Effects of cardiovascular risk factors and pre-existing diseases on the short-term outcome of Takotsubo syndrome.

BACKGROUND: The effects of cardiovascular risk factors (CVRF) on the development of most acute cardiac conditions are well established; however, little is known about the frequency and effects of CVRF in Takotsubo syndrome (TTS) patients. OBJECTIVE: The aim of our study was to compare the frequency of CVRF and pre-existing diseases (PD) of TTS patients to ST-elevation myocardial infarction (STEMI) patients and analyze their effects on short-term outcome. METHODS: We analyzed the frequency of CVRF (hypertension, hyperlipidemia, type II diabetes mellitus, smoking, chronic kidney disease, family history) as well as somatic and psychiatric PD at admission in TTS patients and compared them with STEMI patients. Their effect on short-term outcome was calculated using a combined endpoint of cardiogenic shock, cardiopulmonary resuscitation, mechanical ventilation, and/or in-hospital death. RESULTS: In total, 150 TTS and 155 STEMI patients were included in our study. We observed a higher frequency of psychiatric (30% vs. 7%, p < 0.001), neurological (5% vs. 0%, p = 0.01), and pulmonary (18% vs. 5%, p < 0.001) PD in TTS patients as compared to STEMI patients. There were less smokers (47% vs. 61%, p = 0.03) and patients with hyperlipidemia (24% vs. 51%, p < 0.001) in the TTS cohort than in the STEMI cohort. None of the CVRF or PD behaved as an independent predictor for adverse short-term outcome in TTS patients. CONCLUSION: Psychiatric, neurological, and pulmonary pre-existing diseases are more common in TTS than in STEMI patients. Interestingly, PD and CVRF do not seem to have any impact on the short-term outcome of TTS patients.

The Contribution of Declines in Blood Lead Levels to Reductions in Blood Pressure Levels: Longitudinal Evidence in the Strong Heart Family Study.

BACKGROUND: Chronic lead exposure is associated with both subclinical and clinical cardiovascular disease. We evaluated whether declines in blood lead were associated with changes in systolic and diastolic blood pressure in adult American Indian participants from the SHFS (Strong Heart Family Study). METHODS AND RESULTS: Lead in whole blood was measured in 285 SHFS participants in 1997 to 1999 and 2006 to 2009. Blood pressure and measures of cardiac geometry and function were obtained in 2001 to 2003 and 2006 to 2009. We used generalized estimating equations to evaluate the association of declines in blood lead with changes in blood pressure; cardiac function and geometry measures were considered secondary. Mean blood lead was 2.04 µg/dL at baseline. After ≈10 years, mean decline in blood lead was 0.67 µg/dL. In fully adjusted models, the mean difference in systolic blood pressure comparing the highest to lowest tertile of decline (>0.91 versus <0.27 µg/dL) in blood lead was -7.08 mm Hg (95% CI, -13.16 to -1.00). A significant nonlinear association between declines in blood lead and declines in systolic blood pressure was detected, with significant linear associations where blood lead decline was 0.1 µg/dL or higher. Declines in blood lead were nonsignificantly associated with declines in diastolic blood pressure and significantly associated with declines in interventricular septum thickness. CONCLUSIONS: Declines in blood lead levels in American Indian adults, even when small (0.1-1.0 µg/dL), were associated with reductions in systolic blood pressure. These findings suggest the need to further study the cardiovascular impacts of reducing lead exposures and the importance of lead exposure prevention.

Effect of Austrian COVID-19 lockdowns on acute myocardial infarction frequency and long-term mortality: a multicentre observational study.

OBJECTIVES: The aim of this study was to find out if the decrease in acute myocardial infarction (AMI) admissions during the first COVID-19 lockdowns (LD), which was described by previous studies, occurred equally in all LD periods (LD1, LD2, LD2021), which had identical restrictions. Further, we wanted to analyse if the decrease of AMI admission had any association with the 1-year mortality rate. DESIGN AND SETTING: This study is a prospective observational study of two centres that are participating in the Vienna ST-elevation myocardial infarction network. PARTICIPANTS: A total of 1732 patients who presented with AMI according to the 4th universal definition of myocardial infarction in 2019, 2020 and the LD period of 2021 were included in our study. Patients with myocardial infarction with non-obstructive coronary arteries were excluded from our study. MAIN OUTCOME MEASURES: The primary outcome of this study was the frequency of AMI during the LD periods and the all-cause and cardiac-cause 1-year mortality rate of 2019 (pre-COVID-19) and 2020. RESULTS: Out of 1732 patients, 70% (n=1205) were male and median age was 64 years. There was a decrease in AMI admissions of 55% in LD1, 28% in LD2 and 17% in LD2021 compared with 2019.There were no differences in all-cause 1-year mortality between the year 2019 (11%; n=110) and 2020 (11%; n=79; p=0.92) or death by cardiac causes [10% (n=97) 2019 vs 10% (n=71) 2020; p=0.983]. CONCLUSION: All LDs showed a decrease in AMI admissions, though not to the same extent, even though the regulatory measures were equal. Admission in an LD period was not associated with cardiac or all-cause 1-year mortality rate in AMI patients in our study.

Blood DNA Methylation and Incident Coronary Heart Disease: Evidence From the Strong Heart Study.

Importance: American Indian communities experience a high burden of coronary heart disease (CHD). Strategies are needed to identify individuals at risk and implement preventive interventions. Objective: To investigate the association of blood DNA methylation (DNAm) with incident CHD using a large number of methylation sites (cytosine-phosphate-guanine [CpG]) in a single model. Design, Setting, and Participants: This prospective study, including a discovery cohort (the Strong Heart Study [SHS]) and 4 additional cohorts (the Women's Health Initiative [WHI], the Framingham Heart Study [FHS], the Atherosclerosis Risk in Communities Study ([ARIC]-Black, and ARIC-White), evaluated 12 American Indian communities in 4 US states; African American women, Hispanic women, and White women throughout the US; White men and White women from Massachusetts; and Black men and women and White men and women from 4 US communities. A total of 2321 men and women (mean [SD] follow-up, 19.1 [9.2] years) were included in the SHS, 1874 women (mean [SD] follow-up, 15.8 [5.9] years) in the WHI, 2128 men and women (mean [SD] follow-up, 7.7 [1.8] years) in the FHS, 2114 men and women (mean [SD] follow-up, 20.9 [7.2] years) in the ARIC-Black, and 931 men and women (mean [SD] follow-up, 20.9 [7.2] years) in the ARIC-White. Data were collected from May 1989 to December 2018 and analyzed from February 2019 to May 2021. Exposure: Blood DNA methylation. Main Outcome and Measure: Using a high-dimensional time-to-event elastic-net model for the association of 407 224 CpG sites with incident CHD in the SHS (749 events), this study selected the differentially methylated CpG positions (DMPs) selected in the SHS and evaluated them in the WHI (531 events), FHS (143 events), ARIC-Black (350 events), and ARIC-White (121 events) cohorts. Results: The median (IQR) age of participants in SHS was 55 (49-62) years, and 1359 participants (58.6%) were women. Elastic-net models selected 505 DMPs associated with incident CHD in the SHS beyond established risk factors, center, blood cell counts, and genetic principal components. Among those DMPs, 33 were commonly selected in 3 or 4 of the other cohorts and the pooled hazard ratios from the standard Cox models were significant at P < .05 for 10 of the DMPs. For example, the hazard ratio (95% CI) for CHD comparing the 90th and 10th percentiles of differentially methylated CpGs was 0.86 (0.78-0.95) for cg16604233 (tagged to COL11A2) and 1.23 (1.08-1.39) for cg09926486 (tagged to FRMD5). Some of the DMPs were consistent in the direction of the association; others showed associations in opposite directions across cohorts. Untargeted independent elastic-net models of CHD showed distinct DMPs, genes, and network of genes in the 5 cohorts. Conclusions and Relevance: In this multi-cohort study, blood-based DNAm findings supported an association between a complex blood epigenomic signature and CHD that was largely different across populations.

Can simvastatin reduce COPD exacerbations? A randomised double-blind controlled study.

BACKGROUND: Several studies have shown that statins have beneficial effects in COPD regarding lung function decline, rates and severity of exacerbation, hospitalisation and need for mechanical ventilation. METHODS: We performed a randomised double-blind placebo-controlled single-centre trial of simvastatin at a daily dose of 40 mg versus placebo in patients with Global Initiative for Chronic Obstructive Lung Disease criteria grades 2-4 at a tertiary care pulmonology department in Austria. Scheduled treatment duration was 12 months and the main outcome parameter was time to first exacerbation. RESULTS: Overall, 209 patients were enrolled. In the 105 patients taking simvastatin, time to first exacerbation was significantly longer compared to the 104 patients taking placebo: median 341 versus 140 days (log-rank test p<0.001). Hazard ratio for risk of first exacerbation for the simvastatin group was 0.51 (95% CI 0.34-0.75; p=0.001). Rate of exacerbations was significantly lower with simvastatin: 103 (41%) versus 147 (59%) (p=0.003). The annualised exacerbation rate was 1.45 events per patient-year in the simvastatin group and 1.9 events per patient-year in the placebo group (incidence rate ratio 0.77, 95% CI 0.60-0.99). We found no effect on quality of life, lung function, 6-min walk test and high-sensitivity C-reactive protein. More patients dropped out in the simvastatin group compared to the placebo group (39 versus 29). CONCLUSION: In our single-centre RCT, simvastatin at a dose of 40 mg daily significantly prolonged time to first COPD exacerbation and reduced exacerbation rate.

Cardiac magnetic resonance-derived fibrosis, strain and molecular biomarkers of fibrosis in hypertensive heart disease.

AIMS: Myocardial fibrosis is a relevant component of hypertensive heart disease (HHD). Novel cardiovascular magnetic resonance (CMR) imaging techniques have shown potential in quantification of diffuse cardiac fibrosis, with T1 mapping, and estimating preclinical cardiac dysfunction, with strain analysis. Molecular biomarkers of fibrosis have been related with clinical outcomes and histologically proven myocardial fibrosis. The relationship between these CMR-imaging techniques and circulating biomarkers is not fully understood. METHODS AND RESULTS: CMR was performed on a 3T scanner in 36 individuals with HHD. Extracellular volume fraction (ECV) and the partition coefficient were assessed using the T1 mapping technique shMOLLI. Longitudinal, circumferential and radial strain was assessed using CMR-Feature Tracking. Molecular biomarkers of collagen synthesis (PICP and PIIINP) and collagen degradation (CITP and MMP-1) were measured in blood using commercial kits. Correlation models showed a significant relationship of T1 mapping measures with left atrial diameter, LV mass, LV posterior wall thickness, LV end-diastolic volume and longitudinal strain. In fully adjusted regression models, ECV was associated with left atrial diameter (ß=0.75, P = 0.005) and longitudinal strain (ß = 0.43, P = 0.030); the partition coefficient was associated with LV posterior wall thickness (ß = 0.53, P = 0.046). Strain measures were associated with cardiac geometry, and longitudinal strain was marginally associated with CITP. CONCLUSION: In individuals with HHD, CMR-derived measures of myocardial fibrosis and function are related and might be useful tools for the identification and characterization of preclinical cardiac dysfunction and diffuse myocardial fibrosis. Molecular biomarkers of fibrosis were marginally associated with myocardial strain, but not with the extension of CMR-measured cardiac fibrosis.

Cohort profile: the Hortega Study for the evaluation of non-traditional risk factors of cardiometabolic and other chronic diseases in a general population from Spain.

PURPOSE: The Hortega Study is a prospective study, which investigates novel determinants of selected chronic conditions with an emphasis on cardiovascular health in a representative sample of a general population from Spain. PARTICIPANTS: In 1997, a mailed survey was sent to a random selection of public health system beneficiaries assigned to the University Hospital Rio Hortega's catchment area in Valladolid (Spain) (n=11 423, phase I), followed by a pilot examination in 1999-2000 of 495 phase I participants (phase II). In 2001-2003, the examination of 1502 individuals constituted the Hortega Study baseline examination visit (phase III, mean age 48.7 years, 49% men, 17% with obesity, 27% current smokers). Follow-up of phase III participants (also termed Hortega Follow-up Study) was obtained as of 30 November 2015 through review of health records (9.5% of participants without follow-up information). FINDINGS TO DATE: The Hortega Study integrates baseline information of traditional and non-traditional factors (metabolomic including lipidomic and oxidative stress metabolites, genetic variants and environmental factors, such as metals), with 14 years of follow-up for the assessment of mortality and incidence of chronic diseases. Preliminary analysis of time to event data shows that well-known cardiovascular risk factors are associated with cardiovascular incidence rates, which add robustness to our cohort. FUTURE PLANS: In 2020, we will review updated health and mortality records of this ongoing cohort for a 5-year follow-up extension. We will also re-examine elder survivors to evaluate specific aspects of ageing and conduct geolocation to study additional environmental exposures. Stored biological specimens are available for analysis of new biomarkers. The Hortega Study will, thus, enable the identification of novel factors based on time to event data, potentially contributing to the prevention and control of chronic diseases in ageing populations.

Association of Arsenic Exposure With Cardiac Geometry and Left Ventricular Function in Young Adults.

BACKGROUND: Arsenic exposure has been related to numerous adverse cardiovascular outcomes. The aim of this study was to investigate the cross-sectional and prospective association between arsenic exposure with echocardiographic measures of left ventricular (LV) geometry and functioning. METHODS: A total of 1337 young adult participants free of diabetes mellitus and cardiovascular disease were recruited from the SHFS (Strong Heart Family Study). The sum of inorganic and methylated arsenic concentrations in urine (ΣAs) at baseline was used as a biomarker of arsenic exposure. LV geometry and functioning were assessed using transthoracic echocardiography at baseline and follow-up. RESULTS: Mean follow-up was 5.6 years, and median (interquartile range) of ΣAs was 4.2 (2.8-6.9) µg/g creatinine. Increased arsenic exposure was associated with prevalent LV hypertrophy, with an odds ratio (95% CI) per a 2-fold increase in ΣAs of 1.47 (1.05-2.08) in all participants and of 1.58 (1.04-2.41) among prehypertensive or hypertensive individuals. Measures of LV geometry, including LV mass index, left atrial systolic diameter, interventricular septum, and LV posterior wall thickness, were positively and significantly related to arsenic exposure. Among measures of LV functioning, stroke volume, and ejection fraction were associated with arsenic exposure. CONCLUSIONS: Arsenic exposure was related to an increase in LV wall thickness and LV hypertrophy in young American Indians with a low burden of cardiovascular risk factors. The relationship was stronger in participants with prehypertension or hypertension, suggesting that potential cardiotoxic effects of arsenic might be more pronounced in individuals already undergoing cardiovascular adaptive mechanisms following elevated systemic blood pressure.

Immune-unreactive urinary albumin as a predictor of cardiovascular events: the Hortega Study.

BACKGROUND: We aimed to determine if immune-unreactive albumin excretion (IURAE) is associated with cardiovascular (CV) events in a representative sample of a general population from Spain. METHODS: We included 1297 subjects (mean age ± standard error 48.0 ± 0.2 years, 48% females), who participated in the Hortega Follow-Up Study. The primary endpoint was incidence of fatal and non-fatal CV events. Urinary albumin excretion (UAE) was measured in spot voided urine, frozen at -80°C, by immunonephelometry [immune-reactive albumin excretion (IRAE)] and by high-performance liquid chromatography (HPLC) [total albumin excretion (AE)]. IURAE was calculated as the difference between HPLC measurements and IRAE. We estimated fully adjusted hazard ratios (HRs) of CV incidence by Cox regression for IRAE, IURAE and total AE. RESULTS: After an average at-risk follow-up of 13 years, we observed 172 CV events. urinary albumin to creatinine ratio (UACR) of ≥30 mg/g assessed by IRAE, IURAE or total AE concentrations was observed in 74, 273 and 417 participants, respectively. Among discordant pairs, there were 49 events in those classified as micro- and macroalbuminuric by IURAE, but normoalbuminuric by IRAE. Only the IRAE was a significant independent factor for the incidence of CV events [HR (95% confidence interval) 1.15 (1.04-1.27)]. The association of UAE with CV events was mainly driven by heart failure (HF) [HR 1.33 (1.15-1.55) for IRAE; HR 1.38 (1.06-1.79) for IURAE; HR 1.62 (1.22-2.13) for total AE]. Those subjects who were micro- and macroalbuminuric by both IRAE and IURAE had a significant increase in risk for any CV event, and especially for HF. CONCLUSIONS: IRAE, IURAE and AE were associated with an increased risk for CV events, but IRAE offered better prognostic assessment.

Urinary podocyte-associated molecules and albuminuria in hypertension.

OBJECTIVE: Hypertension-induced podocyte damage and the relationship with UAE is analyzed in diabetic and nondiabetic participants. PATIENTS AND METHODS: Sixty-four hypertensive patients, 30 diabetics, with glomerular filtration rate (eGFR) greater than 60 ml/min per 1.73 m were included. Urinary albumin excretion was measured in morning urine using a nephelometric immunoassay and expressed as albumin/creatinine ratio. Urinary pellets were obtained from fresh urine and mRNA was assessed by real-time quantitative PCR. Likewise, protein podocyte-specific molecules were measured by western blot using specific antibodies. RESULTS: Fourteen nondiabetics and 20 diabetics had increased UAE greater than 30 mg/g. In individuals with increased EUA, the mRNA expression of nephrin and CD2AP was low in diabetics, whereas only nephrin mRNA in nondiabetics. No differences were observed in podocalyxin and aquaporin-1 mRNA levels. Concerning the protein values, in both nondiabetic and diabetic patients, nephrin, CD2AP and podocalyxin were increased in patients with increased UAE, with no differences in aquaporin-1. A significant positive relationship was observed between log UAE and nephrin protein values, and an inverse association observed with mRNA. CONCLUSION: Hypertensive patients who had elevated UAE showed increased urinary excretion of podocyte-specific proteins coupled with a phenotype of decreased mRNA expression. The phenotype of podocyte-specific mRNA and the increment of nephrin can be used as a valuable marker of early glomerular injury.

Urine cadmium levels and albuminuria in a general population from Spain: A gene-environment interaction analysis.

BACKGROUND: The interaction of cadmium with genes involved in oxidative stress, cadmium metabolism and transport pathways on albuminuria can provide biological insight on the relationship between cadmium and albuminuria at low exposure levels. OBJECTIVES: We tested the hypothesis that specific genotypes in candidate genes may confer increased susceptibility to cadmium exposure. METHODS: Cadmium exposure was estimated by inductively coupled plasma mass spectrometry (ICPMS) in urine from 1397 men and women aged 18-85years participating in the Hortega Study, a representative sample of a general population from Spain. Urine albumin was measured by automated nephelometric immunochemistry. Abnormal albuminuria was defined as urine albumin greater than or equal to 30mg/g. RESULTS: The weighted prevalence of abnormal albuminuria was 6.3%. The median level of urine cadmium was 0.39 (IQR, 0.23-0.65) µg/g creatinine. Multivariable-adjusted geometric mean ratios of albuminuria comparing the two highest to the lowest tertile of urine cadmium were 1.62 (95% CI, 1.43-1.84) and 2.94 (95% CI, 2.58-3.35), respectively. The corresponding odds ratios of abnormal albuminuria were 1.58 (0.83, 3.02) and 4.54 (2.58, 8.00). The association between urine cadmium and albuminuria was observed across all participant subgroups evaluated including participants without hypertension, diabetes or chronic kidney disease. We observed Bonferroni-corrected statistically significant interactions between urine cadmium levels and polymorphisms in gene SLC30A7 and RAC1. CONCLUSIONS: Increasing urine cadmium concentrations were cross-sectionally associated with increased albuminuria in a representative sample of a general population from Spain. Genetic variation in oxidative stress and cadmium metabolism and transport genes may confer differential susceptibility to potential cadmium effects.

Prognostic value of bone- and vascular-derived molecular biomarkers in hemodialysis and renal transplant patients: a systematic review and meta-analysis.

BACKGROUND: Patients undergoing hemodialysis and kidney graft recipients are high-risk populations for cardiovascular and all-cause mortality. Fibroblast growth factor 23 (FGF23), osteoprotegerin (OPG), RANK ligand, osteopontin (OPN), Klotho protein and bone morphogenetic protein-7 (BMP-7) are bone- and vascular-derived molecular biomarkers that have been shown to be associated with cardiovascular surrogate end points; however, currently available data on the prognostic value of these biomarkers is inconsistent. The aim of the present study was to conduct a systematic review and meta-analysis in order to summarize the available evidence on the association of molecular biomarkers with mortality in individuals undergoing hemodialysis and renal transplant patients. METHODS: Two databases (MEDLINE and Embase) were systematically searched. Studies were eligible if the association of biomarker and mortality was reported as time-to-event data [hazard Ratio (HR)] or as effect size with a fixed time of follow-up [odds Ratio (OR)]. Abstracted HRs were converted onto a standard scale of effect and combined using a random effects model. RESULTS: From a total of 1170 studies identified in initial searches, 21 met the inclusion criteria. In hemodialysis patients, comparing the lower third with the upper third of baseline FGF23 distribution, pooled HRs (95% confidence intervals) were 1.94 (1.47, 2.56) for all-cause mortality and 2.4 (1.64, 3.51) for cardiovascular mortality. For the same comparison of baseline OPG distribution, pooled HRs were 1.8 (0.95, 3.39) for all-cause mortality and 2.53 (1.29, 4.94) for cardiovascular mortality. Reported risk estimates of RANK ligand, OPN, Klotho protein and BMP-7 were not suitable for pooling; however, only Klotho protein was significantly related to mortality. For kidney graft recipients, four studies that investigated the relationship of FGF23 and OPG with mortality were identified, all of which reported a significant association. CONCLUSIONS: In hemodialysis patients, FGF23 is a predictor of all-cause and cardiovascular mortality, whereas the predictive value of OPG is restricted to cardiovascular mortality. Further studies are needed in order to gain insight into the prognostic value of these biomarkers in renal transplant recipients.

Comparative Study of the Efficacy of Olmesartan/Amlodipine vs. Perindopril/Amlodipine in Peripheral and Central Blood Pressure Parameters After Missed Dose in Type 2 Diabetes.

BACKGROUND: Central aortic blood pressure (CBP) and CBP-derived parameters are independent predictors of cardiovascular risk. Angiotensin II receptor blockers (ARBs) or angiotensin-converting enzyme inhibitors plus calcium channel blockers are the recommended first-line treatments in hypertensive diabetic patients; however, the effect in reducing CBP when a dose is skipped has not been established yet. The aim was to determine whether the fixed-dose combination of olmesartan/amlodipine (OLM/AML) provides equal efficacy and safety as the perindopril/AML (PER/AML) combination in reducing CBP, augmentation index (AIx), and pulse wave velocity (PWV) when a drug dose is missed. METHODS: In this noninferiority, randomized, double-blind, double-dummy parallel group, controlled design trial, 88 patients received either OLM 20-40mg/AML 5-10mg (41 patients) or PER 4-8mg/AML 5-10mg (47 patients) for 24 weeks. The main endpoint was the aortic systolic BP (SBP) after 24 weeks of treatment at 48 hours from the last administration. RESULTS: The OLM/AML combination reached the noninferiority criteria in reducing central systolic BP after 24 weeks of treatment and after the missed dose, compared to the PER/AML combination (-17 and -8mm Hg, respectively). Peripheral BP, AIx, and PWV were significantly lower in both groups after 24 weeks of treatment and 48 hours after the missed dose, observing a trend to a greater reduction in CBP-derived parameters in the OLM/AML group. CONCLUSIONS: The OLM/AML combination is safe, well tolerated, and not inferior to the combination of PER/AML in lowering CBP and CBP-derived parameters in diabetic patients. OLM/AML provides longer-lasting efficacy in terms of CBP reduction compared to PER/AML.

Comparative study of the efficacy of olmesartan/amlodipine vs. perindopril/amlodipine in peripheral blood pressure after missed dose in type 2 diabetes.

INTRODUCTION: Combination therapy is needed to control blood pressure (BP) in a large number of hypertensive patients with diabetes mellitus. Adherence to treatment is a major clinical problem; therefore, the time duration of the antihypertensive action of a drug determines BP control when a dose is skipped. OBJECTIVES: The aim was to determine whether the fixed-dose combination of olmesartan/amlodipine provides equal efficacy and safety as the perindopril/amlodipine combination when a drug dose is missed. METHODS: In this noninferiority trial with a randomized, double-blind, double-dummy parallel group, controlled design, 260 patients received either olmesartan 20-40 mg/amlodipine 5-10 mg or perindopril 4-8 mg/amlodipine 5-10 mg for 24 weeks. The main outcome was the sitting office DBP after 24 weeks of treatment at 48 h from last administration. RESULTS: The olmesartan/amlodipine combination reached noninferiority criteria in reduction of office DBP after 24 weeks of treatment and after the missed dose, compared with the perindopril/amlodipine combination (-11.7 and -10.5 mmHg, respectively). Office SBP and pulse pressure were significantly lower in both groups after 24 weeks of treatment and 48 h after the missed dose, observing a trend to greater SBP reduction in the olmesartan/amlodipine group. CONCLUSIONS: The combination olmesartan/amlodipine is safe, well tolerated, and as effective as the combination of perindopril/amlodipine in the control of essential hypertension in patients with diabetes mellitus. A missed dose does not leave the patients unprotected in both treatments; however, a faster control with less dose increment is observed with olmesartan/amlodipine.

Pulse pressure amplification and its determinants.

BACKGROUND: Pulse pressure (PP) amplification expressed as the peripheral-to-central PP ratio has gained importance in the assessment of cardiovascular phenotypes and cardiovascular risk. The aim of the present study was to assess the relationship between PP amplification, large vessel parameters and peripheral blood pressure (BP) to gain insights into the amplification phenomenon. METHODS: Peripheral BP, central BP and carotid-femoral pulse wave velocity (cfPWV) were assessed using the OMRON M6, SphygmoCor and Complior devices, respectively, in 741 adults attending the hypertension outpatient clinic. Analysis of covariance, partial correlations and multiple linear regression models were performed to assess the relationship between PP amplification, peripheral BP and cfPWV. RESULTS: PP amplification was inversely related to BP group. Women showed lower PP amplification than men (1.24 ± 0.18 and 1.35 ± 0.18, respectively, p < 0.001). Age, female gender and mean arterial pressure were inversely associated with PP amplification (p < 0.001), whereas heart rate and body mass index showed positive associations (p < 0.001 and p = 0.049, respectively). cfPWV was a predictor of PP amplification in men but not in women (p = 0.006 and p = 0.424, respectively). CONCLUSIONS: PP amplification is related to BP: the higher the BP, the lower the PP amplification. Gender, age and body composition have a significant impact on PP amplification.

Carotid-femoral pulse wave velocity assessment by two different methods: implications for risk assessment.

INTRODUCTION: Several devices are available for carotid-femoral pulse wave velocity (cfPWV) measurement, and a cut-off value for reference cfPWV has been established. However, discrepancies between devices have been reported. OBJECTIVES: The aim of the study was to establish the concordance of two common techniques (Complior and SphygmoCor), taking into account the anatomical distance between the measurement sites, and to investigate the impact on cardiovascular risk stratification. METHODS: cfPWV, central and peripheral blood pressure were assessed in patients attending the hypertension outpatient clinic. The subtracted carotid-femoral distance was estimated both according to the manufacturer's recommendations and correcting the obtained values by 10.3%. Bland-Altman plots, Pearson's correlation coefficient, Lin's concordance correlation coefficient and multivariate models were used to investigate the difference in cfPWV. RESULTS: cfPWV assessed in 118 patients (age 55 ±â€Š12 years, 61% hypertensive patients, BMI 28.9 ±â€Š4.4  kg/m2) with the Complior device was lower than that assessed with the SphygmoCor device, regardless of correcting the subtracted carotid-femoral distance (8.7 vs. 10.3  m/s and 9.3  m/s, respectively; P value < 0.001). The average difference was -1.59 ±â€Š1.5 and -0.617 ±â€Š1.39  m/s for corrected and uncorrected SphygmoCor values, respectively, SBP, BMI and female being the main determinants of the difference. Cardiovascular risk stratification changed in up to 40% of the study population, depending on the device and the arterial distance estimation. CONCLUSION: The concordance between the Complior and the SphygmoCor device is poor when the anatomical artery length is controlled for and in the presence of cardiovascular risk factors, resulting in a difference in classification of cardiovascular risk.

Influence of obesity in central blood pressure.

BACKGROUND: Obesity is an important risk factor for cardiovascular disease and has become a major concern in healthcare due to its high prevalence worldwide. The aim of the present study was to investigate the impact of BMI on central blood pressure (BP) and pulse wave velocity (PWV) in normotensive and hypertensive patients. PATIENTS AND METHODS: Normotensive and hypertensive adult patients who attended the outpatient clinic of cardiovascular risk were included. Peripheral BP was obtained in the brachial artery by using an oscillometric device (OMRON M-6). Central aortic BP waveform was reconstructed from the radial artery pressure waveforms (SphygmoCor, AtCor Medical, Sydney, Australia) and central BP was calculated. Carotid-femoral PWV was measured by an automatic device (Complior, Artech, France). RESULTS: We examined a total of 351 patients [50.7% women; 77 patients normal-weight (BMI < 25 kg/m)], 274 patients overweight or obese (BMI ≥25 kg/m). Central SBP showed a positive association with male sex and mean BP, but a negative association with overweight/obesity. PWV was positively associated with age, male sex, central BP, peripheral BP and BP treatment, whereas BMI of at least 25 kg/m led to a decrease in PWV in patients with the same central SBP levels. Likewise, PWV was lower in the overweight/obese group compared to the normal-weight group at the same central SBP. CONCLUSION: Overweight and obesity tend to have lower central SBP as compared to lean patients, mainly in women. Further research is required to assess the interaction between body weight and vascular dynamics and their clinical implications.

Should we look for silent pulmonary embolism in patients with deep venous thrombosis?

BACKGROUND: Asymptomatic or silent pulmonary embolism (S-PE) in patients with deep vein thrombosis has been the focus of numerous publications with the objective of determining the incidence of S-PE and assessing whether its existence has any clinical or therapeutic consequences that outweigh the risks associated with the diagnostic tests performed and the increased healthcare costs. The objectives were to assess the incidence of S-PE using computed tomography angiogram (CTA), to understand the epidemiological factors that might trigger embolism, and to assess whether D-dimer (DD) predicts the existence of S-PE's. METHODS: A prospective and consecutive assessment of 103 hospitalized patients with lower limb DVT in the absence of PE symptoms, using CT scan. DD was quantified before anticoagulation. The risk factors and characteristics of the DVT were studied. A three-year follow-up assessing risk recurrence and clinical outcome was performed. RESULTS: The incidence of S-PE was 66%. In 77% of these cases, the main and lobar pulmonary arteries were affected. Iliac and femoral DVTs most often produced S-PE. ROC curve with a DD value higher than 578 ng/ml provided good sensitivity but low specificity to identify patients with S-PE. Diagnosis entailed higher hospitalization expenses. No significant recurrence rate of thrombotic events was observed in the S-PE group during the follow-up. CONCLUSIONS: The incidence of S-PE in lower-limb DVT is high, but in the absence of symptoms, diagnosis does not appear to be necessary, as there are no short- or long-term clinical or therapeutic consequences.