Paolo Villa

Prognostic Significance of Left Atrial Enlargement in a General Population Results of the PAMELA Study

We estimated the risk of cardiovascular events, cardiovascular mortality, and all-cause mortality associated with left atrium (LA) enlargement alone or combined with echocardiographic left ventricular hypertrophy (LVH) in 1785 representatives of the general population of Monza recruited for the Pressioni Arteriose Monitorate E Loro Associazioni (PAMELA) study. LA enlargement was assessed by measuring LA diameter via echocardiography. LA enlargement was defined as a LA diameter >2.3 cm/m2, whereas LVH was defined as a left ventricular mass index ≥114 g/m2 and 99 g/m2 in men and women, respectively. Death certificates and hospital diagnoses were collected over an average 148 months follow-up. During follow-up, there were 175 deaths (of which 59 for cardiovascular causes) and 139 cardiovascular fatal and nonfatal events. Compared with subjects with neither LA enlargement nor LVH, subjects with isolated LA enlargement exhibited a significant increase in the adjusted risk of combined fatal and nonfatal cardiovascular events (hazard ratio, 2.0; confidence interval, 1–4.1; P=0.04), although not of cardiovascular death or all-cause death. The adjusted (for baseline covariates, including ambulatory blood pressure) risk of fatal and nonfatal cardiovascular events, cardiovascular death, and all-cause death was significantly increased also in subjects with isolated LVH (hazard ratio, 2.2, 3.4, 2.1, respectively; P=0.001 for all), whereas no further increase was seen in subjects with both LA and left ventricular abnormalities. Thus, like LVH, LA enlargement is an independent long-term predictor of cardiovascular events. The cardiovascular risk, however, is not further increased when LA enlargement is superimposed on an increase of LV mass.

Increased nocturnal heart rate and wave reflection are early markers of cardiovascular disease in Williams-Beuren syndrome children.

Objective: Williams–Beuren syndrome (WBS) is a genetic disorder that involves elastin gene causing cardiovascular abnormalities and increased risk. However, data on arterial function in these patients are only few and conflicting. Aim of this study was to evaluate dynamic behaviour of central and peripheral blood pressure (BP) and arterial stiffness parameters early in the course of WBS. Methods: We enrolled 19 WBS paediatric patients (age 13 ± 4 years) and 23 age, height and BP-matched controls (10 ± 4 years). We evaluated 24-h ambulatory BP values via an ambulatory blood pressure monitoring (ABPM) system (Mobil-O-Graph) also capable to calculate 24-h central BP and 24-h arterial stiffness parameters. Carotid-femoral PWV (cf-PWV) was assessed in all WBS individuals (Complior). Results: BP values were similar in WBS and control, during the daytime and the night-time. The same behaviour applies to 24-h central BP. However, during the night, WBS showed heart rate values (HR; 78 ± 10 vs. 71 ± 9 bpm; P < 0.03), augmentation index (Aix; 24.6 ± 13.5% vs. 16.5 ± 8.9%; P = 0.03) and reflection magnitude (68 5.8 vs. 63.5 8.1; P = 0.02) higher than controls. The HR, Aix and reflection magnitude reduction in the day–night shift was lower in WBS than in controls. Cf-PWV in WBS children did not differ when compared with their normalized expected value. Conclusion: In WBS children, the higher night-time HR, Aix and reflection magnitude and their impaired physiological reduction in the day–night shift suggests an abnormal sympathetic cardiovascular control, an augmented wave reflection and an increase in small arteries resistance. These alterations possibly due to a sympathetic overactivity can be regarded as earlier hallmarks of cardiovascular dysfunction in these patients.

New-onset left atrial enlargement in a general population.

Aim: Increased left atrium diameter (LAD) is associated with elevated risk of cardiovascular morbidity and mortality. We evaluated new-onset left atrium enlargement (LAE) and their correlates over a 10-year period in participants of the general population enrolled in the Pressioni Monitorate e Loro Associazioni study. Methods: The study included 1045 participants with normal LAD at baseline evaluation having a readable echocardiogram at the end of follow-up. Cut-points for abnormal LAD were derived from reference values recommended by American Society of Echocardiography. Results: Over a 10-year period, 123 participants (11.8%) progressed to LAE. The incidence of new-onset LAE increased significantly from the lowest to the highest tertile of baseline office, home and 24-h blood pressure (BP); BMI; fasting blood glucose and left ventricular mass index (LVMI). In multivariate analysis, baseline LAD [odds ratio (OR) 3.18, confidence interval (CI) 2.26–4.47, P < 0.001], female sex (OR 3.68, CI 2.20–6.18, P < 0.001), office SBP (OR 1.36, CI 1.08–1.70, P = 0.008), BMI (OR 1.35, CI 1.07–1.69, P = 0.01 and LVMI (OR 1.29, CI 1.01–1.64, P = 0.04) emerged as key correlates of new-onset LAE. Conclusion: The study shows that in the population, long-term changes from normal LAD to LAE are independently driven by several risk factors such as the female sex and an increased baseline LAD, BMI, LVMI and BP, with no predictive superiority of home and ambulatory versus office values. Preventing BP elevations, overweight/obesity and left ventricular hypertrophy may thus all be important for LAE prevention.

Prognostic Significance of Left Atrial Enlargement in a General Population

We estimated the risk of cardiovascular events, cardiovascular mortality, and all-cause mortality associated with left atrium (LA) enlargement alone or combined with echocardiographic left ventricular hypertrophy (LVH) in 1785 representatives of the general population of Monza recruited for the Pressioni Arteriose Monitorate E Loro Associazioni (PAMELA) study. LA enlargement was assessed by measuring LA diameter via echocardiography. LA enlargement was defined as a LA diameter >2.3 cm/m2, whereas LVH was defined as a left ventricular mass index ≥114 g/m2 and 99 g/m2 in men and women, respectively. Death certificates and hospital diagnoses were collected over an average 148 months follow-up. During follow-up, there were 175 deaths (of which 59 for cardiovascular causes) and 139 cardiovascular fatal and nonfatal events. Compared with subjects with neither LA enlargement nor LVH, subjects with isolated LA enlargement exhibited a significant increase in the adjusted risk of combined fatal and nonfatal cardiovascular events (hazard ratio, 2.0; confidence interval, 1–4.1; P=0.04), although not of cardiovascular death or all-cause death. The adjusted (for baseline covariates, including ambulatory blood pressure) risk of fatal and nonfatal cardiovascular events, cardiovascular death, and all-cause death was significantly increased also in subjects with isolated LVH (hazard ratio, 2.2, 3.4, 2.1, respectively; P=0.001 for all), whereas no further increase was seen in subjects with both LA and left ventricular abnormalities. Thus, like LVH, LA enlargement is an independent long-term predictor of cardiovascular events. The cardiovascular risk, however, is not further increased when LA enlargement is superimposed on an increase of LV mass.

Reliability of heart rate as neuroadrenergic marker in the metabolic syndrome.

Background: Metabolic syndrome is characterized by a pronounced sympathetic overactivity as documented by the marked increase in muscle sympathetic nerve traffic (MSNA) as well as in plasma norepinephrine values reported in this condition. Whether and to what extent heart rate (HR) reflects the abovementioned adrenergic alterations in metabolic syndrome remains largely undefined. It is also undefined the validity of the abovementioned adrenergic markers in reflecting the main features of the metabolic syndrome. Methods: In 65 metabolic syndrome patients, aged 56.5 ± 1.3 years (mean ± SEM), we measured over a 30-min resting period blood pressure, HR (ECG), venous plasma norepinephrine (HPLC) and MSNA (microneurography). We also evaluated anthropometric and metabolic variables including HOMA index, correlating them with the adrenergic markers. The same measurements were also made in 48 age-matched healthy controls. Results: HR was significantly greater in the metabolic syndrome patients than in controls (74.6 ± 1.5 versus 67.5 ± 1.5 bpm, P < 0.001) and significantly and directly correlated with the elevated norepinephrine and MSNA values (r = 0.25 and 0.33, P < 0.05 and 0.01, respectively). MSNA was significantly and directly related to blood pressure (r = 0.27 and 0.31 SBP and DBP, respectively, P < 0.05 for both), BMI (r = 0.36, P < 0.01), waist circumference (r = 0.34, P < 0.01), waist-to-hip ratio (r = 0.49, P < 0.01) and plasma insulin (r = 0.57, P < 0.01). In contrast, no significant correlation was detectable between HR or norepinephrine and the abovementioned anthropometric and metabolic variables. Conclusion: Our data show that in the metabolic syndrome not only peripheral but also cardiac sympathetic drive is markedly potentiated and HR can be regarded as a marker of adrenergic overdrive characterizing this clinical condition. The reliability of HR (and of plasma norepinephrine) as sympathetic marker appears to be limited, however, this variable being unable to reflect, at variance from MSNA, the main metabolic and anthropometric abnormalities characterizing the metabolic syndrome.

[OP.6A.02] 24-HOUR SYSTOLIC BLOOD PRESSURE LOAD REPRESENTS AN IMPORTANT VARIABLE IN DETERMINING THE CARDIOVASCULAR RIK PROFILE OF WHITE-COAT HYPERTENSION

Objective: White-coat hypertension (WCH) displays an increased cardiovascular (CV) risk. Scanty are the data available on the impact of 24-hour average blood pressure (BP) load on the increased CV risk in this condition. Design and method: 2051 subjects randomly selected from the general population of Monza (Italy), aged 25 to 74 years, stratified for sex and decades of age, underwent measurement of systolic (S) and diastolic (D) office BP and average 24-hour ambulatory SBP and DBP. Anthropometric variables, serum cholesterol, blood glucose were also measured. During a median follow-up of 156 months hospital admissions for coronary and stroke events were collected. Fatal events were also collected, among which those related to CV causes (ICD-10 from I-0 to I-99) were identified. In the whole population sample, the subjects with both normal office BP (<140/90 mmHg) and normal 24-hour BP (<125/79 mmHg) were defined as normotensives (NT, n. 1001). Among the 356 subjects with high office BP and normal 24-hour BP (WCH), those with 24-hour SBP above and under the median value (118 mmHg) were classified as WCHH and WCHL, respectively. Results: The analysis was carried out on the 1001 NT and on the 356 WCH subjects. During the follow-up 112 deaths and 73 fatal and non fatal CV events. Total mortality was 5.7%, 20.8% and 10.1% in NT, WCHH and WCHL, respectively. Incidence of CV events was 3.4%, 14.6% and 7.3%, in NT, WCHH and WCHL, respectively. Adjusting the data for age, sex, hypercholesterolemia, diabetes mellitus, smoking, obesity, previous CV events and antihypertensive therapy, the risk of all cause death and CV events in WCHH was significantly higher than that of NT (HR 1.8, CI 1.2–2.8, and HR 2.7, CI 1.6–4.7, respectively; p < 0.01 for both). No significant difference was found in the CV risk between WCHL and NT. Conclusions: Although by definition in the normal range, the level of 24-hour ambulatory SBP load is a relevant factor in determining the enhanced CV risk in WCH. Indeed, when the 24-hour SBP values are low, the CV risk of WCH is not different from that displayed by NT.

Prognostic Significance of Left Atrial Enlargement in a General PopulationNovelty and Significance

We estimated the risk of cardiovascular events, cardiovascular mortality, and all-cause mortality associated with left atrium (LA) enlargement alone or combined with echocardiographic left ventricular hypertrophy (LVH) in 1785 representatives of the general population of Monza recruited for the Pressioni Arteriose Monitorate E Loro Associazioni (PAMELA) study. LA enlargement was assessed by measuring LA diameter via echocardiography. LA enlargement was defined as a LA diameter >2.3 cm/m2, whereas LVH was defined as a left ventricular mass index ≥114 g/m2 and 99 g/m2 in men and women, respectively. Death certificates and hospital diagnoses were collected over an average 148 months follow-up. During follow-up, there were 175 deaths (of which 59 for cardiovascular causes) and 139 cardiovascular fatal and nonfatal events. Compared with subjects with neither LA enlargement nor LVH, subjects with isolated LA enlargement exhibited a significant increase in the adjusted risk of combined fatal and nonfatal cardiovascular events (hazard ratio, 2.0; confidence interval, 1–4.1; P=0.04), although not of cardiovascular death or all-cause death. The adjusted (for baseline covariates, including ambulatory blood pressure) risk of fatal and nonfatal cardiovascular events, cardiovascular death, and all-cause death was significantly increased also in subjects with isolated LVH (hazard ratio, 2.2, 3.4, 2.1, respectively; P=0.001 for all), whereas no further increase was seen in subjects with both LA and left ventricular abnormalities. Thus, like LVH, LA enlargement is an independent long-term predictor of cardiovascular events. The cardiovascular risk, however, is not further increased when LA enlargement is superimposed on an increase of LV mass.

Prognostic Significance of Left Atrial Enlargement in a General PopulationNovelty and Significance: Results of the PAMELA Study

We estimated the risk of cardiovascular events, cardiovascular mortality, and all-cause mortality associated with left atrium (LA) enlargement alone or combined with echocardiographic left ventricular hypertrophy (LVH) in 1785 representatives of the general population of Monza recruited for the Pressioni Arteriose Monitorate E Loro Associazioni (PAMELA) study. LA enlargement was assessed by measuring LA diameter via echocardiography. LA enlargement was defined as a LA diameter >2.3 cm/m2, whereas LVH was defined as a left ventricular mass index ≥114 g/m2 and 99 g/m2 in men and women, respectively. Death certificates and hospital diagnoses were collected over an average 148 months follow-up. During follow-up, there were 175 deaths (of which 59 for cardiovascular causes) and 139 cardiovascular fatal and nonfatal events. Compared with subjects with neither LA enlargement nor LVH, subjects with isolated LA enlargement exhibited a significant increase in the adjusted risk of combined fatal and nonfatal cardiovascular events (hazard ratio, 2.0; confidence interval, 1–4.1; P=0.04), although not of cardiovascular death or all-cause death. The adjusted (for baseline covariates, including ambulatory blood pressure) risk of fatal and nonfatal cardiovascular events, cardiovascular death, and all-cause death was significantly increased also in subjects with isolated LVH (hazard ratio, 2.2, 3.4, 2.1, respectively; P=0.001 for all), whereas no further increase was seen in subjects with both LA and left ventricular abnormalities. Thus, like LVH, LA enlargement is an independent long-term predictor of cardiovascular events. The cardiovascular risk, however, is not further increased when LA enlargement is superimposed on an increase of LV mass.