Strict regulations on energy drinks to protect Minors' health in Europe - It is never too late to set things right at home.

The consumption of energy drinks poses significant risks to minors' health, and strict regulations are urgently needed to protect them. The high caffeine, high sugar, and high caloric content of energy drinks have drawn concern from health professionals. The consumption of energy drinks has been linked to unhealthy dietary behaviors, obesity, and mental health problems in adolescents. The psychoactive and stimulant effects of energy drinks are particularly worrisome, and the marketing of these drinks on social media platforms is also a cause for alarm. In light of these concerns, we strongly recommend policy measures, such as restrictions on the sale of energy drinks to minors, to prevent their health risks. The evidence clearly suggests that energy drinks pose significant risks to minors' health and well-being, and regulatory standards must be implemented without further delay.

Role of plakophilin-2 expression on exercise-related progression of arrhythmogenic right ventricular cardiomyopathy: a translational study.

AIMS: Exercise increases arrhythmia risk and cardiomyopathy progression in arrhythmogenic right ventricular cardiomyopathy (ARVC) patients, but the mechanisms remain unknown. We investigated transcriptomic changes caused by endurance training in mice deficient in plakophilin-2 (PKP2cKO), a desmosomal protein important for intercalated disc formation, commonly mutated in ARVC and controls. METHODS AND RESULTS: Exercise alone caused transcriptional downregulation of genes coding intercalated disk proteins. The changes converged with those in sedentary and in exercised PKP2cKO mice. PKP2 loss caused cardiac contractile deficit, decreased muscle mass and increased functional/transcriptomic signatures of apoptosis, despite increased fractional shortening and calcium transient amplitude in single myocytes. Exercise accelerated cardiac dysfunction, an effect dampened by pre-training animals prior to PKP2-KO. Consistent with PKP2-dependent muscle mass deficit, cardiac dimensions in human athletes carrying PKP2 mutations were reduced, compared to matched controls. CONCLUSIONS: We speculate that exercise challenges a cardiomyocyte "desmosomal reserve" which, if impaired genetically (e.g., PKP2 loss), accelerates progression of cardiomyopathy.

Coronavirus disease 2019, hypertension, and renin-angiotensin-aldosterone system inhibitors.

PURPOSE OF REVIEW: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mostly uses the angiotensin-converting enzyme 2 (ACE-2) as cellular receptor for entering the host cells. Some, but not all, animal studies have shown that renin-angiotensin-aldosterone system (RAAS) inhibitors can increase ACE-2 expression. On that premise, it was hypothesized that these agents could make it more likely to develop coronavirus disease 2019 (COVID-19). On the other hand, there was also evidence that being on these agents could lessen the severity of the lung injury in patients with severe SARS-CoV-2 infection. Herein, we review the available evidence on the role of RAAS inhibitors on SARS-CoV-2 and COVID-19 development. RECENT FINDINGS: Recent randomized controlled trials demonstrate that RAAS blockade or withdrawal does not influence the severity of COVID-19 in patients who are already on these medications. Currently, there is no evidence to support stopping RAAS inhibitors in patients hospitalized for COVID-19. Several questions still need to be addressed. Ongoing studies are currently evaluating the de novo use of RAAS inhibitors in patients with COVID-19. Another area that needs to be investigated is whether or not using these medications increase the risk of infection. SUMMARY: The wealth of evidence indicates that ACE inhibitors and angiotensin-receptor blocker administration has no harmful effects on hospitalizations and severity of COVID-19 in patients already on these medications and might even reduce mortality among hypertensive patients diagnosed with COVID-19. More evidence and data need to be collected, and at this time, these agents should not be discontinued.

Protective Effects of Statins Administration in European and North American Patients Infected with COVID-19: A Meta-Analysis.

Severe acute respiratory syndrome coronavirus 2 has spread rapidly throughout the world, becoming an overwhelming global health emergency. The array of injuries caused by this virus is broad and not limited to the respiratory system, but encompassing also extensive endothelial and systemic tissue damage. Since statins effectively improve endothelial function, these drugs may have beneficial effects in patients with coronavirus disease 2019 (COVID-19). Therefore, this investigation aimed to provide an updated overview on the interplay between statins and COVID-19, with particular focus on their potentially protective role against progression toward severe or critical illness and death. A systematic electronic search was performed in Scopus and PubMed up to present time. Data on statins use and COVID-19 outcomes especially in studies performed in Europe and North America were extracted and pooled. A total of seven studies met our inclusion criteria, totaling 2,398 patients (1,075 taking statins, i.e., 44.8%). Overall, statin usage in Western patients hospitalized with COVID-19 was associated with nearly 40% lower odds of progressing toward severe illness or death (odds ratio: 0.59; 95% confidence interval: 0.35-0.99). After excluding studies in which statin therapy was started during hospital admission, the beneficial effect of these drugs was magnified (odds ratio: 0.51; 95% confidence interval: 0.41-0.64). In conclusion, although randomized trials would be necessary to confirm these preliminary findings, current evidence would support a favorable effect of statins as adjuvant therapy in patients with COVID-19. Irrespective of these considerations, suspension of statin therapy seems highly unadvisable in COVID-19 patients.

Consumer wearable technologies to identify and monitor exercise-related arrhythmias in athletes.

PURPOSE OF REVIEW: The aim of this study was to synthesize the current evidence supporting and against the use of wearable devices to detect underlying heart conditions in athletes and the most significant limitations. RECENT FINDINGS: Although several large studies have been conducted to evaluate the ability of wearables devices to identify atrial fibrillation among the general population, no studies evaluating their ability to detect other exercise-related arrhythmias in athletes are very sparse. Most of the studies or case reports are focused on the wearables' reliability and accuracy compared with standard ECG. Only small studies evaluating the accuracy of one wearable device in athletes have been carried out to date. Unfortunately, none of them have investigated their ability to detect specific arrhythmias in the athletic population. SUMMARY: Rapidly detecting dangerous arrhythmias in a symptomatic athlete continues to be an elusive goal. The use of smartphone ECG monitors can provide diagnostic data in athletes with symptoms that could represent a helpful instrument. However, many uncertainties remain and need to be addressed and validated in large-scale trials to incorporate these devices into the healthcare system and be part of an athlete's daily monitoring and healthcare.

Red Blood Cell Distribution Is a Significant Predictor of Severe Illness in Coronavirus Disease 2019.

INTRODUCTION: As red blood cell distribution width (RDW) significantly predicts clinical outcomes in patients with respiratory tract infections and in those with critical illnesses, we performed a critical analysis of the literature to explore the potential prognostic role of this laboratory parameter in coronavirus disease 2019 (COVID-19). METHODS: An electronic search was conducted in Medline, Scopus and Web of Science, using the keywords "coronavirus disease 2019" OR "COVID-19" AND "red blood cell distribution width" OR "RDW" in all fields, up to the present time, with no language restriction. Studies reporting the value of RDW-CV in CO-VID-19 patients with or without severe illness were included in a pooled analysis. RESULTS: The pooled analysis included 3 studies, totaling 11,445 COVID-19 patients' samples (2,654 with severe disease; 23.2%). In all investigations RDW-CV was higher in COVID-19 patients with severe illness than in those with mild disease, with differences between 0.30 and 0.70%. The pooled analysis, despite consistent heterogeneity (I2: 88%), revealed that the absolute RDW-CV value was 0.69% higher (95% CI 0.40-0.98%; p < 0.001) in COVID-19 patients with severe illness compared to those with mild disease. CONCLUSION: These results, along with data published in other studies, support the use of RDW for assessing the risk of unfavorable COVID-19 progression.

Large-scale epidemiological data on vascular disorders of the intestine.

Objectives: This article aims to provide updates on the worldwide epidemiology of vascular disorders of the intestine.Methods: A comprehensive search for obtaining worldwide epidemiologic information on the burden of vascular disorders of the intestine was carried out in the Global Health Data Exchange (GHDx) repository. The condition 'vascular intestinal disorders' was associated with other epidemiologic variables such as year, sex, age, location and socioeconomic status.Results: The current global incidence and mortality of vascular disorders of the intestine are 8.11 per 100,000 cases/year and 1.26 per 100,000 deaths/year, respectively, translating into a death rate of 15.5%. Both global incidence and mortality are 32% higher in the female sex and have both displayed a continuous increase during the past 20 years (+29.3% and +18.4% since 1998, respectively). Incidence and mortality curves appear similar between sexes, with the incidence increasing after the age of 40 years and mortality after the age of 50 years, respectively. The peak of both worldwide incidence and mortality was seen in very elderly people. The death rate increased in parallel with incidence and mortality, from ∼1% to 3% in childhood up to ∼50% after the age of 95 years. Both incidence and mortality displayed a positive association with socioeconomic status. Future projections suggest that incidence and mortality will display 44% and 24% growths by the year 2050.Conclusions: Our analysis demonstrates that the clinical and societal burden of vascular disorders of the intestine is especially higher in women, in the elderly and in people with higher socioeconomic status.

Do genetic polymorphisms in angiotensin converting enzyme 2 (ACE2) gene play a role in coronavirus disease 2019 (COVID-19)?

Although some demographic, clinical and environmental factors have been associated with a higher risk of developing coronavirus disease 2019 (COVID-19) and progressing towards severe disease, altogether these variables do not completely account for the different clinical presentations observed in patients with comparable baseline risk, whereby some subjects may remain totally asymptomatic, whilst others develop a very aggressive illness. Some predisposing genetic backgrounds can hence potentially explain the broad inter-individual variation of disease susceptibility and/or severity. It has been now clearly established that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus causing COVID-19, infects the host cell through biding and being internalized with angiotensin converting enzyme 2 (ACE2), a surface protein expressed in a noticeable number of human cells, especially in those of upper and lower respiratory tracts, heart, kidney, testis, adipose tissue, gastrointestinal system and in lymphocytes. Accumulating evidence now suggests that genetic polymorphisms in the ACE2 gene may modulate intermolecular interactions with the spike protein of SARS-CoV-2 and/or contribute to pulmonary and systemic injury by fostering vasoconstriction, inflammation, oxidation and fibrosis. We hence argue that the development of genetic tests aimed at specifically identifying specific COVID-19-susceptible or -protective ACE2 variants in the general population may be a reasonable strategy for stratifying the risk of infection and/or unfavorable disease progression.

Effects of endurance exercise on serum concentration of calcitonin gene-related peptide (CGRP): a potential link between exercise intensity and headache.

Background Calcitonin gene-related peptide (CGRP) is a powerful neuropeptide that is strongly involved in headache pain pathogenesis by triggering vasodilation, mast cell degranulation and neurogenic inflammation. This evidence has prompted us to investigate the acute influence of endurance exercise on CGRP concentration in blood. Methods The study population consisted of 48 male amateur runners, who ran a half-marathon distance at 75%-85% of maximal oxygen uptake. Blood was drawn before the run (pre-run) and immediately after each runner ended his trial (post-run). The serum concentration of CGRP was measured with a commercial enzyme-linked immunosorbent assay (ELISA) technique. Results Overall, 22/48 subjects (45.8%) reported suffering from headache, three of whom (6.2%) had an exertional headache, whilst 26/48 (54.2%) subjects did not report at least one headache episode during the previous 6 months (i.e. headache-free). All 48 athletes successfully covered the 21.1 km distance. Serum concentration of CGRP significantly increased by 1.5-fold in the entire group, as well as in the headache-positive and headache-free cohorts. Univariate Spearman's correlation revealed that post-run variation of serum CGRP was significantly and inversely associated with running time (r = -0.30; p = 0.036). Conclusions The serum concentration of CGRP is significantly enhanced by medium-distance endurance exercise and the post-exercise increase is dependent on running intensity. Accordingly, high-exercise intensity might be directly related to triggering both exertional headache and/or migraine episodes.

An Estimation of the Worldwide Epidemiologic Burden of Physical Inactivity-Related Ischemic Heart Disease.

PURPOSE: Although physical inactivity (PI) is universally considered a major risk factor for cardiovascular disorders, no previous study has investigated its putative contribution on the societal and healthcare burden of ischemic heart disease (IHD). Therefore, we aimed to provide an objective assessment of the worldwide epidemiology of PI-related IHD. METHODS: An electronic search was performed in the Global Health Data Exchange (GHDx) registry, a large database of health-related data, for assessing the worldwide epidemiology of PI-related IHD. RESULTS: The current burden of PI-related disability-adjusted life years (DALYs) and deaths caused by IHD is 9.1% (15.42 out of 170.27 million DALYs) and 9.9% (5.46 out of 55.14 million deaths), respectively. Women have a ~ 14% higher risk of both PI-related DALYs and mortality. The impact of PI on IHD remains stable around 7% up to the middle age, then gradually increases in parallel with aging, up to over 11%. A ~ 20% higher risk of PI-related DALYs and mortality caused by IHD can be found in countries with middle-to-high socio-demographic index (SDI) compared with countries with lower SDIs. In multivariable analysis, PI-related DALYs and mortality caused by IHD were significantly predicted by female sex, advanced age, and higher SDI. CONCLUSIONS: The results of our analysis suggest that reinforced efforts shall be prioritized and scaled up for broadening and ameliorating the application of physical activity recommendations in populations more vulnerable to the risk of PI-related IHD.

Worldwide burden of LDL cholesterol: Implications in cardiovascular disease.

BACKGROUND AND AIM: an increased value of low-density lipoprotein cholesterol (LDL-C) is now universally considered a major cardiovascular disease (CVD) risk factor. LDL-C is included in the vast majority of worldwide cardiovascular risk prediction algorithms, as well as in the guidelines for cardiovascular risk prevention. We aimed to provide an overview of the worldwide adverse healthcare impact of low-density lipoprotein cholesterol (LDL-C). METHODS AND RESULTS: Data on the epidemiologic burden of LDL-C >1.3 mmol/L were retrieved from Global Health Data Exchange (GHDx) registry. The current burden is 94.92 million disability-adjusted life years (DALYs), with an exponential increase occurred during the past 25 years. 4.32 million deaths can be attributed to LDL cholesterol values > 1.3 mmol/L. DALYs and deaths due to LDL-C have significantly increased in all countries except those with high socio-demographic index. CONCLUSION: More effective structural healthcare policies shall be planned at a worldwide scale for contrasting the epidemics of LDL-C attributable heath loss.

Non-coding RNAs and Coronary Artery Disease.

Coronary artery disease (CAD) is the leading death cause worldwide. Non-coding RNA (ncRNA) are key regulators of genetic expression and thus can affect directly or indirectly the development and progression of different diseases. ncRNA can be classified in several types depending on the length or structure, as long non-coding RNA (lncRNA), microRNA (miRNA) and circularRNA (circRNA), among others. These types of RNA are present within cells or in circulation, and for this reason they have been used as biomarkers of different diseases, therefore revolutionizing precision medicine. Recent research studied the capability of circulating ncRNA to inform about CAD presence and predict the outcome of the disease. In this chapter we present a list of the miRNA, lncRNA and circRNA which are potential biomarkers of CAD.

Prognostic Value of Troponins in Patients With or Without Coronary Heart Disease: Is it Dependent on Structure and Biology?

Convincing evidence has emerged that cardiac troponins (cTns) T and I are the biochemical gold standard for diagnosing cardiac injury, and may also be used as efficient screening and risk stratification tools, especially when measured with the new high-sensitivity (hs-) immunoassays. In this narrative review, we aim to explore and critically discuss the results of recent epidemiological studies that have attempted to characterise the prognostic value of cTns in patients with or without cardiovascular disease, and then interpret this information according to cTn biology. Overall, all recent studies agree that higher blood levels of cTns reflect the larger risk of cardiovascular events and/or death, both in the general population and in patients with cardiovascular disease. Additional evidence has shown that the clinical information provided by assessment of both cTns molecules is greater compared to that of either protein alone, and this is mostly due to differential metabolism and clearance of cTnI and cTnT after release in the bloodstream. Although it seems likely that the prognostic value of these biomarkers may be higher than that of other conventional cardiovascular risk factors such as cholesterol or C reactive protein, large and reliable cost-effectiveness investigations are needed to define whether cTns-based population screening may be biologically plausible, clinically effective and economically sustainable.

Exertional hematuria: definition, epidemiology, diagnostic and clinical considerations.

Exertional hematuria can be considered a subcategory of exercise-induced hematuria, characterized by painless appearance of erythrocytes in urine after recent physical exercise, not directly attributable to external traumatic injuries to the genitourinary system, and spontaneously resolving with rest. Although its frequency has enormous heterogeneity, depending on the athlete population, duration and intensity of exercise, technique used for identifying or quantifying hematuria and relative diagnostic thresholds, what clearly emerges from the scientific literature is that a certain degree of hematuria is commonplace after non-contact sports, especially running. This exertional hematuria, which appears self-limiting, may be attributable to some frequently concomitant causes, involving organs of the genitourinary system, and mostly encompassing bladder or urethral injuries. Renal injuries caused by internal movements, vascular spasm and ischemia are also potential causes of increased glomerular permeability to erythrocytes, whilst the presence of preexisting genitourinary diseases cannot be ruled out, especially when post-exercise hematuria is recurrent or endures. Therefore, whenever hematuria is observed in a random urine specimen, recent sports performance (especially running) should be investigated and urinalyses scheduled for the following days. When no temporal association of hematuria with exercise can be found, when genitourinary traumas have been excluded or hematuria persists for >72 h, specific diagnostic investigations should be planned to identify possible genitourinary diseases.

Sudden Cardiac and Noncardiac Death in Sports: Epidemiology, Causes, Pathogenesis, and Prevention.

Although few doubts remain that physical exercise should be widely promoted for maintenance of health and fitness, the risk of adverse events such as sudden death (especially due to cardiac causes, i.e., sudden cardiac death [SCD]) during exercise remains tangible. The overall risk of sudden death in athletes is relatively low (i.e., usually comprised between 0.1 and 38/100,000 person-years), and globally comparable to that of the general population. However, up to 20% of all sudden death cases are still recorded while exercising. The most frequent underlying disorders encountered in SCD are hypertrophic cardiomyopathy and coronary artery disease (CAD), representing three quarters of all conditions. The risk related to CAD increases with aging (>35 years old), while that attributable to cardiomyopathies or fatal arrhythmias is especially frequent among young people (<35 years old). Taken together, these findings would lead to the conclusion that physical exercise may be seen as an acute trigger of myocardial ischemia or arrhythmias in some predisposed individuals. Nonetheless, the prevalence of coronary atherosclerosis seems to be higher in athletes than in sedentary subjects with comparable risk profile. On the contrary, coronary plaques in physically active subjects appear more stable, thereby attenuating the risk of rupture and subsequent myocardial ischemia. These findings, along with evidence of a considerable increase of peak coronary blood flow during exercise, make it very likely that an imbalance between oxygen demand and supply may be the most frequent cause of myocardial ischemia in athletes suffering SCD and/or cardiac arrest. Therefore, all subjects who wish to practice moderate- to high-intensity exercise are recommended to undergo preparticipation screening and annual follow-up.

Prothrombotic State Induced by Middle-Distance Endurance Exercise in Middle-Aged Athletes.

Since the impact of possible prothrombotic factors on blood coagulation resulting from exercise remains elusive, this study investigated the acute effects of middle-distance endurance running on blood coagulation parameters in middle-aged athletes. The study population consisted of 33 male endurance runners who were engaged in a 21.1 km run under competitive conditions. Blood samples were collected before the run, immediately after the run, and 3 hours after run completion. Samples were assessed for activated partial thromboplastin time (APTT), prothrombin time (PT), fibrinogen, D-dimer, factor VIII (FVIII), von Willebrand factor antigen (VWF:Ag), endogenous thrombin potential (area under the curve of thrombin generation [TGA-AUC]), and peak thrombin generation (TGA-PK). Post-run variations were expressed as delta (Δ). At baseline, APTT was found to be significantly associated with ABO blood group, VWF:Ag, and FVIII; fibrinogen with age; VWF:Ag with BMI, training regimen, and ABO blood group; APTT with FVIII; FVIII with VWF:Ag and ABO blood group; APTT with VWF:Ag; and TGA-PK with ABO blood group, PT, and TGA-AUC. Immediately after the run, statistically significant increases were observed for PT, D-dimer, VWF:Ag, and FVIII, while statistically significant reductions could be observed for APTT, TGA-AUC, and TGA-PK. Fibrinogen values remained unchanged. Significant correlations were observed between Δ VWF:Ag and Δ FVIII, Δ APTT and Δ VWF:Ag, Δ APTT and Δ FVIII, Δ TGA-AUC and Δ TGA-PK, and between Δ D-dimer and Δ TGA-AUC and Δ TGA-PK. No Δ variation was associated with running time. The results of this study seemingly suggest that middle-distance competitive running may evoke several prothrombotic changes in blood coagulation.

Influence of middle-distance running on muscular micro RNAs.

A specific subset of micro RNAs (miRs), including miR-133 and miR-206, is specifically expressed in muscle tissue, so that they are currently defined as muscular miRs (myomiRs). To further elucidate the role of myomiRs in muscle biology, we measured miR-133a and miR-206 in plasma of 28 middle-age recreational athletes. The study population consisted of 28 middle aged, recreation athletes (11 women and 17 men; mean age, 46 years) who completed a 21.1 km, half-marathon. The plasma concentration of miR-133a and miR-206, the serum concentration of creatine kinase (CK) and high-sensitivity (HS) cardiac troponin T (cTnT), as well as capillary lactate, were measured before and immediately after the run. The median serum concentration of total CK (257 versus 175 U/L; p < .001), cTnT (17.8 versus 5.6 ng/L; p < .001), and the plasma values of both miR-133a (4.22 versus 0.64 × 10-4; p < .001) and miR-206 (1.36 versus 0.63 × 10-4; p = .001) were considerably increased immediately after the half-marathon run. In multivariate analysis only post-exercise capillary lactate was found to be independently associated with running time. A significant and independent correlation was observed between plasma variations of the two miRs, but not with other physiological or laboratory parameters. The results of this study suggest that the biological significance of miR-133a and 206 variation after middle-distance running parallels but not overlaps the release of biomarkers of nonspecific tissue damage. Enhanced plasma values of these myomiRs may hence reflect a physiological response to high-intensity and/or prolonged exercise rather than tissue injury.

An Eighteen-Minute Submaximal Exercise Test to Assess Cardiac Fitness in Response to Aerobic Training.

Romagnoli, M, Alis, R, Sanchis-Gomar, F, Lippi, G, and Arduini, A. An 18-minute submaximal exercise test to assess cardiac fitness in response to aerobic training. J Strength Cond Res 32(10): 2846-2852, 2018-We aimed to evaluate the utility of a submaximal heart rate recovery (HRR) test to monitor changes in cardiac fitness after aerobic training. Twenty healthy subjects were assigned to a control (n = 10) or a training (n = 10) group. Subjects in the training group performed 8 weeks of bicycle training, followed by 8 weeks of detraining. Heart rate recovery was assessed after exercises at 65% and 80% HRmax. The HRR test was performed at weeks 0 (W0), 4 (W4), 8 (W8), and 16 (W16) in the training group and at W0 and W8 in the control group. Heart rate recovery indices changed in response to training and detraining. Absolute HRR at 60, 120, and 180 seconds after exercise increased at both exercise intensities at W8 of training (p < 0.01, W8 vs. W0) and returned to the pretraining level after detraining (p > 0.05, W16 vs. W0). Time constants of fast HRR recovery (<1 minute) changed with training (p < 0.05-0.01, W8 vs. W0) and detraining (p > 0.05, W16 vs. W0) but only at 65% HRmax. At the end of the 3-minute recovery period, the predicted heart rate (HR) value (A0) and the HR recovered (Amax) from the monoexponential analysis changed with training (p < 0.05-0.01, W8 vs. W0) and detraining (p > 0.05, W16 vs. W0). We conclude that this novel submaximal HRR test is highly sensitive for monitoring cardiac fitness during training and detraining in healthy people. Because this test is simple, inexpensive, and the data are reliable and easy to analyze, we hope that it may be of interest to the sports science community.

The 'lottery' of cardiovascular risk estimation with Internet-based risk calculators.

The cardiovascular disease (CVD) is the leading cause of disability and premature death around the world. The ongoing publication of systematic and critical literature reviews has contributed to generate a kaleidoscope of guidelines by different scientific organizations. We investigated the accordance among the most popular web-based CVD risk calculators on the Internet. We carried out a simple study, by estimating the risk of CVD using the most popular Internet-based calculators available on the Internet. A Google search was performed, using the keyword "cardiovascular risk calculator", to identify the first 10 websites providing free on-line CVD risk calculators. We arbitrarily selected the cardiovascular profile of two subjects of a typical Western family: a 55-year man at a likely intermediate cardiovascular risk and a 45-year woman at a probable low risk. The score calculated according to the two arbitrary CVD risk profiles, one of whom was supposed to be at intermediate risk and the other at lower risk, was extremely variable. More specifically, the 10-year CVD risk of the 55-year old man varied from 3% to over 25% (median value, 12.9%, interquartile range [IQR], 10.7-19.0%), whereas that of the 45-year women varied between 0% and 4% (median value, 1.2%; IQR, 0.4-2.2%), thus displaying a nearly 10-fold variation in both cases. We concluded from our analysis of 11 different Internet-based CVD risk calculators that the final 10-year risk score can be extremely different, especially for the 55-year old man at predictably intermediate risk.