Combining echo-derived haemodynamic phenotypes and myocardial strain for risk stratification of chronic heart failure with reduced ejection fraction.

AIMS: Echocardiography has shown to categorize heart failure (HF) patients according to haemodynamic profiles. Whether left ventricular (LV) global longitudinal strain (LV-GLS) could integrate echo-derived haemodynamic profiles to risk stratify chronic HF patients is still unknown. METHODS AND RESULTS: Chronic HF outpatients with LV ejection fraction (LV-EF) <50% (n = 351) and LV-GLS assessment were evaluated and divided according to four haemodynamic phenotypes based on LV stroke volume index (SVI), LV filling pressure (LVFP), and right ventricular (RV) function: normal output-normal LVFP (NO-NP), normal output-high LVFP (NO-HP), low output-no RV dysfunction (LO-NRVD), and low output-RV dysfunction (LO-RVD). RV function was defined using the tricuspid annular plane systolic excursion and RV free-wall longitudinal strain. The median follow-up duration was 3.3 years. The combination of all-cause mortality and HF hospitalization was the primary endpoint. Secondary endpoints were all-cause mortality and cardiovascular mortality. The prevalence of NO-NP, NO-HP, LO-NRVD, and LO-RVD were 38%, 22%, 30%, and 10%, respectively. The haemodynamic model independently predicted primary and secondary outcomes, with incremental prognostic information over LV-EF (all P-values <0.001 for C-statistics). When univariate Cox regression analysis was performed to assess the prognostic stratification capability of LV-GLS in different haemodynamic subgroups, we observed a reduction in LV-GLS hazard ratios from the NO-NP to the LO-RVD for every endpoint. CONCLUSION: There was a continuum in LV-GLS impairment across the spectrum of haemodynamic phenotypes and its prognostic value resulted variable depending on the types of chronic HF patients. The highest prognostic information added by LV-GLS was in patients with normal SVI.

Severe Impairment of Left Ventricular Regional Strain in STEMI Patients Is Associated with Post-Infarct Remodeling.

Background: Measures of global left ventricular (LV) systolic function have limitations for the prediction of post-infarct LV remodeling (LVR). Therefore, we tested the association between a new measure of regional LV systolic function­the percentage of severely altered strain (%SAS)- and LVR after acute ST-elevation myocardial infarction (STEMI). As a secondary objective, we also evaluated the association between %SAS and clinical events during follow-up. Methods: Of 177 patients undergoing echocardiography within 24 h from primary percutaneous coronary angioplasty, 172 were studied for 3 months, 167 for 12 months, and 10 died. The %SAS was calculated by dividing the number of LV myocardial segments with ≥−5% peak systolic longitudinal strain by the total number of segments. LVR was defined as the increase in end-diastolic volume >20% at its first occurrence compared to baseline. Results: LVR percentage was 10.2% and 15.8% at 3 and 12 months, respectively. Based on univariable analysis, a number of clinical, laboratory, electrocardiographic and echocardiographic variables were associated with LVR. Based on multivariable analysis, %SAS and TnI peak remained associated with LVR (for %SAS 5% increase, OR 1.226, 95% CI 1.098−1.369, p < 0.0005; for TnI peak, OR 1.025, 95% CI 1.004−1.047, p = 0.022). %SAS and LVR were also associated with occurrence of clinical events at a median follow-up of 43 months (HR 1.02, 95% CI 1.0−1.04, p = 0.0165). Conclusions: In patients treated for acute STEMI, acute %SAS is associated with post-infarct LVR. Therefore, we suggest performing such evaluations on a routine basis to identify, as early as possible, STEMI patients at higher risk.

Value of Left Ventricular Indexed Ejection Time to Characterize the Severity of Aortic Stenosis.

Aims: The assessment of aortic stenosis (AS) severity is still challenging, especially in abnormal hemodynamic conditions. Left ventricular ejection time (LVET) has been historically related to AS severity, but it also depends on heart rate (HR) and systolic function. Our aim was to verify if correcting LVET (LVET index, LVETI) by its determinants is helpful for the assessment of AS severity, irrespective of hemodynamic conditions. Methods and results: We retrospectively studied 152 patients with AS and 378 patients with heart failure and no-AS. At multivariate analysis, LVET (assessed with pulsed-wave Doppler) showed a strong correlation with stroke volume index (SVI) (Beta 0.354; p < 0.001), HR (−0.385; p < 0.001), AS grade (Beta 0.301; p < 0.001) and, less significantly, ejection fraction (LVEF) (Beta 0.108; p = 0.001). AS grade was confirmed to be a major determinant of LVET, irrespective of forward flow (assessed by SVI and transvalvular flow rate) and LVEF (above and below 50%). A regression equation was derived to index LVET (LVETI) to HR and SVI. By using this formula, LVETI detected severe AS more accurately (AUC 0.812, p < 0.001) than LVET alone (AUC 0.755, p for difference = 0.005). Similar results were observed in patients with abnormal flow status. As an exploratory finding, we observed that the highest tertile of LVETI was associated with a higher rate of aortic valve interventions during follow-up. Conclusions: LVETI correlates with AS severity better than uncorrected LVET, independently from hemodynamic conditions, and may help to discriminate severe AS. This finding needs confirmation in larger prospective multicenter studies.

Indirect ultrasound evaluation of left ventricular outflow tract diameter implications for heart failure and aortic stenosis severity assessment.

BACKGROUND: Whereas dependency of left ventricular outflow tract diameter (LVOTD) from body surface area (BSA) has been established and a BSA-based LVOTD formula has been derived, the relationship between LVOTD and aortic root and LV dimensions has never been explored. This may have implications for evaluation of LV output in heart failure (HF) and aortic stenosis (AS) severity. METHODS: A cohort of 540 HF patients who underwent transthoracic echocardiography was divided in a derivation and validation subgroup. In the derivation subgroup (N = 340), independent determinants of LVOTD were analyzed to derive a regression equation, which was used for predicting LVOTD in the validation subgroup (N = 200) and compared with the BSA-derived formula. RESULTS: LVOTD determinants in the derivation subgroup were sinuses of Valsalva diameter (SVD, beta = 0.392, P < .001), BSA (beta = 0.229, P < .001), LV end-diastolic diameter (LVEDD, beta = 0.145, P = .001), and height (beta = 0.125, P = .037). The regression equation for predicting LVOTD with the aforementioned variables (LVOTD = 6.209 + [0.201 × SVD] + [1.802 × BSA] + [0.03 × LVEDD] + [0.025 × Height]) did not differ from (P = .937) and was highly correlated with measured LVOTD (R = 0.739, P < .001) in the validation group. Repeated analysis with LV end-diastolic volume instead of LVEDD and/or accounting for gender showed similar results, whereas BSA-derived LVOTD values were different from measured LVOTD (P < .001). CONCLUSION: Aortic root and LV dimensions affect LVOTD independently from anthropometric data and are included in a new comprehensive equation for predicting LVOTD. This should improve evaluation of LV output in HF and severity of AS when direct LVOTD measurement is difficult or impossible.

New measures of right ventricle-pulmonary artery coupling in heart failure: An all-cause mortality echocardiographic study.

AIMS: Right ventricle-pulmonary artery coupling (RVPAC) has emerged from pathophysiology to clinical interest for prognostic implication in heart failure and is commonly measured as the ratio between tricuspid annular plane systolic excursion and systolic pulmonary artery pressure (TAPSE/SPAP). However, feasibility of SPAP is limited (down to 60% in trials, and maybe lower in clinical practice). We ought to assess the prognostic value of the TAPSE times pulmonary acceleration time (TAPSE x pACT) product and TAPSE to peak tricuspid regurgitation velocity (TAPSE/TRV) ratio as new alternative measures of RVPAC. METHODS AND RESULTS: Two-hundred patients hospitalized with heart failure were followed-up (median time of 2.7 years) and 82 died. Non survivors had significantly lower TAPSE/SPAP, TAPSE x pACT and TAPSE/TRV than survivors (0.31 vs 0.40 mm/mmHg, 130 vs 156 cm·ms, 5.0 vs 5.8 ms, respectively). Four multivariate models were performed, each one including TAPSE, TAPSE/SPAP, TAPSE x pACT or TAPSE/TRV. TAPSE/SPAP resulted the most powerful predictor of mortality (HR 0.74 per mm/mmHg increase, P < 0.001, C-Statistic 0.778), followed by TAPSE x pACT (HR 0.95 per 10 cm·ms increase, P = 0.013, C-Statistic 0.776), TAPSE/TRV (HR 0.76 per ms increase, P < 0.001, C-Statistic 0.774) and TAPSE (HR 0.91 per mm increase, P = 0.003, C-Statistic 0.769). Cutoff values of 140 cm·ms and 5.5 ms were respectively identified for TAPSE x pACT and TAPSE/TRV with receiving operating characteristic analysis for mortality. CONCLUSION: TAPSE x pACT product and TAPSE/TRV ratio are alternative measures of RVPAC for prognostic assessment in heart failure that can be applied if TAPSE/SPAP is not feasible.

Left ventricular output indices in hospitalized heart failure: when "simpler" may not mean "better".

Assessment of left ventricular (LV) output in hospitalized patients with heart failure (HF) is important to determine prognosis. Although echocardiographic LV ejection fraction (EF) is generally used to this purpose, its prognostic value is limited. In this investigation LV-EF was compared with other echocardiographic per-beat measures of LV output, including non-indexed stroke volume (SV), SV index (SVI), stroke distance (SD), ejection time (ET), and flow rate (FR), to determine the best predictor of all-cause mortality in patients hospitalized with HF. A final cohort of 350 consecutive patients hospitalized with HF who underwent echocardiography during hospitalization was studied. At a median follow-up of 2.7 years, 163 patients died. Non-survivors at follow-up had lower SD, SVI and SV, but not ET, FR and LV-EF than survivors. At multivariate analysis, only age, systolic blood pressure, chronic kidney disease, chronic obstructive pulmonary disease, use of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers and SVI remained significantly associated with outcome [HR for SVI 1.13 (1.04-1.22), P = 0.003]. In particular, for each 5 ml/m2 decrease in SVI, a 13% increase in risk of mortality for any cause was observed. SVI is a powerful prognosticator in HF patients, better than other per-beat measures, which may be simpler but partial or incomplete descriptors of LV output. SVI, therefore, should be considered for the routine echocardiographic evaluation of patients hospitalized with HF to predict prognosis.

Right Atrial Pressure Is Associated with Outcomes in Patients with Heart Failure and Indeterminate Left Ventricular Filling Pressure.

BACKGROUND: In a significant proportion of patients with left-sided heart failure (HF), left ventricular filling pressure (LVFP) may not be estimated using echocardiography, so filling pressure status may remain indeterminate. In these patients, mean right atrial pressure (mRAP) has been suggested as a surrogate of LVFP. The aim of this study was to determine whether high mRAP has prognostic value in patients with HF with indeterminate pressure (IP) and whether mRAP-based reclassification of patients with IP has an impact on outcomes. METHODS: A cohort of 465 patients hospitalized with HF was retrospectively studied and divided into groups with normal pressure (n = 102), high pressure (n = 265), and IP (n = 98). A composite end point of all-cause mortality and HF rehospitalization was evaluated after a median follow-up duration of 2.5 years. RESULTS: There were 282 events in the entire population (53 in the normal pressure group, 173 in the high pressure group, and 56 in the IP group; P = .047). High mRAP was independently associated with outcome only in patients with IP (hazard ratio, 2.72; 95% CI, 1.25-5.9; P = .012). Evaluation of LVFP after mRAP-based reclassification of patients with IP resulted in higher risk stratification capability than current recommendations alone (log-rank χ2 = 15.057 vs 8.148). CONCLUSIONS: In patients with inconclusive determination of LVFP, echocardiographic estimation of mRAP is associated with outcomes. This finding corroborates previous observation of mRAP as a surrogate marker of elevated LVFP in left-sided HF and suggests its use in clinical practice.

Paradoxical low-flow phenotype in hospitalized heart failure with preserved ejection fraction.

BACKGROUND: Low flow (LF) in heart failure with preserved ejection fraction (HFpEF) is a paradox but is associated with worse prognosis. Determinants of LF in HFpEF have not been clarified but their assessment could corroborate recognition and definition of such a paradoxical condition. METHODS: A cohort of 193 patients hospitalized with HFpEF was retrospectively studied and divided in a group with LF (N = 45), defined by a left ventricular (LV) stroke volume index (SVI) < 30 ml/m2, and a group with normal flow (N = 148). A small LV cavity was pre-defined as LV end diastolic diameter index (EDDI) below median values (<25 mm/m2 for males and <26 mm/m2 for females). Right ventricular dysfunction (RVD) was defined as the ratio between tricuspid annular plane systolic excursion and systolic pulmonary artery pressure < 0.36 mm/mmHg. An endpoint of all-cause mortality was evaluated after a median follow-up of 2.4 years. RESULTS: RVD (OR = 7.4; P < 0.001), atrial fibrillation (AF) during echocardiography (OR = 3.26; P = 0.008), and small LV cavity (OR = 3.81; P = 0.003) were independently associated with LF. After adjusting for age, body mass index, systolic blood pressure, renal function, chronic obstructed pulmonary disease, use of ACE inhibitors/angiotensin receptor blockers, moderate tricuspid regurgitation, RVD), LF was associated with mortality (HR = 3.69; P < 0.001) whereas the combination of the determinants of LF was not. CONCLUSION: Paradoxical LF in HFpEF is associated with small LV cavity, AF and RVD. None of the combination of different factors associated with LF could substitute direct assessment of LF status in predicting prognosis in this cohort.

Novel Echocardiographic Approach to Hemodynamic Phenotypes Predicts Outcome of Patients Hospitalized With Heart Failure.

BACKGROUND: Although in clinical practice heart failure (HF) patients are classified using left ventricular ejection fraction (LVEF), this categorization is insufficient for prognosis, especially when LVEF is preserved or there is a concomitant right ventricular (RV) dysfunction. We hypothesized that a combined noninvasive evaluation of LV forward flow, filling pressure, and RV function would be better than LVEF in predicting all-cause mortality of hospitalized patients with HF. METHODS: Transthoracic echocardiographic examinations of 603 patients hospitalized with HF were analyzed. In a subsample of 200 patients with HF, LV stroke volume index, LV filling pressure estimation, tricuspid annular plane systolic excursion, and systolic pulmonary artery pressure were combined to determine 4 hemodynamic profiles: normal flow-normal pressure, normal flow-high pressure, low flow without RV dysfunction, and low flow with RV dysfunction profile. This model was then applied in a validation cohort (n=403). RESULTS: Prognosis worsened from the normal flow-normal pressure profile to the low flow with right ventricular dysfunction profile. At the multivariate survival analysis, the model showed independent high risk-stratification capability (P<0.001), even in subgroups of patients with LVEF < or ≥50% (P=0.011 and P<0.001, respectively) and < or ≥40% (P=0.044 and P<0.001, respectively). LVEF and HF classification based on LVEF did not predict outcome. CONCLUSIONS: Echocardiographic-derived profiling of LV forward flow, filling pressure, and RV function allowed categorization of patients hospitalized with HF and predicted all-cause mortality independently of LVEF. This model is based on conventional echocardiography, is easy to apply, and is, therefore, suggested for clinical practice.

From left ventricular ejection fraction to cardiac hemodynamics: role of echocardiography in evaluating patients with heart failure.

In clinical practice heart failure (HF) patients are generally classified on the basis of left ventricular (LV) ejection fraction. This approach, however, has important limitations. According to the definition of HF as a clinical syndrome that results from any impairment of LV filling or ejection of blood, a more articulated hemodynamic categorization of HF patients taking into account both LV forward flow and filling pressure would be desirable. However, the reliability of hemodynamic measures using echocardiographic techniques, which are the most used in current clinical practice for evaluation of HF patients, needs to be clarified. The aim of this article, therefore, is to verify whether echocardiography has acceptable feasibility, accuracy and reproducibility for the noninvasive evaluation of LV hemodynamics. This evaluation is necessary to progress to a hemodynamic characterization of HF patients that would ultimately overcome the HF classification based on ejection fraction.

Echocardiographic Evaluation of Left Ventricular Output in Patients with Heart Failure: A Per-Beat or Per-Minute Approach?

BACKGROUND: Left ventricular (LV) output is a predictor of adverse outcome in patients with heart failure. It can be evaluated using a per-beat approach, measuring stroke volume index (SVI), or a per-minute approach, calculating cardiac index (CI). However, the prognostic value of these two approaches has never been compared. METHODS: A single-center retrospective observational study was conducted in 396 hospitalized patients who underwent echocardiography for suspected heart failure. In a group of 138 consecutive patients, SVI and CI cutoff values of 30 mL/m2 and 2.3 L/min/m2, respectively, were derived to separate normal from low LV forward flow conditions. Subsequently, the association of these values with all-cause mortality was compared in a group of 258 consecutive patients. Median follow-up duration was 2.6 years (interquartile range: 2-3.2 years). RESULTS: After adjustment for other outcome predictors, SVI <30 mL/m2 was independently associated with all-cause mortality with a hazard ratio of 2.67 (95% confidence interval, 1.74-4.1; P < .001), whereas CI was not. Additionally, three different subgroups of SVI (<30, 30-35, and >35 mL/m2) and CI (<1.8, 1.8-2.2, and ≥2.3 L/min/m2) were compared, and no incremental benefit of this risk stratification model was observed. CONCLUSIONS: Low LV output on the basis of a per-beat definition (SVI <30 mL/m2) is strongly associated with all-cause mortality in patients hospitalized with heart failure. A per-minute approach seems to add no further information to risk stratification. These findings may have implications for selecting the LV output index when evaluating prognosis in patients with heart failure.

[Treatment of secondary ischemic mitral regurgitation: controversial issues]. / Aspetti controversi nel trattamento dell'insufficienza mitralica secondaria ischemica.

The presence of secondary mitral regurgitation is an unfavorable prognostic factor in patients with chronic ischemic heart disease. This type of regurgitation can be treated with medical therapy, cardiac resynchronization therapy, surgically or percutaneously but each strategy has controversial aspects. The purpose of this review is to discuss the most debated issues relative to the various modalities available to treat ischemic secondary mitral regurgitation, highlighting also future perspectives.

F13A1 Gene Variant (V34L) and Residual Circulating FXIIIA Levels Predict Short- and Long-Term Mortality in Acute Myocardial Infarction after Coronary Angioplasty.

Factor XIIIA (FXIIIA) levels are independent predictors of early prognosis after acute myocardial infarction (AMI) and the Valine-to-Leucine (V34L) single nucleotide polymorphism (SNP) seems associated with lower AMI risk. Since the long-term AMI prognosis merits deeper investigation, we performed an observational study evaluating relationships between FXIIIA residual levels, cardiovascular risk-factors, and inherited genetic predispositions. FXIIIA V34L was genotyped in 333 AMI patients and a five-year follow-up was performed. FXIIIA levels assessed at day-zero (d0) and four days after AMI (d4), and conventional risk factors were analyzed, focusing on the development of major adverse cardiovascular events (MACE). FXIIIA assessed at d0 and d4 was also an independent MACE predictor in the long-term follow-up (FXIIIAd0, Odds Ratio (OR) = 3.02, 1.79⁻5.1, p = 0.013; FXIIIAd4, OR = 4.46, 2.33⁻8.55, p = 0.0001). FXIIIAd4 showed the strongest MACE association, suggesting that the FXIIIA protective role is maximized when high levels are maintained for longer time. Conversely, FXIIIA levels stratified by V34L predicted MACE at a lesser extent among L34-carriers (Hazard Risk (HR)VV34 = 3.89, 2.19⁻6.87, p = 0.000003; HRL34-carriers = 2.78, 1.39⁻5.57, p = 0.0039), and V34L did not predict all MACE, only multiple-MACE occurrence (p = 0.0087). Finally, in survival analysis, heart failure and death differed significantly from stroke and recurrent ischemia (p = 0.0013), with FXIIIA levels appreciably lower in the former (p = 0.05). Overall, genetically-determined FXIIIA levels have a significant long-term prognostic role, suggesting that a pharmacogenetics approach might help to select those AMI patients at risk of poor prognosis in the need of dedicated treatments.

[Echocardiography in ST-elevation myocardial infarction]. / L'ecocardiografia nell'infarto miocardico con sopraslivellamento del tratto ST.

Echocardiography is an imaging technique of paramount importance for the management of patients with ST-elevation myocardial infarction. In particular, this technique may be useful for diagnosis and is essential for prognosis and to guide drug therapy. The role in the recognition of mechanical complications and in the identification and management of other complications such as pericarditis and left ventricular thrombosis is also crucial. Finally, echocardiography offers important information for the prediction of the arrhythmic risk and the study of left ventricular remodeling. In recent years, speckle-tracking echocardiography has been added to conventional echocardiographic techniques, showing additional value for diagnostic and prognostic indications, but further confirmations are needed.

[How severe is mitral regurgitation? Possibilities and problems of echocardiographic evaluation in clinical practice]. / Quanto è grave un'insufficienza mitralica? Possibilità e problemi della valutazione ecocardiografica nella pratica clinica.

Echocardiography is the most commonly used technique for evaluating patients with mitral regurgitation (MR) and estimating MR severity. However, in clinical practice, echocardiographic assessment of MR severity remains challenging in many cases, particularly in patients with forms of intermediate or borderline severity. The main causes are the improper application of the echocardiographic methods for assessment of MR severity and the lack of a validated standardized approach for quantification of various types of MR, including organic and functional MR. In this review, we describe how best to use echocardiography for assessing MR severity in the light of current knowledge and guidelines.

Biological effects of ticagrelor over clopidogrel in patients with stable coronary artery disease and chronic obstructive pulmonary disease.

Patients with SCAD and concomitant COPD are at high risk of cardiovascular adverse events, due to chronic inflammation, responsible of endothelial dysfunction, oxidative stress and heightened platelet reactivity (PR). The objective of this randomised clinical trial was to test if ticagrelor is superior to clopidogrel in improving endothelial function in patients with stable coronary artery disease (SCAD) and concomitant chronic obstructive pulmonary disease (COPD). Forty-six patients with SCAD and COPD undergoing percutaneous coronary intervention (PCI) were randomly assigned to receive clopidogrel (n=23) or ticagrelor (n=23) on top of standard therapy with aspirin. The following parameters were assessed at baseline and after 1 month: i) rate of apoptosis and ii) nitric oxide (NO) levels in human umbilical vein endothelial cells (HUVECs), iii) levels of reactive oxygen species (ROS) in peripheral blood mononuclear cell, iv) 29 cytokines/chemokines, v) on-treatment PR. The primary endpoint of the study was the 1-month rate of HUVECs apoptosis. The rate of apoptosis after 1 month was significantly lower in patients treated with ticagrelor (7.4 ± 1.3 % vs 9.3 ± 1.5 %, p<0.001), satisfying the pre-specified primary endpoint. In the ticagrelor arm, levels of NO were higher (10.1 ± 2.2 AU vs 8.5 ± 2.6 AU, p=0.03) while those of ROS (4 ± 1.8 AU vs 5.7 ± 2.8 AU, p=0.02) and P2Y12 reactivity units (52 ± 70 PRU vs 155 ± 62 PRU, p<0.001) were lower. There were no differences in cytokines/chemokines levels and aspirin reactivity units between groups. In patients with SCAD and COPD undergoing PCI, ticagrelor, as compared to clopidogrel is superior in improving surrogate markers of endothelial function and on-treatment PR (ClinicalTrials.gov, NCT02519608).

Role of bone mineral density in the inverse relationship between body size and aortic calcification: results from the Baltimore Longitudinal Study of Aging.

OBJECTIVE: There is a J-shaped relationship between body mass index (BMI) and cardiovascular outcomes in elderly patients (obesity paradox). Whether low BMI correlates with aortic calcification (AC) and whether this association is accounted for by bone demineralization is uncertain. METHODS: Presence of AC was evaluated in 687 community-dwelling individuals (49% male, mean age 67 ± 13 years) using CT images of the thoracic, upper and lower abdominal aorta, and scored from 0 to 3 according to number of sites that showed any calcification. Whole-body bone mineral density (BMD) was evaluated by dual-energy X-ray absorptiometry. Predictors of AC were assessed by logistic regression, and the role of BMD using mediation analysis. RESULTS: Age and cardiovascular risk factors were positively associated while both BMI (r = -0.11, p < 0.01) and BMD (r = -0.17, p < 0.0001) were negatively associated with AC severity. In multivariate models, lower BMI (OR 0.96, 95%CI 0.92-0.99, p = 0.01), older age, higher systolic blood pressure, use of lipid-lowering drugs and smoking were independent predictors of AC. A nonlinear relationship between BMI and AC was noticed (p = 0.03), with decreased AC severity among overweight participants. After adjusting for BMD, the coefficient relating BMI to AC was reduced by 14% and was no longer significant, whereas BMD remained negatively associated with AC (OR 0.82, 95%CI 0.069-0.96, p = 0.01), with a trend for a stronger relationship in older participants. CONCLUSION: Low BMI is associated with increased AC, possibly through calcium mobilization from bone, resulting in low BMD. Prevention of weight loss and bone demineralization with aging may help reducing AC.

Impact of central obesity on the estimation of carotid-femoral pulse wave velocity.

BACKGROUND: Studies have found that central obesity is associated with higher carotid-femoral pulse wave velocity (PWV). However, traveled distance (TD) measured over the body surface can be substantially overestimated with wider waist circumference (WC). We sought to investigate whether central obesity biases the estimation of PWV and whether this bias explains the association between PWV and different measures of adiposity. METHODS: Seven hundred eleven participants (49.5% men) from the Baltimore Longitudinal Study of Aging with PWV, anthropometrics, and quantification of different fat depots by computed tomography and dual x-ray absorptiometry were included. TD and relative PWV were estimated with a tape measure over the body surface or linear distances taken from radiological images, unaffected by obesity. RESULTS: A significant association was found between wider WC and a greater difference between the 2 TD measurements and their respective PWV in both sexes (r ≥ 0.34; P < 0.001). This overestimation bias appeared to be generally higher in women than men (0.27 m/sec for each unit increase in WC; P < 0.0001). When TD estimated over the body surface was used to calculate PWV, greater WC, total body fat, subcutaneous fat, and visceral fat were all associated with higher PWV (P < 0.05 for all). However, when PWV was calculated using TD estimated from radiological images or body height, only the association with visceral fat held significant. CONCLUSIONS: When TD is measured over the body surface, the role of obesity on PWV is substantially overestimated. After accounting for this bias, PWV was still independently associated with visceral fat but not with other measures of adiposity, confirming its contribution to arterial stiffening.