Grazia Canciello

Cardiovascular ultrasound exploration contributes to predict incident atrial fibrillation in arterial hypertension: the Campania Salute Network.

BACKGROUND Interaction of cardiovascular (CV) risk factors with structural and hemodynamic alterations as combined promoters of atrial fibrillation (AF) is not yet well studied. We designed an observational, longitudinal, retrospective study to predict risk of incident AF by combination of CV risk profile, target organ damage and therapy in hypertensive patients. METHODS AND RESULTS We studied 7062 hypertensive patients without history of AF or prevalent CV disease, with ejection fraction (EF) of ≥50%, and no more than stage III chronic kidney disease. The patients were selected from an open registry, the Campania-Salute Network, collecting information from general practitioners and community hospitals, in the Campania Region, Southern Italy, networked with the Hypertension Center of Federico II University Hospital in Naples. The end-point of the present analysis was the detection of first episode of AF by ECG or hospital admission, at any point throughout follow-up (median 36months [IQR=10-74]). During follow-up, AF developed in 117 patients. Baseline older age, greater left atrial diameter (LAd), left ventricular mass (LVM), and intimal medial thickness (IMT) were independent predictors of AF (all p<0.0001), with no effect of CV risk factors. Beta-blockers and diuretics increased risk of incident AF; use of medications inhibiting renin-angiotensin system (RAS) reduced risk by 50% (all p<0.002). CONCLUSIONS Older age, increased LAd, and markers of target organ damage (increased LVM and IMT), identify the hypertensive phenotype at highest risk for AF. CV risk factors do not exhibit significant, independent association. Patients on anti-RAS therapy are exposed to lower risk of incident AF.

Left Ventricular Hypertrophy Regression During Antihypertensive Treatment in an Outpatient Clinic (the Campania Salute Network)

Background Regression of left ventricular (LV) hypertrophy (LVH) has been a goal in clinical trials. This study tests the external validity of results of clinical trials on LVH regression using a large registry from a tertiary care center, to identify phenotypes less likely to achieve regression of LVH. Methods and Results Patients from the Campania Salute Network, free of prevalent cardiovascular disease, but with echocardiographic LVH (defined as LV mass index [LVMi] >47 g/m2.7 in women and >50 g/m2.7 in men) were included. During a median follow‐up of 67 months, clear‐cut regression of LVH was documented in 14% of patients (13±8% reduction of initial LVMi) or 23% when also considering those with a reduction of LVMi ≥5 g/m2.7. Patients with persistent LVH were older with longer duration of hypertension, suboptimal blood pressure (BP) control, larger body mass index, LV mass, and carotid intima‐media thickness and included more women and subjects with diabetes mellitus, isolated systolic hypertension, and metabolic syndrome (all P<0.05). Number and class of antihypertensive drugs during follow‐up did not differ between groups. In multiple logistic regression analysis, older age, female sex, obesity, higher baseline LVMi and carotid intima‐media thickness, and suboptimal BP control were significant covariates of persistent LVH (all P≤0.01), independent of diabetes, duration of hypertension, isolated systolic hypertension, follow‐up time and number and class of antihypertensive drugs. Conclusions Early initiation of antihypertensive treatment, aggressive BP control, and attention to metabolic aspects are critical to avoid irreversible LVH.

Differential effect of obesity on prevalence of cardiac and carotid target organ damage in hypertension (the Campania Salute Network)

BACKGROUND Whether increasing body mass index (BMI) is independently associated with parallel increased prevalence of hypertensive vascular and cardiac target organ damage (TOD) needs further clarification. METHODS We analyzed 8815 hypertensive patients without prevalent cardiovascular disease, participating in the Campania Salute Network, grouped into BMI classes (normal 20-24.9kg/m2, overweight 25-29.9kg/m2 and obese ≥30kg/m2). Vascular and cardiac TOD was defined as ultrasound plaque (intima-media thickness>1.5mm) in >1 of the common or internal carotid arteries and echocardiographic left ventricular (LV) hypertrophy (LVH) (LV mass/height2.7>47g/m2.7 in women and >50g/m2.7 in men), respectively. RESULTS A majority of patients were either overweight (49%) or obese (27%). In spite of more use of combination therapy, the obese group had higher blood pressure (BP) and prevalence of TOD. In multivariate logistic analyses, obesity was associated with a 6.9 times higher prevalence of LVH (95% confidence interval [CI] 5.84-8.17, p=0.0001), independent of significant associations with female sex, age, diabetes mellitus, office systolic BP, antihypertensive and antiplatelet treatment. In contrast, only a 17% increased prevalence of carotid plaques (OR=1.17; 95% CI 1.02-1.33, p=0.02) was found in obese patients independent of significant effect of male sex, older age and higher clinic systolic BP, an association that disappeared once effect of metabolic risk factors and related therapy was also considered. CONCLUSIONS In hypertensive patients participating in the Campania Salute Project, concomitant obesity was associated with a modestly increased prevalence of carotid plaques and a pronounced increase in prevalent LVH.

Higher pulse pressure and risk for cardiovascular events in patients with essential hypertension: The Campania Salute Network:

Background Increased pulse pressure is associated with structural target organ damage, especially in elderly patients, increasing cardiovascular risk. Design In this analysis, we investigated whether high pulse pressure retains a prognostic effect also when common markers of target organ damage are taken into account. Methods We analysed an unselected cohort of treated hypertensive patients from the Campania Salute Network registry (n = 7336). Participants with available cardiac and carotid ultrasound were required to be free of prevalent cardiovascular disease, with ejection fraction ≥50%, and no more than stage III Chronic Kidney Disease. The median follow-up was 41 months and end-point was occurrence of major cardiovascular events (i.e. fatal and non-fatal stroke or myocardial infarction and sudden death). Based on current guidelines, pulse pressure ≥60 mm Hg was classified as high pulse pressure (n = 2356), at the time of the initial visit, whereas pulse pressure <60 mm Hg was considered normal (n = 4980). Results High pulse pressure patients were older, more likely to be women and diabetic, while receiving more antihypertensive medications than normal pulse pressure (all p < 0.0001). High pulse pressure exhibited greater prevalence of left ventricular hypertrophy, and carotid plaque than normal pulse pressure (all p < 0.0001). In Cox regression, high pulse pressure patients had 57% increased hazard of major cardiovascular events, compared to normal pulse pressure (hazard ratio = 1.57; 95% confidence interval: 1.12–2.22, p = 0.01), an effect that was independent of significant prognostic impact of older age, male sex, diabetes, left ventricular hypertrophy, carotid plaque and less prescription of anti-renin–angiotensin system therapy. Conclusions High pulse pressure is a functional marker of target organ damage, predicting cardiovascular events in hypertensive patients, even independently of well-known structural markers of target organ damage.

Depressed myocardial energetic efficiency is associated with increased cardiovascular risk in hypertensive left ventricular hypertrophy

Background and purpose: Myocardial mechano-energetic efficiency (MEE) can be easily approximated by the ratio of stroke work [i.e. SBP times stroke volume (SV)] to a rough estimate of energy consumption, the ‘double product’ [SBP times heart rate (HR)], which can be simplified as SV/HR. We evaluated whether MEE is associated with adverse prognosis in relation to the presence of left ventricular hypertrophy (LVH). Methods: Hypertensive participants of the Campania Salute Network (n = 12 353) without prevalent coronary or cerebrovascular disease and with ejection fraction more than 50% were cross-sectionally and longitudinally analyzed, over a median follow-up of 31 months. MEE was estimated by echocardiographic SV (z-derived)/(HR × 0.6). Results: Due to the close relation with left ventricular mass (LVM) (P < 0.0001), MEE was normalized for LVM (MEEi) and divided into quartiles. The lowest quartile of MEEi (<0.29 ml/s per g) was considered ‘low MEEi’. MEEi was greater in women than in men (P < 0.0001). Progressively lower MEEi was associated with older age, male sex, obesity, diabetes, LVH, concentric geometry, inappropriate LVM and diastolic dysfunction, more use of antihypertensive therapy, and higher BP (all P < 0.002). In Cox regression, after controlling for LVH, age, sex, and average follow-up SBP, low MEEi exhibited increased hazard of composite fatal and nonfatal cardiovascular end-points (P < 0.01), independently of antihypertensive therapy and associated cardiovascular risk factors. Conclusion: A simple estimate of low myocardial mechano-energetic efficiency is associated with altered metabolic profile, LVH, concentric left ventricular geometry, and diastolic dysfunction and predicts cardiovascular end-points, independently of age, sex, LVH antihypertensive therapy, and cardiovascular risk factors.

Development of Left Ventricular Hypertrophy in Treated Hypertensive Outpatients: The Campania Salute Network

There is little information on left ventricular (LV) hypertrophy (LVH) development during antihypertensive treatment. We evaluate incident LVH in a treated hypertensive cohort, the Campania Salute Network registry. We analyzed prospectively 4290 hypertensives (aged 50.3±11.1 years, 40% women) with at least 1-year follow-up, without LVH at baseline. Incident LVH was defined as the first detection of echocardiographic LV mass index ≥47 in women or ≥50 g/m2.7 in men. During a median 48-month follow-up, 915 patients (21.3%) developed LVH. They were older, more frequently women, and obese (P<0.0001), with initial higher fasting glucose, diastolic and systolic blood pressure, LV mass index, lower heart rate and glomerular filtration rate, longer hypertension history and follow-up, and higher average systolic blood pressure during follow-up (all P<0.05), despite a more frequent treatment with Ca++-channel blockers and diuretics (both P<0.02). At multivariable Cox regression, incident LVH was independently associated with older age, female sex, obesity, higher average systolic blood pressure during follow-up, and initial greater LV mass index (all P<0.02). By categorizing patients according to obesity and sex, obesity independently increased the risk for incident LVH in both sexes (obese versus nonobese men: hazard ratio, 1.34; confidence interval, 1.05–1.72; P=0.019; and obese versus nonobese women: hazard ratio, 1.34; confidence interval, 1.08–1.66; P=0.007). Despite more aggressive antihypertensive therapy, 21% of hypertensive patients develop clear-cut LVH. After adjusting for confounders, risk of incident LVH is particular relevant among women and is further increased by the presence of obesity. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT02211365.

Effect of diabetes and metabolic syndrome on myocardial mechano-energetic efficiency in hypertensive patients. The Campania Salute Network

Reduced myocardial mechano-energetic efficiency (MEE), estimated as stroke volume/heart rate ratio per g of left ventricular (LV) mass (LVM), and expressed in μl s−1 g−1 (MEEi), is a strong predictor of cardiovascular (CV) events, independently of LV hypertrophy and other confounders, including type II diabetes (DM). Decreased MEEi is more frequent in patients with diabetes. In the present analysis we evaluated the interrelation among MEEi, DM and metabolic syndrome (MetS) in the setting of arterial hypertension. Hypertensive patients from the Campania Salute Network, free of prevalent CV disease and with ejection fraction >50% (n=12 503), were analysed. Coexistence of MetS and DM was ordinally categorized into 4 groups: 8235 patients with neither MetS nor DM (MetS−/DM−); 502 without MetS and with DM (MetS−/DM+); 3045 with MetS and without DM (MetS+/DM−); and 721 with MetS and DM (MetS+/DM+). After controlling for sex, systolic blood pressure, body mass index, relative wall thickness (RWT), antihypertensive medications and type of antidiabetic therapy, MEEi was 333 μl s−1 g−1 in MetS−/DM−, 328 in MetS−/DM+, 326 in MetS+/DM− and 319 in MetS+/DM+ (P for trend <0.0001). In pairwise comparisons (Sidak-adjusted), all conditions, except MetS−/DM+, were significantly different from MetS−/DM− (all P<0.02). No statistical difference was detected between MetS−/DM+ and MetS+/DM−. Both MetS and DM are associated with decreased MEEi in hypertensive patients, independently to each other, but the reduction is statistically less evident for MetS−/DM+. MetS+/DM+ patients have the lowest levels of MEEi, consistent with the alterations of energy supply associated with the combination of insulin resistance with insulin deficiency.

Determinants of decline of renal function in treated hypertensive patients: the Campania Salute Network

Background Hypertension is a leading cause of chronic kidney disease (CKD) and a decrease in glomerular filtration rate (GFR) is associated with a higher prevalence of hypertension and an increased proportion of suboptimal blood pressure (BP) control. Methods To investigate characteristics associated with GFR decline, we selected 4539 hypertensive patients from the Campania Salute Network (mean age 53 ± 11 years) with at least 3 years of follow-up (FU) and no more than Stage III CKD. GFR was calculated at baseline and at the last available visit using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. GFR decline was defined as a ≥30% decrease from initial GFR for patients in Stage III CKD or by a composite ≥30% decrease from baseline and a final value of <60 for those < with Stage III or higher CKD. Results At a mean FU of 7.5 years, 432 patients (10%) presented with GFR decline. Those patients were older, more likely to be diabetic, with lower GFR and ejection fraction, higher systolic and lower diastolic BP and higher left ventricular (LV) mass and relative wall thickness at baseline; during FU, patients with GFR decline exhibited higher systolic BP, took more drugs and developed more atrial fibrillation (all P < 0.02). The probability of GFR decline was independently associated with older age, prevalent diabetes, baseline lower GFR, higher systolic BP during FU, FU duration, increased LV mass and incident AF with no impact from antihypertensive and antiplatelet medications. Conclusions During antihypertensive therapy, kidney function declines in patients with initially lower GFR, increased LV mass and suboptimal BP control during FU.

Validation of Left Atrial Volume Estimation by Left Atrial Diameter from the Parasternal Long-Axis View

Background: Measurement of left atrial (LA) volume (LAV) is recommended for quantification of LA size. Only LA anteroposterior diameter (LAd) is available in a number of large cohorts, trials, or registries. The aim of this study was to evaluate whether LAV may be reasonably estimated from LAd. Methods: One hundred forty consecutive patients referred to our outpatient clinics were prospectively enrolled to measure LAd from the long‐axis view on two‐dimensional echocardiography. LA orthogonal dimensions were also taken from apical four‐ and two‐chamber views. LAV was measured using the Simpson, area‐length, and ellipsoid (LAVe) methods. The first 70 patients were the learning series and the last 70 the testing series (TeS). In the learning series, best‐fitting regression analysis of LAV‐LAd was run using all LAV methods, and the highest values of F were chosen among the regression equations. In the TeS, the best‐fitting regressions were used to estimate LAV from LAd. Results: In the learning series, the best‐fitting regression was linear for the Spearman method (r2 = 0.62, F = 111.85, P = .0001) and area‐length method (r2 = 0.62, F = 112.24, P = .0001) and powered for the LAVe method (r2 = 0.81, F = 288.41, P = .0001). In the TeS, the r2 value for LAV prediction was substantially better using the LAVe method (r2 = 0.89) than the Simpson (r2 = 0.72) or area‐length (r2 = 0.70) method, as was the intraclass correlation (&rgr; = 0.96 vs &rgr; = 0.89 and &rgr; = 0.89, respectively). In the TeS, the sensitivity and specificity of LA dilatation by the estimated LAVe method were 87% and 90%, respectively. Conclusions: LAV can be estimated from LAd using a nonlinear equation with an elliptical model. The proposed method may be used in retrospective analysis of existing data sets in which determination of LAV was not programmed. HighlightsLAV can be estimated from LA linear dimension using nonlinear equations.The most reliably estimated LAV is obtained using the ellipsoid model.The proposed method might be helpful for retrospective analysis of existing data sets in which determination of LAV was not programmed.

Left ventricular hypertrophy offsets the sex difference in cardiovascular risk (the Campania Salute Network)

BACKGROUND In general, women have lower risk for cardiovascular disease. We tested whether this sex-specific protection persists also in the presence of hypertensive left ventricular hypertrophy (LVH). METHODS 12,329 women and men with hypertension and free from prevalent cardiovascular disease enrolled in the prospective Campania Salute Network registry were followed over a median of 4.1years. Subjects were grouped according to the absence or the presence of LVH identified by echocardiography using validated sex-specific cut-off values of LV mass index (>47g/m2.7 in women and >50g/m2.7 in men). Main outcome was major cardiovascular events (MACE; combined acute coronary syndromes, stroke, hospitalization for heart failure and incident atrial fibrillation). RESULTS The cardiovascular risk profile accompanying LVH did not differ between sexes, but presence of obesity and diabetes carried higher probability for LVH in women, and LVH was more prevalent in women than men (43.4 vs. 32.1%, p<0.001). Among patients without LVH (n=7764), women had a 35% lower hazard rate (HR) for MACE (n=179) than men (95% confidence interval [CI] 0.44-0.96, p=0.031) in Cox regression analysis adjusting for cardiovascular risk factors and antihypertensive treatment during follow up. In contrast, among patients with LVH (n=4565), women had a similar HR for MACE as men (HR 0.94 [95% CI 0.69-1.30], p=0.720). CONCLUSION This study demonstrates that presence of LVH in hypertension offsets the female sex-protection in cardiovascular risk. Thus among hypertensive subjects with LVH, women and men have comparable cardiovascular risk.