Periodontitis: a future risk of acute coronary syndrome? A follow-up study over 3 years

BACKGROUND: Periodontitis has been associated with cardiovascular disease. We assess if the recurrence of acute coronary syndrome (ACS) could be predicted by preceding medical and periodontal conditions. METHODS: A total of 165 consecutive subjects with ACS and 159 medically healthy, matched control subjects were examined and followed for 3 years. Periodontitis was defined by alveolar bone loss. Subgingival microbial samples were studied by the checkerboard DNA-DNA hybridization method. RESULTS: The recurrence of ACS was found in 66 of 165 (40.0%) subjects, and a first ACS event was found in seven of 159 (4.4%) subjects among baseline control subjects. Subjects who later had a second ACS event were older (P <0.001). Significantly higher serum levels of high-density lipoprotein (P <0.05), creatinine (P <0.01), and white blood cell (WBC) counts (P <0.001) were found in subjects with future ACS. Periodontitis was associated with a first event of ACS (crude odds ratio [OR]: 10.3:1; 95% confidence interval [CI]: 6.1 to 17.4; P <0.001) and the recurrence of ACS (crude OR: 3.6:1; 95% CI: 2.0 to 6.6; P <0.001). General linear modeling multivariate analysis, controlling for age and the prediction of a future ACS event, identified that WBC counts (F = 20.6; P <0.001), periodontitis (F = 17.6; P <0.001), and serum creatinine counts (F = 4.5; P <0.05) were explanatory of a future ACS event. CONCLUSIONS: The results of this study indicate that recurrent ACS events are predicted by serum WBC counts, serum creatinine levels, and a diagnosis of periodontitis. Significantly higher counts of putative pathogens are found in subjects with ACS, but these counts do not predict future ACS events.

Sudden cardiac arrest during acute coronary occlusion - who is at risk?

Many people with acute myocardial infarction die from sudden cardiac arrest before reaching the hospital. The current clinical understanding of the mechanisms and risk factors surrounding sudden cardiac death is limited. However, 2 factors related to sudden death, namely the occluded coronary vessel (right coronary, left circumflex, or left anterior descending artery) and the extent of collateral circulation, are of potential relevance. Recent data suggest that the risk differs between the different coronary arteries and that coronary collateral circulation seems to have an important protective 'antiarrhythmic' effect. This editorial will address possible mechanisms and potential implications in clinical practice.

Controversies in cardiovascular medicine: Chronic stable coronary artery disease: drugs vs. revascularization

Coronary artery disease remains the leading cause of mortality in most industrialized countries, although age-standardized mortality related to coronary artery disease (CAD) has decreased by more than 40% during the last two decades. Coronary atherosclerosis may cause angina pectoris, myocardial infarction, heart failure, arrhythmia, and sudden death. Medical management of atherosclerosis and its manifestation aims at retardation of progression of plaque formation, prevention of plaque rupture, and subsequent events and treatment of symptoms, when these occur as well as treatment of the sequelae of the disease. Revascularization by either percutaneous coronary intervention (PCI) or coronary artery bypass surgery (CABG) is performed as treatment of flow-limiting coronary stenosis to reduce myocardial ischaemia. In high-risk patients with acute coronary syndromes (ACS), a routine invasive strategy with revascularization in most patients provides the best outcome with a significant reduction in death and myocardial infarction compared with an initial conservative strategy. Conversely, the benefit of revascularization among patients with chronic stable CAD has been called into question. This review will provide information that revascularization exerts favourable effects on symptoms, quality of life, exercise capacity, and survival, particularly in those with extensive CAD and documented moderate-to-severe ischaemia. Accordingly, CABG and PCI should be considered a valuable adjunct rather than an alternative to medical therapy.

Percutaneous coronary interventions in Europe: prevalence, numerical estimates, and projections based on data up to 2004

AIMS: A registry mandated by the European Society of Cardiology collects data on trends in interventional cardiology within Europe. Special interest focuses on relative increases and ratios in new techniques and their distributions across Europe. We report the data through 2004 and give an overview of the development of coronary interventions since the first data collection in 1992. METHODS AND RESULTS: Questionnaires were distributed yearly to delegates of all national societies of cardiology represented in the European Society of Cardiology. The goal was to collect the case numbers of all local institutions and operators. The overall numbers of coronary angiographies increased from 1992 to 2004 from 684 000 to 2 238 000 (from 1250 to 3930 per million inhabitants). The respective numbers for percutaneous coronary interventions (PCIs) and coronary stenting procedures increased from 184 000 to 885 000 (from 335 to 1550) and from 3000 to 770 000 (from 5 to 1350), respectively. Germany was the most active country with 712 000 angiographies (8600), 249 000 angioplasties (3000), and 200 000 stenting procedures (2400) in 2004. The indication has shifted towards acute coronary syndromes, as demonstrated by rising rates of interventions for acute myocardial infarction over the last decade. The procedures are more readily performed and perceived safer, as shown by increasing rate of "ad hoc" PCIs and decreasing need for emergency coronary artery bypass grafting (CABG). In 2004, the use of drug-eluting stents continued to rise. However, an enormous variability is reported with the highest rate in Switzerland (70%). If the rate of progression remains constant until 2010 the projected number of coronary angiographies will be over three million, and the number of PCIs about 1.5 million with a stenting rate of almost 100%. CONCLUSION: Interventional cardiology in Europe is ever expanding. New coronary revascularization procedures, alternative or complementary to balloon angioplasty, have come and gone. Only stenting has stood the test of time and matured to the default technique. Facilitated access to PCI, more complete and earlier detection of coronary artery disease promise continued growth of the procedure despite the uncontested success of prevention.

Bacterial profile and burden of periodontal infection in subjects with a diagnosis of acute coronary syndrome

BACKGROUND: Periodontitis has been identified as a potential risk factor in cardiovascular diseases. It is possible that the stimulation of host responses to oral infections may result in vascular damage and the inducement of blood clotting. The aim of this study was to assess the role of periodontal infection and bacterial burden as an explanatory variable to the activation of the inflammatory process leading to acute coronary syndrome (ACS). METHODS: A total of 161 consecutive surviving cases admitted with a diagnosis of ACS and 161 control subjects, matched with cases according to their gender, socioeconomic level, and smoking status, were studied. Serum white blood cell (WBC) counts, high- and low-density lipoprotein (HDL/LDL) levels, high-sensitivity C-reactive protein (hsC-rp) levels, and clinical periodontal routine parameters were studied. The subgingival pathogens were assayed by the checkerboard DNA-DNA hybridization method. RESULTS: Total oral bacterial load was higher in the subjects with ACS (mean difference: 17.4x10(5); SD: 10.8; 95% confidence interval [CI]: 4.2 to 17.4; P<0.001), and significant for 26 of 40 species including Porphyromonas gingivalis, Tannerella forsythensis, and Treponema denticola. Serum WBC counts, hsC-rp levels, Streptococcus intermedius, and Streptococcus sanguis, were explanatory factors to acute coronary syndrome status (Nagelkerke r2=0.49). CONCLUSION: The oral bacterial load of S. intermedius, S. sanguis, Streptococcus anginosus, T. forsythensis, T. denticola, and P. gingivalis may be concomitant risk factors in the development of ACS.

Admission glycaemia and outcome in patients with acute coronary syndrome

Some studies of patients with acute myocardial infarction have reported that hyperglycaemia at admission may be associated with a worse outcome. This study sought to evaluate the association of blood glucose at admission with the outcome of unselected patients with acute coronary syndrome (ACS). Using the Acute Myocardial Infarction and unstable angina in Switzerland (AMIS Plus) registry, ACS patients were stratified according to their blood glucose on admission: group 1: 2.80-6.99 mmol/L, group 2: 7.00-11.09 mmol/L and group 3: > 11.10 mmol/L. Odds ratios for in-hospital mortality were calculated using logistic regression models. Of 2,786 patients, 73% were male and 21% were known to have diabetes. In-hospital mortality increased from 3% in group 1 to 7% in group 2 and to 15% in group 3. Higher glucose levels were associated with larger enzymatic infarct sizes (p<0.001) and had a weak negative correlation with angiographic or echographic left ventricular ejection fraction. High admission glycaemia in ACS patients remains a significant independent predictor of in-hospital mortality (adjusted OR 1.08; 95% confidence intervals [CI] 1.05-1.14, p<0.001) per mmol/L. The OR for in-hospital mortality was 1.04 (95% CI 0.99-1.1; p=0.140) per mmol/L for patients with diabetes but 1.21 (95% CI 112-1.30; p<0.001) per mmol/L for non-diabetic patients. In conclusion, elevated glucose level in ACS patients on admission is a significant independent predictor of in-hospital mortality and is even more important for patients who do not have known diabetes.

Biolimus-eluting stent with biodegradable polymer versus sirolimus-eluting stent with durable polymer for coronary revascularisation (LEADERS): a randomised non-inferiority trial

BACKGROUND: A novel stent platform eluting biolimus, a sirolimus analogue, from a biodegradable polymer showed promising results in preliminary studies. We compared the safety and efficacy of a biolimus-eluting stent (with biodegradable polymer) with a sirolimus-eluting stent (with durable polymer). METHODS: We undertook a multicentre, assessor-blind, non-inferiority study in ten European centres. 1707 patients aged 18 years or older with chronic stable coronary artery disease or acute coronary syndromes were centrally randomised by a computer-generated allocation sequence to treatment with either biolimus-eluting (n=857) or sirolimus-eluting (n=850) stents. The primary endpoint was a composite of cardiac death, myocardial infarction, or clinically-indicated target vessel revascularisation within 9 months. Analysis was by intention to treat. 427 patients were randomly allocated to angiographic follow-up, with in-stent percentage diameter stenosis as principal outcome measure at 9 months. The trial is registered with ClinicalTrials.gov, number NCT00389220. FINDINGS: We analysed all randomised patients. Biolimus-eluting stents were non-inferior to sirolimus-eluting stents for the primary endpoint at 9 months (79 [9%] patients vs 89 [11%], rate ratio 0.88 [95% CI 0.64-1.19], p for non-inferiority=0.003, p for superiority=0.39). Frequency of cardiac death (14 [1.6%] vs 21 [2.5%], p for superiority=0.22), myocardial infarction (49 [5.7%] vs 39 [4.6%], p=0.30), and clinically-indicated target vessel revascularisation (38 [4.4%] vs 47 [5.5%], p=0.29) were similar for both stent types. 168 (79%) patients in the biolimus-eluting group and 167 (78%) in the sirolimus-eluting group had data for angiographic follow-up available. Biolimus-eluting stents were non-inferior to sirolimus-eluting stents in in-stent percentage diameter stenosis (20.9%vs 23.3%, difference -2.2% [95% CI -6.0 to 1.6], p for non-inferiority=0.001, p for superiority=0.26). INTERPRETATION: Our results suggest that a stent eluting biolimus from a biodegradable polymer represents a safe and effective alternative to a stent eluting sirolimus from a durable polymer in patients with chronic stable coronary artery disease or acute coronary syndromes. FUNDING: Biosensors Europe SA, Switzerland.

Autonomic function and prothrombotic activity in women after an acute coronary event

BACKGROUND: The link between decreased heart rate variability (HRV) and atherosclerosis progression is elusive. We hypothesized that reduced HRV relates to increased levels of prothrombotic factors previously shown to predict coronary risk. METHODS: We studied 257 women (aged 56 +/- 7 years) between 3 and 6 months after an acute coronary event and obtained very low frequency (VLF), low frequency (LF), and high frequency (HF) power, and LF/HF ratio from 24-hour ambulatory ECG recordings. Plasma levels of activated clotting factor VII (FVIIa), fibrinogen, von Willebrand factor antigen (VWF:Ag), and plasminogen activator inhibitor-1 (PAI-1) activity were determined, and their levels were aggregated into a standardized composite index of prothrombotic activity. RESULTS: In bivariate analyses, all HRV indices were inversely correlated with the prothrombotic index explaining between 6% and 14% of the variance (p < 0.001). After controlling for sociodemographic factors, index event, menopausal status, cardiac medication, lifestyle factors, self-rated health, metabolic variables, and heart rate, VLF power, LF power, and HF power explained 2%, 5%, and 3%, respectively, of the variance in the prothrombotic index (p < 0.012). There were also independent relationships between VLF power and PAI-1 activity, between LF power and fibrinogen, VWF:Ag, and PAI-1 activity, between HF power and FVIIa and fibrinogen, and between the LF/HF power ratio and PAI-1 activity, explaining between 2% and 3% of the respective variances (p < 0.05). CONCLUSIONS: Decreased HRV was associated with prothrombotic changes partially independent of covariates. Alteration in autonomic function might contribute to prothrombotic activity in women with coronary artery disease (CAD).

Effect of oral melatonin on the procoagulant response to acute psychosocial stress in healthy men: a randomized placebo-controlled study

Acute mental stress is a potent trigger of acute coronary syndromes. Catecholamine-induced hypercoagulability with acute stress contributes to thrombus growth after coronary plaque rupture. Melatonin may diminish catecholamine activity. We hypothesized that melatonin mitigates the acute procoagulant stress response and that this effect is accompanied by a decrease in the stress-induced catecholamine surge. Forty-five healthy young men received a single oral dose of either 3 mg melatonin (n = 24) or placebo medication (n = 21). One hour thereafter, they underwent a standardized short-term psychosocial stressor. Plasma levels of clotting factor VII activity (FVII:C), FVIII:C, fibrinogen, D-dimer, and catecholamines were measured at rest, immediately after stress, and 20 min and 60 min post-stress. The integrated change in D-dimer levels from rest to 60 min post-stress differed between medication groups controlling for demographic and metabolic factors (P = 0.047, eta(p)(2) = 0.195). Compared with the melatonin group, the placebo group showed a greater increase in absolute D-dimer levels from rest to immediately post-stress (P = 0.13; eta(p)(2) = 0.060) and significant recovery of D-dimer levels from immediately post-stress to 60 min thereafter (P = 0.007; eta(p)(2) = 0.174). Stress-induced changes in FVII:C, FVIII:C, fibrinogen, and catecholamines did not significantly differ between groups. Oral melatonin attenuated the stress-induced elevation in the sensitive coagulation activation marker D-dimer without affecting catecholamine activity. The finding provides preliminary support for a protective effect of melatonin in reducing the atherothrombotic risk with acute mental stress.

Surgical versus percutaneous revascularization of coronary artery disease in diabetic patients

Morbidity and mortality related to coronary artery disease (CAD) remain a great challenge in patients with diabetes mellitus. Revascularization of CAD is an important therapeutic intervention owing to its impact on both symptoms and prognosis. The optimal revascularization strategy continues to evolve due to the advent of new technologies and improved peri-procedural outcome with both percutaneous coronary interventions and coronary artery bypass grafting. Although clinical outcome following coronary artery bypass is worse in diabetic as opposed to non-diabetic patients, surgical revascularization tends to be associated with better outcome in stable patients with multivessel disease and reduced left ventricular function. The advent of drug-eluting stents has challenged the supremacy of coronary artery bypass grafting and has become a valuable alternative to surgery. The safety and efficacy of drug-eluting stents in the treatment of patients with diabetes and multivessel disease is currently under investigation in several ongoing randomized controlled trials. Percutaneous coronary intervention is the therapy of choice in patients with acute coronary syndromes, particularly ST-elevation myocardial infarction. The focus of this review is to present the current evidence, define the role of percutaneous and surgical revascularization in the treatment of diabetic patients with CAD, and propose a tailored approach for clinical decision-making.

Increased circulating placental growth factor during percutaneous coronary intervention is associated with applied radiocontrast agent

BACKGROUND AND AIM OF THE STUDY: Recent studies have suggested placental growth factor (PlGF) and vascular endothelial growth factor (VEGF) as promising new biomarkers for risk stratification in acute coronary syndromes (ACS). However, little is known about the influence of percutaneous coronary intervention (PCI) on circulating PlGF and VEGF levels. METHODS: Thirty-five patients with ACS, 27 patients with stable coronary artery disease (sCAD), and nine healthy controls were enrolled in the study. Although all patients with ACS and 14 patients with stable angina pectoris underwent PCI, 13 patients with coronary artery disease required no revascularization (sCAD). PlGF and VEGF plasma concentrations were measured by immunoassay during and at the end of PCI and coronary angiography. RESULTS: Plasma PlGF levels were comparable in patients with ACS and sCAD on admission. Although coronary angiography or heparin alone did not alter PlGF and VEGF levels, immediately after PCI a dramatic increase was seen in circulating PlGF and a decrease in VEGF, which was independent of the clinical presentation of the patients, heparin administration, or the angiographic procedure itself, but was associated with the extent of coronary artery disease and the amount of the injected contrast media. In-vitro experiments revealed that radiocontrast agents induced the release of PlGF from endothelial cells without altering PlGF mRNA expression. CONCLUSION: Patients undergoing PCI exhibit an increase in circulating PlGF, probably caused by posttranslational modifications of radiocontrast agents in endothelial cells. Therefore, analysis of plasma PlGF and VEGF levels may consider the timing of blood sampling with respect to PCI and contrast media exposure.

Validity of Charlson Comorbidity Index in patients hospitalised with acute coronary syndrome. Insights from the nationwide AMIS Plus registry 2002-2012

OBJECTIVE This study aimed to assess the impact of individual comorbid conditions as well as the weight assignment, predictive properties and discriminating power of the Charlson Comorbidity Index (CCI) on outcome in patients with acute coronary syndrome (ACS). METHODS A prospective multicentre observational study (AMIS Plus Registry) from 69 Swiss hospitals with 29 620 ACS patients enrolled from 2002 to 2012. The main outcome measures were in-hospital and 1-year follow-up mortality. RESULTS Of the patients, 27% were female (age 72.1±12.6 years) and 73% were male (64.2±12.9 years). 46.8% had comorbidities and they were less likely to receive guideline-recommended drug therapy and reperfusion. Heart failure (adjusted OR 1.88; 95% CI 1.57 to 2.25), metastatic tumours (OR 2.25; 95% CI 1.60 to 3.19), renal diseases (OR 1.84; 95% CI 1.60 to 2.11) and diabetes (OR 1.35; 95% CI 1.19 to 1.54) were strong predictors of in-hospital mortality. In this population, CCI weighted the history of prior myocardial infarction higher (1 instead of -0.4, 95% CI -1.2 to 0.3 points) but heart failure (1 instead of 3.7, 95% CI 2.6 to 4.7) and renal disease (2 instead of 3.5, 95% CI 2.7 to 4.4) lower than the benchmark, where all comorbidities, age and gender were used as predictors. However, the model with CCI and age has an identical discrimination to this benchmark (areas under the receiver operating characteristic curves were both 0.76). CONCLUSIONS Comorbidities greatly influenced clinical presentation, therapies received and the outcome of patients admitted with ACS. Heart failure, diabetes, renal disease or metastatic tumours had a major impact on mortality. CCI seems to be an appropriate prognostic indicator for in-hospital and 1-year outcomes in ACS patients. CLINICALTRIALSGOV IDENTIFIER NCT01305785.

Cost-effectiveness of ticagrelor and generic clopidogrel in patients with acute coronary syndrome in Switzerland

QUESTION UNDER STUDY The aim of this study was to evaluate the cost-effectiveness of ticagrelor and generic clopidogrel as add-on therapy to acetylsalicylic acid (ASA) in patients with acute coronary syndrome (ACS), from a Swiss perspective. METHODS Based on the PLATelet inhibition and patient Outcomes (PLATO) trial, one-year mean healthcare costs per patient treated with ticagrelor or generic clopidogrel were analysed from a payer perspective in 2011. A two-part decision-analytic model estimated treatment costs, quality-adjusted life years (QALYs), life years and the cost-effectiveness of ticagrelor and generic clopidogrel in patients with ACS up to a lifetime at a discount of 2.5% per annum. Sensitivity analyses were performed. RESULTS Over a patient's lifetime, treatment with ticagrelor generates an additional 0.1694 QALYs and 0.1999 life years at a cost of CHF 260 compared with generic clopidogrel. This results in an Incremental Cost Effectiveness Ratio (ICER) of CHF 1,536 per QALY and CHF 1,301 per life year gained. Ticagrelor dominated generic clopidogrel over the five-year and one-year periods with treatment generating cost savings of CHF 224 and 372 while gaining 0.0461 and 0.0051 QALYs and moreover 0.0517 and 0.0062 life years, respectively. Univariate sensitivity analyses confirmed the dominant position of ticagrelor in the first five years and probabilistic sensitivity analyses showed a high probability of cost-effectiveness over a lifetime. CONCLUSION During the first five years after ACS, treatment with ticagrelor dominates generic clopidogrel in Switzerland. Over a patient's lifetime, ticagrelor is highly cost-effective compared with generic clopidogrel, proven by ICERs significantly below commonly accepted willingness-to-pay thresholds.