Maurizio Bentivoglio

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.

Atrial Fibrillation in Hypertension: Predictors and Outcome

Abstract—Incidence, determinants, and outcome of atrial fibrillation in hypertensive subjects are incompletely known. We followed for up to 16 years 2482 initially untreated subjects with essential hypertension. At entry, all subjects were in sinus rhythm. Subjects with valvular heart disease, coronary artery disease, preexcitation syndrome, thyroid disorders, or lung disease were excluded. During follow-up, a first episode of atrial fibrillation occurred in 61 subjects at a rate of 0.46 per 100 person-years. At entry, subjects with future atrial fibrillation differed (all P <0.05) from those without by age (59 versus 51 years), office, and 24-hour systolic blood pressure (165 and 144 versus 157 and 137 mm Hg, respectively), left ventricular mass (58 versus 49 g/height[m]2.7), and left atrial diameter (3.89 versus 3.56 cm). Age and left ventricular mass (both P <0.001) were the sole independent predictors of atrial fibrillation. For every 1 standard deviation increase in left ventricular mass, the risk of atrial fibrillation was increased 1.20 times (95% CI, 1.07 to 1.34). Atrial fibrillation became chronic in 33% of subjects. Age, left ventricular mass, and left atrial diameter (all P <0.01) were independent predictors of chronic atrial fibrillation. Ischemic stroke occurred at a rate of 2.7% and 4.6% per year, respectively, among subjects with paroxysmal and chronic atrial fibrillation. These data indicate that in hypertensive subjects with sinus rhythm and no other major predisposing conditions, risk of atrial fibrillation increases with age and left ventricular mass. Increased left atrial size predisposes to chronicization of atrial fibrillation.

Risk of Cardiovascular Disease in Relation to Achieved Office and Ambulatory Blood Pressure Control in Treated Hypertensive Subjects

OBJECTIVE We investigated the prognostic impact of 24-h blood pressure control in treated hypertensive subjects. BACKGROUND There is growing evidence that ambulatory blood pressure improves risk stratification in untreated subjects with essential hypertension. Surprisingly, little is known on the prognostic value of this procedure in treated subjects. METHODS Diagnostic procedures including 24-h noninvasive ambulatory blood pressure monitoring were undertaken in 790 subjects with essential hypertension (mean age 48 years) before therapy and after an average follow-up of 3.7 years (2,891 patient-years). RESULTS At the follow-up visit, 26.6% of subjects achieved adequate office blood pressure control (<140/90 mm Hg), and 37.3% of subjects achieved adequate ambulatory blood pressure control (daytime blood pressure <135/85 mm Hg). Months or years after the follow-up visit, 58 patients suffered a first cardiovascular event. Event rate was lower (0.71 events/100 person-years) among the subjects with adequate ambulatory blood pressure control than among those with higher blood pressure levels (1.87 events/100 person-years) (p = 0.0026). Ambulatory blood pressure control predicted a lesser risk for subsequent cardiovascular disease independently of other individual risk factors (RR 0.36; 95% confidence intervals: 0.18 to 0.70; p = 0.003), including age, diabetes and left ventricular hypertrophy. Office blood pressure control was associated with a nonsignificant lesser risk of subsequent events (RR 0.63; 95% confidence intervals: 0.31 to 1.31; p = NS). In-treatment ambulatory blood pressure was more potent than pre-treatment blood pressure for prediction of subsequent cardiovascular disease. CONCLUSIONS Ambulatory blood pressure control is superior to office blood pressure control for prediction of individual cardiovascular risk in treated hypertensive subjects.

C-reactive protein as a marker for cardiac ischemic events in the year after a first, uncomplicated myocardial infarction

The prognostic role of C-reactive protein levels in patients with a first acute myocardial infarction, an uncomplicated in-hospital course, and the absence of residual ischemia on a predischarge ergometer test and with an echocardiographic ejection fraction > or = 50% has not been described. C-reactive protein was determined during hospitalization in 64 patients (55 men, mean age 64.6 +/- 10.4 years). The patients were followed up for 13 +/- 4 months and the following cardiac events were recorded: cardiac death, new-onset angina pectoris, and recurrent myocardial infarction. Patients who developed cardiac events during the follow-up period had significantly higher C-reactive protein values than patients without events (3.61 +/- 2.83 vs 1.48 +/- 2.07 mg/dl, p <0.001). The probability of cumulative end points was: 6%, 12%, 31%, and 56% (p = 0.006; RR 3.55; confidence interval 1.56 to 8.04), respectively, in patients stratified by quartiles of C-reactive protein (< 0.45, 0.45 to 0.93, 0.93 to 2.55 and > 2.55 mg/dl). In the Cox regression model, only increased C-reactive protein levels were independently related to the incidence of subsequent cardiac events (chi-square 9.8, p = 0.001). Thus, increased C-reactive protein levels are associated with a worse outcome among patients with a first acute myocardial infarction, an uncomplicated in-hospital course without residual ischemia on the ergometer test, and with normal left ventricular function.

Association Between Periodontal Disease and Left Ventricle Mass in Essential Hypertension

Abstract—Chronic periodontitis has been associated with an increased risk for cardiovascular disease. Left ventricular mass is an established independent predictor of cardiovascular disease. In the present cross-sectional study, we tested the association between periodontitis and left ventricular mass in subjects with essential hypertension. One hundred four untreated subjects with essential hypertension underwent clinical examinations, including echocardiographic study, laboratory tests, and assessment of periodontal status according to the community periodontal index of treatment needs (CPITN). With increasing severity of periodontitis, there was a progressive increase in left ventricle mass. Mean values (g/height2.7) were 39.0 (±2.7) in CPITN 0 (periodontal health), 40.2 (±6.4) in CPITN 1 (gingival bleeding), 42.7 (±6.8) in CPITN 2 (calculus), 51.4 (±11.7) in CPITN 3 (pockets 4 to 5 mm), and 76.7 (±11.3) in CPITN 4 (pockets ≥6 mm) (overall F 51.2;P <0.0001). Body surface area (P =0.04), systolic (P <0.0001) and diastolic (P <0.01) blood pressure, and left ventricular mass (P <0.0001) were determinants of a composite of CPITN 3 and 4. In a multivariate logistic analysis, left ventricular mass was the sole determinant (P <0.0001) of CPITN stages 3 and 4. Our findings suggest a direct association between severity of periodontitis and left ventricular mass in subjects with essential hypertension. Periodontal evaluation might contribute to refine cardiovascular risk assessment in hypertensive subjects.

Improved cardiovascular risk stratification by a simple ECG index in hypertension

BACKGROUND We determined the prognostic value of the Cornell/strain [C/S] index, a simple electrocardiographic (ECG) index for left ventricular hypertrophy (LVH) defined by the presence of either a classic strain pattern or a Cornell voltage (sum of R in aVL + S in V(3)) >2.0 mV in women or 2.4 mV in men, or both. METHODS In a prospective, cohort study, 2190 initially untreated subjects (age 51 [+/- 12], 47% women) with essential hypertension without prior events were followed for up to 14 years (median, 5 years). RESULTS Prevalence of LVH at entry was 16.3% by using the C/S index, which yielded 33.6% sensitivity and 91.0% specificity. Other ECG criteria for LVH including Sokolow-Lyon, Romhilt-Estes, Framingham, Cornell, and strain alone, achieved a lower sensitivity and prevalence. Over the subsequent follow-up, 244 patients experienced a first major cardiovascular event. Event rate (x 100 person-years) was 2.01 in those without and 4.44 in those with LVH by the C/S index (P <.001). After adjustment for age, sex, smoking, and other counfounders, the C/S index identified subjects at increased risk of events (relative risk 1.76; 95% confidence interval 1.32-2.33). The C/S index achieved the highest population-attributable risk (16.1%) for cardiovascular events. CONCLUSIONS A simple ECG index that can be quickly measured from nondigital machines and without algorithms identifies LVH in a consistent proportion (16.3%) of hypertensive subjects. The LVH defined by such technique allows identification of individuals at high risk for cardiovascular events.

Echocardiographic left ventricular hypertrophy as related to arterial pressure and plasma norepinephrine concentration in arterial hypertension. Reversal by atenolol treatment.

We tried to assess relationships between echocardiographic left ventricular hypertrophy (LVH), arterial pressure levels, and plasma norepinephrine concentration (NE) in 20 previously untreated stable hypertensive patients with LVH, and in 11 healthy normotensive control subjects. Interventricular septal (IVS) thickness, posterior wall (PW) thickness, and left ventricular mass index (LVMI) were related to arterial pressure levels and to NE by univariate and multivariate regression analyses. In addition, after 18 months of monotherapy with atenolol (carried out in nine of 20 patients), the relationship between echocardiographic changes and degree of pressure reduction was tested. Before treatment, PW thickness weakly correlated with systolic (r = 0.55; p less than 0.01) and mean (r = 0.50; p less than 0.05) arterial pressure. IVS thickness weakly correlated with NE (r = 0.53; p less than 0.05). On this relatively small sample, multivariate regression analysis showed an association of both IVS thickness (R = 0.57; p less than 0.05) and PW thickness (R = 0.58; p less than 0.05) with mean arterial pressure (MAP) and NE. After atenolol, there was a reduction in IVS thickness (1.15 to 1.02 cm; p less than 0.01), PW thickness (1.08 to 0.99 cm; p less than 0.01), and LVMI (136.3 to 113.8 g/m2; p less than 0.01), besides a significant reduction in blood pressure and heart rate. The degree of pressure reduction induced by treatment did not correlate the change in IVS or PW thickness. In contrast, the change in diastolic and mean arterial pressure positively correlated the change in LVMI (r = 0.72 and r = 0.75, respectively; both p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Usefulness of the severity and extent of wall motion abnormalities as prognostic markers of an adverse outcome after a first myocardial infarction treated with thrombolytic therapy

The prognostic value of wall motion score index (WMSI), assessed at predischarge after a first acute myocardial infarction (AMI) in the thrombolytic era, is still not well known. One-hundred forty-four consecutive patients with a first AMI treated with thrombolytic therapy underwent exercise testing and echocardiography at rest before discharge and were followed-up for a mean period of 18 months. During follow-up, there were 32 cardiac events (12 patients had cardiac deaths, 8 had unstable angina pectoris, 1 had nonfatal reinfarction, and 11 patients had congestive heart failure). The patients who experienced any cardiac event had a higher WMSI (1.67+/-0.15 vs. 1.30+/-0.16, p<0.0001), a higher end-systolic volume (75.1+/-34 vs. 59.5+/-22 ml, p<0.01), and a lower ejection fraction (47+/-16% vs. 55+/-10%, p<0.001) at predischarge than patients without events. The incidence of a positive predischarge exercise testing did not differ between patients with and without cardiac events (22% vs. 24%, p = NS). Multivariate Cox regression analysis, including clinical, exercise results, and echocardiographic parameters, showed that the most powerful predictor of a subsequent event was a resting WMSI > or =1.50 before discharge (chi-square 17.8, p<0.0001). Thus, in patients with a first AMI who underwent thrombolysis, the severity and extent of echocardiographically detected wall motion abnormalities are important independent predictors of cardiac events.

Plasma norepinephrine and left ventricular hypertrophy in systemic hypertension

The relations between some pressure and humoral factors, and some echocardiographic indexes of left ventricular (LV) hypertrophy were studied in 64 patients with essential hypertension. Fifty-seven percent of these patients showed echocardiographic evidence of LV hypertrophy (LV mass greater than 215 g). Multivariate stepwise regression analysis showed that only mean blood pressure (BP) and circulating norepinephrine (NE) levels were significantly related to LV mass index in the group of patients with LV hypertrophy. However, mean BP was the only factor related to LV mass index in the subgroup of patients with LV hypertrophy and plasma NE within the normal laboratory range, whereas NE was the sole factor related to LV mass index in the subgroup with LV hypertrophy and abnormally elevated NE levels (greater than mean + 2 standard deviations of the normal laboratory range). Correlation of LV mass index vs NE was -0.35 (not significant) in the former group of patients and 0.89 (p less than 0.01) in the latter group. NE showed no relation with the echocardiographic variables in the hypertensive patients without LV hypertrophy; in this group, diastolic BP was the only factor related to LV mass index. Circulating NE levels were slightly higher in patients with LV hypertrophy (213 +/- 68 ng/liter) than in those without LV hypertrophy (187 +/- 46 ng/liter), but differences were not significant when adjusting NE for age. Plasma renin activity was not dissimilar in the absence or presence of hypertrophy. In conclusion, our findings suggest that NE might be associated with pressure factors in regulating LV hypertrophy development only in a subgroup of hypertensive patients characterized by echocardiographic LV hypertrophy and abnormally elevated circulating NE levels.

Prognostic value of left ventricular hypertrophy and geometry in patients with a first, uncomplicated myocardial infarction.

BACKGROUND The prognostic impact of left ventricular (LV) geometry on cardiovascular risk for patients with a first, uncomplicated acute myocardial infarction (AMI), and echocardiographic ejection fraction > or =50% has not been well described. METHODS AND RESULTS Accordingly, 111 AMI consecutive patients (mean age 59.3+/-10 years) performed echocardiographic examination at predischarge. LV mass was calculated by means of Devereuxs formula and subsequently indexed by body surface area. Fifty-three patients had LV hypertrophy and 58 patients had normal LV mass. The two groups were homogeneous for demographic, clinical and angiographic variables as well as for the incidence of residual ischemia on predischarge stress testing. During follow-up period there were 24 cardiac events (cardiac death, unstable angina and non-fatal reinfarction) in the 53 patients with LV hypertrophy and only four events in the remaining 58 patients without LV hypertrophy (RR=2.45; CI=1.76-3.41; P<0.0001). The patients with concentric LV hypertrophy showed a higher incidence of events (64%) than patients with eccentric LV hypertrophy (32%, P<0. 05) and patients with normal geometry and mass (6%, P<0.0001). Multivariate Cox regression model identified concentric geometry as the most powerful predictor of combined end-points (chi(2)=32.7, P<0. 0001). CONCLUSIONS An increased LV mass and concentric geometry resulted important independent markers of an adverse outcome in patients with a first, uncomplicated myocardial infarction and good LV function.