Fibroblast growth factor 23, the ankle-brachial index,and incident peripheral artery disease in the Cardiovascular Health Study

Background

Fibroblast growth factor 23 (FGF23) has emerged as a novel risk factor for mortality and cardiovascular events. Its association with the ankle-brachial index (ABI) and clinical peripheral artery disease (PAD) is less known.

Methods

Using data (N = 3143) from the Cardiovascular Health Study (CHS), a cohort of community dwelling adults >65 years of age, we analyzed the cross-sectional association of FGF23 with ABI and its association with incident clinical PAD events during 9.8 years of follow up using multinomial logistic regression and Cox proportional hazards models respectively.

Results

The prevalence of cardiovascular disease (CVD) and traditional risk factors like diabetes, coronary artery disease, and heart failure increased across higher quartiles of FGF23. Compared to those with ABI of 1.1–1.4, FGF23 per doubling at baseline was associated with prevalent PAD (ABI < 0.9) although this association was attenuated after adjusting for CVD risk factors, and kidney function (OR 0.91, 95% CI 0.76–1.08). FGF23 was not associated with high ABI (>1.4) (OR 1.06, 95% CI 0.75–1.51). Higher FGF23 was associated with incidence of PAD events in unadjusted, demographic adjusted, and CVD risk factor adjusted models (HR 2.26, 95% CI 1.28–3.98; highest versus lowest quartile). The addition of estimated glomerular filtration and urine albumin to creatinine ratio to the model however, attenuated these findings (HR 1.46, 95% CI, 0.79–2.70).

Conclusions

In community dwelling older adults, FGF23 was not associated with baseline low or high ABI or incident PAD events after adjusting for confounding variables. These results suggest that FGF23 may primarily be associated with adverse cardiovascular outcomes through non atherosclerotic mechanisms.     

A gender perspective on short- and long term mortality in ST-elevation myocardial infarction — A report from the SWEDEHEART register

Background

Previous studies of patients admitted for ST-elevation myocardial infarction [STEMI] have indicated that women have a higher risk of early mortality than do men. These studies have presented limited information on gender related differences in the short term and almost no information on the long term.

Methods and results

We analysed a prospective, consecutively included STEMI population consisting of 54,146 patients (35% women). This population consists of almost all patients hospitalised in Sweden between January 1, 1995 and December 31, 2006 as recorded in the SWEDEHEART register (formerly RIKS-HIA). Follow-up time ranged from one to 13 years (mean 4.6). Women had a lower probability of being given reperfusion therapy, odds ratio [OR] 0.83 (95% confidence interval [CI] 0.79–0.88). During the time these STEMI patients were in the hospital, 13% of the women and 7% of men died, multivariable adjusted OR 1.21 (95% CI 1.11–1.32). During the follow up period, 46% of the women died as compared with 32% of the men. There was, however, no gender difference in age-adjusted risk of long term mortality (hazard ratio [HR] 0.98, 95% CI 0.95–1.01) whereas the multivariable adjusted risk was lower in women (HR 0.92, 95% CI 0.89–0.96). The long term risk of re-infarction was the same in men and women (HR 0.98, 95% CI 0.93–1.03) whereas men in the youngest group had a higher risk than women in that age group (HR 0.82, 95% CI 0.72–0.94).

Conclusion

In STEMI, women had a higher risk of in-hospital mortality but the long-term risk of death was higher in men. More studies are needed in the primary percutaneous coronary intervention (pPCI) era that are designed to determine why women fare worse than men after STEMI during the first phase when they are in hospital.     

Adherence to dietary guidelines and cardiovascular disease risk in the EPIC-NL cohort

Background

Global and national dietary guidelines have been created to lower chronic disease risk. The aim of this study was to assess whether greater adherence to the WHO guidelines (Healthy Diet Indicator (HDI)); the Dutch guidelines for a healthy diet (Dutch Healthy Diet-index (DHD-index)); and the Dietary Approaches to Stop Hypertension (DASH) diet was associated with a lower risk of cardiovascular disease (CVD), coronary heart disease (CHD) or stroke.

Methods

A prospective cohort study was conducted among 33,671 healthy Dutch men and women aged 20–70 years recruited into the EPIC-NL study during 1993–1997. We used Cox regression adjusted for relevant confounders to estimate the hazard ratios per standard deviation increase in score and 95% confidence intervals (CI) of the associations between the dietary guidelines and CVD, CHD and stroke risk.

Results

After an average follow-up of 12.2 years, 2752 CVD cases were documented, including 1630 CHD cases and 527 stroke cases. We found no association between the HDI (0.98, 95% CI 0.94; 1.02) or DHD-index (0.96, 95% CI 0.92; 1.00) and CVD incidence. Similar results were found for these guidelines and CHD or stroke incidence. Higher adherence to the DASH diet was significantly associated with a lower CVD (0.92, 95% CI 0.89; 0.96), CHD (0.91, 95% CI 0.86; 0.95), and stroke (0.90, 95% CI 0.82; 0.99) risk.

Conclusion

The HDI and the DHD-index were not associated with CVD risk, while the DASH diet was significantly associated with a lower risk of developing CVD, CHD and stroke.     

Relative contribution of obesity and serum adiponectin to the development of hypertension

Aims

The aim of this study was to investigate the association between serum adiponectin level and new-onset hypertension, and the relative contribution of obesity and low serum adiponectin levels to the development of hypertension in normotensive men and women.

Methods

We analyzed 1553 adults (584 men and 969 women) without hypertension, aged 40–70 years, who had participated in a cohort study in both time periods from 2005 to 2008 for baseline and 2008 to 2011 for follow-up. We divided participants into sex-specific tertiles according to serum adiponectin levels. We defined the highest tertile of serum adiponectin as ‘high adiponectin’. Participants were then stratified into four groups: the non-obese with high adiponectin; the non-obese with low adiponectin; the obese with high adiponectin; and the obese with low adiponectin.

Results

During an average of 2.6 years of follow-up, 79 men (13.5%) and 99 women (10.2%) developed hypertension. Low serum adiponectin level was an independent predictor of new-onset hypertension in men (Odds Ratio[OR]: 1.99; 95% CI: 1.03–3.86). The Obese men with low adiponectin had an increased risk of new-onset hypertension compared with the control group (OR: 2.80; 95% CI: 1.35–5.81). In postmenopausal women, the obese subjects with low adiponectin had an increased risk of new-onset hypertension compared with the control group (OR: 2.41; 95% CI 1.16–5.04).

Conclusion

Low serum adiponectin levels were associated with an increased risk of new-onset hypertension in men and postmenopausal women.     

Changes in all-cause and cardiovascular disease mortality in three different Finnish population cohorts with and without diabetes

Background

We aimed to assess changes in cardiovascular (CVD) and all-cause mortality among diabetic and non-diabetic individuals between three large study cohorts with baseline assessments of 10 years apart and followed up for 10 years.

Methods

Six population surveys were carried out in 1972, 1977, 1982, 1987, 1992 and 1997 in Finland. For the analyses we combined the 1972 and 1977 cohorts (cohort 1), the 1982 and 1987 cohorts (cohort 2) and similarly also the 1992 and 1997 cohorts (cohort 3).

Results

Age-adjusted hazard ratio (HR) of all-cause mortality and CVD in men without diabetes showed that both had a statistically significant decreased risk of all-cause mortality compared to the first cohort. No statistically significant changes in all-cause mortality were observed in men and women with diabetes between the latter two cohorts compared with the first after controlling for several covariates. In both men and women without diabetes, cohort 2 (men, HR = 0.65; 95% CI 0.51–0.82; women, HR = 0.54; 95% CI 0.32–0.89) and cohort 3 (men, HR = 0.32; 95% CI 0.22–0.47; women, HR = 0.31; 95% CI 0.14–0.68) showed a statistically significant decreased risk of CVD mortality compared to cohort 1. Age-adjusted HRs in regard to CVD mortality in men (HR = 0.22; 95% CI 0.07–0.69) and women (HR = 0.22; 95% CI 0.05–0.99) with diabetes of cohort 3 were statistically significantly lower than in cohort 1.

Conclusions

There seems to be a decrease in CVD mortality in people with diabetes indicating that treatment of diabetes and cardiovascular risk factors in diabetes patients may have improved during the last decade.     

Peripheral artery disease and outcomes after myocardial infarction: An individual-patient meta-analysis of 28,771 patients in CAPRICORN,EPEHESUS, OPTIMAAL and VALIANT

Objectives

To examine the prevalence of peripheral artery disease (PAD) and the relationship between PAD and cardiovascular (CV) outcomes in subjects with left ventricular systolic dysfunction, heart failure or both after acute myocardial infarction (MI).

Background

PAD is associated with poorer prognosis in patients with stable and unstable coronary heart disease but whether PAD is associated with worse outcomes following substantial acute MI is unknown.

Methods

Univariate and multivariate Cox proportional hazards modelling was used to compare clinical outcomes in an individual-patient meta-analysis of 4 trials (CAPRICORN, EPHESUS, OPTIMAAL and VALIANT).

Results

Of the 28,771 patients randomized, 2357 (8.2%) had PAD. These patients were older and had more co-morbidity and were less likely to be prescribed aspirin or a beta-blocker compared to patients without PAD. Over a mean follow-up of 2.7 years, 5121 (17.8%) patients died and 15,055 (52.3%) experienced CV death or hospitalization. PAD was an independent predictor of all individual and composite CV outcomes examined (including heart failure), with the exception of stroke. In patients with PAD (compared to those without PAD), the adjusted hazard ratio (HR) for all-cause mortality was 1.25 (95% CI 1.15–1.37; p < 0.001) and the HR for CV death, non-fatal MI, non-fatal stroke or heart failure hospitalization was 1.24 (1.16–1.33; p < 0.001).

Conclusions

PAD is common and is an independent predictor of worse outcomes in patients already at high risk after MI because of left ventricular systolic dysfunction, heart failure or both. These patients represent an important group for intensive application of secondary preventive therapies.     

Comparative cancer risk associated with methotrexate,other non-biologic and biologic disease-modifying anti-rheumatic drugs

Objective

There is little information comparing the potential risk of cancer across conventional and biologic disease-modifying anti-rheumatic drugs (DMARDs) in patients with rheumatoid arthritis (RA). Methotrexate has not been the focus of most contemporary pharmacoepidemiologic studies of cancer.

Methods

We conducted a comparative effectiveness study with cancer as the outcome. A large observational cohort of RA was followed up from 2001 to 2010. Reports of any cancer prompted a confirmation process that included adjudication of the primary cancer records. We used a propensity score (PS) with relevant covariates and cohort trimming to improve the balance between DMARD cohorts. Cox proportional hazard regression models were constructed to estimate the risk of cancer with various DMARDs, all compared with methotrexate.

Results

We identified 6806 DMARD courses for analysis (1566 methotrexate; 904 nbDMARDs; 3761 TNF antagonists; 408 abatacept; and 167 rituximab). Non-biologic DMARDs (HR 0.17, 95% CI 0.05–0.65) and TNF antagonists (HR 0.29, 95% CI 0.05–0.65) were associated with a reduced adjusted risk of cancer compared with methotrexate. Abatacept (HR 1.55, 95% CI 0.40–5.97) and rituximab (HR 0.42, 95% CI 0.07–2.60) were similar in risk of cancer with methotrexate. These results were robust to sensitivity analyses. After controlling for DMARD exposures, risk factors for cancer included male gender, age, and alcohol consumption.

Conclusions

Cancer risk was elevated for methotrexate users compared with nbDMARDs and TNF antagonists.     

Gender differences in homocysteine concentrations,a population-based cross-sectional study

Background and aims

High concentrations of homocysteine are considered a risk factor for atherosclerosis and coronary artery disease. The aim of this study was to assess whether or not there are gender differences in the plasma concentrations of homocysteine.

Hyperuricemia and risk of stroke: A systematic review and meta-analysis of prospective studies

Introduction

Hyperuricemia may be associated with an increased risk of stroke, but to date results from prospective studies have been inconsistent. This study aimed to evaluate the association between hyperuricemia and risk of stroke incidence and mortality by performing a meta-analysis.

Materials and methods

Studies were identified by searching multiple electronic databases through July 13, 2013, and by reviewing reference lists of obtained articles. Prospective studies reported a multivariate-adjusted estimate, represented as relative risk (RRs) with 95% confidence intervals (CIs) for the association between hyperuricemia and risk of stroke incidence and mortality were eligible. A random-effects model was used to compute the pooled risk estimate.

Results

A total of fourteen articles including results from 15 prospective studies with 22,571 cases of stroke and 1,042,358 participants were included in the meta-analysis. Overall, presence of hyperuricemia was associated with a significantly greater risk of both stroke incidence (RR, 1.22; 95% CI, 1.02–1.46) and mortality (RR, 1.33; 95% CI, 1.24–1.43). In addition, the pooled estimate of multivariate RRs of stroke incidence and mortality were 1.08 (95% CI: 0.85–1.38); 1.26 (95% CI: 1.14–1.40) among men and 1.25 (95% CI: 1.04–1.46); 1.41 (95% CI: 1.31–1.52) among women respectively.

Conclusions

Results from this meta-analysis indicate that hyperuricemia may modestly increase the risks of both stroke incidence and mortality. Future studies should explore whether hyperuricemia is a modifiable risk factor for stroke.     

The influence of sex and age on the relationship between sleep duration and metabolic syndrome in Korean adults

Aims

To investigate the influence of sex and age on the relationship between sleep duration and metabolic syndrome in a nationally representative population.

Methods

We used data from the Korea National Health and Nutrition Examination Survey (2001–2010) and enrolled 24,511 participants aged 20–79 years. Sleep duration was categorized into five groups: ≤5, 6, 7 (referent), 8, and ≥9 h/day. Age was categorized into three groups: younger (20–39 y), middle-aged (40–59 y), and older (60–79 y). The association between sleep duration and metabolic syndrome was assessed in the total, separately in men and women, then in six groups based on sex and age.

Results

The prevalence of metabolic syndrome by sleep category demonstrated a U-shaped pattern in the total population. However, after adjusting for age, education, occupation, exercise, smoking, alcohol, and body mass index, the prevalence of metabolic syndrome increased in long sleepers (OR 1.31; 95% CI 1.14–1.51) but not in short sleepers (OR 1.00; 95% CI 0.89–1.11). The relationship between sleep duration and metabolic syndrome varied by sex and age–long sleep (≥9 h/day) was positively associated with metabolic syndrome only in younger (OR 2.13; 95% CI 1.38–3.28) and middle-aged (OR 1.63; 95% CI 1.21–2.21) women. Short sleep (≤5 h/day) was not associated with metabolic syndrome in any sex and age groups. However, extremely short sleep (≤4 h/day) was associated with metabolic syndrome in middle-aged men (OR 1.76, 95% CI 1.05–2.96).

Conclusion

These data suggest that sex and age significantly modify the relationship between sleep duration and metabolic syndrome.     

Self-reported habitual snoring and risk of cardiovascular disease and all-cause mortality

Objective

Inconsistent findings have reported the association between self-reported habitual snoring and risk of cardiovascular disease (CVD) and all-cause mortality. We conducted a meta-analysis to investigate whether self-reported habitual snoring was an independent predictor for CVD and all-cause mortality using prospective observational studies.

Methods

Electronic literature databases (PubMed, Medline, Embase, Cochrane Library, Wanfang database, and China National Knowledge Infrastructure) were searched for publications prior to September 2013. Only prospective studies evaluating baseline habitual snoring and subsequent risk of CVD and all-cause mortality were selected. Pooled adjust hazard risk (HR) and corresponding 95% confidence intervals (CI) were calculated for categorical risk estimates.

Results

Eight studies with 65,037 subjects were analyzed. Pooled adjust HR was 1.26 (95% CI 0.98–1.62) for CVD, 1.15 (95% CI 1.05–1.27) for coronary heart disease (CHD), and 1.26 (95% CI 1.11–1.43) for stroke comparing habitual snoring to non-snorers. Pooled adjust HR was 0.98 (95% CI 0.78–1.23) for all-cause mortality in a random effect model comparing habitual snoring to non-snorers. Habitual snoring appeared to increase greater stroke risk among men (HR 1.54; 95% CI: 1.09–2.17) than those in women (HR 1.22; 95% CI: 1.05–1.41).

Conclusions

Self-reported habitual snoring is a mild but statistically significant risk factor for stroke and CHD, but not for CVD and all-cause mortality. However, whether the risk is attributable to obstructive sleep apnea syndrome or snoring alone remains controversial.     

Desphospho-uncarboxylated matrix Gla-protein is associated with mortality risk in patients with chronic stable vascular disease

Background

Vitamin K is the essential co-factor for activation of matrix Gla-protein (MGP), the natural inhibitor of tissue calcification. Biologically inactive, desphospho-uncarboxylated MGP (dp-ucMGP) is a marker of vascular vitamin K status and is described to predict mortality in patients with heart failure and aortic stenosis. We hypothesized that increased dp-ucMGP might be associated with mortality risk in clinically stable patients with chronic vascular disease.

Materials and methods

We examined 799 patients (mean age 65.1 ± 9.3 years) who suffered from myocardial infarction, coronary revascularization or first ischemic stroke (pooled Czech samples of EUROASPIRE III and EUROASPIRE-stroke surveys), and followed them in a prospective cohort study. To estimate the 5-year all-cause and cardiovascular mortality we ascertained vital status and declared cause of death. Circulating dp-ucMGP and desphospho–carboxylated MGP (dp-cMGP) were measured by ELISA methods (IDS and VitaK).

Results

During a median follow-up of 2050 days (5.6 years) 159 patients died. In the fully adjusted multivariate Cox proportional hazard model, the patients in the highest quartile of dp-ucMGP (≥977 pmol/L) had higher risk of all-cause and cardiovascular 5-year mortality [HRR 1.89 (95% CI, 1.32–2.72) and 1.88 (95% CI, 1.22–2.90)], respectively. Corresponding HRR for dp-cMGP were 1.76 (95% CI, 1.18–2.61) and 1.79 (95% CI, 1.12–2.57).

Conclusions

In patients with overt vascular disease, circulating dp-ucMGP and dp-cMGP were independently associated with the risk of all-cause and cardiovascular mortality. Since published results are conflicting regarding the dp-cMGP, we propose only circulating dp-ucMGP as a potential biomarker for assessment of additive cardiovascular risk.     

Smoking, alcohol consumption, and Raynaud's phenomenon in middle age

Background

Data suggest Raynaud’s phenomenon shares risk factors with cardiovascular disease. Studies of smoking, alcohol consumption, and Raynaud’s have produced conflicting results and were limited by small sample size and failure to adjust for confounders. Our objective was to determine whether smoking and alcohol are independently associated with Raynaud’s in a large, community-based cohort.

Methods

By using a validated survey to classify Raynaud’s in the Framingham Heart Study Offspring Cohort, we performed sex-specific analyses of Raynaud’s status by smoking and alcohol consumption in 1840 women and 1602 men. Multivariable logistic regression analyses were used to examine the relationship of Raynaud’s to smoking and alcohol consumption.

Results

Current smoking was not associated with Raynaud’s in women but was associated with increased risk in men (adjusted odds ratio [OR] 2.59, 95% confidence interval [CI], 1.11-6.04). Heavy alcohol consumption in women was associated with increased risk of Raynaud’s (adjusted OR 1.69, 95% CI, 1.02-2.82), whereas moderate alcohol consumption in men was associated with reduced risk (adjusted OR 0.51, 95% CI, 0.29-0.89). In both genders, red wine consumption was associated with a reduced risk of Raynaud’s (adjusted OR 0.59, 95% CI, 0.36-0.96 in women and adjusted OR 0.30, 95% CI, 0.15-0.62 in men).

Conclusions

Our data suggest that middle-aged women and men may have distinct physiologic mechanisms underlying their Raynaud’s, and thus sex-specific therapeutic approaches may be appropriate. Our data also support the possibility that moderate red wine consumption may protect against Raynaud’s.     

Association of serum adiponectin with risk for cardiovascular events in patients with peripheral arterial disease

Objects

Adiponectin exerts anti-atherogenic and anti-inflammatory properties and may be important as a biomarker for cardiovascular disease (CVD). We examined whether serum adiponectin was linked with future cardiovascular events or all-cause death in patients with peripheral arterial disease (PAD).

Methods

The study prospectively included 468 patients (58% male) with symptomatic PAD. Serum total adiponectin was determined by an in-house immunoassay. We used Cox regression, adjusted for age, gender, BMI, systemic hypertension, smoking status, diabetes mellitus, previous myocardial infarction (MI), ankle-brachial index (ABI), symptoms of leg ischemia, total cholesterol, and use of β-blockers (BAB) and angiotensin-converting enzyme (ACE) inhibitors to assess possible relationship between serum adiponectin and time to first non-fatal cardiovascular event, and all-cause death.

Results

During the median follow-up of 3.5 years, 215 new cases of non-fatal cardiovascular events and 97 all-cause deaths were detected. Adjusted Cox-regression analysis showed that a 1 mg/l increase in serum adiponectin was associated with a decrease in the risk of non-fatal cardiovascular events to 0.68, (95% CI 0.47–0.99) in men, but not in women (HR 0.96 95% CI 0.55–1.70). The relative risk of adverse non-fatal cardiovascular events was 77% higher in male patients within the lower adiponectin tertile, when compared with those in the higher tertile (95% CI 1.05–2.97). Moreover, serum adiponectin was the only significant independent predictor of non-fatal cardiovascular events for men with severe PAD (HR = 0.37, 95% CI, 0.16–0.89; p = 0.026), whereas previous MI (p = 0.92) and ABI (p = 0.08) failed to reach statistical significance in the multivariable model.We did not obtain any significant associations between serum adiponectin and all-cause mortality. Multivariable model revealed that age and previous MI were independently associated with risk for all-cause death.

Conclusions

Lower levels of serum adiponectin were significantly associated with an increased risk for future non-fatal cardiovascular events in men with symptomatic PAD, but not in women.     

Risk factors for incident atrial fibrillation with and without left atrial enlargement in women

Background

Left atrial (LA) enlargement facilitates induction and/or maintenance of atrial fibrillation (AF). However, little is known about risk factors for AF with normal LA size.

Methods

We prospectively followed 34713 initially healthy women for incident AF. Information on echocardiographic LA size at first AF diagnosis was abstracted from medical charts during AF confirmation. LA enlargement was defined as LA diameter > 40 mm. Using a competing risk approach, we constructed Cox proportional-hazards models to calculate hazard ratios (HR) and 95% confidence intervals (CI) of risk factors for incident AF with and without LA enlargement, respectively.

Results

Among 796 women with incident AF and available LA size, 328 (41%) had LA enlargement. In multivariable competing risk models, the relationship between age and incident AF was stronger in those with (HR 1.12, 95% CI 1.10–1.14) versus without (HR 1.08, 95% CI 1.06–1.09) LA enlargement (p for difference < 0.0001). Body weight was associated with AF only in the presence of LA enlargement (HR per 10 kg 1.34, 95% CI 1.26-1.43; versus 1.07, 95% CI 0.998–1.14, p for difference < 0.0001). Hypertension and height were significantly associated with AF both in the presence (HR 1.99, 95% CI 1.49–2.65; and HR per 10 cm 1.36, 95% CI 1.13–1.63) and absence (1.55, 1.25–1.92 and 1.29, 1.10–1.50) of LA enlargement (p for difference 0.17 and 0.66, respectively).

Conclusions

These data suggest that LA enlargement explains much of the increased AF risk associated with obesity and age. In contrast, height and hypertension appear to also influence AF risk through other mechanisms besides LA enlargement.     

Baseline serum uric acid level as a predictor of cardiovascular disease related mortality and all-cause mortality: A meta-analysis of prospective studies

Objective

Serum uric acid (SUA) levels have been used to predict cardiovascular and all-cause mortality event, but the data have yielded conflicting results. We investigated whether SUA was an independent predictor for cardiovascular or all-cause mortality with prospective studies by meta-analysis.

Methods

Pubmed and Embase were searched without language restrictions for publications available till April 2013. Only prospective studies on cardiovascular or all-cause mortality related to SUA levels were included. Pooled adjust relative risk (RR) and corresponding 95% confidence intervals (CI) were calculated separately for the highest vs. lowest category or the lowest vs. middle category.

Results

For the highest SUA, eleven studies with 172,123 participants were identified and analyzed. Elevated SUA increased risk of all-cause mortality (RR 1.24; 95% CI 1.09–1.42) and cardiovascular mortality (RR 1.37; 95% CI 1.19–1.57). Subgroup analyses showed that elevated SUA significantly increase the risk of all-cause mortality among men (RR 1.23; 95% CI 1.08–1.42), but not in women (RR 1.05; 95% CI 0.79–1.39). Risk of cardiovascular mortality appeared to be more pronounced among women (RR 1.35; 95% CI 1.06–1.72). The association between extremely low SUA and mortality was reported in three studies; we did not perform a pooled analysis because of high degree of heterogeneity in these studies.

Conclusions

Baseline SUA level is an independent predictor for future cardiovascular mortality. Elevated SUA appears to significantly increase the risk of all-cause mortality in men, but not in women. Whether low SUA levels are predictors of mortality is still inconclusive.     

Relationship between white blood cell count and nonalcoholic fatty liver disease

Background

Higher levels of white blood cell (WBC) count are known to be associated with metabolic syndrome and insulin resistance. Nonalcoholic fatty liver disease (NAFLD) is also considered a hepatic manifestation of insulin resistance.

Aims

The present study aimed to determine the relation between WBC count and the presence of NAFLD based on abdominal sonographic findings.

Methods

A cross-sectional study with 3681 healthy subjects (2066 men, 1615 women) undergoing medical check-up was conducted. The odds ratios (ORs) and 95% confidence intervals (CIs) for NAFLD were calculated using multivariate logistic regression analyses across WBC quartiles.

Results

A graded independent relationship between higher levels of WBC count and the prevalence risk of NAFLD was observed. After adjusting for age, smoking status, regular exercise, body mass index (BMI), blood pressure, fasting plasma glucose, triglyceride, and HDL-cholesterol, the ORs (95% CIs) for NAFLD according to WBC quartiles were 1.00, 1.48 (1.10–1.98), 1.59 (1.18–2.14), and 1.84 (1.35–2.51) for men and 1.00, 1.15 (0.67–1.96), 1.88 (1.13–3.11), and 2.74 (1.68–4.46) for women.

Conclusions

WBC count was found to be independently associated with the presence of NAFLD regardless of classical cardiovascular risk factors and other components of metabolic syndrome.     

Comparative assessment of the HAS-BLED score with other published bleeding risk scoring schemes,for intracranial haemorrhage risk in a non-atrial fibrillation population: The Chin-Shan Community Cohort Study

Background

The HAS-BLED score is a validated bleeding risk model for predicting major bleeding events in anticoagulated individuals with atrial fibrillation (AF). It remains uncertain whether the HAS-BLED score could identify non-AF individuals at risk of developing intracranial haemorrhage (ICH), which is the most intractable and devastating major bleeding complication.

Methods

We assessed the predictive value of a modified HAS-BLED and other bleeding risk scoring models to predict the risk for ICH in the Chin-Shan Community Cohort, which followed 1899 women and 1703 men, aged > 35 years, for a median of 15.9 years. ICH events (including haemorrhagic strokes) were ascertained according to questionnaires and the national register database.

Results

Of 3524 individuals without baseline AF, 54 ICH events occurred during follow-up. The risk for ICH was raised with increasing HAS-BLED scores, and was significantly associated with uncontrolled hypertension and older age (Odds Ratios [95% confidence interval (CI)], 4.2[2.3–7.6] and 1.9[1.1–3.4], respectively). Among the five bleeding risk scoring schemes tested, HAS-BLED had highest general discrimination performance (c-statistic [95% CI], 0.72 [0.67–0.78]), and better ability to discriminate between those who were at risk for ICH and who were not (NRI, net reclassification improvement, all p < 0.05, compared to other four scoring schemes).

Conclusion

The HAS-BLED score had the highest general discrimination performance and best ability to discriminate risk for ICH. This score may be of clinical use in predicting the risk for occurrence of ICH among non-AF individuals.     

Impact of short-term mechanical circulatory support with extracorporeal devices on postoperative outcomes after emergency heart transplantation: Data from a multi-institutional Spanish cohort

Objectives

We sought to investigate the potential impact of preoperative short-term mechanical circulatory support (MCS) with extracorporeal devices on postoperative outcomes after emergency heart transplantation (HT).

Methods

We conducted an observational study of 669 patients who underwent emergency HT in 15 Spanish hospitals between 2000 and 2009. Postoperative outcomes of patients bridged to HT on short-term MCS (n = 101) were compared with those of the rest of the cohort (n = 568). Short-term MCS included veno-arterial extracorporeal membrane oxygenators (VA-ECMOs, n = 23), and both pulsatile-flow (n = 53) and continuous-flow (n = 25) extracorporeal ventricular assist devices (VADs). No patient underwent HT on intracorporeal VADs.

Results

Preoperative short-term MCS was independently associated with increased in-hospital postoperative mortality (adjusted odds-ratio 1.75, 95% CI 1.05–2.91) and overall post-transplant mortality (adjusted hazard-ratio 1.60, 95% CI 1.15–2.23). Rates of major surgical bleeding, cardiac reoperation, postoperative infection and primary graft failure were also significantly higher among MCS patients. Causes of death and survival after hospital discharge were similar in MCS and non-MCS candidates. Increased risk of post-transplant mortality affected patients bridged on pulsatile-flow extracorporeal VADs (adjusted hazard-ratio 2.21, 95% CI 1.48–3.30) and continuous-flow extracorporeal VADs (adjusted hazard-ratio 2.24, 95% CI 1.20–4.19), but not those bridged on VA-ECMO (adjusted hazard-ratio 0.51, 95% CI 0.21–1.25).

Conclusions

Patients bridged to emergency HT on short-term MCS are exposed to an increased risk of postoperative complications and mortality. In our series, preoperative bridging with VA-ECMO resulted in comparable post-transplant outcomes to those of patients transplanted on conventional support.     

Cardiovascular risk prediction in the general population with use of suPAR,CRP, and Framingham Risk Score

Background

The inflammatory biomarkers soluble urokinase plasminogen activator receptor (suPAR) and C-reactive protein (CRP) independently predict cardiovascular disease (CVD). The prognostic implications of suPAR and CRP combined with Framingham Risk Score (FRS) have not been determined.

Methods

From 1993 to 1994, baseline levels of suPAR and CRP were obtained from 2315 generally healthy Danish individuals (mean [SD] age: 53.9 [10.6] years) who were followed for the composite outcome of ischemic heart disease, stroke and CVD mortality.

Results

During a median follow-up of 12.7 years, 302 events were recorded. After adjusting for FRS, women with suPAR levels in the highest tertile had a 1.74-fold (95% confidence interval [CI]: 1.08–2.81, p = 0.027) and men a 2.09-fold (95% CI: 1.37–3.18, p < 0.001) increase in risk compared to the lowest tertile. Including suPAR and CRP together resulted in stronger risk prediction with a 3.30-fold (95% CI: 1.36–7.99, p < 0.01) increase for women and a 3.53-fold (1.78–7.02, p < 0.001) increase for men when both biomarkers were in the highest compared to the lowest tertile. The combined extreme tertiles of suPAR and CRP reallocated individuals predicted to an intermediate 10-year risk of CVD of 10–20% based on FRS, to low (< 10%) or high (> 20%) risk categories, respectively. This was reflected in a significant improvement of C statistics for men (p = 0.034) and borderline significant for women (p = 0.054), while the integrated discrimination improvement was highly significant (P ≤ 0.001) for both genders.

Conclusions

suPAR provides prognostic information of CVD risk beyond FRS and improves risk prediction substantially when combined with CRP in this setting.