Carlo Porcellati

Ambulatory blood pressure. An independent predictor of prognosis in essential hypertension.

To determine the prognostic significance of ambulatory blood pressure, we prospectively followed for up to 7.5 years (mean, 3.2) 1187 subjects with essential hypertension and 205 healthy normotensive control subjects who had baseline off-therapy 24-hour noninvasive ambulatory blood pressure monitoring. Prevalence of white coat hypertension, defined by an average daytime ambulatory blood pressure lower than 131/86 mm Hg in women and 136/87 mm Hg in men in clinically hypertensive subjects, was 19.2%. Cardiovascular morbidity, expressed as the number of combined fatal and nonfatal cardiovascular events per 100 patient-years, was 0.47 in the normotensive group, 0.49 in the white coat hypertension group, 1.79 in dippers with ambulatory hypertension, and 4.99 in nondippers with ambulatory hypertension. After adjustment for traditional risk markers for cardiovascular disease, morbidity did not differ between the normotensive and white coat hypertension groups (P = .83). Compared with the white coat hypertension group, cardiovascular morbidity increased in ambulatory hypertension in dippers (relative risk, 3.70; 95% confidence interval, 1.13 to 12.5), with a further increase of morbidity in nondippers (relative risk, 6.26; 95% confidence interval, 1.92 to 20.32). After adjustment for age, sex, diabetes, and echocardiographic left ventricular hypertrophy (relative risk versus subjects with normal left ventricular mass, 1.82; 95% confidence interval, 1.02 to 3.22), cardiovascular morbidity in ambulatory hypertension was higher (P = .0002) in nondippers than in dippers in women (relative risk, 6.79; 95% confidence interval, 2.45 to 18.82) but not in men (P = .91). Our findings suggest that ambulatory blood pressures stratifies cardiovascular risk in essential hypertension independent of clinic blood pressure and other traditional risk markers including echocardiographic left ventricular hypertrophy.(ABSTRACT TRUNCATED AT 250 WORDS)

Circadian blood pressure changes and left ventricular hypertrophy in essential hypertension.

The effects of circadian blood pressure (BP) changes on the echocardiographic parameters of left ventricular (LV) hypertrophy were investigated in 235 consecutive subjects (137 unselected untreated patients with essential hypertension and 98 healthy normotensive subjects) who underwent 24-hour noninvasive ambulatory blood pressure monitoring (ABPM) and cross-sectional and M-mode echocardiography. In the hypertensive group, LV mass index correlated with nighttime (8:00 PM to 6:00 AM) systolic (r = 0.51) and diastolic (r = 0.35) blood pressure more closely than with daytime (6:00 AM to 8:00 PM) systolic (r = 0.38) and diastolic (r = 0.20) BP, or with casual systolic (r = 0.33) and diastolic (r = 0.27) BP. Hypertensive patients were divided into two groups by presence (group 1) and absence (group 2) of a reduction of both systolic and diastolic BP during the night by an average of more than 10% of the daytime pressure. Casual BP, ambulatory daytime systolic and diastolic BP, sex, body surface area, duration of hypertension, prevalence of diabetes, quantity of sleep during monitoring, funduscopic changes, and serum creatinine did not differ between the two groups. LV mass index, after adjustment for the age, the sex, the height, and the daytime BP differences between the two groups (analysis of covariance) was 82.4 g/m2 in the normotensive patient group, 83.5 g/m2 in hypertensive patients of group 1 and 98.3 g/m2 in hypertensive patients of group 2 (normotensive patients vs. group 1, p = NS; group 1 vs. group 2, p = 0.002).(ABSTRACT TRUNCATED AT 250 WORDS)

Prognostic Significance of Serial Changes in Left Ventricular Mass in Essential Hypertension

BACKGROUND Increased left ventricular (LV) mass predicts an adverse outcome in patients with essential hypertension. The purpose of this study was to determine the relation between changes in LV mass during antihypertensive treatment and subsequent prognosis. METHODS AND RESULTS Procedures including echocardiography and 24-hour ambulatory blood pressure (BP) monitoring were performed in 430 patients with essential hypertension before therapy and after 1217 patient-years. Months or years after the follow-up visit, 31 patients suffered a first cardiovascular morbid event. The patients with a decrease in LV mass from the baseline to follow-up visit were compared with those with an increase in LV mass. There were 15 events (1.78 per 100 person-years) in the group with a decrease in LV mass and 16 events (3.03 per 100 person-years) in the group with an increase in LV mass (P=.029). In a Cox model, the lesser cardiovascular risk in the group with a decrease in LV mass (hazard ratio [HR], 0.46; 95% CI, 0.22 to 0.99) remained significant (P=.04) after adjustment for age (HR, 1.06; 95% CI, 1.03 to 1.10; P=.0008) and baseline LVH at ECG (HR, 3.85; 95% CI, 1.52 to 9.78; P=.012). In that model, baseline LV mass bordered on statistical significance (HR, 1.01; 95% CI, 1.00 to 1.03; P=.06). In the subset with LV mass > 125 g/m2 at the baseline visit (26% of subjects), the event rate was lower among the subjects who achieved regression of LVH than in those who did not (1.58 versus 6.27 events per 100 person-years; P=.002). This difference held in the multivariate analysis (HR, 0.18; 95% CI, 0.05 to 0.68). CONCLUSIONS In essential hypertension, a reduction in LV mass during treatment is a favorable prognostic marker that predicts a lesser risk for subsequent cardiovascular morbid events. Such an association is independent of baseline LV mass, baseline clinic and ambulatory BP, and degree of BP reduction.

Ambulatory Blood Pressure Is Superior to Clinic Blood Pressure in Predicting Treatment-Induced Regression of Left Ventricular Hypertrophy

Background In cross-sectional studies, ambulatory blood pressure (ABP) correlates more closely than clinic BP with the organ damage of hypertension. Whether ABP predicts development or regression o...

Adverse Prognostic Significance of New Diabetes in Treated Hypertensive Subjects

Abstract—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 4.70×100 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.

Ambulatory Pulse Pressure A Potent Predictor of Total Cardiovascular Risk in Hypertension

A wide pulse pressure (PP) is a marker of increased artery stiffness and high cardiovascular (CV) risk. To investigate the prognostic value of ambulatory PP, which is currently unknown, we studied 2010 initially untreated subjects with uncomplicated essential hypertension (mean age, 51.7 years; 52% men). All subjects underwent baseline procedures including 24-hour noninvasive ambulatory blood pressure (BP) monitoring. The mean duration of follow-up was 3.8 years (range, 0 to 11 years), and CV morbidity and mortality were the outcome measures. There were 200 major CV events (2.61 per 100 person-years), 36 of which were fatal (0.47 per 100 person-years). In the 3 tertiles of the distribution of office PP, the rate of total CV events (per 100 persons per year) was 1.38, 2. 12, and 4.34, respectively, and that of fatal events was 0.12, 0.30, and 1.07 (log-rank test, both P<0.01). In the 3 tertiles of the distribution of average 24-hour PP, the rate of total CV events was 1.19, 1.81, and 4.92, and that of fatal events was 0.11, 0.17, and 1. 23 (log-rank test, both P<0.01). After controlling for several independent risk markers including white coat hypertension and nondipper status, we found that ambulatory PP was associated with the biggest reduction in the -2 log likelihood statistics for CV morbidity (P<0.05 versus office PP). In each of the 3 tertiles of office PP, CV morbidity and mortality increased from the first to the third tertile of average 24-hour ambulatory PP (log-rank test, all P<0.01). Age, left ventricular hypertrophy, and nondipper status were independent predictors of CV mortality, and the further predictive effect of ambulatory PP (P<0.001) was marginally but not significantly superior to that of office PP and average 24-hour systolic BP. We conclude that ambulatory PP is a potent risk marker in essential hypertension. CV morbidity is more closely predicted by ambulatory than by office PP even after control for multiple risk factors.

Adverse prognostic significance of concentric remodeling of the left ventricle in hypertensive patients with normal left ventricular mass.

OBJECTIVES We examined the prognostic significance of concentric remodeling of the left ventricle in patients with essential hypertension and normal left ventricular mass on echocardiography. BACKGROUND An echocardiographic pattern of concentric remodeling of the left ventricle has been associated with clinical features of increased cardiovascular risk, but the independent prognostic value of this finding in hypertensive patients with normal left ventricular mass has not been established. METHODS Six hundred ninety-four patients with essential hypertension and normal left ventricular mass (< 125 g/m2) on echocardiography were prospectively followed up for < or = 7.7 years (mean 2.71). Baseline echocardiography and 24-h noninvasive ambulatory blood pressure monitoring were performed in all patients at the time of initial diagnostic evaluation. Concentric remodeling was defined by the thickness of the septum or posterior wall divided by the left ventricular radius at end-diastole > or = 0.45. RESULTS Prevalence of concentric remodeling was 39.2%. During follow-up there were 29 cardiovascular morbid events. Cardiovascular morbidity, expressed as the combined number of fatal and nonfatal events per 100 patient-years, was 1.53 in the overall study group, 1.12 in the subgroup with normal left ventricular geometry and 2.39 in that with concentric remodeling. After assessment of the independent association with several covariates (age, gender, diabetes, left ventricular mass index, mean clinic blood pressure and mean 24-h ambulatory blood pressure) in Cox proportional hazard models, the risk of cardiovascular morbid events was higher in the group with concentric remodeling than in that with normal geometry (relative risk 2.56, 95% confidence interval 1.20 to 5.45, p < 0.01). CONCLUSIONS Concentric remodeling of the left ventricle, defined by the thickness of the septum or posterior wall divided by the left ventricular radius at end-diastole > or = 0.45, is an important and independent predictor of increased cardiovascular risk in hypertensive patients with normal left ventricular mass on echocardiography.

Relation Between Serum Uric Acid and Risk of Cardiovascular Disease in Essential Hypertension: The PIUMA Study

The question of serum uric acid as an independent risk factor in subjects with essential hypertension remains controversial. For up to 12 years (mean, 4.0) we followed 1720 subjects with essential hypertension. At entry, all subjects were untreated and all were carefully screened for absence of cardiovascular disease, renal disease, cancer, and other important disease. Outcome measures included total cardiovascular events, fatal cardiovascular events, and all-cause mortality. During 6841 person-years of follow-up there were 184 cardiovascular events (42 fatal) and 80 deaths from all causes. In the 4 quartiles of serum uric acid (division points: 0.268, 0.309, and 0.369 mmol/L [4.5, 5.2, and 6.2 mg/dL] in men; 0.190, 0.232, and 0.274 mmol/L [3.2, 3.9, and 4.6 mg/dL] in women), the rate (per 100 person-years) of cardiovascular events was 2.51, 1.48, 2.66, and 4.27, that of fatal cardiovascular events was 0.41, 0.33, 0.38, and 1.23, and that of all-cause deaths was 1.01, 0.55, 0.93, and 2.01, respectively. The relation between uric acid and event rate was J-shaped in both genders. After adjustment for age, gender, diabetes, total cholesterol/HDL cholesterol ratio, serum creatinine, left ventricular hypertrophy, ambulatory blood pressure, and use of diuretics during follow-up, uric acid levels in the highest quartile were associated with increased risk for cardiovascular events (relative risk, 1.73; 95% CI, 1.01 to 3.00), fatal cardiovascular events (relative risk, 1.96; 95% CI, 1.02 to 3.79), and all-cause mortality (relative risk, 1.63; 95% CI, 1.02 to 2.57) in relation to the second quartile. In untreated subjects with essential hypertension, raised uric acid is a powerful risk marker for subsequent cardiovascular disease and all-cause mortality.

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, β-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/β-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/β-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.

Changes in cardiovascular risk by reduction of left ventricular mass in hypertension: a meta-analysis.

BACKGROUND Some studies have suggested that serial changes in left ventricular (LV) mass in hypertensive subjects predict the subsequent risk of cardiovascular disease. The aim of this meta-analysis was to evaluate the prognostic impact of LV hypertrophy regression in hypertension. METHODS We undertook a meta-analysis of studies that reported echocardiographic LV mass before and during antihypertensive therapy, with subsequent assessment of cardiovascular events. The aims of this meta-analysis were: 1) to compare subjects with LV hypertrophy (LVH) during treatment (persistence or new development of LVH) with those with LVH at baseline, but not during treatment (regression of LVH); and 2) to compare subjects with LVH at baseline, but not during treatment with those without LVH both before and during treatment (regression of LVH versus persistently normal LV mass). RESULTS The four eligible studies included 1064 hypertensive subjects (41% women) aged 45 to 51 years who repeated the echocardiographic study 3 to 10 years after the initial examination. The definition of LVH was based on a LV mass corrected by body surface area >125 g/m(2) in two studies and >110 g/m(2) (for women) and 124 g/m(2) (for men) in two studies. Compared with subjects with lack of regression or new development of LVH, those with LVH regression showed a reduced risk of subsequent cardiovascular disease (odds ratio 0.41, 95% CI 0.21 to 0.78, P =.007). Compared with subjects with regression of LVH, those with persistently normal LV mass showed a similar risk of subsequent events (odds ratio 0.64, 95% CI = 0.31 to 1.30, P =.21). CONCLUSION Compared with persistence or new development of LV hypertrophy, regression of LV hypertrophy during antihypertensive treatment is associated with a marked reduction in risk for subsequent cardiovascular disease.