Effect of calcium or vitamin D supplementation on vascular outcomes: A meta-analysis of randomized controlled trials

Background

Whether calcium or vitamin D supplementation reduces serious vascular outcomes in older people remains unclear. We conducted a meta-analysis based on randomized controlled trials to evaluate the effect of calcium or vitamin D supplementation on the risk of major cardiovascular outcomes.

Methods

We performed electronic searches in PubMed, Embase, and the Cochrane Library to identify relevant randomized controlled trials. Odds ratios (ORs) were used to measure the effect of calcium or vitamin D supplementation on the risk of major vascular outcomes with a random-effect model.

Results

Of the 1643 identified studies, we included 11 trials reporting data on 50,252 individuals. These studies reported 2685 major cardiovascular events, 1097 events of myocardial infarction, and 1350 events of stroke. Calcium or vitamin D supplementation did not have an effect on major cardiovascular events (OR, 1.03; 95% confidence interval [CI]: 0.94–1.12; P = 0.54), myocardial infarction (OR, 1.08; 95% CI: 0.96–1.22; P = 0.21), or stroke (OR, 1.01; 95% CI: 0.91–1.13; P = 0.80) when compared to the effect with a placebo. Subgroup analysis indicated that calcium supplementation alone might play an important role in increasing the risk of major cardiovascular events, myocardial infarction, and stroke, but this difference could not be identified as statistically significant. Furthermore, males seem to experience more harmful effects with supplements of calcium or vitamin D than the effects experienced by females.

Conclusions

Calcium supplementation might increase the risk of major cardiovascular events, myocardial infarction, and stroke compared to the risk with a placebo.     

Cardiovascular magnetic resonance-derived intramyocardial hemorrhage after STEMI: Influence on long-term prognosis,adverse left ventricular remodeling and relationship with microvascular obstruction

Background

T2 weighted cardiovascular magnetic resonance (CMR) can detect intramyocardial hemorrhage (IMH) after ST-elevation myocardial infarction (STEMI). The long-term prognostic value of IMH beyond a comprehensive CMR assessment with late enhancement (LE) imaging including microvascular obstruction (MVO) is unclear. The value of CMR-derived IMH for predicting major adverse cardiac events (MACE) and adverse cardiac remodeling after STEMI and its relationship with MVO was analyzed.

Methods

CMR including LE and T2 sequences was performed in 304 patients 1 week after STEMI. Adverse remodeling was defined as dilated left ventricular end-systolic volume indexes (dLVESV) at 6 months CMR.

Results

During a median follow-up of 140 weeks, 47 MACE (10 cardiac deaths, 16 myocardial infarctions, 21 heart failure episodes) occurred. Predictors of MACE were ejection fraction (HR .95 95% CI [.93–.97], p = .001, per %) and IMH (HR 1.17 95% CI [1.03–1.33], p = .01, per segment). The extent of MVO and IMH significantly correlated (r = .951, p < .0001). dLVESV was present in 40% of patients. CMR predictors of dLVESV were: LVESV (OR 1.11 95% CI [1.07–1.15], p < .0001, per ml/m²), infarct size (OR 1.05 95% CI [1.01–1.09], p = .02, per %) and IMH (OR 1.54 95% CI [1.15–2.07], p = .004, per segment). Addition of T2 information did not improve the LE and cine CMR-model for predicting MACE (.744 95% CI [.659–.829] vs. .734 95% CI [.650–.818], p = .6) or dLVESV (.914 95% CI [.875–.952] vs. .913 95% CI [.875–.952], p = .9).

Conclusions

IMH after STEMI predicts MACE and adverse remodeling. Nevertheless, with a strong interrelation with MVO, the addition of T2 imaging does not improve the predictive value of LE-CMR.     

Postoperative arrhythmias in adults with congenital heart disease: Incidence and risk factors

Background

Little is known about the clinical impact of arrhythmias after surgery for congenital heart disease (CHD) in adults. Therefore, we investigated the prevalence of in-hospital arrhythmias after CHD surgery and their impact on clinical outcome.

Methods

This was a multicenter retrospective study and included adults who underwent congenital cardiac surgery between January 2009 and December 2011. Clinical events were defined as all cause mortality, heart failure (HF) requiring medical treatment, thrombo-embolic event, major infections and permanent pacemaker (PM) implantation.

Results

Overall, 419 patients were included (mean age 38 ± 14 years, 55% male). Arrhythmias occurred in 134 patients (32%) and included supraventricular tachycardia (SVT, n = 100), bradycardias (n = 47) and ventricular tachycardia (VT, n = 19). In multivariate analysis age ≥ 40 years at surgery (OR 2.48, 95% Cl 1.40–4.60, P = 0.003), NYHA class ≥ II (OR 2.42, 95% Cl 1.18–4.67, P = 0.009), significant subpulmonary AV-valve regurgitation (OR 2.84, 95% Cl 1.19–6.72, P = 0.018), coronary bypass time (OR 1.35/60 minute increase, 95% Cl 1.06–1.82, P = 0.019) and CK-MB (OR 1.05 per 10 U/L increase, 95% Cl 1.01–1.09, P = 0.021) were associated with in-hospital arrhythmias. Overall, 58 clinical events occurred in 55 patients (13%) and included in the majority of the cases permanent PM implantation (5%), HF (4%) and death (2%). In-hospital arrhythmias were independently associated with clinical events (OR 7.80, 95% CI 2.41–25.54, P = 0.001).

Conclusion

Arrhythmias are highly prevalent after congenital heart surgery in adults and are associated with worse clinical outcome. Older and symptomatic patients with significant valvular heart disease at baseline are at risk of in-hospital arrhythmias.     

Tobacco smoking and intestinal metaplasia: Systematic review and meta-analysis

Background

The evaluation of specific risk factors for early endpoints in the gastric carcinogenesis pathway may further contribute to the understanding of gastric cancer aetiology.

Aims

To quantify the relation between smoking and intestinal metaplasia through systematic review and meta-analysis.

Methods

Articles providing data on the association between smoking and intestinal metaplasia were identified in PubMed^®, Scopus^® and Web of Science™, searched until April 2014, and through backward citation tracking. Summary odds ratio estimates and 95% confidence intervals were computed using the DerSimonian and Laird method. Heterogeneity was quantitatively assessed using the I² statistic.

Results

A total of 32 articles were included in this systematic review and 19 provided data for meta-analysis. Smoking was defined as ever vs. never (crude estimates, six studies, summary odds ratio = 1.54, 95% confidence interval: 1.12–2.12, I² = 67.4%; adjusted estimates, seven studies, summary odds ratio = 1.26, 95% confidence interval: 0.98–1.61, I² = 65.0%) and current vs. non-smokers (crude estimates, seven studies, summary odds ratio = 1.27, 95% confidence interval: 0.88–1.84, I² = 73.4%; adjusted estimates, two studies, summary odds ratio 1.49, 95% confidence interval: 0.99–2.25, I² = 0.0%).

Conclusion

The weak and non-statistically significant association found through meta-analysis of the available evidence does not confirm smoking as an independent risk factor for intestinal metaplasia.     

Drug-eluting balloons for coronary artery disease: A meta-analysis of randomized controlled trials

Background

Drug-eluting balloons (DEB) are attractive new alternatives to drug-eluting stents (DES) for percutaneous coronary interventions. We aimed to systematically review the efficacy and safety of DEB in the treatment of coronary artery disease (CAD).

Methods

MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials (CENTRAL) were searched in December 2011 for eligible randomized controlled trials. Primary outcomes were target lesion revascularization (TLR), major adverse cardiac events (MACE) and mortality. Secondary outcomes were late lumen loss, minimal lumen diameter and binary restenosis.

Results

Five studies involving 349 patients were included. Compared to controls, DEB improved angiographic measures with no significant effect on clinical outcomes in the overall CAD population. There is clear superiority of DEB in patients with in-stent restenosis in TLR (OR 0.17, 95% CI 0.07 to 0.38, p < 0.0001, I² = 0%), MACE (OR 0.22, 95% CI 0.10 to 0.51, p = 0.0005, I² = 13%), late lumen loss (in-stent: MD − 0.51, 95% CI − 0.73 to − 0.28, p < 0.00001, I² = 60%; in-segment: MD − 0.51, 95% CI − 0.77 to − 0.24, p = 0.0002, I² = 72%;), minimal lumen diameter (in-stent: MD 0.49, 95% CI 0.05 to 0.93, p = 0.03, I² = 85%; in-segment: MD 0.49, 95% CI 0.13 to 0.86, p = 0.008, I² = 79%) and binary restenosis (in-stent: OR 0.15, 95% CI 0.05 to 0.47, p = 0.001, I² = 37%; in-segment: OR 0.11, 95% CI 0.05 to 0.27, p < 0.00001, I² = 17%).

Conclusions

Our findings support the current recommendation of using DEB in in-stent restenosis. Large, well-conducted trials are essential in determining the application of DEB in other lesion types as well as exploring device-specific efficacy and safety profiles.     

The association of asthma and atrial fibrillation — A nationwide population-based nested case–control study

Background

Asthma and atrial fibrillation (AF) have been reported to be related to an increased risk of cardiovascular events. However, the relationship between asthma and AF has not been fully elucidated. The purpose of this study was to examine the association between asthma and AF risk.

Methods

We conducted a population-based nested case–control study including a total of 7439 newly-diagnosed adult patients with AF and 10,075 age-, gender-, comorbidity-, and cohort entry date-matched subjects without AF from the Taiwan National Health Insurance database. Exposure to asthma as well as medications including bronchodilators and corticosteroid before the index date was evaluated to investigate the association between AF and asthma as well as concurrent medications.

Results

AF patients were 1.2 times (adjusted OR 1.2, 95% CI 1.109–1.298) more likely to be associated with a future occurrence of asthma independent of comorbidities and treatment with corticosteroids and bronchodilator. In addition, the risks of new-onset AF were significantly higher among current users of inhaled corticosteroid, oral corticosteroids, and bronchodilators. Newly users (within 6 months) have the highest risk (inhaled corticosteroid: OR, 2.13; 95% CI, 1.226–3.701, P = 0.007; oral corticosteroid: OR, 1.932; 95% CI, 1.66–2.25, P < 0.001; non-steroid bronchodilator: OR, 2.849; 95% CI, 2.48–3.273, P < 0.001). A graded association with AF risk was also observed among subjects treated with corticosteroid (inhaled and systemic administration) and bronchodilators. New users (within 6 months) of these medications had the highest risk of AF (ICS: OR, 2.13; 95% CI, 1.226–3.701, P = 0.007; oral corticosteroid: OR, 1.932; 95% CI, 1.66–2.25, P < 0.001; non-steroid bronchodilator: OR, 2.849; 95% CI, 2.48–3.273, P < 0.001). A graded association with AF risk was also observed among subjects treated with ICS or bronchodilator.

Conclusions

Asthma was associated with an increased risk of developing future AF.     

Significant association between angiotensin-converting enzyme gene insertion/deletion polymorphism and risk of recurrent miscarriage: A systematic review and meta-analysis

Background

Many studies have investigated the association between angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism and risk of recurrent miscarriage, but the impact is unclear due to inconsistencies among those studies. This study aimed to quantify the strength of the association between ACE I/D polymorphism and recurrent miscarriage risk by performing a systematic review and meta-analysis.

Design and Methods

We searched PubMed, Embase, Web of Science, and Wanfang Medicine databases for eligible articles relating the association between ACE I/D polymorphism and risk of recurrent miscarriage in humans. We estimated the summary odds ratios (ORs) with their 95% confidence intervals (95% CIs) to assess the association.

Results

Eleven studies with a total of 3357 individuals were included in this meta-analysis. Compared to the ACE II genotype, DD and ID were both associated with increased risk of recurrent miscarriage (OR _{DD versus II} = 1.81, 95% CI 1.23–2.66, P = 0.003; OR _{ID versus II} = 1.50, 95% CI 1.25–1.80, P < 0.001). Sensitivity analyses further confirmed the association above. No evidence of publication bias was observed.

Conclusion

Meta-analyses of available data show a significant association between ACE I/D polymorphism and recurrent miscarriage risk, and the ACE polymorphic D allele contributes to increased risk of recurrent miscarriage.     

Advanced glycation/glycoxidation endproduct carboxymethyl-lysine and incidence of coronary heart disease and stroke in older adults

Background

Advanced glycation/glycoxidation endproducts (AGEs) accumulate in settings of increased oxidative stress – such as diabetes, chronic kidney disease and aging – where they promote vascular stiffness and atherogenesis, but the prospective association between AGEs and cardiovascular events in elders has not been previously examined.

Methods

To test the hypothesis that circulating levels of N^?-carboxymethyl-lysine (CML), a major AGE, increase the risk of incident coronary heart disease and stroke in older adults, we measured serum CML by immunoassay in 2111 individuals free of prevalent cardiovascular disease participating in a population-based study of U.S. adults ages 65 and older.

Results

During median follow-up of 9.1 years, 625 cardiovascular events occurred. CML was positively associated with incident cardiovascular events after adjustment for age, sex, race, systolic blood pressure, anti-hypertensive treatment, diabetes, smoking status, triglycerides, albumin, and self-reported health status (hazard ratio [HR] per SD [0.99 pmol/l] increase = 1.11, 95% confidence interval [CI] = 1.03–1.19). This association was not materially attenuated by additional adjustment for C-reactive protein, estimated glomerular filtration rate (eGFR), and urine albumin/creatinine ratio. Findings were similar for the component endpoints of coronary heart disease and stroke.

Conclusions

In this large older cohort, CML was associated with an increased risk of cardiovascular events independent of a wide array of potential confounders and mediators. Although the moderate association limits CML’s value for risk prediction, these community-based findings provide support for clinical trials to test AGE-lowering therapies for cardiovascular prevention in this population.     

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.     

A pilot study investigating the effects of continuous positive airway pressure treatment and weight-loss surgery on autonomic activity in obese obstructive sleep apnea patients

Background

We have previously demonstrated that severity of obstructive sleep apnea (OSA) as measured by the apnea–hypopnea index (AHI) is a significant independent predictor of readily-computed time-domain metrics of short-term heart rate variability (HRV).

Methods

We aimed to assess time-domain HRV measured over 5-min while awake in a trial of obese subjects undergoing one of two OSA therapies: weight-loss surgery (n = 12, 2 males, median and interquartile range (IQR) for BMI 43.7 [42.0, 51.4] kg/m², and AHI 18.1 [16.3, 67.5] events/h) or continuous positive airway pressure (CPAP) (n = 15, 11 males, median BMI 33.8 [31.3, 37.9] kg/m², and AHI 36.5 [24.7, 77.3] events/h). Polysomnography was followed by electrocardiography during wakefulness; measurements were repeated at 6 and 12–18 months post-intervention.

Results

Despite similar measurements at baseline, subjects who underwent surgery exhibited greater improvement in short-term HRV than those who underwent CPAP (p = 0.04).

Conclusions

Our data suggest a possible divergence in autonomic function between the effects of weight loss resulting from bariatric surgery, and the amelioration of obstructive respiratory events resulting from CPAP treatment. Randomized studies are necessary before clinical recommendations can be made.     

Premature cardiovascular mortality in lymphoma patients treated with (R)-CHOP regimen — A national multicenter study

Background

Premature cardiovascular mortality related to chemotherapy and occurred in lymphoma survivors before disease progression is one of significant clinical failure of modern hematology. The aim of this retrospective analysis was to evaluate early cardiovascular mortality and its predictors in patients treated with the (R)-CHOP regimen.

Methods

The study assessed 610 patients: 581 patients were treated with non-liposomal doxorubicin (cumulative dose of 337 ± 96 mg/m2), and 29 patients with liposomal non-pegylated doxorubicin (cumulative dose of 237 ± 126 mg/m2). Their present status, history of cardiovascular diseases and associated risk factors were recorded.

Results

The analysis identified 93 deaths (15.5%): 51 cases (55%) related to lymphoma disease progression and 28 (30%) to cardiovascular complications. Multivariate Cox analysis revealed history of previous heart diseases (HR = 4.71; CI: 3.82–5.6; p < 0.001), ECG rhythm abnormalities related to chemotherapy (HR = 4,78; CI: 3.63–5.92; p = 0,01), and lack of complete remission (HR = 2.73; CI: 1.78–3.66; p = 0.03), as the independent predictors for cardiovascular death. Neither decreased LVEF nor increasing cumulative dose of anthracyclines had a significant predictive value for cardiovascular prognosis.

Conclusions

The study indicated that cardiovascular mortality in lymphoma patients treated with (R)-CHOP regimen is relatively high and ECG monitoring may be the most effective in cardiological risk assessment. The unfavorable outcome depended on lack of complete remission that seems to be a consequence of patients' individual susceptibility for cardiac events, which should become a purpose of further trials.     

Metformin is associated with reduced risk of pancreatic cancer in patients with type 2 diabetes mellitus: A systematic review and meta-analysis

Aims

Recent epidemiological studies indicated that use of metformin might decrease the risk of various cancers among patients with type 2 diabetes mellitus (T2DM). However, its influence on pancreatic cancer was controversial. Therefore, we did a meta-analysis of currently available observational studies on the issue.

Methods

We did a PubMed and ISI Web of Science search for observational articles. The pooled relative risk (RR) was estimated using a random-effect model. Heterogeneity was evaluated using I² statistic. Subgroup analysis was performed to explore the source of heterogeneity and confirm the overall estimates. Publication bias was also examined.

Results

The analysis included 11 articles (13 studies) comprising 10 cohort studies and 3 case–control studies. Use of metformin was associated with a significant lower risk of pancreatic cancer [RR 0.63, 95% confidence internal (CI) 0.46–0.86, p = 0.003]. In a total 11 subgroup analyses, 5 provided the consistent result with pooled effect estimates of overall analysis. No publication bias was detected by Begg's (Z = −0.79, p = 0.428) and Egger's test (t = −0.92, p = 0.378).

Conclusions

From present observational studies, use of metformin appears to be associated with a reduced risk of pancreatic cancer in patients with T2DM. Further investigation is needed.     

Early intravenous beta-blockers in patients with acute coronary syndrome—A meta-analysis of randomized trials

Background

Intravenous (IV) beta-blockade is currently a Class IIa recommendation in early management of patients with acute coronary syndromes (ACS) without obvious contraindications.

Methods

We searched the PubMed, EMBASE and the Cochrane Register for Controlled Clinical Trials for randomized clinical trials from 1965 through December, 2011, comparing intravenous beta-blockers administered within 12 hours of presentation of ACS with standard medical therapy and/or placebo. The primary outcome assessed was the risk of short-term (in-hospital mortality-with maximum follow up duration of 90 days) all-cause mortality in the intervention group versus the comparator group. The secondary outcomes assessed were ventricular tachyarrhythmias, myocardial reinfarction, cardiogenic shock, and stroke. Pooled treatment effects were estimated using relative risk with Mantel–Haenszel risk ratio, using a random-effects model.

Results

Sixteen studies enrolling 73,396 participants met the inclusion ⁄ exclusion criteria. In- hospital mortality was reduced 8% with intravenous beta-blockers, RR = 0.92 (95% CI, 0.86–1.00; p = 0.04) when compared with controls. Moreover, intravenous beta-blockade reduced the risk of ventricular tachyarrhythmias (RR = 0.61; 95 % CI 0.47–0.79; p = 0.0003) and myocardial reinfarction (RR = 0.73, 95 % CI 0.59–0.91; p = 0.004) without increase in the risk of cardiogenic shock, (RR = 1.02; 95% CI 0.77–1.35; p = 0.91) or stroke (RR = 0.58; 95 % CI 0.17–1.98; p = 0.38).

Conclusions

Intravenous beta-blockers early in the course of appropriate patients with ACS appears to be associated with significant reduction in the risk of short-term cardiovascular outcomes, including a reduction in the risk of all-cause mortality.     

Preoperative renal dysfunction and clinical outcomes of cardiac surgery in octogenarians

Background

The proportion of elderly individuals is growing and the prevalence of chronic kidney disease (CKD) among elderly people undergoing cardiac surgery is increasing constantly. The aim of this study was to determine the influence of different degrees of preoperative renal dysfunction on postoperative outcomes in patients older than 80 years of age.

Methods

This is an observational study that included adult patients undergoing cardiac surgery in which data were collected prospectively. Patients were divided into groups according to their preoperative plasma creatinine and eGFR levels.

Results

From February 1997 to January 2010, 318 octogenarians underwent cardiac surgery. Of these, 140 patients (44%) had abnormal preoperative creatinine levels. A significantly higher incidence of postoperative sepsis (4% vs. 17%, p 0.03), CVA (1% vs. 6%, p 0.03), and prolonged hospital stay (16 ± 13 vs. 20 ± 16 days, p 0.04) were detected in patients with preoperative kidney dysfunction. Subgroup analysis revealed that preoperative CKD stage IV (eGFR 15–30 ml/min/1.73 m²) but not CKD stage III (eGFR 30–60 ml/min/1.73 m²) and preoperative creatinine > 1.8 mg/dl were independently associated with increased incidence of postoperative CVA (OR 4; 95% CI 0.07–0. 8, p = 0.05 for eGFR, and OR 7.8; 95% CI 1.2–60, p = 0.003 for creatinine). However, no significant increment in postoperative mortality with decreasing eGFR or increasing preoperative creatinine was demonstrated.

Conclusions

A substantial increase in the risk of postoperative CVA and sepsis, but not mortality, was demonstrated in octogenarians with advanced but not mild degrees of preoperative CKD. Compared to younger patients, a high burden of comorbidities in octogenarians may have a greater influence on outcomes post cardiac surgery than impaired renal function. Our data may provide a rationale for modified risk stratification in octogenarian candidates for cardiac surgery.     

Are treatments for vasovagal syncope effective? A meta-analysis

Background

Therapies used to treat vaso-vagal syncope (VVS) recurrence have not been proven effective in single studies.

Methods

Comprehensive search of PubMed, EMBASE and Cochrane Central databases of published trials was done. Randomized or non-randomized studies, comparing the intervention of interest to control group(s), with the endpoint of spontaneous recurrence or syncope on head-up tilt test, were included. Data were extracted on an intention-to-treat basis. Study heterogeneity was analyzed by Cochran's Q statistics. A random-effect analysis was used.

Results

α-adrenergic agonists were found effective (n = 400, OR 0.19, CI 0.06–0.62, p < 0.05) in preventing VVS recurrence. β-blockers were not found to be effective when only randomized studies comparing β-blockers to non-pharmacologic agents were assessed (9 studies, n = 583, OR 0.48, CI 0.22–1.04, p = 0.06). Tilt-training had no effect when only randomized studies were considered (4 studies, n = 298, OR 0.47, CI 0.21–1.05, p = 0.07). Selective serotonin reuptake inhibitors were found effective (n = 131, OR 0.28, CI 0.10–0.74, p < 0.05), though the analysis contained only 2 studies. Pacemakers were found effective in preventing syncope recurrence when all studies were analyzed (n = 463, OR 0.13, CI 0.05–0.36, p < 0.05). However, studies comparing active pacemaker to sensing mode only did not show benefit (3 studies, n = 162, OR 0.45, CI 0.09–2.14, p = 0.32).

Conclusions

This meta-analysis highlights the totality of evidence for commonly used medications used to treat VVS, and the requirement for larger, double-blind, placebo controlled trials with longer follow-up.     

Carotid intima-media thickness progression predicts cardiovascular events in Japanese patients with type 2 diabetes

Aims

The aim of this retrospective study was to investigate the relationship between progression of carotid intima-media thickness (cIMT) and cardiovascular events in Japanese patients with type 2 diabetes mellitus (T2DM) and free of history of cardiovascular events.

Methods

Patients with T2DM (n = 342) without history of cardiovascular events whose cIMT was assessed more than twice by ultrasonography were recruited and followed up for cardiovascular events.

Results

During a mean follow-up of 7.6 years, 56 (16.4%) cardiovascular events (27 coronary events and 29 cerebrovascular events) were recorded. Multivariate analysis with the Cox proportional hazard model identified cIMT progression as a significant determinant of cardiovascular events, with a hazard ratio (HR) of 2.24 (95% confidence interval; CI, 1.25–4.03, P < 0.01), in addition to baseline cIMT. The Kaplan–Meier curves also showed significantly higher event rate in patients with high cIMT progression compared with those with low cIMT progression (log-rank χ² = 6.65; P < 0.01). Furthermore, the combination of high baseline cIMT and high cIMT progression was a significant predictor of cardiovascular events.

Conclusion

Our findings suggest that cIMT progression, in addition to baseline cIMT, is a predictor of cardiovascular events in patients with T2DM without history of cardiovascular events, and that the combination of cIMT progression and baseline cIMT has a strong predictive power for such events.     

Effects of successful percutaneous lower extremity revascularization on cardiovascular outcome in patients with peripheral arterial disease

Background

Lower extremity peripheral arterial disease (LE-PAD) reduces walking capacity and is associated with an increased cardiovascular risk. Endovascular revascularization of LE-PAD improves walking performance and quality of life. In the present study, we determined whether successful lower limbs revascularization also impacts cardiovascular outcome in LE-PAD patients.

Methods

479 consecutive LE-PAD patients at stage II of Fontaine's classification, with ankle/brachial index ≤ 0.90 and one or more stenosis > 50% in at least one leg artery, were enrolled in the study. According to the Trans-Atlantic Inter Society Consensus II recommendations, 264 (55.1%) underwent percutaneous lower extremity angioplasty (PTA group), while 215 (44.9%) were managed with conservative therapy (MT group). The incidence of major cardiovascular events (including cardiovascular death, myocardial infarction, ischemic stroke, coronary and carotid revascularizations) was prospectively analyzed by Kaplan–Meier curves. Crude and adjusted HRs (95% CI) of developing a cardiovascular event were calculated by Cox analysis.

Results

No baseline differences were observed among the groups, except for a lower maximum walking distance in the PTA group. During a median follow-up of 21 months (12.0–29.0), the incidence of cardiovascular events was markedly lower in PTA compared to MT patients (6.4% vs. 16.3%; p = 0.003), and patients in the MT group showed a 4.1-fold increased cardiovascular risk compared to patients in the PTA group, after adjustment for potential confounders (95% CI 1.22–13.57, p = 0.023).

Conclusions

This study shows that successful revascularization of LE-PAD patients affected by intermittent claudication, in addition to improving functional status, reduces the occurrence of future major cardiovascular events.     

High post-clopidogrel platelet reactivity assessed by a point-of-care assay predicts long-term clinical outcomes in patients with ST-segment elevation myocardial infarction who underwent primary coronary stenting

Background

Recent studies have shown that post-clopidogrel high platelet reactivity (HPR), assessed by a point-of-care assay, is associated with a higher risk of adverse events after percutaneous coronary intervention (PCI). We assessed the clinical impact of HPR by the VerifyNow P2Y12 point-of-care assay in 181 patients with ST-segment elevation myocardial infarction (STEMI) who underwent primary PCI with drug-eluting stents (DES) at 3 hospitals.

Methods

The primary endpoint of the study was the 12-month major adverse cardiovascular events (MACE), which comprised cardiovascular death, nonfatal MI and ischemic stroke. All patients received a single loading dose of 600 mg clopidogrel and 300 mg aspirin followed by a daily maintenance dose of 75 mg clopidogrel and 100 mg aspirin.

Results

A P2Y12 reaction unit (PRU) ≥ 282 (AUC 0.719, 95% CI 0.588–0.851, p = 0.004, sensitivity 68.8%, specificity 73.8%) was the optimal cut-off value in predicting 12-month MACE by receiver operating characteristic curve analysis. Occurrence of MACE was significantly more frequent in patients with HPR (PRU ≥ 282) compared to patients without HPR (20.4% vs. 3.9%, HR 6.24, 95% CI 2.05–18.99, p = 0.001). By multivariate analysis, HPR (HR 3.84, 95% CI 1.17–12.58, p = 0.026) and elderly patients above 80 years of age (HR: 8.13, 95% CI 1.79–37.03, p = 0.007) were found to be the significant predictors of 12-month MACE. The MACE-free survival rate was significantly lower in patients with HPR compared to patients without HPR (p < 0.001).

Conclusion

HPR assessed by a point-of-care assay was able to predict 12-month MACE in patients with STEMI who underwent primary PCI with DES.     

Cangrelor infusion is associated with an increased risk for bleeding: Meta-analysis of randomized trials

Context

Aggressive antiplatelet strategies unquestionably cause extra hemorrhagic risks. Bleeding episodes are associated with poor outcomes including increased mortality. However, lack of uniform reporting and adjudication of bleeding events might prevent objective evaluation of the efficacy/safety profile of antithrombotic agents.

Objective

We analyzed the bleeding rates by several previously used bleeding scales (TIMI, GUSTO, ACUITY, and BARC) after cangrelor in recent head-to-head randomized, controlled clinical trials (RCTs).

Results

Data for meta-analyses were pooled from 3 RCTs (CHAMPION-PLATFORM, CHAMPION-PCI and CHAMPION-PHOENIX) including 25,106 patients. In addition, the bleeding risks were also assessed from the small (n = 210) BRIDGE RCT. Cangrelor caused a significantly increased risk for major bleeding at 48 h according to the ACUITY scale (RR: 1.51, 95% CI: 1.32–1.72, p < 0.00001); however, this impact was less prominent according to less sensitive bleeding scales (GUSTO severe: RR: 1.21, 95% CI: 0.70–2.11, p = 0.49; TIMI major: RR: 1.00, 95% CI: 0.59–1.68, p = 0.99). There was also an obvious trend towards an increased risk for any transfusions (RR: 1.31, 95% CI: 0.97–1.77, p = 0.08) and TIMI major + minor bleeding events (RR: 1.30, 95% CI: 0.96–1.76, p = 0.09).

Conclusions

Cangrelor on top of aspirin or/and clopidogrel increases the risk for early bleeding events after PCI; however, it largely depends on the bleeding definition used, and how this excess risk of bleeding was captured. The bleeding hazard needs to be verified in the ongoing FDA secondary cangrelor review.     

Cardiovascular events in a prehypertensive Chinese population: Four-year follow-up study

Objectives

This study aimed to determine the occurrence of cardiovascular (CV) events in a prehypertensive Chinese population.

Methods

Participants meeting the JNC 7 diagnostic criteria for prehypertension (n = 30,027) and ideal blood pressure (n = 15,614) were enrolled in this prospective, observational cohort. New CV events were collected during follow-up of 38–53 months (mean 47.58 ± 3.19 months). A multivariate Cox proportional hazard regression model was used to analyze factors influencing CV events.

Results

Four hundred sixty-one CV events occurred during the follow-up period. Cumulative incidence rates for total CV events, cerebral infarct, cerebral hemorrhage, myocardial infarct, and deaths due to CV in the prehypertensive population were 1.19%, 0.57%, 0.20%, 0.23%, and 0.23%, respectively. These rates were higher than those of the ideal blood pressure group (0.67%, 0.27%, 0.12%, 0.17%, and 0.15% respectively). After correcting for traditional CV risk factors, relative risks (RRs) for total CV events, cerebral infarct and cerebral hemorrhages in the prehypertensive population were 1.32 (95% confidence intervals (CI): 1.06–1.65), 1.55 (95% CI: 1.10–2.18) and 1.40 (95% CI: 0.82–2.37) higher than those in the ideal blood pressure population. Compared to the ideal blood pressure group, the prehypertensive population was older, more likely male, and had higher triglycerides, total cholesterol, low-density lipoprotein cholesterol, and body mass index (p < 0.05).

Conclusion

Prehypertension is an independent risk factor for total CV events and stroke.