Editor comment: Antihypertensive drugs and cancer—more fakes than facts

In recent time, the misinterpretation of scientific evidence and the dissemination of fake news on health-related issues through social media has raised major concerns. An example has been the dissemination through these channels of questionable and uncritical reports, not free from multiple potential bias, on the possibility of an increased risk of cancer related to use of antihypertensive drugs. This is a topic of huge impact for millions of hypertensive patients, who are prescribed to be on chronic treatment for years to reduce the risk of major cardiovascular events. Therefore, it must not be contaminated by fake or twisted news, spread to the public without any caution. The article by Battistoni et al.1 offers a concise summary of the scientific data available on this topic, and shows the almost complete lack of hard evidence about the potential oncogenic effect of the major classes of antihypertensive drugs currently used. Based on available evidence, by now, it seems thus unjustified to promote or encourage the banning of antihypertensive drugs because of an unproven risk of neoplasms, an issue which should be further explored in depth by carefully designed and conducted experimental and clinical studies. Most of the laboratories make use of the Friedewald formula to assess low-density lipoprotein cholesterol (LDL-C). The accuracy of this approach, however, crucially depends on triglyceride concentrations. Since hypertriglyceridaemia is a characteristic trait of the lipid profile in chronic kidney disease (CKD), the here present study by Bauer et al.2 examined the accuracy of the Friedewald formula in this population. The Friedewald formula yielded lower LDL-C concentrations in CKD than direct enzymatic measurements, which may lead to undersupply of this cardiovascular high-risk population. A novel formula for the calculation of LDL-C was derived (LDL-C = cholesterol − HDL − triglycerides/7.98) as the optimal equation. Vascular calcification is considered a hallmark of atherosclerosis, and its early identification may allow a better stratification into high-risk individuals with poor outcomes.3 Here a structured PubMed search identified 18F-sodium fluoride (18F-NaF) positron emission tomography as the most suitable technique for detecting micro-calcification.4 An other extensive literature review documented the abdominal aortic calcification as highly prevalent in the general population and prevalence and extent increase with age. Risk factors include traditional cardiovascular risk factors and decreased bone mineral density. Abdominal aortic calcification is shown to contribute to arterial stiffness and is a strong predictor of cardiovascular events and mortality.5 Several therapies to inhibit arterial calcification have been developed but investigated in small clinical trials. Large studies with long follow-up must be carried out to show whether inhibition of abdominal aortic and micro-calcification would reduce cardiovascular risk. The association of resting heart rate (HR) with cardiovascular outcomes, especially heart failure, is well established.6 Indeed, even if HR is ubiquitously perceived as a major risk marker in clinical medicine, whether HR is mainly an integrated marker of risk associated with other features, or rather a genetic origin risk marker, is still a matter of debate. Here a multivariable-adjusted analysis of multiple points of resting HR suggests that about 25% of the observed HR variance can be attributed to additive genetic factors.7 This finding is in the lower range of previously published estimates from family studies. Approximately 50% of the HR variance remained unexplained, which can be attributed to underlying interactions between genetic and environmental effects, and to unaccounted genetic effects, such as dominance or epigenetic factors. Cardiovascular disease (CVD) is heavily influenced by pro-inflammatory dietary factors, including simple carbohydrates and saturated fat, which exert deleterious effects on vascular health and are associated with systemic inflammation. Here, the data from the Seven Countries Study of Cardiovascular Diseases were used to examine the effect of diet-associated inflammation on prediction of outcome at 50 years of follow-up.8 The energy-adjusted Dietary Inflammatory Index was used to quantify the effect of diet on systemic inflammation. Positive linear correlations were observed between the cohort-average energy-adjusted Dietary Inflammatory Index score and both overall death rates and major CVD mortality rates but not cancer. Interesting, adjusting for systolic blood pressure (SBP), cholesterol, and smoking habits did not modify these correlations. Results from this long-term follow-up study are consistent with a recommendation to increase consuming an anti-inflammatory diet characterized by high concentrations of fruits and vegetables and low consumption of simple carbohydrates and fats. High body mass index (BMI) is associated with several adverse cardiovascular and metabolic effects. However, most of the studies in this area have been conducted in middle-aged and older persons,9 with only a few studies having quantified the risk for early CVD and all-cause and CVD-related mortality in younger individuals, and none powered to reliably investigate the effect of severe obesity in young women. To overcome this gap, here in this large, nationwide, registry-based prospective cohort study of young women (28 ± 5 years), slightly J-shaped relations between increasing BMI and several CVD outcomes were observed, and women with low–normal BMI at about 22 kg/m2 had the lowest risk, with a detectable increase in risk already within the normal weight range (22.5–<25 kg/m2) for myocardial infarction (MI), ischaemic stroke and CVD death, and markedly increased relative risks among the obese women. The highest risk for MI was found in severely obese women (BMI ≥35 kg/m2), where, after adjustment for relevant baseline factors, the risk was four times higher than in women from the reference BMI group.10 Bibliometric analysis of scientific publications is a method of studying the growth patterns of a research field, measuring the performance and productivity of researchers by the volume and impact of their published work, as well as evaluating the contribution and collaboration of authors, institutions or countries in the field as well as identifying subject gaps in the field. The first bibliometric analysis of publications in the field of lifestyle-based preventive cardiology has here shown an exponential growth rate of publications, with the USA making the highest contribution to global publications and total citation counts. The European Journal of Preventive Cardiology published the largest number of articles in this field.11 The authors observed that some topics, e.g. obesity, exercise were highly considered, while others, such as smoking cessation or suboptimum adherence to dietary and physical activity guidelines among hospital staff, under-represented. Smoking has been consistently associated with increased cardiovascular risk in adults.12 Here two studies have investigated further the risks associated with smoking habit. Although the exposure to tobacco products often starts in early life, evidence for the possible adverse effects on the cardiovascular system of the young is scarce. A systematic review and meta-analysis of 12 clinical studies involving 5279 young individuals up to 21 years old showed that smoking exposure was associated with subclinical vascular damage.13 This association was observed irrespective of active or passive exposure which presents important implications regarding parental smoking and educational institution and workplace hazards. In France, where the daily smoking prevalence is among the highest in high-income European countries, 250 813 hospital stays, i.e. 21% of all stays for a cardiovascular condition, were estimated as attributable to smoking. If the number of current smokers had been 10% lower or if the prevalence of smoking in the population had dropped to below 20%, 5867 stays and 25 911 stays, respectively, would have been prevented.14 The inverse association between cardiorespiratory fitness (CRF) and mortality has been well established and is independent of age, sex, ethnicity, and comorbidities. In addition to estimation of CRF, exercise stress testing data provide the clinician with a multitude of valuable predictive and diagnostic indicators.15 In the present issue, two studies are dedicated to this important clinical tool. Several exercise risk scores, combining multiple exercise variables, have been developed and validated as prognostic tools. In this issue of the journal, Harb et al.16 studied a cohort of 126 356 patients referred to the Cleveland Clinic for an exercise stress test between 1991 and 2015. Patients’ data from the tests, including their exercise capacity, HR response to exercise and HR recovery were used to calculate a novel score, A-BEST (Age Based on Exercise Stress Testing). This score was sex-specific and consisted of three components (exercise capacity, chronotropic reserve index and HR recovery), taking also into account the use of negative chronotropic medications. After a mean follow-up of 8.7 years, the authors found that more than half of patients between 50 and 60 years old were physiologically younger than their chronological age, as indicated by their A-BEST score. Higher exercise capacity and a higher chronotropic reserve index were associated with improved survival whereas abnormal HR recovery was associated with a 53% increased risk of mortality. Higher A-BEST scores were associated with a 5% increased risk of death. The haemodynamic response to exercise has a central role in assessing the physiological response to exercise and is predictive of future CVD. The expected physiological blood pressure (BP) response to dynamic upright exercise is an increase in SBP, no change or a slight drop in diastolic BP, and, thus, widening of the pulse pressure. However, there is currently no consensus on the normal SBP response to exercise. The aim of the study presented here was to assess the normal SBP response to exercise in relation to workload in a large group of male and female adults free from CVD and risk factors.17 The study included 3839 healthy subjects (1620 female), SBP, HR, and workload (watt) from more than two-time points from each test were extracted and SBP/watt-slope and the SBP/watt-ratio at peak exercise were calculated. Furthermore, age- and sex-specific mean values, standard deviations and 90th and 95th percentiles were determined. Females had lower mean peak SBP than males but workload-indexed SBP measures were markedly higher in females. In the reference equation to predict SBP max, the authors included age, sex, exercise capacity, resting SBP, and height. CVD, diabetes, and obesity, account for roughly two-thirds of deaths worldwide. Metabolic syndrome is an important precursor to CVD and other chronic conditions and, the clustering of risk factors that define it (high waist circumference, dyslipidaemia, hypertension, and insulin resistance) are commonly associated with sedentary lifestyles. In recent decades, several studies have shown that increasing amounts of physical activity can help to reduce BP, improve insulin resistance and lipid disorders, including raising HDL and lowering triglycerides. Ekblom-Bak et al.18 explored the association of leisure-time physical activity CVD incidence and mortality and all-cause mortality in a population-based sample with and without established metabolic syndrome. Similarly, Hernáez et al.19 evaluated the association between leisure-time physical activity and a range of markers of HDL characteristics and functionality in a sample of nearly 300 individuals at high risk of CVD. The authors showed that physical activity of different intensities attenuated cardiovascular risk and mortality in patients with metabolic syndrome and was associated not only with greater circulating levels of HDL but also with better markers of high-density lipoprotein functionality. Conflict of interest: none declared.