Relative Risk Of Cardiovascular Death Research Articles

Is there a shift from cardiovascular to cancer death in lipid-lowering trials? A systematic review and meta-analysis.

Lipid-lowering therapy (LLT) reduces cardiovascular (CV) events, but data are conflicting on all-cause mortality, especially among older adults. Though LLT does not induce cancer, some randomized clinical trials (RCTs) found a pattern of increased cancer death under LLT. Our objective was to assess a possible shift from CV to cancer death in LLT trials (i.e. an increase in cancer and decrease in CV death) and to investigate potential subgroups at risk. We performed a systematic review and meta-analysis. We retrieved RCTs from MEDLINE, Embase, and Cochrane Central until 08/2023. We extracted the number of CV and cancer deaths in the treatment vs. in the control arm, calculated the relative risk (RR) by dividing the risk of death in the treatment over the risk of death in the control group and then pooled them using random-effect meta-analysis. We performed subgroup analyses on primary and secondary prevention, and according to different age cut-offs. We included 27 trials with 188'259 participants (23 statin; 4 ezetimibe trials). The trials reported 4056 cancer deaths, 2061 under LLT and 1995 in control groups. Overall, there was no increased risk of cancer mortality (RR 1.03, 95% confidence interval 0.97-1.10), with no difference between primary and secondary prevention. In the subgroup analyses for RCTs with ≥15% of participants aged ≥75 years, the RR of cancer death was 1.11 (1.00-1.23), while the RR for CV death was 0.96 (0.91-1.01). For RCTs with a mean age ≥ 70 years, the RR for cancer death was 1.21 (0.99-1.47). LLT does not lead to a shift from CV to cancer death. However, there might be a possible shift with a pattern of increased cancer deaths in trials with more older adults, particularly ≥75 years. Individual participant data from LLT trials should be made public to allow further investigations. CRD42021271658.

Predictive value of cardiovascular risk factors in the formation of cardiovascular and all-cause mortality: results of a 27-year cohort prospective study

Aim. To study the prognostic significance of cardiovascular risk factors (RFs) in the formation of all-cause and cardiovascular mortality based on the results of a 27-year prospective cohort study of Tomsk population of both sexes aged 20-59 years.Material and methods. The object of study was random house-to-house sample of Tomsk population. In total, 1546 people (630 men and 916 women) aged 20-59 were examined. In 1988-1991, the prevalence of following cardiovascular RFs was studied: hypertension (HTN), overweight, smoking, alcohol consumption, hypercholesterolemia (HCE), low high-density lipoprotein cholesterol levels (hypo-HDL-emia), hypertriglyceridemia (HTG). All examination methods used were strictly standardized. To determine the RF, the criteria generally accepted in epidemiological studies were used. Over 27 years of follow-up, 330 deaths were recorded, including 142 due to cardiovascular disease.Results. In the multivariate Cox proportional hazard model, the following va­riables were studied: HTN, overweight, smoking, alcohol consumption, HCE, hypo-HDL-emia, HTG, coronary artery disease (CAD) (according to epi­demio­logical criteria), and age. The strongest predictor of of all-cause death was frequent alcohol use (relative risk (RR) 2,75). Smoking increased the risk of death by 2,72 times. Among former smokers, the risk of all-cause death was 1,9 times higher compared to non-smokers. HTN increases the death risk by 1,61 times. Each year of life lived increases the death risk by 1,06 times. The most significant risk factor for death from CVD was frequent alcohol consumption (RR 3,01). Smoking increases the cardiovascular death risk by 2,28 times. Among former smokers, the RR of cardiovascular death was 1,91. HTN increases the risk of cardiovascular mortality by 1,84 times compared with people with normal blood pressure. Each year of life lived increases the risk of cardiovascular death by 1,1 times. In multivariate analysis, overweight, HCE, hypo-HDL-emia, HTG did not have a significant independent effect on the all-cause and cardiovascular death risk.Conclusion. In a 27-year cohort prospective study, independent predictors of all-cause and cardiovascular mortality, along with hypertension and age, were lifestyle risk factors, such as smoking and frequent alcohol consumption.

M7. Effects of the angiotensin receptor–neprilysin inhibitor/sacubitril-valsartan administration on quality of life and outcome in heart failure with reduced ejection fraction: a meta analysis

Abstract Background and Aims Improved quality of life is a mayor treatment goal in heart failure. Based on the PARADIGM-HF trial, ARNI was found improved quality of life in heart failure with reduced ejection fraction (HFrEF). The aims of this study are to evaluate the quality of life and outcome patient HFrEF after ARNI administration. Methods and Result Published scientific articles is searched through PubMed database with inclusion criteria were Randomized Control Trial (RCT) or observational study in the last 10 years (2014 - 2021), the QoL is measured by Kansas City Cardiomyopathy Score (KCCQ). A total of 4 RCTs and 3 observational studies were selected. There was significantly increase in KCCQ Overall Summary score (MD = 2.01 [95% CI, 1.07, 2.96], p < 0.00001). There was also significantly increase in KCCQ physical limitation domain (MD = 1.21[95% CI, 0.12, 2.30], p = 0.03), QoL domain (MD = 2.66[95% CI, 0.64, 4.69], p = 0.010) and social limitation domain (MD = 1.97[95% CI, 0.98, 2.95], p < 0.0001). The relative risk in HFrEF patients for first hospital admission was 0.82 (95% CI, 0.77, 0.87, p < 0.00001) and relative risk for cardiovascular death was 0.81(95% CI, 0.76, 0.87, p < 0.00001). Hypotension was found as significant adverse event after treatment with ARNI (RR = 1.57 [95% CI, 1.41, 1.75], p < 0.00001). Conclusion ARNI was found significantly improved quality of life, reduced morbidity and mortality in patient HFrEF compared with control but might causes a serious adverse event such as hypotension. Due to limitation data of adverse event, a further investigation might be needed.

Cause of Death After Surgical Aortic Valve Replacement: SWEDEHEART Observational Study.

BackgroundPrior studies showed that life expectancy in patients who underwent surgical aortic valve replacement (AVR) was lower than in the general population. Explanations for this shorter life expectancy are unknown. The aim of this nationwide, observational cohort study was to investigate the cause‐specific death following surgical AVR.Methods and ResultsWe included 33 018 patients who underwent primary surgical AVR in Sweden between 1997 and 2018, with or without coronary artery bypass grafting. The SWEDEHEART (Swedish Web‐System for Enhancement and Development of Evidence‐Based Care in Heart Disease Evaluated According to Recommended Therapies) register and other national health‐data registers were used to obtain and characterize the study cohort and to identify causes of death, categorized as cardiovascular mortality, cancer mortality, or other causes of death. The relative risks for cause‐specific mortality in patients who underwent AVR compared with the general population are presented as standardized mortality ratios. During a mean follow‐up period of 7.3 years (maximum 22.0 years), 14 237 (43%) patients died. The cumulative incidence of death from cardiovascular, cancer‐related, or other causes was 23.5%, 8.3%, and 11.6%, respectively, at 10 years, and 42.8%, 12.8%, and 23.8%, respectively, at 20 years. Standardized mortality ratios for cardiovascular, cancer‐related, and other causes of death were 1.79 (95% CI, 1.75–1.83), 1.00 (95% CI, 0.97–1.04), and 1.08 (95% CI, 1.05–1.12), respectively.ConclusionsWe found that life expectancy following AVR was lower than in the general population. Lower survival after AVR was explained by an increased relative risk of cardiovascular death. Future studies should focus on the role of earlier surgery in patients with asymptomatic aortic stenosis and on optimizing treatment and follow‐up after AVR.RegistrationURL: https://www.clinicaltrials.gov; Unique identifier: NCT02276950.

Pharmacoeconomic Analysis of Sitagliptin/Metformin for the Treatment of Type 2 Diabetes Mellitus: A Cost-Effectiveness Study

ObjectivesTo assess the cost-effectiveness and cost utility of sitagliptin/metformin for the treatment of type 2 diabetes mellitus compared to those of glibenclamide/metformin in a semiprivate hospital and to compare the cost-effectiveness and cost utility of sitagliptin/metformin in a semiprivate hospital to those in the public health system (PHS) of Ecuador in 2019. MethodsA cost-effectiveness study considering the probability of cardiovascular death as the outcome and quality-adjusted life-year as a measure of utility, estimating direct medical costs in US dollars by a model case from the perspective of the third payer. The results will be presented as an incremental cost-effectiveness ratio. One-way and 2-way sensitivity analyses with tornado diagrams were performed. ResultsDirect medical costs were lower at the hospital than from the PHS in Ecuador. Considering the drugs metformin/sitagliptin, the total cost was $35.69 less in the hospital ($880.38) than from the comparator ($916.07). The highest percentage of direct medical costs corresponded to drugs (between 63.94% and 84.65%). An ICER of –$19 131.61 was obtained at the Hospital Un Canto a la Vida and –$1621.85 at PHS. In addition, the cost per quality-adjusted life-year earned was $611.11. Sensitivity analysis showed that the probability of drug use and the relative risk of cardiovascular death associated with such prescription were parameters that most affected the model. ConclusionsThe combination therapy metformin/sitagliptin compared to metformin/glibenclamide was shown not to be cost-effective in the Hospital Un Canto a la Vida, and highly cost-effective in the PHS.

Empagliflozin reduced the combined relative risk of cardiovascular death and hospitalization for heart failure (primary endpoint) by 25 percent in adults with and without diabetes who had heart failure with reduced ejection fraction

Empagliflozin reduced the combined relative risk of cardiovascular death and hospitalization for heart failure (primary endpoint) by 25 percent in adults with and without diabetes who had heart failure with reduced ejection fraction

Effects of ambient temperature on cardiovascular disease: a time-series analysis of 229288 deaths during 2009-2017 in Qingdao, China

ABSTRACT The association between ambient temperature and cardiovascular mortality varied by regions, populations, and climates. We estimated the relative risk (RR) of cardiovascular mortality using 229,288 death cases of cardiovascular disease in Qingdao China from 1 January 2009, to 31 December 2017. A distributed lag non-linear model was used. The temperature showed a negative association with the cardiovascular mortality. The RR of cardiovascular death at −4.8 °C was 2.05 (95% CI: 1.55, 2.69). The high temperature had acute and short-term effects with the maximum risk occurring 0 day of exposure. The low temperature had the greatest effect on the 4th lag day. The cold temperature effect was stronger for males than females. The estimates of temperature-related cardiovascular mortality risk were higher in people age ≥75 years. Our study showed that the cold and hot ambient temperature had a relationship with the risk of cardiovascular mortality.

Sex differences in mineralocorticoid receptor antagonist trials: a pooled analysis of three large clinical trials.

Women with heart failure (HF) are under-represented in individual randomized clinical trials (RCTs). Little is known about sex-specific treatment effects in HF medications. We evaluated sex differences in the response to mineralocorticoid receptor antagonists (MRAs) in major HF MRA trials, including a broad spectrum of left ventricular ejection fraction (LVEF). Individual patient data fixed-effect meta-analysis was performed using 6167 patients (31.4% were women) recruited in three placebo-controlled RCTs: Randomized Aldactone Evaluation Study (RALES), Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure (EMPHASIS-HF) and Spironolactone for Heart Failure with Preserved Ejection Fraction (TOPCAT)-Americas. Compared to men, women were older, had higher body mass index and lower glomerular filtration rate. They also had higher LVEF and poorer New York Heart Association functional class and were less likely to be taking angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers. Placebo-arm event rates were lower for women compared with men (15.4 vs. 22.1 per 100 person-year; P=0.002). MRAs reduced consistently, in men and women, the relative risk for cardiovascular death or HF hospitalization (P for interaction=0.83), cardiovascular death (P for interaction=0.44) and all-cause death (P for interaction=0.19). These findings remained consistent after adjustment for potential confounders, regardless of LVEF. There was no sex-specific impact of MRA on the rate of hyperkalaemia and worsening renal function during the median 22 months of follow-up. In three large MRA RCTs, women were substantially different from men with regard to their clinical features and event rates. Nonetheless, this meta-analysis supports a consistent and beneficial MRA effect regardless of sex.

Ivabradine Improves Cardiac Function and Increases Exercise Capacity in Patients with Chronic Heart Failure.

To systematically review and conduct a meta-analysis of the ivabradine-induced improvement in cardiopulmonary function, exercise capacity, and primary composite endpoints in patients with chronic heart failure (CHF).This study was a systematic review and meta-analysis.Databases, including PubMed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), and Clinical Trials and European Union Clinical Trials, were searched for randomized placebo-controlled trials. The efficacy and safety of ivabradine treatment in patients with CHF were assessed and compared to those of the standard anti-heart failure treatment. Review Manager 5.3 software was used to analyze the relative risk (RR) for dichotomous data and the mean difference (MD) for continuous data.In total, 22 studies with 24,562 patients were included. Cardiopulmonary function analysis showed that treatment with added ivabradine reduced the heart rate (MD = -17.30, 95% confidence interval (CI): 19.52--15.08, P < 0.00001), significantly increased the left ventricular ejection fraction (LVEF) (MD = 3.90, 95% CI: 0.40-7.40, P < 0.0001), and led to a better New York Heart Association (NYHA) classification. Ivabradine significantly reduced the minute ventilation/carbon dioxide production (VE/VCO2) (MD = -2.68, 95% CI: -4.81--0.55, P = 0.01) and improved the peak VO2 (MD = 2.80, 95% CI: 1.05-4.55, P = 0.002) and the exercise capacity, including the exercise duration with a submaximal load (MD = 7.82, 95% CI: -2.57--18.21, P < 0.00001) and the 6-minute walk distance. The RR of cardiovascular death or worsening heart failure was significantly decreased (RR = 0.93, 95% CI: 0.87--0.98, P = 0.01) in the patients treated with ivabradine. Additionally, the RRs of heart failure and hospitalization also decreased (RR = 0.91, 95% CI: 0.85--0.97, P = 0.006; RR = 0.86, 95% CI: 0.79--0.93, P = 0.0002). Safety analysis showed no significant difference in the RR of severe adverse events between the ivabradine group and the standard anti-heart failure treatment group (P = 0.40). However, ivabradine significantly increased the RR of visual symptoms in CHF patients (RR = 3.82, 95% CI: 1.80--8.13, P = 0.0005).Existing evidence showed that adding ivabradine treatment significantly improved the cardiopulmonary function and increased the exercise capacity of patients with CHF. Adding ivabradine to the standard anti-heart failure treatment reduced the mortality and hospitalization risk and improved the quality of life. Finally, ivabradine significantly increased the RR of visual symptoms in CHF patients.This is the first systematic review and meta-analysis to focus on the efficacy of ivabradine, which improved the cardiac function and increased the exercise capacity in patients with chronic heart failure (CHF). Therefore, this study will help evaluate the quality of life after adding ivabradine to the treatment of patients with CHF, even though there are differences in the standard for resting heart rate, left ventricular ejection fraction (LVEF), and New York Heart Association (NYHA) class in the included studies. This hybrid effect might be smaller when analyzed separately but might have a higher heterogeneity when analyzed in multiple studies.

Outcomes of Patients with Significant Obesity Undergoing TAVR or SAVR in the Randomized PARTNER 2A Trial

ABSTRACT Background: Patients with severe aortic stenosis (AS) at intermediate surgical risk, treated with transcatheter aortic valve replacement (TAVR) or surgical aortic valve replacement (SAVR) have similar 2-year survival. Significant obesity (SigOb), defined as body mass index (BMI) ≥ 35 kg/m2, has been associated with increased surgical risk and post-operative complications. There are no data comparing clinical outcomes after SAVR versus TAVR in patients with SigOb. Methods: In the PARTNER 2A trial, 2032 patients with severe AS and intermediate surgical risk were randomized to TAVR with the SAPIEN XT valve or SAVR. After excluding 32 patients who had very low BMI < 18.5 kg/m2, the remaining 2000 patients were categorized based on BMI at baseline to SigOb or not SigOb, and compared in regards to 2-year risk of adverse cardiovascular events. Results: A total of 250 patients (12.5%) were SigOb and were younger, more often female, and more frequently diabetic. The 30-day and 2-year rates of the primary composite endpoint death and disabling stroke as well as the risks of its components, were similar for patients with versus without SigOb. However, the 2-year relative risk of cardiovascular death was lower with TAVR versus SAVR for SigOb patients (5.7% vs 15.4%, p = 0.02; HR 0.36, 95% CI 0.15–0.88) but not for not SigOb patients (10.6% vs 10.7%, p = 0.91; HR 0.98, 95% CI 0.73–1.32; p interaction = 0.03). These results remained consistent after multivariable adjustment. Conclusions: In the PARTNER 2A Trial, intermediate-risk patients with severe AS and BMI ≥ 35 kg/m2 undergoing TAVR experienced significantly lower cardiovascular mortality than similar patients undergoing SAVR.

Uric acid is associated with long-term adverse cardiovascular outcomes in patients with acute coronary syndrome undergoing percutaneous coronary intervention

Background and aimsEvidence links uric acid (UA) with the promotion of cardiovascular disease. We assessed the prognostic value of UA on long-term major adverse outcomes (MACE) in patients with acute coronary syndrome (ACS), undergoing percutaneous coronary intervention (PCI). MethodsAs primary endpoint, we assessed the association of UA (continuous and dichotomized) with MACE, including cardiovascular death, myocardial infarction (MI) and stroke, using Cox regression and propensity matching. As secondary endpoints, the influence of hyperuricemia (defined as UA levels > 6.0 mg/dl in women, and >7.0 mg/dl in men) was analysed separately for cardiovascular death, MI, and stroke. The incremental prognostic value of UA was tested using the net reclassification improvement (NRI), and the integrated discrimination improvement (IDI). ResultsWe included 1215 patients. Hyperuricemia was present in 356 (29.3%) patients. Mean follow-up was 5.5 years.UA (HR 1.091 [1.035–1.150]; p = 0.001) and hyperuricemia (HR 1.750 [1.388–2.207]; p < 0.001) were significantly associated with MACE. Results were consistent between Cox regression and propensity matched analysis. Patients with hyperuricemia had a 1.6-fold increased relative risk for cardiovascular death (p = 0.005) and a 1.5-fold increased risk for MI (p = 0.032). For stroke, hyperuricemia only constituted a confounder (HR 1.104; p = 0.970). The prognostic accuracy of an established risk prediction model was significantly increased by adding UA (continuous NRI p = 0.004; categorical NRI p = 0.029; IDI p = 0.002). ConclusionsOur data suggest an independent association of elevated UA with long-term MACE in ACS patients undergoing PCI. Whether lowering UA might be beneficial remains to be elucidated in large clinical trials.

Trastornos hipertensivos en el embarazo: repercusión a largo plazo en la salud cardiovascular de la mujer

Pregnancy-induced hypertension (PIH) induces maternal and fetal damage, but it can also be the beginning of future metabolic and vascular disorders. The relative risk of chronic hypertension after PIH is between 2.3 and 11, and the likelihood of subsequent development of type 2 diabetes is multiplied by 1.8. Women with prior preeclampsia/eclampsia have a twofold risk of stroke and a higher frequency of arrhythmias and hospitalization due to heart failure. Furthermore, a tenfold greater risk for long-term chronic kidney disease is observed as well.The relative risk of cardiovascular death is 2.1 times higher compared to the group without pregnancy-induced hypertension problems, although the risk is between 4 and 7 times higher in preterm birth associated with gestational hypertension or pre-existing hypertensionThe postpartum period is a great opportunity to intervene on lifestyle, obesity, make an early diagnosis of chronic hypertension and DM and provide the necessary treatments to prevent cardiovascular complications in women.

Polypharmacy and major adverse events in atrial fibrillation: observations from the AFFIRM trial.

Polypharmacy, as the use of five or more drugs, has commonly been associated with the elderly and multiple co-morbidities and related to impairment of clinical state and adverse outcomes, in general population. Limited data are available on the relationship between polypharmacy and adverse outcomes in atrial fibrillation (AF). We describe the prevalence of polypharmacy and AF, and its association with major adverse events, such as stroke and cardiovascular (CV) death. For this study, we analysed all AFFIRM Trial patients with complete pharmacological data. Polypharmacy was recorded in 40% of 4056 AF patients. The crude incidence of CV death was 3.45% patient-years among patients with polypharmacy, vs 1.65% patient-years without polypharmacy. Kaplan-Meier analysis showed that patients with polypharmacy had a higher cumulative incidence of CV death (p<0.001). Cox regression analysis demonstrated that female gender (p=0.038), diabetes mellitus (p=0.029), previous myocardial infarction (MI) (p=0.004), prior stroke (p=0.011) and polypharmacy (p=0.029) were independently associated with CV death. Polypharmacy was associated with an adjusted relative risk of 1.30 (95% CI 1.03-1.64) for CV death. A linear increase in the number of drugs was significantly associated with CV death. No significant association was found with stroke occurrence. Polypharmacy is highly prevalent in AF patients and associated with a worse clinical outcome, conferring 30% excess relative risk for CV death. Thus, polypharmacy may be a health status marker. Strategies to reduce inappropriate prescription and polypharmacy should be tested in prospective longitudinal studies of AF patients.

HM4 - How Much Evidence Do We Need Before Implementing Pharmacogenomic Testing In The Clinic?

Consensus on the evidence required to recommend clinical pharmacogenomic testing is unclear. A formal assessment of pharmacogenomic evidence levels in relation to other clinical interventions, such as avoiding drug-drug interactions (DDI), may be helpful for policymakers. The objective of this study was to quantitatively compare the evidence levels of two contested drug-attenuating interactions with clopidogrel antiplatelet therapy, and assess the value of obtaining additional evidence to inform clinical practice guidelines. We developed analogous value of information (VOI) decision models for: (1) avoidance of proton pump inhibitors (PPIs) in clopidogrel patients, and (2) pharmacogenomic-guided antiplatelet selection, both versus no intervention. Interaction-specific parameters and model structures were the only dissimilarities. We calculated the expected value of obtaining perfect information (EVPI) per patient, and the expected population value of obtaining additional information through future studies (EVSI). Current evidence for interaction-1 was slightly less uncertain (a 20% probability of making a non-optimal recommendation) than for interaction-2 (23%). The relative risk for cardiovascular death (conferred by concomitant PPI use in interaction-1, and reduced-function CYP2C19 alleles in interaction-2) was the greatest source of uncertainty in both models. The expected value of perfect information for interaction-1 was $139 per patient, compared to $242 per patient for interaction-2. In simulated 10,000-patient clinical trials, the expected population value of future research for interaction-1 was $2 million, versus $110 million for interaction-2. The evidence levels for clopidogrel DDI and pharmacogenomic effects appear to be fairly similar. However, the value of conducting future research on clopidogrel pharmacogenomics is higher because of greater uncertainty about the impact of pharmacogenomic testing on cardiovascular mortality. Our findings imply that evidence-based clinical guidelines for DDI and pharmacogenomic effects should be generally similar with regard to direction and strength of recommendation. This contrasts to some degree with current guidelines and drug labeling.

MORTALITY AND LOST YEARS OF LIFE AS A RESULT OF CARDIOVASCULAR PREMATURE DEATHS

Aim. Disability and Life-Year Loss (DALYs) is an important healthcare indicator. The first step in DALYs estimation is the measurement of lost years of life due to premature death. To explore the age-sex related statistics of cardiovascular (CV) deaths in Russian Federation (RF); lost years of life (LYL) due to premature death; and to compare those in different regions of RF with the parameter by 100 thousands of population.Material and methods. Russan Statistic Agency (RosStat) data on population and mortality by age intervals and gender for the year 2012.For each age interval the values of CVM and LYL were calculated.Results. The relative risk of cardiovascular death is much higher in men than in women at the age 30–62; maximum of additional death risk (by 100 thousands) is in age groups of 60–90 years. The portion of those who died from CVD at &lt;60 y. o. is 30% in men and 8,4% in women; at &gt;80 y. o. — 18,8% and 48,2%, respectively. The portion of CVM from total mortality in 2012 is 55,4%; at the same time LYL proportion from the entire premature deaths was 38% (36% for men and 42% for women). LYL due to premature CD death was 9797 by 100 thousands in RF in general (13211,9 in men and 6854,2 in women with the variety in different regions from 2058 to 10889 in women and from 3350 to 22122 in men, by 100 thousands).Conclusion. Further investigation required to clarify higher risk for men in economically active ages and significant regional variability in LYL.

0015: Validation and recalibration of the Systematic coronary risk evaluation (SCORE) in a coronary Tunisian population

Development of a validated risk prediction model for cardiovascular death in coronary patients is a high priority for strategies of therapy. We sought to validate and recalibrate of the SCORE (Systematic coronary risk evaluation) risk chart based on Tunisian national mortality data and average major cardiovascular risk factor levels. Baseline data were collected between 1997 and 2004 in 146 male patients aged 52.4 ± 9 years hospitalized with STEMI treated with fibrinolysis in 68 % of patients and not revascularized early in 32% of patients. Vital status was checked and causes of death were obtained in 2011 after a mean follow up of 9.6 years. The expected cardiovascular mortality was calculated by applying the SCORE equation for high risk populations on the basis of the level of risk factors in the total population, in the diabetic and non-diabetic population and was compared with the observed mortality in each group. Correction factor was calculated for each group. Univariate analysis was used for statistical analysis. The optimum threshold of SCORE , allowing for an optimal sensitivity and specificity, was determined by the ROC curve (receiver operating characteristic). For risk thresholds 5% and that determined from the ROC curve of the European SCORE sensitivity, specificity values were calculated. The total number of cardiovascular death at 10 years is 18 with a mortality of 12.3%. The average of SCORE in our population was 8.73+/-5.12% with extremes ranging from 1 to 32%. The European SCORE was strongly correlated in our cohort to the occurrence of cardiovascular death at 10 years (p <0.0001). The correction factor of SCORE is calculated to 2.7 in diabetic group, 1 in non-diabetic group and 1.4 for the total population. The ROC curve has a c index ( AUC ) = 0.73 corresponding to the risk threshold of 9.12%. The relative risk of cardiovascular death at 10 years of SCORE for the 9.12% threshold is calculated at 3.6. For the risk threshold for 9.12%, sensitivity was calculated at 66.7% and specificity at 68.8%. For the risk threshold for 5%, sensitivity was calculated at 94.9% and specificity at 17.96%. SCORE is validated in coronary male Tunisian patients with and recalibrated using correction factors. Validation on a larger population and multi-ethnic remains our future desire.

Recommendations for physical activity within the general population: is this all what we need to keep us healthy?

In the natural habitat of our ancestors, physical activity was not a preventive intervention but a matter of survival. From our genetic pool genes were selected which were very effective in regulating food intake and utilization. This was a clear survival advantage in periods of food deprivation, because they could rely on larger previously generated energy stores. Unfortunately, our selected gene pool has not changed dramatically since then, but we are no longer faced with long periods of food deprivation, and we are no longer forced to run several miles to chase our food. In addition to this ‘old’ genotype, physical inactivity is one important risk factor for the development of several diseases. Several landmark studies around 1990 clearly documented that physical inactivity is a modifiable risk factor for cardiovascular disease and several other chronic diseases, including diabetes mellitus, cancer, obesity, hypertension, bone and joint diseases, and depression. Immediately it became evident that increasing physical activity and exercise would be a powerful tool to reduce the overall incidence of cardiovascular and even all-cause mortality. Over the years many studies in more than 100,000 individuals have clearly documented that the higher the level of physical fitness, the less likely an individual will suffer premature cardiovascular death. The importance of fitness for the risk of overall death becomes very clear in one of the landmark studies of Jonathan Myers and colleagues in 2002. In this trial the authors studied a total of 6213 consecutive men referred for treadmill exercise testing. Among these individuals 3679 individuals had an abnormal exercise test result or a history of cardiovascular events. The rest were classified as healthy. Comparing the relative risk of a healthy but unfit individual with a fit subject but having signs for cardiovascular disease, the risk to die from any cause was much higher for the unfit healthy individual. This clearly shows that being unfit is even worse than being overweight, having diabetes or other risk factors for premature death. Therefore, improving fitness warrants at least as much attention as other risk factors, such as body mass index (BMI), smoking, diabetes or hypertension. Moreover, improving physical activity reduces these common risk factors and therefore may potentiate its beneficial effects. One challenging question of the present time is how much we have to exercise, how often and what kind of exercise is beneficial in influencing the relative risk of cardiovascular death. To answer this question maybe we should look back again to our ancestors to see what they did in their daily life. They walked longer distances and hunted for the food they needed. So one can imagine that if we were able to increase these forms of exercise, we may reach our goal. In 1995 the Centers for Disease Control and Prevention (CDC) and the American College of Sports Medicine (ACSM) published a recommendation stating that ‘Every US adult should accumulate 30 minutes or more of moderateintensity physical activity on most, preferably all, days of the week’. The purpose of these recommendations was to provide a clear and easy to understand guidance for the general population to engage in physical activity. This recommendation was updated in 2007 and specifically extended to adults aged 65 and over. In comparison with the recommendations of 1995, several important points were adjusted: (1) the frequency was fixed to 5 days per week, (2) vigorous-intensity physical activity was incorporated into what is complementary to moderate-intensity, (3) the recommended aerobic activity is in addition to routine daily activity, (4) musclestrengthening activities besides aerobic activities are recommended. In addition to all of the recommendations on physical activity for adults, the Canadian Society for Exercise Physiology (CSEP) recently published physical activity guidelines for children aged 0 to 4 years. In their recommendations they state that:

Left ventricular hypertrophy in Fabry disease: a practical approach to diagnosis

Left ventricular hypertrophy (LVH) is prevalent and associated with a poor long-term prognosis. The Framingham Heart Study, for example, showed that LVH was present in 15–20% of adults, and that, for each 50 g/m2 increment of left ventricular mass, the relative risk of cardiovascular death increased by 1.73 in men and 2.12 in women.1 Although hypertension, obesity and valvulopathies account for most causes of LVH, it is important to investigate patients with otherwise unexplained LVH since many causes are treatable. Although several electrocardiographic (ECG) criteria for the identification of LVH are available, additional investigations [notably transthoracic echocardiography (echo)] are invariably required due to the lack of sensitivity and specificity of ECG. The European Association of Echocardiography definition of LVH includes the demonstration of interventricular septal and/or posterior wall thickness in end-diastole ≥13 mm.2 Echocardiography can additionally interrogate valve function and characterize LVH as concentric (uniform mechanism, e.g. LV pressure overload, myocardial infiltration), or eccentric [e.g. asymmetrical septal hypertrophy in hypertrophic cardiomyopathy (HCM)]. After the identification of LVH, a practical approach to its further assessment includes a clinical review with targeted investigations aimed firstly to exclude common causes; e.g. hypertension, obesity and valve disease. Thereafter, evaluation involves a systematic approach to exclude less common causes, e.g. hypertrophic and other cardiomyopathies, myocardial infiltration, metabolic disorders, and syndromic conditions associated with LVH. Table 1 provides a systematic scheme incorporating clinical pearls and diagnostic pointers to help target adjunctive investigations and help identify the aetiology of LVH. Disorders causing or associated with LVH are arranged in a pathological hierarchical manner with common conditions appearing first, followed by rarities. View this table: Table 1 Clinical characteristics of conditions causing left ventricular hypertrophy and diagnostic pointers Many heart muscle disorders presenting with LVH are due to inherited mutations in genes encoding contractile proteins of the cardiac sarcomere, metabolic pathways, …

Suicide and Cardiovascular Death after a Cancer Diagnosis

BackgroundReceiving a diagnosis of cancer is a traumatic experience that may trigger immediate adverse health consequences beyond the effects of the disease or treatment.MethodsUsing Poisson and negative binomial regression models, we conducted a historical cohort study involving 6,073,240 Swedes to examine the associations between a cancer diagnosis and the immediate risk of suicide or death from cardiovascular causes from 1991 through 2006. To adjust for unmeasured confounders, we also performed a nested, self-matched case-crossover analysis among all patients with cancer who died from suicide or cardiovascular diseases in the cohort.ResultsAs compared with cancer-free persons, the relative risk of suicide among patients receiving a cancer diagnosis was 12.6 (95% confidence interval [CI], 8.6 to 17.8) during the first week (29 patients; incidence rate, 2.50 per 1000 person-years) and 3.1 (95% CI, 2.7 to 3.5) during the first year (260 patients; incidence rate, 0.60 per 1000 person-years). The relative risk of cardiovascular death after diagnosis was 5.6 (95% CI, 5.2 to 5.9) during the first week (1318 patients; incidence rate, 116.80 per 1000 person-years) and 3.3 (95% CI, 3.1 to 3.4) during the first 4 weeks (2641 patients; incidence rate, 65.81 per 1000 person-years). The risk elevations decreased rapidly during the first year after diagnosis. Increased risk was particularly prominent for cancers with a poor prognosis. The case-crossover analysis largely confirmed results from the main analysis.ConclusionsIn this large cohort study, patients who had recently received a cancer diagnosis had increased risks of both suicide and death from cardiovascular causes, as compared with cancer-free persons. (Funded by the Swedish Council for Working Life and Social Research and others.)

Role of Elevated Heart Rate in the Development of Cardiovascular Disease in Hypertension

That elevated heart rate (HR) is a risk factor for cardiovascular morbidity and mortality in healthy people as well as in patients with cardiac diseases is supported by numerous epidemiological association studies.1–4 Increased HR has been recognized as a negative prognostic factor independent of many other clinical parameters that can influence the HR, including physical activity scores, left ventricular function, or use of β-blockers. Thus, HR appears to satisfy all epidemiological criteria for being considered as a true risk factor, and its predictive value for cardiovascular disease appeared to be as strong as that of most important cardiovascular risk factors. This is particularly true for the results obtained in hypertensive patients. Elevated HR is a common feature among hypertensive individuals.1 Among the young hypertensive subjects participating in the HARVEST study, >15% had a baseline resting HR ≥85 bpm and 27% had a HR ≥80 bpm.5 According to the Tensiopulse study, which evaluated 38 145 patients cared for by 2000 general practitioners all across Italy, >30% of the hypertensive patients had a resting HR ≥80 bpm.6 In a large French population, untreated hypertensive subjects had approximately a 6-bpm faster HR than normotensive individuals.7 Elevated HR is frequently associated with high blood pressure (BP) and metabolic disturbances and increases the risk of new onset hypertension and diabetes.1 Many experimental data obtained both in animals and in human beings support the importance of HR as a true risk factor for atherosclerosis and cardiovascular disease, providing convincing evidence for this pathogenetic mechanism.1–3 The pathogenetic connection between HR and cardiovascular disease has been discussed in several reports1–3,8,9 and is beyond the scope of this review. ### High HR as a Precursor of Hypertension, Obesity, and Diabetes Numerous studies have demonstrated that tachycardia is frequently associated with hypertension in …