A new technique for assessing arterial pressure wave forms and central pressure with tissue Doppler

Background

Arterial diameters enlarge in response to wall thickening, plaques, and many atherosclerotic risk factors. We hypothesized that right common carotid artery (RCCA) diameter would be independently associated with cardiac disease and improve risk discrimination.

Methods

In a middle-aged, biracial population (baseline n = 11225), we examined associations between 1 standard deviation increments of baseline RCCA diameter with prevalent myocardial infarction (MI) and incident cardiac events (MI or cardiac death) using logistic regression and Cox proportional hazards models, respectively. Areas under the receiver operator characteristic curve (AUC) were used to estimate model discrimination.

Results

MI was present in 451 (4%) participants at baseline (1987–89), and incident cardiac events occurred among 646 (6%) others through 1999. Adjusting for IMT, RCCA diameter was associated with prevalent MI (female OR = 2.0, 95%CI = 1.61–2.49; male OR = 1.16, 95% CI = 1.04–1.30) and incident cardiac events (female HR = 1.75, 95% CI = 1.51–2.02; male HR = 1.27, 95% CI = 1.15–1.40). Associations were attenuated but persisted after adjustment for risk factors (not including IMT) (prevalent MI: female OR = 1.73, 95% CI = 1.40–2.14; male OR = 1.14, 95% CI = 1.02–1.28, and incident cardiac events: female HR = 1.26, 95% CI = 1.08–1.48; male HR = 1.19, 95% CI = 1.08–1.32). After additional adjustment for IMT, diameter was associated with incident cardiac events in women (HR = 1.18, 95% CI = 1.00–1.40) and men (HR = 1.17, 95% CI = 1.06–1.29), and with prevalent MI only in women (OR = 1.73; 95% CI = 1.37–2.17). In women, when adjustment was limited, diameter models had larger AUC than other models.

Conclusion

RCCA diameter is an important correlate of cardiac events, independent of IMT, but adds little to overall risk discrimination after risk factor adjustment.     

Atherosclerotic plaques occur in absence of intima-media thickening in both systemic sclerosis and systemic lupus erythematosus: a duplexsonography study of carotid and femoral arteries and follow-up for cardiovascular events

Introduction

The objective of this cross-sectional and retrospective cohort study was (1) to determine the usefulness of intima-media thickness (IMT) in contrast to plaque assessment, (2) to examine the value of additive femoral artery sonography and (3) to identify potential risk factors for atherosclerosis and incident cardiovascular events in systemic sclerosis (SSc) and systemic lupus erythematosus (SLE) patients.

Methods

In this study, 90 SSc and 100 SLE patients were examined by duplexsonography. IMT was measured in common carotid and common femoral arteries, plaques were assessed in common, internal and external carotid and common, proximal superficial and deep femoral arteries. Different definitions of pathological IMT (pIMT) were compared with the presence of plaque. Results were evaluated in relation to traditional and non-traditional risk factors for baseline atherosclerosis (logistic regression) and their predictive value for cardiovascular events during follow-up (cox regression).

Results

Definite atherosclerosis occurred frequently without signs of subclinical atherosclerosis in both diseases: pIMT >0.9 mm was present in only 17/59 (28.9%) SSc and 13/49 (26.5%) SLE patients with already present atherosclerotic plaques. Using age-adjusted pIMT definitions, this rate was even lower (5.1-10.3% in SSc, 14.3-26.5% in SLE). Plaques were located only at the carotid or only at the femoral arteries in 26 (13.7%) and 24 (12.6%) patients, respectively. Age and nicotine pack-years were independently associated with atherosclerotic plaques in SLE and SSc patients, as well as the cumulative prednisolone dose in SSc subgroup, and ssDNA positive SLE patients had a lower risk for atherosclerotic plaque. During follow-up (available for 129/190 (67.9%) patients, 650 person-years), cardiovascular events occurred more often in patients with coronary heart disease (adjusted-hazards ratio (HR) 10.19, 95% confidence interval (CI) 3.04 to 34.17, P <0.001), male patients (adjusted-HR 8.78, 95% CI 2.73 to 28.19, P <0.001) and in patients with coexistent carotid and femoral plaques (adjusted-HR 5.92, 95% CI 1.55 to 22.67, P = 0.009). Patients with solely carotid or femoral plaque were not at higher risk.

Conclusion

Atherosclerotic plaque lesions can be found frequently in absence of intima-media thickening in both SSc and SLE patients. As well as routine sonography of carotid arteries, the sonography of femoral arteries is recommended to identify additional atherosclerotic lesions and to detect patients at a high risk for cardiovascular events.     

Carotid artery intima-media thickness, carotid plaque and coronary heart disease and stroke in Chinese

Background

Our aim was to prospectively investigate the association between carotid artery intima-media thickness (IMT) as well as carotid plaque and incidence of coronary heart disease (CHD) and stroke in Chinese, among whom data are limited.

Methods and Findings

We conducted a community-based cohort study composed of 2190 participants free of cardiovascular disease at baseline in one community. During a median 10.5-year follow up, we documented 68 new cases of coronary heart disease and 94 cases of stroke. The multivariate relative risks (RRs) associated with a change of 1 standard deviation of maximal common carotid IMT were 1.38 (95% confidence interval [CI], 1.12–1.70) for CHD and 1.47 (95% CI, 1.28–1.69) for stroke. The corresponding RRs with internal carotid IMT were 1.47 (95% CI, 1.21–1.79) for CHD and 1.52 (95% CI, 1.31–1.76) for stroke. Carotid plaque measured by the degree of diameter stenosis was also significantly associated with increased risk of CHD (p for trend<0.0001) and stroke (p for trend<0.0001). However, these associations were largely attenuated when adjusting for IMT measurements.

Conclusions

This prospective study indicates a significant association between carotid IMT and incidence of CHD and stroke in Chinese adults. These measurements may be useful for cardiovascular risk assessment and stratification in Chinese.     

Carotid Atherosclerotic Disease Predicts Cardiovascular Events in Hemodialysis Patients: A Prospective Study

Background

To evaluate the predictive value of carotid atherosclerotic disease (CAD) and intima-media thickness (IMT) on incident cardiovascular disease and mortality in hemodialysis patients.

Methods

Multicenter, observational, prospective study including 110 patients, followed-up to 6 years. Carotid doppler ultrasonographic findings were classified in 4 degrees of severity: 1) IMT <0.9 mm, 2) IMT >0.9 mm, 3) carotid plaque with stenosis <50% and 4) plaque with stenosis >50%. The associations between IMT and CAD and cardiovascular events, total and cardiovascular mortality were assessed.

Results

83% of the patients had atherosclerotic plaques (CAD degrees 3-4). During follow-up, 29.1% of patients experienced cardiovascular events, and 28.2% died, 38.7% of cardiovascular origin. The presence of plaques was associated with cardiovascular events (p = 0.03) while calcified plaques were associated with both cardiovascular events (p = 0.01), cardiovascular mortality (p = 0.03) and non-significantly with overall mortality (p = 0.08) in the survival analysis. Carotid IMT was not associated with outcomes. Cardiovascular events correlated with CAD severity (HR 2.27, 95% CI 1.13-4.54), age (HR 1.04, 1.01-1.06), previous cardiovascular disease (HR 1.75, 1.05-4.42), dyslipidemia (HR 2.25, 1.11-4.53), lipoprotein (a) (HR 1.01, 1.00-1.02), troponin I (HR 3.89, 1.07-14.18), fibrinogen levels (HR 1.38, 0.98-1.94) and antiplatelet therapy (HR 2.14, 1.04-4.4). In an age-adjusted multivariate model, cardiovascular events were independently associated with previous coronary artery disease (HR 3.29, 1.52-7.15) and lipoprotein (a) (HR 1.01, 1.00-1.02).

Conclusions

The presence of carotid plaques and, especially, calcified plaques, are predictors of new cardiovascular events and cardiovascular mortality in hemodialysis patients, while IMT was not. The prognostic value of calcified plaques should be confirmed in future studies.     

Is Hepatitis C Associated with Atherosclerotic Burden? A Systematic Review and Meta-Analysis

Background and Aims

Increasing evidence demonstrates that hepatitis C virus (HCV) infection is associated with atherosclerosis. However, there are contrasting findings in several studies that the atherosclerotic burden is not associated with HCV infections. Therefore, we performed a meta-analysis to clarify if HCV infection is associated with atherosclerosis compared to non-infected people.

Methods

Standard guidelines for performance of meta-analysis were followed.

Results

A thorough database search performed by two independent investigators identified 14 eligible studies for analysis. The data from 11 studies were synthesized to report unadjusted odds ratios (ORs) for carotid atherosclerosis; the pooled unadjusted OR (95% confidence interval (CI)) was 1.65 (1.21, 2.09). By synthesizing the data from 8 studies to report adjusted ORs for carotid atherosclerosis the pooled multi-confounder adjusted OR (95% CI) was 1.76 (1.20, 2.32). However, the numbers of studies on coronary or femoral atherosclerosis were limited and not enough for analysis.

Conclusions

Our meta-analysis indicats that HCV infection is associated with carotid atherosclerosis independent of classical risk factors. Therefore, we would recommend for HCV infected patients to be counseled on their risk for carotid atherosclerosis.     

Extremely short duration high intensity interval training substantially improves insulin action in young healthy males

Background

Impaired glucose tolerance (IGT) is a prediabetic state. If IGT can be prevented from progressing to overt diabetes, hyperglycemia-related complications can be avoided. The purpose of the present study was to examine whether pioglitazone (ACTOS^®) can prevent progression of IGT to type 2 diabetes mellitus (T2DM) in a prospective randomized, double blind, placebo controlled trial.

Methods/Design

602 IGT subjects were identified with OGTT (2-hour plasma glucose = 140–199 mg/dl). In addition, IGT subjects were required to have FPG = 95–125 mg/dl and at least one other high risk characteristic. Prior to randomization all subjects had measurement of ankle-arm blood pressure, systolic/diastolic blood pressure, HbA_1C, lipid profile and a subset had frequently sampled intravenous glucose tolerance test (FSIVGTT), DEXA, and ultrasound determination of carotid intima-media thickness (IMT). Following this, subjects were randomized to receive pioglitazone (45 mg/day) or placebo, and returned every 2–3 months for FPG determination and annually for OGTT. Repeat carotid IMT measurement was performed at 18 months and study end. Recruitment took place over 24 months, and subjects were followed for an additional 24 months. At study end (48 months) or at time of diagnosis of diabetes the OGTT, FSIVGTT, DEXA, carotid IMT, and all other measurements were repeated. Primary endpoint is conversion of IGT to T2DM based upon FPG ≥ 126 or 2-hour PG ≥ 200 mg/dl. Secondary endpoints include whether pioglitazone can: (i) improve glycemic control (ii) enhance insulin sensitivity, (iii) augment beta cell function, (iv) improve risk factors for cardiovascular disease, (v) cause regression/slow progression of carotid IMT, (vi) revert newly diagnosed diabetes to normal glucose tolerance.

Conclusion

ACT NOW is designed to determine if pioglitazone can prevent/delay progression to diabetes in high risk IGT subjects, and to define the mechanisms (improved insulin sensitivity and/or enhanced beta cell function) via which pioglitazone exerts its beneficial effect on glucose metabolism to prevent/delay onset of T2DM.

Trial Registration

clinical trials.gov identifier: NCT00220961     

Effect of changes in contractility on the index of myocardial performance in the dysfunctional left ventricle

Background

Carotid plaque severity and morphology can affect cardiovascular prognosis. We evaluate both the importance of echographically assessed carotid artery plaque geometry and morphology as predictors of death in hospitalised cardiological patients.

Methods

541 hospitalised patients admitted in a cardiological division (age = 66 ± 11 years, 411 men), have been studied through ultrasound Duplex carotid scan and successively followed-up for a median of 34 months. Echo evaluation assessed plaque severity and morphology (presence of heterogeneity and profile).

Results

361 patients showed carotid stenosis (67% with <50% stenosis, 18% with 50–69% stenosis, 9% with >70% stenosis, 4% with near occlusion and 2% with total occlusion). During the follow-up period, there were 83 all-cause deaths (15% of the total population). Using Cox's proportional hazard model, age (RR 1.06, 95% CI 1.03–1.09, p = 0.000), ejection fraction > 50% (RR = 0.62, 95% CI 0.4–0.96, p = 0.03), treatment with statins (RR = 0.52, 95% CI 0.29–0.95, p = 0.34) and the presence of a heterogeneous plaque (RR 1.6; 95% CI, 1.2 to 2.14, p = 0.002) were independent predictors of death. Kaplan – Meier survival estimates have shown the best outcome in patients without plaque, intermediate in patients with homogeneous plaques and the worst outcome in patients with heterogeneous plaques (90% vs 79% vs 73%, p = 0.0001).

Conclusion

In hospitalised cardiological patients, carotid plaque presence and morphology assessed by ultrasound are independent predictors of death.     

Effect of Helicobacter pylori eradication on gastric precancerous lesions: A systematic review and meta-analysis

Background

The question of whether eradication of Helicobacter pylori (Hp) can reverse gastric precancerous lesions, including intestinal metaplasia, remains uncertain, leading to ongoing debate. Therefore, a meta-analysis was performed to evaluate the effect of Hp eradication on gastric precancerous lesions.

Materials and Methods

PubMed, Embase, Cochrane Library, Web of Science, Scopus database, and ClinicalTrials.gov were systematically searched from inception to April 2023 for studies that explored the impact of Hp eradication on gastric precancerous lesions. Risk ratios (RRs) and their 95% confidence intervals (95% CIs) were selected as the effect size. We used the random-effects model to assess pooled data. We also performed quality assessments, subgroup analyses, and sensitivity analyses.

Results

Fifteen studies were included. Compared with placebo, Hp eradication could significantly prevent the progression of gastric precancerous lesions (RR = 0.87, 95% CI: 0.81–0.94, p < 0.01) and reverse them (RR = 1.32, 95% CI: 1.17–1.50, p < 0.01). Then, specific precancerous lesions were further explored. The progression of intestinal metaplasia was significantly prevented by Hp eradication compared to placebo or no treatment (RR = 0.80, 95% CI: 0.69–0.94, p < 0.01). Moreover, compared with placebo or no treatment, Hp eradication also improved chronic atrophic gastritis (RR = 1.84, 95% CI: 1.30–2.61, p < 0.01) and intestinal metaplasia (RR = 1.41, 95% CI: 1.15–1.73, p < 0.01). However, in terms of preventing dysplasia progression (RR = 0.86, 95% CI: 0.37–2.00) and improving dysplasia (RR = 0.89, 95% CI: 0.47–1.70), Hp eradication had no advantage compared to placebo or no treatment.

Conclusions

Hp eradication therapy could prevent the progression of gastric precancerous lesions and reverse them. Notably, intestinal metaplasia can be reversed, but this may only be appropriate for patients with epigenetic alterations and milder lesions.     

log(TG)/HDL-C is related to both residual cardiometabolic risk and β-cell function loss in type 2 diabetes males

Background

To study the relationship between the intima-media thickness (IMT) of the carotid artery and the stage of chronic kidney disease (CKD) based on the estimated glomerular filtration rate (eGFR) and diabetic nephropathy graded by the urinary albumin excretion (UAE) in the patients with type 2 diabetes mellitus.

Methods

A cross-sectional study was performed in 338 patients with type 2 diabetes mellitus. The carotid IMT was measured using an ultrasonographic examination.

Results

The mean carotid IMT was 1.06 ± 0.27 mm, and 42% of the subjects showed IMT thickening (≥ 1.1 mm). Cerebrovascular disease and coronary heart disease were frequent in the patients with IMT thickening. The carotid IMT elevated significantly with the stage progression of CKD (0.87 ± 0.19 mm in stage 1, 1.02 ± 0.26 mm in stage 2, 1.11 ± 0.26 mm in stage 3, and 1.11 ± 0.27 mm in stage 4+5). However, the IMT was not significantly different among the various stages of diabetic nephropathy. The IMT was significantly greater in the diabetic patients with hypertension compared to those without hypertension. The IMT positively correlated with the age, the duration of diabetes mellitus, and the brachial-ankle pulse wave velocities (baPWV), and negatively correlated with the eGFR. In a stepwise multivariate regression analysis, the eGFR and the baPWV were independently associated with the carotid IMT.

Conclusions

Our study is the first report showing a relationship between the carotid IMT and the renal parameters including eGFR and the stages of diabetic nephropathy with a confirmed association between the IMT and diabetic macroangiopathy. Our study further confirms the importance of intensive examinations for the early detection of atherosclerosis and positive treatments for hypertension, dyslipidaemia, obesity, as well as hyperglycaemia are necessary when a reduced eGFR is found in diabetic patients.     

Fine Particulate Air Pollution and the Progression of Carotid Intima-Medial Thickness: A Prospective Cohort Study from the Multi-Ethnic Study of Atherosclerosis and Air Pollution

Background

Fine particulate matter (PM_2.5) has been linked to cardiovascular disease, possibly via accelerated atherosclerosis. We examined associations between the progression of the intima-medial thickness (IMT) of the common carotid artery, as an indicator of atherosclerosis, and long-term PM_2.5 concentrations in participants from the Multi-Ethnic Study of Atherosclerosis (MESA).

Methods and Results

MESA, a prospective cohort study, enrolled 6,814 participants at the baseline exam (2000–2002), with 5,660 (83%) of those participants completing two ultrasound examinations between 2000 and 2005 (mean follow-up: 2.5 years). PM_2.5 was estimated over the year preceding baseline and between ultrasounds using a spatio-temporal model. Cross-sectional and longitudinal associations were examined using mixed models adjusted for confounders including age, sex, race/ethnicity, smoking, and socio-economic indicators. Among 5,362 participants (5% of participants had missing data) with a mean annual progression of 14 µm/y, 2.5 µg/m³ higher levels of residential PM_2.5 during the follow-up period were associated with 5.0 µm/y (95% CI 2.6 to 7.4 µm/y) greater IMT progressions among persons in the same metropolitan area. Although significant associations were not found with IMT progression without adjustment for metropolitan area (0.4 µm/y [95% CI −0.4 to 1.2 µm/y] per 2.5 µg/m³), all of the six areas showed positive associations. Greater reductions in PM_2.5 over follow-up for a fixed baseline PM_2.5 were also associated with slowed IMT progression (−2.8 µm/y [95% CI −1.6 to −3.9 µm/y] per 1 µg/m³ reduction). Study limitations include the use of a surrogate measure of atherosclerosis, some loss to follow-up, and the lack of estimates for air pollution concentrations prior to 1999.

Conclusions

This early analysis from MESA suggests that higher long-term PM_2.5 concentrations are associated with increased IMT progression and that greater reductions in PM_2.5 are related to slower IMT progression. These findings, even over a relatively short follow-up period, add to the limited literature on air pollution and the progression of atherosclerotic processes in humans. If confirmed by future analyses of the full 10 years of follow-up in this cohort, these findings will help to explain associations between long-term PM_2.5 concentrations and clinical cardiovascular events. Please see later in the article for the Editors'' Summary     

One-year health status outcomes of unstable angina versus myocardial infarction: a prospective, observational cohort study of ACS survivors

Background

Unstable angina (UA) patients have lower mortality and reinfarction risks than ST-elevation (STEMI) or non-ST elevation myocardial infarction (NSTEMI) patients and, accordingly, receive less aggressive treatment. Little is known, however, about the health status outcomes (angina, physical function, and quality of life) of UA versus MI patients among survivors of an ACS hospitalization.

Methods

In a cohort of 1,192 consecutively enrolled ACS survivors from two Kansas City hospitals, we evaluated the associations between ACS presentation (UA, NSTEMI, and STEMI) and one-year health status (angina, physical functioning and quality of life), one-year cardiac rehospitalization rates, and two-year mortality outcomes, using multivariable regression modeling.

Results

After multivariable adjustment for demographic, hospital, co-morbidity, baseline health status, and treatment characteristics, UA patients had a greater prevalence of angina at 1 year than STEMI patients (adjusted relative risk [RR] = 1.42; 95% CI [1.06, 1.90]) and similar rates as NSTEMI patients (adjusted RR = 1.1; 95% CI [0.85, 1.42]). In addition, UA patients fared no better than MI patients in Short Form-12 physical component scores (UA vs. STEMI score difference -0.05 points; 95% CI [-2.41, 2.3]; UA vs. NSTEMI score difference -1.91 points; 95% CI [-4.01, 0.18]) or Seattle Angina Questionnaire quality of life scores (UA vs. STEMI score difference -1.39 points; 95% CI [-5.63, 2.85]; UA vs. NSTEMI score difference -0.24 points 95% CI [-4.01, 3.54]). Finally, UA patients had similar rehospitalization rates as MI patients (UA vs. STEMI adjusted hazard ratio [HR] = 1.31; 95% CI [0.86, 1.99]; UA vs. NSTEMI adjusted HR = 1.03; 95% CI [0.73, 1.47]), despite better 2-year survival (UA vs. STEMI adjusted HR = 0.51; 95% confidence interval (CI) [0.28, 0.95]; UA vs. NSTEMI adjusted HR = 0.40; 95% CI [0.24, 0.65]).

Conclusion

Although UA patients have better survival rates, they have similar or worse one-year health status outcomes and cardiac rehospitalization rates as compared with MI patients. Clinicians should be aware of the adverse health status outcome risks for UA patients and consider close monitoring for the opportunity to improve their health status and minimize the need for subsequent rehospitalization.     

Effect of streptozotocin-induced diabetes on myocardial blood flow reserve assessed by myocardial contrast echocardiography in rats

Background

Hypertension and type 2 diabetes are common co-morbidities. Preliminary studies suggest that thiazolidinediones reduce blood pressure (BP). We therefore used ambulatory BP to quantify BP lowering at 6–12 months with rosiglitazone used in combination with metformin or sulfonylureas compared to metformin and sulfonylureas in people with type 2 diabetes.

Methods

Participants (n = 759) in the multicentre RECORD study were studied. Those taking metformin were randomized (open label) to add-on rosiglitazone or sulfonylureas, and those on sulfonylurea to add-on rosiglitazone or metformin.

Results

24-Hour ambulatory BP was measured at baseline, 6 months and 12 months. At 6 and 12 months, reductions in 24-hour ambulatory systolic BP (sBP) were greater with rosiglitazone versus metformin (difference at 6 months 2.7 [95% CI 0.5–4.9] mmHg, p = 0.015; 12 months 2.5 [95% CI 0.2–4.8] mmHg, p = 0.031). Corresponding changes for ambulatory diastolic BP (dBP) were comparable (6 months 2.7 [95% CI 1.4–4.0] mmHg, p < 0.001; 12 months 3.1 [95% CI 1.8–4.5] mmHg, p < 0.001). Similar differences were observed for rosiglitazone versus sulfonylureas at 12 months (sBP 2.7 [95% CI 0.5–4.9] mmHg, p = 0.016; dBP 2.1 [95% CI 0.7–3.4] mmHg, p = 0.003), but differences were smaller and/or not statistically significant at 6 months (sBP 1.5 [95% CI -0.6 to 3.6] mmHg, p = NS; dBP 1.3 [95% CI 0.0–2.5] mmHg, p = 0.049). Changes in BP were not accompanied by compensatory increases in heart rate, did not correlate with basal insulin sensitivity estimates and were not explained by changes in antihypertensive therapy between the various strata.

Conclusion

When added to metformin or a sulfonylurea, 12-month treatment with rosiglitazone reduces ambulatory BP to a greater extent than when metformin and a sulfonylurea are combined.

Trial registration

NCT00379769 http://clinicaltrials.gov/     

Carotid Artery Longitudinal Displacement,Cardiovascular Disease and Risk Factors: The Multi-Ethnic Study of Atherosclerosis

Background

Associations between carotid artery longitudinal displacement, cardiovascular disease risk factors, and events were evaluated in a large, multi-ethnic cohort.

Materials and Methods

A novel, reproducible protocol was developed for measuring right common carotid artery longitudinal displacement using ultrasound speckle-tracking. Total longitudinal displacement was measured in 389 randomly selected participants from the Multi-Ethnic Study of Atherosclerosis that were free of cardiovascular disease at baseline. Univariate analyses and Pearson Correlations were used to define relationships between longitudinal displacement with traditional cardiovascular risk factors and traditional measures of arterial stiffness. Hazard ratios of longitudinal displacement for cardiovascular disease and coronary heart disease events were compared using Cox proportional hazards models.

Results

Participants were a mean (standard deviation) 59.0 (8.7) years old, 48% female, 39% White, 26% Black, 22% Hispanic, and 14% Chinese. They had 19 (4.9%) cardiovascular disease and 14 (3.6%) coronary heart disease events over a mean 9.5 years of follow-up. Less longitudinal displacement was associated with Chinese (β = -0.11, p = 0.02) compared to White race/ethnicity and greater longitudinal displacement was associated with higher carotid intima-media thickness (β = 0.26, p = 0.004). Longitudinal displacement was not associated with other cardiovascular disease risk factors or markers of arterial stiffness. After adjustment for age and sex, and heart rate, Chinese race/ethnicity (β = -0.10, p = 0.04) and carotid intima-media thickness (β = 0.30 p = 0.003) were associated independently with longitudinal displacement. Longitudinal displacement predicted coronary heart disease (Hazard ratio [HR] 3.3, 95% Confidence intervals [CI] 0.96–11.14, p = 0.06) and cardiovascular disease (HR 2.1, 95% CI 0.6–7.3, p = 0.23) events.

Conclusions

Less longitudinal displacement is associated with Chinese ethnicity and greater carotid artery longitudinal displacement is associated with thicker intima-media thickness. Longitudinal displacement may predict adverse coronary heart disease and cardiovascular disease events.     

Endothelial Progenitor Cells Predict Cardiovascular Events after Atherothrombotic Stroke and Acute Myocardial Infarction. A PROCELL Substudy

Introduction

The aim of this study was to determine prognostic factors for the risk of new vascular events during the first 6 months after acute myocardial infarction (AMI) or atherothrombotic stroke (AS). We were interested in the prognostic role of endothelial progenitor cells (EPC) and circulating endothelial cells (CEC)

Methods

Between February 2009 and July 2012, 100 AMI and 50 AS patients were consecutively studied in three Spanish centres. Patients with previously documented coronary artery disease or ischemic strokes were excluded. Samples were collected within 24h of onset of symptoms. EPC and CEC were studied using flow cytometry and categorized by quartiles. Patients were followed for up to 6 months. NVE was defined as new acute coronary syndrome, transient ischemic attack (TIA), stroke, or any hospitalization or death from cardiovascular causes. The variables included in the analysis included: vascular risk factors, carotid intima-media thickness (IMT), atherosclerotic burden and basal EPC and CEC count. Multivariate survival analysis was performed using Cox regression analysis.

Results

During follow-up, 19 patients (12.66%) had a new vascular event (5 strokes; 3 TIAs; 4 AMI; 6 hospitalizations; 1 death). Vascular events were associated with age (P = 0.039), carotid IMT≥0.9 (P = 0.044), and EPC count (P = 0.041) in the univariate analysis. Multivariate Cox regression analysis showed an independent association with EPC in the lowest quartile (HR: 10.33, 95%CI (1.22–87.34), P = 0.032] and IMT≥0.9 [HR: 4.12, 95%CI (1.21–13.95), P = 0.023].

Conclusions

Basal EPC and IMT≥0.9 can predict future vascular events in patients with AMI and AS, but CEC count does not affect cardiovascular risk.     

Additive Effect of Anemia and Renal Impairment on Long-Term Outcome after Percutaneous Coronary Intervention

Introduction

Anemia and renal impairment are important co-morbidities among patients with coronary artery disease undergoing Percutaneous Coronary Intervention (PCI). Disease progression to eventual death can be understood as the combined effect of baseline characteristics and intermediate outcomes.

Methods

Using data from a prospective cohort study, we investigated clinical pathways reflecting the transitions from PCI through intermediate ischemic or hemorrhagic events to all-cause mortality in a multi-state analysis as a function of anemia (hemoglobin concentration <120 g/l and <130 g/l, for women and men, respectively) and renal impairment (creatinine clearance <60 ml/min) at baseline.

Results

Among 6029 patients undergoing PCI, anemia and renal impairment were observed isolated or in combination in 990 (16.4%), 384 (6.4%), and 309 (5.1%) patients, respectively. The most frequent transition was from PCI to death (6.7%, 95% CI 6.1–7.3), followed by ischemic events (4.8%, 95 CI 4.3–5.4) and bleeding (3.4%, 95% CI 3.0–3.9). Among patients with both anemia and renal impairment, the risk of death was increased 4-fold as compared to the reference group (HR 3.9, 95% CI 2.9–5.4) and roughly doubled as compared to patients with either anemia (HR 1.7, 95% CI 1.3–2.2) or renal impairment (HR 2.1, 95% CI 1.5–2.9) alone. Hazard ratios indicated an increased risk of bleeding in all three groups compared to patients with neither anemia nor renal impairment.

Conclusions

Applying a multi-state model we found evidence for a gradient of risk for the composite of bleeding, ischemic events, or death as a function of hemoglobin value and estimated glomerular filtration rate at baseline.     

B-type natriuretic peptide is a long-term predictor of all-cause mortality, whereas high-sensitive C-reactive protein predicts recurrent short-term troponin T positive cardiac events in chest pain patients: a prognostic study

Background

Few studies have addressed whether the combined use of B-type natriuretic peptide (BNP) and high-sensitive C-reactive protein (hsCRP) improves risk stratification for mortality and cardiovascular events in a population with chest pain and suspected acute coronary syndromes (ACS). Therefore, we wanted to assess the incremental prognostic value of these biomarkers with respect to long-term all-cause mortality and recurrent troponin T (TnT) positive cardiac events in 871 patients admitted to the emergency department.

Methods

Blood samples were obtained immediately following admission.

Results

After a follow-up period of 24 months, 129 patients had died. The BNP levels were significantly higher among patients dying than in long-term survivors (401 (145–736) versus 75 (29–235) pq/mL [median, 25 and 75% percentiles], p = 0.000). In a multivariable Cox regression model for death within 2 years, the hazard ratio (HR) for BNP in the highest quartile (Q4) was 5.13 (95% confidence interval (CI), 1.97–13.38) compared to the lowest quartile (Q1) and was associated with all-cause mortality above and beyond age, congestive heart failure and the index diagnosis ST-segment elevation myocardial infarction. HsCRP rendered no prognostic information for all-cause mortality. However, within 30 days, the adjusted HR for patients with recurrent TnT cardiac positive events hsCRP in Q4 was 14.79 (95% CI, 1.89–115.63) compared with Q1 and was associated with recurrent ischemic events above and beyond age, hypercholesterolemia and TnT values at admission.

Conclusion

BNP may act as a clinically useful biomarker when obtained at admission in an unselected patient population following hospitalization with chest pain and potential ACS, and may provide complementary prognostic information to established risk determinants at long-term follow-up. Our data do not support the hypothesis that the additional assessment of hsCRP will lead to better risk stratification for survival than BNP alone.

Trial registration

NCT00521976     

Phase III Trials of Standard Chemotherapy with or without Bevacizumab for Ovarian Cancer: A Meta-Analysis

Background

Platinum-based standard chemotherapy improves survival of ovarian cancer (OC), but the five-year survival rate remains below 50%. Antiangiogenic agents (7.5 or 15 mg/kg Bevacizumab, Bev) plus to standard chemotherapy improve progression-free survival (PFS) not overall survival (OS) in completed randomized controlled trials (RCTs). The efficacy and safety of two doses of Bev + standard chemotherapy remain controversial.

Methods

MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Cochrane databases and ClinicalTrials.gov were searched. The outcomes of eligible RCTs included PFS, OS and toxicities. Hazard ratio (HR) and relative risk (RR) were used for the meta-analysis and were expressed with 95% confidence intervals (CIs).

Results

Bev + chemotherapy improved PFS (HR, 0.82; 95% CI, 0.75 to 0.89; P = .000) and OS (HR, 0.87; 95% CI, 0.77 to 0.99; P = .026) in newly diagnosed OC (2 trials, 2776 patients), and PFS (HR, 0.48; 95% CI, 0.41 to 0.57; P = .000) in recurrent OC (2 trials, 845 patients). Bev + chemotherapy increased non-CNS bleeding (RR, 3.63; 95% CI, 1.81 to 7.29; P = .000), hypertension grade ≥ 2 (RR, 4.90; 95% CI, 3.83 to 6.25; P = .000), arterial thromboembolism (RR, 2.29; 95% CI, 1.33 to 3.94; P = .003), gastrointestinal perforation (RR, 2.90; 95% CI, 1.44 to 5.82; P = .003), and proteinuria grade ≥ 3 (RR, 6.63; 95% CI 3.17 to 13.88; P = .000). No difference was observed between the two Bev doses in PFS (HR, 1.04; 95% CI, 0.88 to 1.24) or OS (HR, 1.15, 95% CI, 0.88 to 1.50), but 15 mg/kg Bev increased toxicities.

Conclusion

Bev + standard chemotherapy delayed progression for newly diagnosed and recurrent OC, and improved survival for newly diagnosed OC. The 7.5 mg/kg dose appeared to be optimal for newly diagnosed OC patients with high risk for progression.     

Serial Measurements of N-Terminal Pro-Brain Natriuretic Peptide in Patients with Coronary Heart Disease

Objective

To assess the prognostic value of 12-months N-Terminal Pro-Brain Natriuretic Peptide (NT-proBNP) levels on adverse cardiovascular events in patients with stable coronary heart disease.

Methods

NT-proBNP concentrations were measured at baseline and at 12-months follow-up in participants of cardiac rehabilitation (median follow-up 8.96 years). Cox-proportional hazards models evaluated the prognostic value of log-transformed NT-proBNP levels, and of 12-months NT-proBNP relative changes on adverse cardiovascular events adjusting for established risk factors measured at baseline.

Results

Among 798 participants (84.7% men, mean age 59 years) there were 114 adverse cardiovascular events. 12-months NT-proBNP levels were higher than baseline levels in 60 patients (7.5%) and numerically more strongly associated with the outcome in multivariable analysis (HR 1.65 [95% CI 1.33–2.05] vs. HR 1.41 [95% CI 1.12–1.78], with a net reclassification improvement (NRI) of 0.098 [95% CI 0.002–0.194] compared to NRI of 0.047 [95% CI −0.0004–0.133] for baseline NT-proBNP levels. A 12-month 10% increment of NT-proBNP was associated with a HR of 1.35 [95% CI 1.12–1.63] for the onset of an adverse cardiovascular event. Subjects with a 12-month increment of NT-proBNP had a HR of 2.56 [95% CI 1.10–5.95] compared to those with the highest 12-months reduction.

Conclusions

Twelve-months NT-proBNP levels after an acute cardiovascular event are strongly associated with a subsequent event and may provide numerically better reclassification of patients at risk for an adverse cardiovascular event compared to NT-proBNP baseline levels after adjustment for established risk factors.     

The impact of a 6-year comprehensive community trial on the awareness, treatment and control rates of hypertension in Iran: experiences from the Isfahan healthy heart program

Background

Acute mental stress may contribute to the cardiovascular disease progression via autonomic nervous system controlled negative effects on the endothelium. The joint effects of stress-induced sympathetic or parasympathetic activity and endothelial function on atherosclerosis development have not been investigated. The present study aims to examine the interactive effect of acute mental stress-induced cardiac reactivity/recovery and endothelial function on the prevalence of carotid atherosclerosis.

Methods

Participants were 81 healthy young adults aged 24-39 years. Preclinical atherosclerosis was assessed by carotid intima-media thickness (IMT) and endothelial function was measured as flow-mediated dilatation (FMD) using ultrasound techniques. We also measured heart rate, respiratory sinus arrhythmia (RSA), and pre-ejection period (PEP) in response to the mental arithmetic and speech tasks.

Results

We found a significant interaction of FMD and cardiac RSA recovery for IMT (p = 0.037), and a significant interaction of FMD and PEP recovery for IMT (p = 0.006). Among participants with low FMD, slower PEP recovery was related to higher IMT. Among individuals with high FMD, slow RSA recovery predicted higher IMT. No significant interactions of FMD and cardiac reactivity for IMT were found.

Conclusions

Cardiac recovery plays a role in atherosclerosis development in persons with high and low FMD. The role of sympathetically mediated cardiac activity seems to be more important in those with impaired FMD, and parasympathetically mediated in those with relatively high FMD. The development of endothelial dysfunction may be one possible mechanism linking slow cardiac recovery and atherosclerosis via autonomic nervous system mediated effect.     

Establishment and ultrasound characteristics of atherosclerosis in rhesus monkey

Background

Atherosclerosis is one of the main risk factors cause acute cerebral-cardio vascular diseases. It's of great significance to establish an atherosclerosis animal model that can mimic the characteristics and nature course of human patients. Therefore, a rhesus monkey model was induced by high-fat diet to monitor their lipid profile and intima-media thickness (IMT) of artery walls and study atherosclerosis progression.

Methods

Fifty male rhesus monkeys were enrolled in this study. All of these monkeys were aged 7 to 14 years with BMI >30 kg/m². They were fed with high-fat diet containing 10% of fat for the first 48 weeks. Use ultrasound to measure the IMT at bilateral common carotid arteries and their bifurcations and aorta (AO) of the monkeys, and screen out the individuals with thickened IMT for the next phase. In the next 48 weeks, some of these monkeys (n = 4) were fed with standard diet containing 3% fat. Meanwhile the other monkeys (n = 5) were fed with high-fat diet for another 48 weeks. Their serum lipid level was monitored and arterial IMT was also determined periodically.

Results

Serum lipid level of all 50 monkeys elevated after fed with high-fat diet for the first 48 weeks. IMT thickening at right common carotid bifurcation and aorta (AO) was thickened in 9 monkeys. Furthermore, 4 of these 9 monkeys were fed with standard diet and other 5 monkeys were fed with high-fat diet in the following 48 weeks. The serum lipid level of the 4 monkeys recovered and their IMT at RBIF and AO did not progress. However, the lipid level of other 5 monkeys remained high, and their IMT thickening of AO progressed, and plaques and calcification focuses were found at the anterior wall of aorta near the bifurcation of common iliac artery.

Conclusions

After high-fat diet induction for 96 weeks, serum lipid levels of rhesus monkeys elevated significantly, which subsequently caused IMT thickening and plaques formation. When IMT thickening occurred, further vascular injury may be prevented by reducing diet fat content. Our study indicates that vascular injury of high-fat diet induced rhesus monkey is similar to that of human in position and progression.