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Risk assessment and risk prediction have become essential in the prevention of cardiovascular disease. Even though risk prediction tools are recommended in the European guidelines, they are not adequately implemented in clinical practice. Risk prediction tools are meant to estimate prognosis in an unbiased and reliable way and to provide objective information on outcome probabilities. They support informed treatment decisions about the initiation or adjustment of preventive medication. Risk prediction tools facilitate risk communication to the patient and their family, and this may increase commitment and motivation to improve their health. Over the years many risk algorithms have been developed to predict 10-year cardiovascular mortality or lifetime risk in different populations, such as in healthy individuals, patients with established cardiovascular disease and patients with diabetes mellitus. Each risk algorithm has its own limitations, so different algorithms should be used in different patient populations. Risk algorithms are made available for use in clinical practice by means of – usually interactive and online available – tools. To help the clinician to choose the right tool for the right patient, a summary of available tools is provided. When choosing a tool, physicians should consider medical history, geographical region, clinical guidelines and additional risk measures among other things. Currently, the U-prevent.comwebsite is the only risk prediction tool providing prediction algorithms for all patient categories, and its implementation in clinical practice is suggested/advised by the European Association of Preventive Cardiology.

Due to an increasing number of older adults with (risk factors for) cardiovascular disease (CVD), the sum of older adults eligible for lipid-lowering drugs will increase. This has risen questions about benefits and harms of lipid-lowering therapy in older adults with a varying number of (cardiovascular) comorbidities and functional status. The heterogeneity in physical and functional health increases with age, leading to a much wider variety in cardiovascular risk and life expectancy than in younger adults. We suggest treatment decisions on hypercholesterolaemia in adults aged ≥75 years should shift from a strictly 10-year cardiovascular risk-driven approach to a patient-centred and lifetime benefit-based approach. With this, estimated 10-year risk of CVD should be placed into the perspective of life expectancy. Moreover, frailty and safety concerns must be taken into account for a risk–benefit discussion between clinician and patient. Based on the Dutch addendum ‘Cardiovascular Risk Management in (frail) older adults’, our approach offers more detailed information on when not to initiate or deprescribe therapy than standard guidelines. Instead of using traditional risk estimating tools which tend to overestimate risk of CVD in older adults, use a competing risk adjusted, older adults-specific risk score (available at https://u-prevent.com). By filling in a patient’s (cardiovascular) health profile (eg, cholesterol, renal function), the tool estimates risk of CVD and models the effect of medication in terms of absolute risk reduction for an individual patient. Using this tool can guide doctors and patients in making shared decisions on initiating, continuing or deprescribing lipid-lowering therapy.

Risk assessment have become essential in the prevention of cardiovascular disease. Even though risk prediction tools are recommended in the European guidelines, they are not adequately implemented in clinical practice. Risk prediction tools are meant to estimate prognosis in an unbiased and reliable way and to provide objective information on outcome probabilities. They support informed treatment decisions about the initiation or adjustment of preventive medication. Risk prediction tools facilitate risk communication to the patient and their family, and this may increase commitment and motivation to improve their health. Over the years many risk algorithms have been developed to predict 10-year cardiovascular mortality or lifetime risk in different populations, such as in healthy individuals, patients with established cardiovascular disease and patients with diabetes mellitus. Each risk algorithm has its own limitations, so different algorithms should be used in different patient populations. Risk algorithms are made available for use in clinical practice by means of – usually interactive and online available – tools. To help the clinician to choose the right tool for the right patient, a summary of available tools is provided. When choosing a tool, physicians should consider medical history, geographical region, clinical guidelines and additional risk measures among other things. Currently, the U-prevent.com website is the only risk prediction tool providing prediction algorithms for all patient categories, and its implementation in clinical practice is suggested/advised by the European Association of Preventive Cardiology.

Introduction We evaluated the relationship between adipokine plasma concentrations and body fat distribution and the metabolic syndrome.Methods In a cohort of 1215 patients with clinically manifest vascular disease the relation between subcutaneous adipose tissue, visceral adipose tissue, waist circumference, body mass index and plasma concentrations of adipsin, chemerin, monocyte chemoattractant protein-1, migration inhibitory factor, nerve growth factor, resistin, plasma amyloid A1, adiponectin, leptin, plasminogen activator inhibitor-1 and hepatic growth factor were cross-sectionally assessed with linear regression and adjusted for age and gender. The relation between adipokines and the metabolic syndrome was cross-sectionally evaluated using logistic regression. An adipokine profile was developed to measure the effect of combined rather than single adipokines.Results Adiposity was related to higher nerve growth factor, hepatic growth factor, migration inhibitory factor, leptin and adipsin and with lower chemerin, plasminogen activator inhibitor-1, resistin, plasma amyloid A1 and adiponectin. The strongest positive relations were between body mass index and adipsin (β 0.247; 95% CI 0.137–0.356) and leptin (β 0.266; 95% CI 0.207–0.324); the strongest negative relations were between body mass index and plasma amyloid A1 (β –0.266; 95% CI –0.386 to –0.146) and visceral adipose tissue and adiponectin (β –0.168; 95% CI –0.226 to –0.111). There was no relation between subcutaneous adipose tissue and adipokines. Odds for the metabolic syndrome were higher with each 1 SD higher hepatic growth factor (OR 1.21; 95% CI 1.06–1.38) and leptin (OR 1.26; 95% CI 1.10–1.45) and lower with each 1 SD higher adiponectin (OR 0.73; 95% CI 0.64–0.83) and resistin (OR 0.85; 95% CI 0.74–0.97). The adipokine profile was related to the metabolic syndrome (OR 1.03; 95% CI 1.00–1.06).Conclusion Plasma concentrations of adipokines are related to obesity and body fat distribution. The relation between adipokine concentrations and the metabolic syndrome is independent of visceral adipose tissue.

Background The ratio of estimated glomerular filtration rate (eGFR) to kidney size reflects the kidney’s capacity for filtration per kidney volume or kidney length. High ratios of eGFR to kidney size, which might indicate glomerular hyperfiltration, could be related to kidney function decline, cardiovascular disease and mortality.Methods In 6926 patients with clinically manifest vascular disease, we evaluated the relationship between eGFR/kidney size and the risk of cardiovascular events and all-cause mortality using Cox regression. Quartiles were made for eGFR/kidney size, using the second quartile as the reference category. In 1516 patients with second measurements of eGFR, linear regression was used to evaluate the relationship between eGFR/kidney size and annual kidney function decline.Results The relationship between eGFR/kidney size and all-cause mortality followed a reversed J-shaped curve with increased risk for the lowest (hazard ratio (HR) 1.17; 95% confidence interval (CI) 1.01–1.36) and highest quartile (HR 1.04; 95% CI 0.87–1.25) of eGFR/volume, and for the lowest (HR 1.37;95%CI 1.19–1.59) and highest quartile (HR 1.28; 95% CI 1.06–1.54) of eGFR/length. The risk for cardiovascular events was increased for the lowest quartile of eGFR/length (HR 1.55; 95% CI 1.33–1.82). An increase in eGFR/volume and eGFR/length, was related to a greater kidney function decline, β −0.34 (95% CI −0.42 to −0.26) and β −0.55 (95% CI −0.63 to −0.48) ml/min/1.73 m2per year respectively.Conclusions High eGFR/volume and eGFR/length, which might indicate glomerular hyperfiltration, are related to kidney function decline. High eGFR/length confers an increased risk for all-cause mortality in patients with clinically manifest vascular disease.

Aims Cardiovascular fixed-dose combination pills, or polypills, may help address the widespread lack of access and adherence to proven medicines. Initiation of polypill-based care typically entails switching from current separately taken medications. Given the heterogeneity in usual care, there is interest in the impact of polypill treatment across different patterns of prior medication regimen.Methods A total of 2004 participants with established cardiovascular disease or estimated 5-year cardiovascular risk of over 15% were randomised to polypill-based treatment (aspirin 75 mg, simvastatin 40 mg, lisinopril 10 mg and either atenolol 50 mg or hydrochlorothiazide 12.5 mg) or usual care. Baseline medications were classified by potency relative to polypill components. Estimated cardiovascular risk reduction was calculated by combining risk factor changes with results seen in meta-analyses of previous randomised trials.Results For cholesterol reduction conferred by polypills, there was a dose response across baseline statin groups, with mean low-density lipoprotein (LDL)-cholesterol differences of 0.37, 0.22, 0.14 and 0.07 mmol/L among patients taking no statin, less potent, equipotent and more potent statin at baseline, respectively. Similarly there were differences in mean systolic BP of 5.4, 6.2, 3.3 and 1.8 mmHg among patients taking 0, 1, 2 or 3 BP-lowering agents. Among patients taking more potent statins at baseline, there was no significant difference in LDL-cholesterol but there were benefits for BP and aspirin adherence. Similar results were seen among patients taking 3 BP-lowering agents at baseline. Switching to a polypill-based strategy resulted in estimated cardiovascular relative risk reductions across a wide range of usual care patterns of antiplatelet, statin and BP-lowering therapy prescribing.Conclusion Adherence benefits from switching to a polypill resulted in risk factor changes that were at least as good as usual care across a wide variety of treatment patterns, including equally potent or more potent regimens. The benefits of switching to polypill-based care were greatest among those stepped up from partial treatment or less potent treatment.

Background Cardiovascular disease remains the major contributor to morbidity and mortality. In routine care for patients with an elevated cardiovascular risk or with symptomatic cardiovascular disease information is mostly collected in an unstructured manner, making the data of limited use for structural feedback, quality control, learning and scientific research.Objective The Utrecht Cardiovascular Cohort (UCC) initiative aims to create an infrastructure for uniform registration of cardiovascular information in routine clinical practice for patients referred for cardiovascular care at the University Medical Center Utrecht, the Netherlands. This infrastructure will promote optimal care according to guidelines, continuous quality control in a learning healthcare system and creation of a research database.Methods The UCC comprises three parts. UCC-1 comprises enrolment of all eligible cardiovascular patients in whom the same information will be collected, based on the Dutch cardiovascular management guideline. A sample of UCC-1 will be invited for UCC-2. UCC-2 involves an enrichment through extensive clinical measurements with emphasis on heart failure, cerebral ischaemia, arterial aneurysms, diabetes mellitus and elevated blood pressure. UCC-3 comprises on-top studies, with in-depth measurements in smaller groups of participants typically based on dedicated project grants. All participants are followed up for morbidity and mortality through linkage with national registries.Conclusion In a multidisciplinary effort with physicians, patients and researchers the UCC sets a benchmark for a learning cardiovascular healthcare system. UCC offers an invaluable resource for future high quality care as well as for first-class research for investigators.

Background The radiodensity of epicardial adipose tissue may provide information on cardiovascular risk in addition to epicardial adipose tissue volume. The aim of this study was to quantify the relation between cardiovascular risk factors and the radiodensity of epicardial adipose tissue in patients at high risk of cardiovascular disease.Design This was a cross-sectional study in 140 patients at high risk of cardiovascular disease.Methods Patients from the Secondary Manifestations of ARTerial disease (SMART) cohort study were invited to undergo cardiac computed tomography angiography. The radiodensity (in Hounsfield units; HU) and volume (in cm3) of epicardial adipose tissue were quantified semi-automatically. Multivariable linear regression was used to quantify the relation between cardiovascular risk factors and the radiodensity of epicardial adipose tissue.Results The cardiovascular risk factors most strongly associated with epicardial adipose tissue density were sex, body mass index and visceral fat, with a lower adipose tissue attenuation of 3.5 HU (95% confidence interval (CI) 2.0–5.0 HU) for female sex, 1.6 HU (95%CI 0.2–2.9 HU) for body mass index >25 kg/m2and 1.3 HU (95% CI 0.6–2.0 HU) for a one standard deviation higher quantity of visceral fat, adjusted for age, sex, coronary artery bypass graft history and epicardial adipose tissue volume.Conclusion Low epicardial adipose tissue computed tomography attenuation is associated with an adverse cardiovascular risk factor profile in patients at high risk of cardiovascular disease, independent of the volume of epicardial adipose tissue and waist circumference. These findings support the potential role for epicardial adipose tissue radiodensity as a valid biomarker of cardiovascular risk. Adipose tissue radiodensity may be a more sensitive marker than epicardial adipose tissue volume with which to study the contribution of epicardial adipose tissue to the coronary atheromatous disease process.

Aims Several genes are related to blood pressure (BP) levels in adults, but it is largely unknown whether these genes also determine BP early in life.Methods Systolic BP (SBP) and diastolic BP (DBP) were measured in 720 5-year-old children from the WHeezing-Illnesses-STudy-LEidsche-Rijn (WHISTLER) birth cohort in sitting and supine positions using a semi-automatic oscillometric device. Illumina chip technology was used to genotype 18, 19, 11 and 12 single nucleotide polymorphisms associated with adult SBP, DBP, mean arterial pressure (MAP) and hypertension, respectively, in the children’s DNA and separate weighted genetic risk scores (GRSs) were constructed. The associations are reported as linear regression coefficients (mmHg BP in childhood/GRS score point) or odds ratios (highest childhood BP quintile/hypertension GRS score point).Results A higher GRS for SBP was related to higher supine SBP (0.37, 95% CI 0.01 to 0.7), but not to supine DBP (−0.05, 95% CI −0.4 to 0.3) or supine MAP (0.19, 95% CI −0.1 to 0.5). A higher GRS for DBP was related to a higher supine SBP (0.66, 95% CI 0.1 to 1.2), but not to supine DBP (−0.07, 95% CI −0.6 to 0.4) or supine MAP (0.28, 95% CI −0.2 to 0.7). With the sitting BP measurements, the GRSs for SBP and DBP were related to neither SBP nor DBP. No association was found between GRS for MAP and SBP, DBP or MAP. Hypertension GRS was not associated with a higher BP in children.Conclusions Higher scores for adult derived diastolic and systolic BP genes appear to be related to higher supine systolic BP at age 5 years.

Aims Recent data indicate that fixed-dose combination (FDC) pills, polypills, can produce sizeable risk factor reductions. There are very few published data on the consistency of the effects of a polypill in different patient populations. It is unclear for example whether the effects of the polypill are mainly driven by the individuals with high individual risk factor levels. The aim of the present study is to examine whether baseline risk factor levels modify the effect of polypill treatment on low-density lipoprotein (LDL)-cholesterol, blood pressure (BP), calculated cardiovascular relative risk reduction and adverse events.Methods This paper describes a post-hoc analysis of a randomised, placebo-controlled trial of a polypill (containing aspirin 75 mg, simvastatin 20 mg, lisinopril 10 mg and hydrochlorothiazide 12.5 mg) in 378 individuals without an indication for any component of the polypill, but who had an estimated five-year risk for cardiovascular disease ≥7.5%. The outcomes considered were effect modification by baseline risk factor levels on change in LDL-cholesterol, systolic BP, calculated cardiovascular relative risk reduction and adverse events.Results The mean LDL-cholesterol in the polypill group was 0.9 mmol/l (95% confidence interval (CI): 0.8–1.0) lower compared with the placebo group during follow-up. Those with a baseline LDL-cholesterol >3.6 mmol/l achieved a greater absolute LDL-cholesterol reduction with the polypill compared with placebo, than patients with an LDL-cholesterol ≤3.6 mmol/l (−1.1 versus −0.6 mmol/l, respectively). The mean systolic BP was 10 mm Hg (95% CI: 8–12) lower in the polypill group. In participants with a baseline systolic BP >135 mm Hg the polypill resulted in a greater absolute systolic BP reduction with the polypill compared with placebo, than participants with a systolic BP ≤ 135 mm Hg (−12 versus −7 mm Hg, respectively). Calculated from individual risk factor reductions, the mean cardiovascular relative risk reduction was 48% (95% CI: 43–52) in the polypill group. Both baseline LDL-cholesterol and estimated cardiovascular risk were significant modifiers of the estimated cardiovascular relative risk reduction caused by the polypill. Adverse events did not appear to be related to baseline risk factor levels or the estimated cardiovascular risk.Conclusion This study demonstrated that the effect of a cardiovascular polypill on risk factor levels is modified by the level of these risk factors. Groups defined by baseline LDL-cholesterol or systolic BP had large differences in risk factor reductions but only moderate differences in estimated cardiovascular relative risk reduction, suggesting also that patients with mildly increased risk factor levels but an overall raised cardiovascular risk benefit from being treated with a polypill.

Background Patients with cardiovascular disease might be at increased risk of non-vascular mortality due to shared risk factors. Our aim was to evaluate causes of death and years of life lost (YLL) in patients with different manifestations of vascular disease.Design The design was a prospective cohort study.Methods A total of 5911 patients with stable coronary artery disease, cerebrovascular disease, peripheral artery disease (PAD), abdominal aortic aneurysm or polyvascular disease were followed-up for mortality. Cause-specific standardised mortality ratios (SMRs) and YLL, compared to the Dutch population, were estimated. Determinants for cause-specific mortality were evaluated using competing risks models.Results During a median follow-up of 6.0 years (interquartile range (IQR): 3.1–9.2), 958 (16.2%) patients died. All-cause mortality was increased compared to the general population (SMR: 1.26, 95% confidence interval (CI): 1.18–1.34). Patients with PAD and polyvascular disease were at highest risk, especially for ischaemic heart disease (SMR: 2.52, 95% CI: 1.70–3.60 and SMR: 3.97, 95% CI: 3.18–4.90, respectively). Patients with PAD were at increased risk of dying from cancer (SMR: 1.67, 95% CI: 1.25–2.17). On average, patients with vascular disease of ≥50 years died 7.8 years younger than the general population, with 80% of the excess YLL attributable to cardiovascular disease. In middle-aged patients the excess YLL were about 10 years, of which 24% were lost due to cancer. Important determinants for mortality were male gender, smoking, physical inactivity, renal insufficiency and polyvascular disease.Conclusions Patients with manifest vascular disease are at increased risk of both cardiovascular and cancer mortality, particularly patients with PAD or polyvascular disease. On average, patients with vascular disease of ≥50 years die 7.8 years younger than the general population.

Background Inflammation is important in atherosclerosis development. Whether common causes of inflammation, such as allergies and infections, already exert this influence in early childhood is unknown. The objective of this study was to investigate the association between both allergies and infections with children’s vasculature.Design This was a longitudinal study in a general population cohort.Methods In 390 five-year-olds of the WHISTLER (Wheezing-Illnesses-Study-LEidsche-Rijn) birth cohort, carotid intima-media thickness (CIMT) and arterial stiffness were obtained ultrasonographically. Physician-diagnosed allergies and infections and recent prescriptions of systemic antihistamines and antibiotics were obtained, as well as parental history of allergies. General linear regression was performed with vascular characteristics as dependent variables and measures of inflammation as independent variables.Results Having both a positive parental history of allergy and an allergy diagnosis showed 15.0 µm (95% confidence interval (CI): 2.3–27.8, p= 0.02) larger CIMT than not having such history and diagnosis. Having a positive parental history of allergy only showed 11.9 µm (0.87–23.0, p= 0.04) larger CIMT. Recent use of antihistamines and antibiotics showed 18.8 µm (1.6–35.9, p= 0.03) and 16.1 µm (4.5–27.7, p= 0.01) larger CIMT, respectively. Childhood infections were not clearly related to vascular parameters. Neither allergy nor infections were associated with arterial stiffness.Conclusion An allergic predisposition is already associated with thicker arterial walls in early childhood.

Background The SPRINT trial showed a beneficial effect of systolic blood pressure treatment targets of 120 mmHg on cardiovascular risk compared to targets of 140 mmHg. However, differences in medication use, most importantly diuretics, are suggested as an alternative explanation. This post-hoc analysis aimed to determine whether the reduced event rate can be attributed to changes in systolic blood pressure (ΔSBP).Methods Analyses were based on all 9361 participants of the SPRINT trial. ΔSBP was defined as the change between baseline and 6-month follow-up systolic blood pressure. Major cardiovascular events were myocardial infarction, other acute coronary syndromes, stroke, heart failure, or cardiovascular death. Cox regression was used to describe the relation between ΔSBP and major cardiovascular events. Analyses were performed separately for patients in the lowest tertile of baseline systolic blood pressure, as the SPRINT trial reported the highest treatment effect in this subgroup.Results The relation between ΔSBP and major cardiovascular events was a hazard ratio per 10 mmHg decrease of 0.93 (95% confidence interval 0.89–0.98). Similar results were found within the lowest tertile of baseline systolic blood pressure: hazard ratio per 10 mmHg decrease 0.91 (95% confidence interval 0.82–1.01).Conclusion Our results show that lowering blood pressure prevents cardiovascular disease. However, not all the positive effects in the SPRINT trial could be explained by ΔSBP. Alternative explanations, such as differences in medication use, should be considered for the positive findings of the SPRINT trial.