Marina De Marco

Cardiovascular and Metabolic Predictors of Progression of Prehypertension Into Hypertension The Strong Heart Study

Prehypertension (defined by the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure) frequently evolves to hypertension (HTN) and increases cardiovascular risk. It is unclear whether metabolic and/or cardiac characteristics favor development of HTN in prehypertensive subjects. We evaluated baseline anthropometric, laboratory, and echocardiographic characteristics of 625 untreated prehypertensive participants in the Strong Heart Study, without prevalent cardiovascular disease (63% women; 22% with diabetes mellitus; mean age: 59±7 years) to identify predictors of the 4-year incidence of HTN. Diabetes mellitus was assessed by American Diabetic Association criteria, and a diabetes-specific definition of HTN was used. Four-year incidence of HTN was 38%. Incident HTN was independently predicted by baseline systolic blood pressure (odds ratio [OR]: 1.60 per 10 mm Hg; 95% CI: 1.30 to 2.00; P<0.0001), waist circumference (OR: 1.10 per 10 cm; 95% CI: 1.01 to 1.30; P =0.04), and diabetes mellitus (OR: 2.73; 95% CI=1.77 to 4.21; P<0.0001), with no significant effect for age, sex, hemoglobin A1c, homeostatic model assessment index, C-reactive protein, fibrinogen, low-density lipoprotein and high-density lipoprotein cholesterol, triglycerides, plasma creatinine, or urine albumin:creatinine ratio. Higher left ventricular mass index (OR: 1.15 per 5 g/m2.7; 95% CI: 1.01 to 1.25; P =0.03) or stroke volume index (OR: 1.25 per 5 mL/m2.04; 95% CI: 1.10 to 1.50; P =0.03) was also identified, together with baseline systolic blood pressure and the presence of diabetes mellitus, as an independent predictor of incident HTN, without an additional predictive contribution from other anthropometric, metabolic, or echocardiographic parameters (all P>0.10). Thus, progression to HTN in 38% of Strong Heart Study prehypertensive participants could be predicted by higher left ventricular mass and stroke volume in addition to baseline systolic blood pressure and prevalent diabetes mellitus.

Does Information on Systolic and Diastolic Function Improve Prediction of a Cardiovascular Event by Left Ventricular Hypertrophy in Arterial Hypertension

Left ventricular (LV) mass (LVM) is the most important information requested in hypertensive patients referred for echocardiography. However, LV function also predicts cardiovascular (CV) risk independent of LVM. There is no evidence that addition of LV function significantly improves model prediction of CV risk compared with LVM alone. Thus, composite fatal and nonfatal CV or cerebrovascular events were evaluated in 5380 hypertensive outpatients (2336 women, 298 diabetics, and 1315 obese subjects) without prevalent CV disease (follow-up: 3.5±2.8 years). We compared 5 risk models using Cox regression and adjusting for age and sex: (1) LV mass normalized for height in meters2.7 (LVMi); (2) LVMi, concentric LV geometry, by relative wall thickness (>0.43), ejection fraction, and transmitral diastolic pattern (by thirtiles of mitral deceleration index); (3) LVMi, LV geometry, midwall shortening, and mitral deceleration index thirtiles; (4) as No. 2 with the addition of left atrial dilatation (>23 mm); and (5) as No. 3 with the addition of left atrial dilatation. Individual hazard functions were compared using receiving operating characteristic curves and z statistics. Areas under the curves increased from 0.60 in the model with the sole LVMi to 0.62 in the others (all P values for differences were not significant). The additional information on systolic and diastolic function decreased the contribution (Wald statistics) of LVMi in the Cox model without improving the model ability to predict CV risk. We conclude that risk models with inclusion of information on LV geometry and systolic and diastolic function, in addition to LVMi, do not improve the prediction of CV events but rather redistribute the impact of individual predictors within the risk variance.

Excessive increase in left ventricular mass identifies hypertensive subjects with clustered geometric and functional abnormalities.

Background Left ventricular mass (LVM) exceeding needs to sustain haemodynamic load has been termed ‘inappropriate left ventricular mass’. We hypothesized that inappropriate LVM identifies hypertensive patients with clustered cardiac geometric and functional abnormalities. Methods For this purpose, 359 hypertensive individuals without prevalent cardiovascular disease underwent Doppler echocardiography. Observed LVM exceeding more than 28% of the value predicted for individual cardiac work, body size and sex was defined as inappropriate LVM. Concentric left ventricular geometry was defined as age-adjusted relative wall thickness (RWT) greater than 0.40. Systolic dysfunction was defined as ejection fraction less than 50% or midwall shortening less than 14.7%. Diastolic dysfunction was defined as isovolumic relaxation time (IVRT) greater than 100 ms, E-velocity deceleration time greater than 220 ms or age and heart rate-normalized early/late (E/A) ratio less than 0.66. Left ventricular hypertrophy (LVH) was defined as an LVM index greater than 49.2 g/m2.7 in men and 46.7 g/m2.7 in women. Results As expected, inappropriate LVM was associated with higher RWT, lower left ventricular systolic function, longer IVRT and prolonged E-deceleration time (all P < 0.05). Patients with inappropriate LVM had a higher prevalence of concentric geometry (65.5 versus 40.4%), systolic dysfunction (67.9 versus 47.4%) and diastolic dysfunction (46.4 versus 39%; all P < 0.001) than those with LVH. Inappropriate LVM had greater sensitivity (0.89 versus 0.54) and specificity (0.82 versus 0.62; both P < 0.01) than LVH in identifying patients with clustered left ventricular concentric geometry, systolic and diastolic dysfunction. Conclusions Inappropriate LVM is associated with a cluster of concentric left ventricular geometry, delayed left ventricular relaxation and reduced systolic performance. Compared with LVH, inappropriate LVM is more accurate at identifying patients with clustered left ventricular geometric and functional abnormalities.

Increased left ventricular mass in pre-liver transplantation cirrhotic patients

Objective Severe liver disease is associated with abnormalities in cardiac geometry and function. We aimed to assess the prevalence of these abnormalities and to determine if they represent an adaptation of the heart to the haemodynamic overload associated with liver dysfunction. Methods Seventy cirrhotic patients underwent standard Doppler echocardiography, as a screening evaluation for liver transplantation, and were compared with 70 normal subjects matched for age and sex. The values of echocardiographically measured left ventricular mass (LVM) were compared with those predicted from individual haemodynamic load, sex and height, which represent the compensatory values. LVM was considered inappropriately high when the observed/predicted LVM ratio was >128%. Results Cirrhotic patients had higher LVM index (40.6 ± 11.2 vs. 36.3 ± 7.7 g/m2.7; P = 0.009)), similar values of ejection fraction, but lower intrinsic wall mechanics (P < 0.01) compared to controls. The observed/predicted LVM ratio was also significantly increased (117.7 ± 30.2 vs. 106.5 ± 16.8%; P < 0.01) and prevalence of inappropriate LVM was almost three-fold higher in cirrhotic patients (27.7 vs. 10.0%; P < 0.05) than in controls. Cirrhotic patients also presented mild impairment of left ventricular systolic function, documented by lower values of midwall shortening. Conclusions Patients with severe liver disease have LVM values exceeding the compensatory needs to sustain haemodynamic overload, associated with subclinical systolic dysfunction.

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.

Cardiac Geometry and Function in Diabetic or Prediabetic Adolescents and Young Adults: The Strong Heart Study

OBJECTIVE The aim of this study was to evaluate whether diabetes (DM) and impaired fasting glucose (IFG) were associated with early alterations in left ventricular geometry and function in a large population of adolescents and young adults independently of major confounders. RESEARCH DESIGN AND METHODS We analyzed echocardiographic data of 1,624 14- to 39-year-old participants (mean age 26.6 ± 7.7 years; 57% female) without prevalent cardiovascular disease from the fourth Strong Heart Study examination; 179 (11%) participants had DM and 299 (18%) had IFG. RESULTS Participants with DM and IFG were older and more often obese and hypertensive than participants with normal fasting glucose (NFG) (all P < 0.05). After adjustment for age, sex, systolic blood pressure, and body fat, diabetic and IFG participants had higher left ventricular mass index than those with NFG (41.5 ± 8.7 and 39.6 ± 9.2 vs. 35.6 ± 7.8 g/m2.7) and reduced stress-corrected midwall shortening (98 ± 8.6 and 99 ± 7.5 vs. 101 ± 8.5%; all P < 0.05). The prevalence of left ventricular hypertrophy was higher in DM (20%) and IFG (17%) than in NFG participants (12%; P < 0.05). Compared with the other groups, DM was also associated with higher prevalence of inappropriate left ventricular mass, concentric geometry, and more diastolic abnormalities independently of covariates (all P < 0.05). CONCLUSIONS In a population of adolescents and young adults, DM is independently associated with early unfavorable cardiovascular phenotype characterized by increased left ventricular mass, concentric geometry, and early preclinical systolic and diastolic dysfunction; early cardiovascular alterations are also present in participants with prediabetes.

Arterial Stiffness Is Associated With Carotid Atherosclerosis in Hypertensive Patients (The Campania Salute Network)

BACKGROUND Pulse pressure/stroke volume indexed to height(2.04) (PP/SVi) is a validated measure of arterial stiffness, but its relation to carotid atherosclerosis is unknown. METHODS Clinical, echocardiographic, and carotid ultrasound data from 6,209 hypertensive patients without prevalent cardiovascular (CV) disease in the Campania Salute Network were analyzed. The population was grouped into tertiles of PP/SVi. From carotid ultrasound, peak and mean intima-media thickness (IMT) and presence of carotid plaques in the common and internal carotid arteries were reported. RESULTS Increasing PP/SVi tertile was associated with a parallel increase in age, blood pressure, total serum cholesterol and the number of antihypertensive drugs used (all P < 0.01). Higher PP/SVi was also associated with greater peak and mean IMT (all P < 0.01), also when adjusting for age, gender, blood pressure, lipid profile, and diabetes mellitus (all P < 0.01). Similarly, compared to the lower PP/SVi tertile, the multiple adjusted prevalence ratio of carotid plaque was 7 (95% confidence interval (CI) 1-13, P < 0.03) in the middle tertile and 21 (95% CI 15-28, P < 0.0001) in the upper tertile, independently of confounders. CONCLUSION In treated hypertensive patients participating in the Campania Salute Network, higher PP/SVi is associated with carotid atherosclerosis independent of well-known clinical confounders.

Mitral Annular Calcification and Incident Ischemic Stroke in Treated Hypertensive Patients: The LIFE study.

Background Fibro-calcification of the mitral annulus (MAC) has been associated with increased risk of ischemic stroke in general populations. This study was performed to assess whether MAC predicts incidence of ischemic stroke in treated hypertensive patients with left ventricular hypertrophy (LVH). Methods Baseline and follow-up clinical and echocardiographic parameters were assessed in 939 hypertensive patients with electrocardiogram (ECG) LVH participating in the Losartan Intervention for Endpoint reduction in hypertension (LIFE) echocardiography substudy (66±7 years; 42% women; 11% with diabetes) who did not have aortic or mitral valve stenosis or prosthesis. Results MAC was found in 458 patients (49%). Patients with MAC were older (68±7 vs. 65±7 years); were more often women (47% vs. 37%); had higher baseline systolic blood pressure (BP) (175±14 vs. 172±15mm Hg), left atrial diameter (4.0±0.5 vs. 3.8±0.6cm), and left ventricular mass index (58±13 vs. 55±12g/m(2.7)) and included more patients with proteinuria (30% vs. 21%; all P < 0.01). During a mean follow-up of 4.8 years, 58 participants had an ischemic stroke. Risk of incident ischemic stroke was significantly related to presence of MAC (log rank = 9; P < 0.01). In multivariable Cox regression analysis models, MAC was associated with increased risk of ischemic stroke (hazard ratio = 1.78-2.35), independent of age, baseline or time-varying systolic BP, prevalence or incidence of atrial fibrillation, history of previous cerebrovascular disease, and other well-recognized confounders, such as sex, time-varying left ventricular mass, left atrial diameter, and urinary albumin/creatinine ratio (all P < 0.05). Conclusions MAC is common in treated hypertensive patients with ECG LVH and is an independent predictor of incident ischemic stroke.

Hemodynamic Correlates of Abnormal Aortic Root Dimension in an Adult Population: The Strong Heart Study

Background We evaluated the relationship of aortic root dimension (ARD) with flow output and both peripheral and central blood pressure, using multivariable equations predicting ideal sex‐specific ARD at a given age and body height. Methods and Results We measured echocardiographic diastolic ARD at the sinuses of Valsalva in 3160 adults (aged 42±16 years, 61% women) from the fourth examination of the Strong Heart Study who were free of prevalent coronary heart disease, and we compared measured data with the theoretical predicted value to calculate a z score. Central blood pressure was estimated by applanation tonometry of the radial artery in 2319 participants. ARD z scores were divided into tertiles representing small, normal, and large ARD. Participants with large ARD exhibited greater prevalence of central obesity and higher levels of inflammatory markers and lipids (0.05<P<0.0001). Stroke volume, heart rate, and both cuff and central diastolic blood pressure were progressively greater from small to large ARD (all P<0.0001). Pulse pressure was higher in small ARD (P<0.0001). In multivariable analysis, ARD z score was related positively to stroke volume, either cuff or central diastolic blood pressure, and negatively to pulse pressure. Large ARD was also independently correlated to higher waist circumference and percentages of neutrophils and plasminogen activator inhibitor‐1 (all P<0.01). Conclusions Aortic root dilatation is associated with high diastolic blood pressure, high stroke volume, central fat distribution, and inflammatory status. In contrast, at a given diastolic blood pressure and stroke volume, aortic root dilatation is associated with lower pulse pressure and systolic blood pressure.

Effect of bariatric surgery on left ventricular geometry and function in severe obesity

SUMMARY OBJECTIVE Weight loss improves cardiac abnormalities associated with severe obesity. We evaluated the impact of weight loss following laparoscopic gastric bypass (LGBP) on left ventricular (LV) geometry and function in obese patients. METHODS Twenty-six patients with severe obesity (41 ± 8 years, 50% women) underwent Doppler echocardiograms before and after LGBP, to measure LV geometry, excess of LV mass relative to hemodynamic load and systolic and diastolic function. RESULTS Pre-operatively, 85% of patients exhibited LVH, and 62% hypertension and metabolic syndrome, reflecting high cardiometabolic risk. After 8 ± 4 months of follow-up, the average weight loss was 19 ± 8%. Weight loss was significantly associated with improved metabolic parameters and reduced heart rate (-9 bpm), systolic (-11 mmHg) and diastolic (-6 mmHg) blood pressure (all p < 0.02). After surgery, there was significant reduction in relative wall thickness (0.43 ± 0.07 versus 0.39 ± 0.06), LV mass index (63 ± 14 g/m(2.7) versus 49 ± 10 g/m(2.7)) and excess of LV mass in relation to hemodynamic load (all p < 0.004). LVH remained in 54% of patients, hypertension in 23% and metabolic syndrome in 27%. Ejection fraction and Doppler indices of diastolic function did not change significantly, even after adjusting for changes in heart rate. All favorable changes in LV geometry and function were also confirmed in the subgroup with <9 month follow-up (median), whereas no further improvement could be detected in patients with longer follow-up. CONCLUSIONS In patient with severe obesity, LV geometry and systolic function improved rapidly after LGBP, without evidence of further improvement during prolonged follow-up.