme inhibitors (ACEIs), angiotensin-receptor blockers (ARBs), or calcium-channel blockers (CCBs), with diuretics, beta-blockers, or placebo in hypertensive or high-risk subjects without CHF at entry. Both fixed- and random-effect models were used. In trials vs. placebo, the risk of CHF was reduced by 21% with ACEIs (P = 0.007), whereas the effect of ARBs and CCBs was not significant (random-effect models). Thus, CCBs did not increase the risk of CHF. In trials vs. diuretics/beta-blockers, no differences were found between ACEIs and comparators [odds ratio (OR) 1.02; 95% confidence interval (CI) 0.84-1.24], whereas CCBs were associated with an 18% higher risk of CHF (OR 1.18; 95% CI 1.00-1.39; P = 0.048). Therefore, ACEIs were not superior to diuretics/beta-blockers for the prevention of CHF. Because heterogeneity between trials was significant, we investigated potential sources of heterogeneity by meta-regression. The risk of CHF decreased by 24% (P < 0.001) for each 5 mmHg reduction in systolic BP. The risk of CHF was 19% less with ACEIs/ARBs than CCBs (P < 0.001) and 16% less in studies without multiple risk factors required for entry (P = 0.009). CONCLUSION: BP reduction is beneficial for the prevention of CHF. Over and beyond BP reduction, the protective effect of ACEIs and ARBs is greater than that of CCBs.

Echocardiographic left ventricular hypertrophy in hypertension: marker for future events or mediator of events?

PURPOSE OF REVIEW: To discuss the most relevant studies on the prognostic impact of echocardiographic left ventricular hypertrophy in hypertension. RECENT FINDINGS: There is abundant evidence from epidemiological studies that increased left ventricular mass identifies hypertensive patients at increased risk of major cardiac and cerebrovascular events. Looking at the geometric patterns of the left ventricle, concentric remodelling and concentric left ventricular hypertrophy carry the highest risk for adverse events. Patients with left ventricular hypertrophy reversal as an effect of treatment are exposed to a lesser risk of events as compared with patients with persistence of left ventricular hypertrophy. Reversal of concentric remodelling predicts a lesser risk of adverse events compared with persistence of remodelling. Experimental evidence is accumulating that several haemodynamic and nonhaemodynamic factors which are able to promote progression of atherosclerosis through plaque growth and destabilization may also induce left ventricular hypertrophy by acting on myocyte and interstitium. Increased left ventricular mass may also be a causative factor for reduced pumping performance and arrhythmias. SUMMARY: Increased left ventricular mass is a marker of cardiovascular risk because it reflects and integrates the long-term level of activity of factors inducing progression of atherosclerosis. Increased left ventricular mass may also mediate myocardial ischaemia with potential evolution towards heart failure and arrhythmias.

Impact of blood pressure variability on cardiac and cerebrovascular complications in hypertension.

BACKGROUND: The independent prognostic value of daytime and night-time blood pressure (BP) variability estimated by noninvasive 24-h BP monitoring is unclear. METHODS: We followed 2649 initially untreated subjects with essential hypertension for up to 16 years (mean, 6). Variability of BP was estimated by the standard deviation of daytime or night-time systolic BP (SBP) and diastolic BP (DBP). A BP variability either less than or equal to the group median or greater than the group median (12.7/10.4 mm Hg for daytime SBP/DBP and 10.8 and 8.9 mm Hg for night-time SBP/DBP) identified subjects at low or high BP variability. RESULTS: During follow-up there were 167 new cardiac and 122 new cerebrovascular events. The rate of cardiac events (x100 person-years) was higher (all P < .05) in the subjects with high than in those with low BP variability (daytime SBP: 1.45 v 0.72, daytime DBP: 1.29 v 0.91; night-time SBP: 1.58 v 0.62; night-time DBP: 1.32 v 0.85). The rate of cerebrovascular events was also higher (all P < .05) in the subjects with high than in those with low BP variability. In a multivariate analysis, after adjustment for several confounders, a high night-time SBP variability was associated with a 51% (P = .024) excess risk of cardiac events. The relation of daytime BP variability to cardiac events and that of daytime and night-time BP variability to cerebrovascular events lost significance in the multivariate analysis. CONCLUSIONS: An enhanced variability in SBP during the night-time is an independent predictor of cardiac events in initially untreated hypertensive subjects.

Ambulatory blood pressure and cardiovascular outcome in relation to perceived sleep deprivation.

Sleep deprivation induced by cuff inflations during overnight blood pressure (BP) monitoring might interfere with the prognostic significance of nighttime BP. In 2934 initially untreated hypertensive subjects, we assessed the perceived quantity of sleep during overnight BP monitoring. Overall, 58.7%, 27.7%, 9.7%, and 4.0% of subjects reported a sleep duration perceived as usual (group A), <2 hours less than usual (group B), 2 to 4 hours less than usual (group C), and >4 hours less than usual (group D). Daytime BP did not differ across the groups (all Ps not significant). Nighttime BP increased from group A to D (124/75, 126/76, 128/77, and 129/79 mm Hg, respectively; all Ps for trend <0.01). Over a median follow-up period of 7 years there were 356 major cardiovascular events and 176 all-cause deaths. Incidence of total cardiovascular events and deaths was higher in the subjects with a night/day ratio in systolic BP >10% compared with those with a greater day-night BP drop in the group with perceived sleep duration as usual or <2 hours less than usual (both P<0.01), not in the group with duration of sleep >or=2 hours less than usual (all Ps not significant). In a Cox model, the independent prognostic value of nighttime BP for total cardiovascular end points and all-cause mortality disappeared in the subjects with perceived sleep deprivation >or=2 hours. In conclusion, nighttime BP rises and loses its prognostic significance in the hypertensive subjects who perceive a sleep deprivation by >or=2 hours during overnight monitoring.

The clinical significance of white-coat and masked hypertension.

OBJECTIVE: Self-measured blood pressure (BP) and 24-hour ambulatory blood pressure (ABP) monitoring are used to define the arbitrary clinical categories of masked hypertension (MH) and white-coat hypertension (WCH). Severity of target organ damage and incidence of major cardiovascular events are greater in patients with MH than in patients whose BP is normal both inside and outside the doctor's office. METHODS: We reviewed studies that addressed the prognostic impact of MH and WCH. RESULTS: Overall, WCH was associated with a better outcome and MH to a poor outcome. We, however, need the criteria to identify the clinically normotensive patients at elevated pretest probability of MH in whom a broad use of self-measured home BP and 24-hour ambulatory BP as screening tests may be appropriate and cost effective. Clinical management of patients with MH should continue to be based on current guidelines and mostly related to target organ damage and associated clinical conditions because of the normal values of clinic BP in these patients. WCH is generally defined by the coexistence of persistently high office BP with normal daytime or 24-hour ABP. Daytime ABP normalcy has been defined by values<135/85 mmHg. Data, however, suggest that incidence of cardiovascular events tends to increase consistently above the cut-off value of 130/80 mmHg for daytime BP. CONCLUSION: The long-term outcome of patients with WCH remains uncertain. Data suggesting an increased risk of stroke need to be confirmed in wide-scale studies.

Validation of the A&D wrist-cuff UB-511 (UB-512) device for self-measurement of blood pressure.

OBJECTIVES: To determine the accuracy of the A&D UB-511 (UB-512) oscillometric wrist-cuff device for self-measurement of blood pressure, the only difference between the two devices being the size of storage memory. METHODS: Device evaluation was performed according to the modified British Hypertension Society protocol released in 1993. Eighty-five study participants with characteristics outlined in the British Hypertension Society protocol were recruited among those attending our out-patient clinic. The device was evaluated according to the various steps of the protocol. The non-dominant arm was used for blood pressure measurement. To maintain the wrist at cardiac level during validation, the arm was kept horizontal at the mid-sternum level and supported by a soft table. The wrist was kept extended. Sequential readings were taken for the main validation test. Outcome was classified according to the criteria of the British Hypertension Society recommendations, which are based on four strata of accuracy differing from the mercury standard by 5, 10 and 15 mmHg, or more. RESULTS: The device achieved a British Hypertension Society grade B for systolic and a grade B for diastolic blood pressure. The device tended to overestimate arm blood pressure, the mean difference (+/-1 SD) between device and observers being 4.3+/-8.7 mmHg for systolic blood pressure and 3.7+/-8.1 mmHg for diastolic blood pressure for observer 2, and 4.4+/-8.6 mmHg for systolic blood pressure and 3.8+/-7.9 mmHg for diastolic blood pressure for observer 1. In a logistic regression analysis, age was the sole predictor of an achieved difference between device and mercury column by 5 mmHg or less (hazard ratio 1.020; 95% confidence interval 1.003-1.04; P=0.024). CONCLUSIONS: These data show that the A&D UB-511 (UB-512) device satisfies the British Hypertension Society recommendations with a grade B/B. The device tends to overestimate cuff blood pressure and its accuracy increases with age.

Day-to-day variability of electrocardiographic diagnosis of left ventricular hypertrophy in hypertensive patients. Influence of electrode placement.

OBJECTIVE: Although electrocardiography (ECG) is recommended in all subjects with hypertension, no information is available on the influence exerted by random changes in the placement of electrodes on the day-to-day variability of ECG criteria for diagnosis of left ventricular hypertrophy (LVH). METHODS: In a multicentre, randomized study, two standard 12-lead ECG were recorded, 24 h apart, from 276 consecutive hypertensive patients (mean age 65 +/- 12 years, 49.6% men). Overall, 142 patients were randomized to ECG with the position of electrodes marked on the skin using a dermographic pen and 134 to traditional ECG without marking the position of electrodes. Day-to-day variability of ECG criteria for LVH was compared between the two groups. RESULTS: Coefficients of variation (SD of the difference between paired voltage measurements divided by the mean value) varied consistently among subjects randomized to ECG without dermographic pen, ranging from 30% (R wave in lead I) to 81% (R wave in lead V5). Dermographic pen led to a lesser variability of ECG voltages with consequent reduction in the coefficients of variation, which ranged from 26% (R-wave amplitude in lead I) to 43% (R-wave amplitude in lead V5). The proportion of subjects who changed classification status for LVH ('reclassification rate') from the first to the second ECG session (LVH present in session 1 and absent in session 2, or vice versa) decreased for effect of dermographic pen from 11 to 4% (P = 0.040) with the Cornell voltage, from 19 to 11% (P = 0.029) with the Sokolow-Lyon voltage, and from 18 to 7% with the Romhilt-Estes criterion (P = 0.018), but not with other criteria. In particular, the typical strain and the Cornell strain were associated with the lowest reclassification rates regardless of dermographic pen. CONCLUSIONS: Random changes in the position of ECG electrodes strongly impair the day-to-day reproducibility of Cornell voltage, Sokolow-Lyon and Romhilt-Estes criteria for LVH. The typical strain and Cornell strain criteria showed a lesser spontaneous day-to-day variability.

Validation of the A&D UA-705 device for self-measurement of blood pressure according to the British Hypertension Society protocol.

OBJECTIVES: We tested the accuracy of the UA-705 blood pressure semi-automatic monitor. METHODS: Device evaluation was performed according to the modified British Hypertension Society protocol released in 1993. Eighty-five patients with characteristics outlined in the British Hypertension Society protocol were recruited among those attending our out-patient clinic. Sequential readings were taken for the main validation test. Outcome was classified according to the British Hypertension Society criteria, which are based on four zones of accuracy differing from the mercury standard by 5, 10 and 15 mmHg, or more. RESULTS: The mean blood pressure difference (+ or -1 SD) between device and observers was 0.4 mmHg (SD 7.7) for systolic blood pressure and 0.3 mmHg (SD 8.2) for diastolic blood pressure. Overall, 96% (observer 1) and 95% (observer 2) of readings between device and observers differed by 15 mmHg or less for both systolic and diastolic blood pressure. The device achieved a grade A for both systolic and diastolic blood pressure. CONCLUSIONS: This study shows that the A&D UA-705 device satisfies the British Hypertension Society standard for accuracy by achieving a grade A for both systolic and diastolic blood pressure.

Regression of left ventricular hypertrophy and prevention of stroke in hypertensive subjects.

BACKGROUND: Left ventricular hypertrophy (LVH) is a risk marker for stroke and its regression confers protection from stroke. The relationship between serial LVH changes and risk of stroke has never been investigated in a mixed population of hypertensive subjects with and without LVH. METHODS: In this study, 880 initially untreated hypertensive subjects (mean age 48 years, office blood pressure (BP) 155/98 mm Hg; 24-h BP 137/87 mm Hg) underwent tests including echocardiography and 24-h ambulatory BP monitoring at entry and after a median of 3.5 years, still in the absence of cardiovascular events. RESULTS: Months or years after the follow-up study, 34 of these subjects developed a first cerebrovascular event (stroke in 21, transient ischemic attack in 13). Event rate (x 100 patients per year) was 0.25 among the subjects who never developed echocardiographic LVH or with regression of LVH, versus 1.16 among the subjects with lack of regression or new development of LVH (log-rank test: P = .00001). Serial electrocardiogram (ECG) changes failed to define groups at different risk. In a Cox analysis, the risk of cerebrovascular events was 2.8 times higher (95% CI: 1.18-6.69) in the subset with lack of regression or new development of LVH than in that with LVH regression or persistently normal LV mass. Such effect was independent of age (P = .001) and 24-h systolic BP (P = .003). CONCLUSIONS: In a mixed hypertensive population with and without LVH at entry, serial changes in the echocardiographic indexes of LVH predict subsequent cerebrovascular events independently of office and ambulatory BP and other individual risk factors.

Is the development of diabetes with antihypertensive therapy a problem?--Pro.

Some questions about new-onset diabetes (NOD) must still be completely addressed: 1) its incidence; 2) the possible association between NOD and some classes of antihypertensive drugs; and 3) its prognostic impact. It is well known that diuretics and beta blockers can increase plasma glucose and, in available hypertension trials, diuretics and beta blockers caused a higher incidence of NOD than new antihypertensive drugs. NOD heralds a high risk of major cardiovascular events, but the absolute difference between old and new drugs was too small to significantly drive the differences in cardiovascular event rates between the two groups of treatment. This evidence suggests a judicious use of drugs more frequently associated with NOD in subjects at high risk of diabetes (impaired fasting glucose, overweight, family history of diabetes, low high-density lipoprotein cholesterol levels). The lowest effective dose of these drugs should be used, plasma glucose should be checked periodically, and concomitant lifestyle measures to prevent diabetes should be implemented with resolution.

Do angiotensin II receptor blockers increase the risk of myocardial infarction?

AIMS: The uncertainty surrounding safety of angiotensin receptor blockers (ARBs) increased after publication of experimental and clinical studies which suggested an excess risk of myocardial infarction (MI) in people treated with ARBs. METHODS AND RESULTS: We performed a meta-analysis of randomised clinical trials, which compared ARBs with either a placebo or active drugs different from ARBs. Overall, ARBs were not associated with an excess risk of MI [odds ratio (OR): 1.03 in a random-effect model and 1.02 in a fixed-effect model]. In pre-specified subgroup analyses, incidence of MI did not differ between ARBs and either placebo (OR: 0.96; 95% CI: 0.84-1.10) or angiotensin-converting enzyme (ACE)-Inhibitors (OR: 0.99; 95% CI: 0.91-1.07). Incidence of MI was slightly higher with ARBs than with drug classes different from ACE-Inhibitors (OR: 1.16; P=0.06 in a random-effect model and 0.017 in a fixed-effect model). Cardiovascular mortality did not differ between ARBs and drugs different from ARBs (OR: 1.00 in a random-effect model and 0.99 in a fixed-effect model) and it was slightly lesser with ARBs than with placebo (OR: 0.91; 95% CI: 0.83-0.99; P=0.042) in a pre-specified subgroup analysis. CONCLUSION: Our findings do not support the hypothesis that ARBs increase the risk of MI.

Angiotensin-converting enzyme inhibitors and calcium channel blockers for coronary heart disease and stroke prevention.

We investigated whether protection from coronary heart disease (CHD) and stroke conferred by angiotensin-converting enzyme inhibitors (ACEIs) and calcium channel blockers (CCBs) in hypertensive or high-risk patients may be explained by the specific drug regimen. We extracted summary statistics regarding CHD and stroke from 28 outcome trials that compared either ACEIs or CCBs with diuretics, beta-blockers, or placebo for a total of 179,122 patients, 9509 incident cases of CHD, and 5971 cases of stroke. CHD included myocardial infarction and coronary death. In placebo-controlled trials, ACEIs decreased the risk of CHD (P<0.001), and CCBs reduced stroke incidence (P<0.001). There were no significant differences in CHD risk between regimens based on diuretics/beta-blockers and regimens based on ACEIs (P=0.46) or CCBs (P=0.52). The risk of stroke was reduced by CCBs (P=0.041) but not by ACEIs (P=0.15) compared with diuretics/beta-blockers. Because heterogeneity between trials was significant, we investigated potential sources of heterogeneity by metaregression. Examined covariates were the reduction in systolic blood pressure (BP), drug treatment (ACEIs versus CCBs), their interaction term, sex, age at randomization, year of publication, and duration of treatment. Prevention of CHD was explained by systolic BP reduction (P<0.001) and use of ACEIs (P=0.028), whereas prevention of stroke was explained by systolic BP reduction (P=0.001) and use of CCBs (P=0.042). These findings confirm that BP lowering is fundamental for prevention of CHD and stroke. However, over and beyond BP reduction, ACEIs appear superior to CCBs for prevention of CHD, whereas CCBs appear superior to ACEIs for prevention of stroke.

New-onset diabetes in treated hypertensive patients.

Interpretation of some recent trials in hypertension opened a debate on the clinical value of new-onset diabetes in treated hypertensive patients. It is not completely clear whether certain antihypertensive drug classes are associated with a higher risk for developing type 2 diabetes when compared with other classes. Some longitudinal studies suggest that new-onset diabetes in treated hypertensive subjects carries a risk for subsequent cardiovascular disease similar to that of previously known diabetes. In a study, plasma glucose before treatment and diuretic treatment were independent predictors of new-onset diabetes in hypertensive patients, independent of confounding factors. We estimated that one cardiovascular event associated with new-onset diabetes might be prevented for every 385 to 449 patients treated with "new," rather than "old," antihypertensive drugs for approximately 4 years. These observations suggest that concern about the risk for new-onset diabetes should prompt a more judicious use of diuretics and beta-blockers in the treatment of hypertension. These drugs should be given cautiously in subjects who are at increased risk for new-onset diabetes, owing to impaired fasting glucose or obesity. The lowest effective dose should be used, and plasma glucose should be carefully monitored.

Asymptomatic left ventricular systolic dysfunction in essential hypertension: prevalence, determinants, and prognostic value.

Prevalence, determinants, and prognostic value of asymptomatic left ventricular systolic dysfunction (LVSD) in uncomplicated subjects with essential hypertension are still incompletely known. We studied 2384 initially untreated subjects with hypertension, no previous cardiovascular disease, and no symptoms or physical signs of congestive heart failure (CHF). These subjects were studied at entry and followed for up to 17 years (mean 6.0). Asymptomatic LVSD (ALVSD), defined by an echocardiographic ejection fraction <50%, was found in 3.6% of subjects. Cigarette smoking (P=0.013), increased left ventricular (LV) mass (P=0.001), and higher 24-hour heart rate (P=0.014) were independent correlates of ALVSD. During follow-up, a first cardiovascular event occurred in 227 subjects, and 24 of these events were hospitalizations for symptomatic CHF. Incidence of CHF per 100 persons per year was 0.12 in patients without and 1.48 in patients with ALVSD (log-rank test P=0.0001). In a Cox model, after adjustment for age (P=0.0001), LV mass (P=0.0001), and cigarette smoking (P=0.039), LVSD conferred a markedly increased risk for CHF (odds ratio, 9.99; 95% confidence interval, 3.67 to 27.2). Incidence of coronary (0.84 versus 0.62x100 person years) and cerebrovascular (0.80 versus 0.62x100 person years) events did not differ (all P=NS) between subjects with and without ALVSD. ALVSD is a potent and early marker of evolution toward severe CHF requiring hospitalization in subjects with essential hypertension.

White-coat hypertension in adults.

White-coat hypertension is defined by the coexistence of persistently high office blood pressure (BP) with normal self-measured or ambulatory blood pressure. The prognostic impact of white-coat hypertension is a subject of debate. Cardiovascular morbidity seems to be lower in white-coat hypertension than in ambulatory hypertension, and, according to some but not all studies, is not dissimilar between white-coat hypertension and clinical normotension. In a large collaborative study including individual data from four prospective cohort studies, the incidence of stroke tended to increase in the white-coat hypertension group in the long run, crossing the hazard curve of the ambulatory hypertension by the ninth year of follow-up. These data raise the hypothesis, to be tested in future studies, that white-coat hypertension might not be a benign condition for stroke in the long term. Further studies are needed in order to: (1) test whether white-coat hypertension is really a benign condition for stroke in the long term; (2) compare, in patients with white-coat hypertension, a regimen based on life-style measures without drugs and a standard regimen consisting of life-style measures with the possible addition of drugs. On the basis of current evidence, it is reasonable to suggest a treatment based on life-style measures in the low-risk stratum of patients with white-coat hypertension under the conditions of correct definition, absence of comorbid conditions and target-organ damage, and adequate follow-up

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) > or =240 mg/dl (> or =6.22 mmol/l) or high-density lipoprotein (HDL) cholesterol (HDL-C) <40 mg/dl (1.05 mmol/l) or low-density lipoprotein (LDL) cholesterol (LDL-C) > or =160 mg/dl (4.13 mmol/l) or TC/HDL-C ratio >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 > or =6.22 mmol/l, 2.23 with a HDL-C <1.05 mmol/l (95% CI 1.06-4.70), 2.83 with a LDL-C > or =4.91 mmol/l (95% CI 1.48-5.42) and 3.90 with a TC/HDL-C ratio >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.

Regression of left ventricular hypertrophy and cardiovascular risk changes in hypertensive patients.

Hypertensive left ventricular hypertrophy (LVH) may be detected in about one third of people with hypertension. When an individual with elevated blood pressure develops LVH, the risk of adverse cardiovascular events in the ensuing years almost doubles even in the absence of symptoms. Because of this high added risk, hypertension and other modifiable risk factors should be managed aggressively with lifestyle measures and drugs. LVH can be considered a biological assay which reflects and integrates the long-term exposure not only to pressure overload, but also to several hemodynamic and non-hemodynamic factors which may promote progression and instabilization of atherosclerotic lesions and, ultimately, lead to adverse clinical events. LVH can partially or totally regress following antihypertensive treatment and lifestyle changes including losing excessive weight and decreasing salt intake. Angiotensin II antagonists and ACE-inhibitors seem to be the most effective drugs for reversing LVH. Evidence is accumulating that regression of LVH is associated with a significant reduction in the subsequent risk of cardiovascular disease. According to a recent meta-analysis, effective reversal of LVH is associated with a 59% lesser risk of subsequent adverse events as compared with the persistence or new development of LVH.

Calcium channel blockade to prevent stroke in hypertension: a meta-analysis of 13 studies with 103,793 subjects.

BACKGROUND: The possibility that specific antihypertensive treatments may prevent the occurrence of stroke more effectively than other treatments remains unproved. We undertook a meta-analysis to assess whether calcium channel blockers (CCBs) are associated with a lesser risk of stroke as compared with other antihypertensive drugs. METHODS: Through Medline we identified 13 major studies conducted in hypertensive subjects for a total of 103,793 subjects. Overall, there were 4040 incident cases of stroke, 1789 among 43,053 subjects randomized to CCBs and 2251 among 60,740 subjects randomized to different antihypertensive drugs. RESULTS: Considering all 13 trials, a pooled reduction in the risk of stroke was observed among subjects allocated to CCBs (odds ratio 0.90, 95% confidence interval [95% CI] 0.84-0.96; P =.002). The risk of stroke was significantly lower among subjects allocated to dihydropyridine CCBs than among those randomized to alternative drugs (odds ratio 0.90, 95% CI 0.84-0.97; P =.006), whereas the effect of non-dihydropyridine CCBs did not achieve significance (odds ratio 0.92, 95% CI 0.81-1.04). In a meta-regression analysis of these trials, the protection from stroke conferred by CCBs appeared unrelated to the degree of systolic blood pressure reduction. CONCLUSIONS: These findings suggest that CCBs decrease the risk of stroke more effectively than other treatments in patients with essential hypertension and that such an effect might not be completely explained by a better antihypertensive response. Calcium channel blockers should be considered in hypertensive subjects at increased risk of stroke.

Adverse prognostic significance of new diabetes in treated hypertensive subjects.

Diabetes may develop in nondiabetic hypertensive subjects during treatment, but the long-term cardiovascular implications of this phenomenon are not clear. We determined the prognostic value of new diabetes in hypertensive subjects. In a long-term cohort study, 795 initially untreated hypertensive subjects, 6.5% of whom with type 2 diabetes, underwent diagnostic procedures including 24-hour ambulatory blood pressure (BP) monitoring and electrocardiography (ECG). Procedures were repeated after a median of 3.1 years in the absence of cardiovascular events. Follow-up duration was 1 to 16 years (median 6.0). New diabetes occurred in 5.8% of subjects initially without diabetes. Antihypertensive treatment included a diuretic in 53.5% of these subjects, versus 30.4% of those in whom diabetes did not develop (P=0.002). Plasma glucose at entry (P=0.0001) and diuretic treatment on follow-up (P=0.004) were independent predictors of new diabetes. Subsequent to the follow-up visit, a first cardiovascular event occurred in 63 subjects. Event rate in nondiabetic subjects at both visits, new diabetes, and diabetes at entry were 0.97, 3.90, and 4.70x100 person-years, respectively (P=0.0001). After adjustment for several confounders, including 24-hour ambulatory BP, the relative risk of events was 2.92 (95% CI: 1.33 to 6.41; P=0.007) in the group with new diabetes and 3.57 (95% CI: 1.65 to 7.73; P=0.001) in the group with previous diabetes, when compared with the group persistently free of diabetes. In treated hypertensive subjects, occurrence of new diabetes portends a risk for subsequent cardiovascular disease that is not dissimilar from that of previously known diabetes.

Meta-Analysis of effectiveness or lack thereof of angiotensin-converting enzyme inhibitors for prevention of heart failure in patients with systemic hypertension.

We undertook a meta-analysis of large, randomized controlled trials in hypertensive subjects that compared angiotensin-converting enzyme (ACE) inhibitors with different classes of antihypertensive drugs. Compared with subjects randomized to drugs different from ACE inhibitors, those treated with ACE inhibitors did not show a different risk of congestive heart failure (CHF) (odds ratio 1.03, 95% confidence interval 0.96 to 1.12, p = 0.407). The degree of protection from CHF associated with the use of ACE inhibitors showed a nonsignificant trend to increase with age and the degree of blood pressure control. Thus, the hypothesis that ACE inhibitors are superior to other antihypertensive drugs for prevention of CHF in hypertension remains unproven.