The association between a genetic variant in the SULF2 gene, metabolic parameters and vascular disease in patients at high cardiovascular risk.

Clearance of triglyceride-rich lipoproteins (TRLs) is mediated by several receptors, including heparan sulfate proteoglycans (HSPGs). Sulfate glucosamine-6-O-endosulfatase-2 is a gene related to the regulation of HSPG. A variant in this gene, rs2281279, has been shown to be associated with triglycerides and insulin resistance. Objective: To determine the relationship between rs2281279, metabolic parameters and vascular events, and type 2 diabetes mellitus (T2DM) in patients at high cardiovascular risk and whether APOE genotype modifies this relationship. Methods: Patients (n = 4386) at high cardiovascular risk from the Utrecht Cardiovascular Cohort-Second Manifestations of Arterial Disease study were stratified according to their imputed rs2281279 genotype: AA (n = 2438), AG (n = 1642) and GG (n = 306). Effects of rs2281279 on metabolic parameters, vascular events and T2DM were analyzed with linear regression and Cox models. Results: There was no relationship between imputed rs2281279 genotype and triglycerides, non-high-density lipoprotein (HDL)-cholesterol, insulin and quantitative insulin sensitivity check index. During a median follow-up of 11.8 (IQR, 9.3-15.5) years, 1026 cardiovascular events and 320 limb events occurred. The presence of the G allele in rs2281279 did not affect the risk of vascular events [hazard ratio (HR), 1.03; 95% confidence interval (CI), 0.94-1.14] or limb events (HR, 0.92; 95% CI, 0.77-1.10). The presence of the G allele in rs2281279 did not affect the risk of T2DM (HR, 1.09; 95% CI, 0.94-1.27). The presence of the minor G allele of rs2281279 was associated with a beneficial risk profile in ε2ε2 patients, but not in ε3ε3 patients. Conclusions: Imputed rs2281279 genotype is not associated with metabolic parameters and does not increase the risk of vascular events or T2DM in patients at high risk for cardiovascular disease.

Compliance with the DASH diet and risk of all-cause and cardiovascular mortality in patients with myocardial infarction.

BACKGROUND & AIMS: The Dietary Approaches to Stop Hypertension (DASH) diet has been shown to effectively reduce blood pressure and body weight, but its effectiveness for reducing (cardiovascular) mortality rates has never been assessed in a clinical trial. Causal effects of dietary interventions are difficult to measure, due to practical limitations of randomized controlled diet trials. Target trial emulation can be used to improve causal inference in observational data. The aim of this study was to emulate a target trial assessing the relationship between compliance with the DASH diet and cardiovascular and all-cause mortality risk in patients with established CVD. METHODS: Using data from the Alpha Omega Cohort, we emulated a DASH diet trial in patients with a history of myocardial infarction (MI). Inverse probability of treatment weighting (IPTW) was used to balance confounders over DASH-compliant and non-DASH-compliant participants. Hazard ratios (HRs) were estimated with IPT-weighted Cox models. RESULTS: Of 4365 patients (79% male, median age 69 years, >80% treated with lipid- and blood pressure-lowering medication), 598 were classified as DASH-compliant (compliance score ≥5 out of 9). During a median follow-up of 12.4 years, 2035 deaths occurred of which 903 (44%) were of cardiovascular origin. DASH compliance was not associated with all-cause mortality (HR 0.92, 95%CI 0.0.80-1.06) and cardiovascular mortality (HR 0.90, 95%CI 0.72-1.11). CONCLUSIONS: In an emulated target trial on the DASH diet in the Alpha Omega cohort no relation was found between DASH compliance and risk of all-cause and cardiovascular mortality in patients with a history of MI. The DASH diet's effects may have been modified in this population by concomitant use of blood pressure-lowering medications.

Blood pressure and cholesterol measurements in primary care: cross-sectional analyses in a dynamic cohort.

BACKGROUND: Guidelines on cardiovascular risk management (CVRM) recommend blood pressure (BP) and cholesterol measurements every 5 years in men aged ≥40 years and (post-menopausal) women aged ≥50 years. AIM: To evaluate CVRM guideline implementation. DESIGN & SETTING: Cross-sectional analyses in a dynamic cohort using primary care electronic health record (EHR) data from the Julius General Practitioners' Network (JGPN) (n = 388 929). METHOD: Trends (2008-2018) were assessed in the proportion of patients with at least one measurement (BP and cholesterol) every 1, 2, and 5 years, in those with:1. a history of cardiovascular disease (CVD) and diabetes mellitus (DM);2. a history of DM only;3. a history of CVD only;4. a cardiovascular risk assessment (CRA) indication based on other medical history, or;5. no CRA indication.Trends were evaluated over time using logistic regression mixed-model analyses. RESULTS: Trends in annual BP and cholesterol measurement increased for patients with a history of CVD from 37.0% to 48.4% (P<0.001) and 25.8% to 40.2% (P<0.001). In the 5-year window from 2014-2018, BP and cholesterol measurements were performed respectively in 78.5% and 74.1% of all men aged ≥40 years and 82.2% and 78.5% of all women aged ≥50 years. Least measured were patients without a CRA indication (men 60.2% and 62.4%; women 55.5% and 59.3%). CONCLUSION: The fairly high frequency of CVRM measurements available in the EHR of patients in primary care suggests an adequate implementation of the CVRM guideline. As nearly all individuals visit the GP at least once within a 5-year time window, improvement of CVRM remains possible, especially in those without a CRA indication.

Adiposity and the development of dyslipidemia in APOE ε2 homozygous subjects: A longitudinal analysis in two population-based cohorts.

BACKGROUND AND AIMS: Familial dysbetalipoproteinemia (FD), characterized by remnant lipoprotein accumulation and premature cardiovascular disease, occurs in homozygous carriers of the APOE ε2 allele, but genetic predisposition alone does not suffice for the clinical phenotype. Cross-sectional studies suggest that a second metabolic hit - notably adiposity or insulin resistance - is required, but the association between these risk factors and development of FD has not been studied prospectively. METHODS: For this study, we evaluated 18,987 subjects from two large prospective Dutch population-based cohorts (PREVEND and Rotterdam Study) of whom 118 were homozygous APOE ε2 carriers. Of these, 69 subjects were available for prospective analyses. Dyslipidemia - likely to be FD - was defined as fasting triglyceride (TG) levels >3 mmol/L in untreated subjects or use of lipid lowering medication. The effect of weight, body mass index (BMI), waist circumference, type 2 diabetes mellitus and non-TG metabolic syndrome on development of dyslipidemia was investigated. RESULTS: Eleven of the 69 ε2ε2 subjects (16%) developed dyslipidemia - likely FD - during follow-up. Age-, sex- and cohort-adjusted risk factors for the development of FD were BMI (OR 1.19; 95%CI 1.04-1.39), waist circumference (OR 1.26 95%CI 1.01-1.61) and presence of non-TG metabolic syndrome (OR 4.39; 95%CI 1.04-18.4) at baseline. Change in adiposity during follow-up was not associated with development of dyslipidemia. CONCLUSIONS: Adiposity increases the risk of developing an FD-like lipid phenotype in homozygous APOE ε2 subjects. These results stress the importance of healthy body weight in subjects at risk of developing FD.

Treatment of hypercholesterolaemia in older adults calls for a patient-centred approach.

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 prediction tools in cardiovascular disease prevention: A report from the ESC Prevention of CVD Programme led by the European Association of Preventive Cardiology (EAPC) in collaboration with the Acute Cardiovascular Care Association (ACCA) and the Association of Cardiovascular Nursing and Allied Professions (ACNAP).

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.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.

Severe hypertriglyceridaemia and pancreatitis in a patient with lipoprotein lipase deficiency based on mutations in lipoprotein lipase (LPL) and apolipoprotein A5 (APOA5) genes.

A 44-year-old woman was admitted with pancreatitis caused by hypertriglyceridaemia (fasting triglycerides 28 mmol/L). She used oral contraceptives and ezetimibe 10 mg. She was overweight (body mass index 29.7 kg/m2). Diabetes mellitus was ruled out, as were nephrotic syndrome, alcohol abuse, hypothyroidism and dysbetalipoproteinaemia. Genetic analysis revealed mutations in two genes involved in triglyceride metabolism (apolipoprotein A5 and lipoprotein lipase [LPL]). The LPL activity was 45% compared with pooled healthy controls. The post-heparin triglyceride reduction was 6%, compared with a normal reduction of >20%. The patient was initially treated with gemfibrozil, but this was discontinued due to side effects. Dietary triglyceride restriction and discontinuation of the oral contraceptives lowered the plasma triglycerides within 2 weeks to 3.4 mmol/L. Hypertriglyceridaemia is a risk factor for pancreatitis and cardiovascular disease, and has a broad differential diagnosis including genetic causes. Patients can achieve near-normal triglyceride values with a low-fat diet only.

Comorbidity in patients with cardiovascular disease in primary care: a cohort study with routine healthcare data.

BACKGROUND: Comorbidity is a major public health issue, which challenges health care configured around single diseases. AIM: To provide an overview of frequent disease combinations of one and two additional chronic diseases and groups among patients with cardiovascular disease (CVD) in general practice. DESIGN AND SETTING: Medical record data from the Julius General Practitioners' Network of 226 670 patients registered in 2015-2016 in Utrecht, the Netherlands, were collected and examined. METHOD: Prevalences and combinations of one and two comorbid conditions were determined, by age and sex, in four populations of patients with CVD: heart failure, peripheral arterial disease (PAD), coronary heart disease (CHD), or stroke. Using logistic regression analyses, the authors examined whether comorbid conditions were significantly more prevalent in patients with a specific cardiovascular condition compared with those without. RESULTS: Low vision, diabetes mellitus, back/neck problems, osteoarthritis, chronic obstructive pulmonary disease (COPD), and cancer were the most prevalent non-cardiovascular conditions and ranked in the top five of non-cardiovascular comorbid conditions in the different CVDs studied, irrespective of patient age and sex. Of these, diabetes, COPD, and low vision were statistically significantly more prevalent in all four cardiovascular conditions when compared with patients without the respective disease. Over the life span, the majority of the comorbid conditions were most prevalent in patients with heart failure, directly followed by those with PAD; they were less prevalent in patients with CHD and stroke. CONCLUSION: Comorbid conditions are very common in patients with CVD, even in younger age groups. To ensure efficient and effective treatment, organisational adaptations may be required in the healthcare system to accommodate comorbid conditions in patients with CVD.

Risk prediction tools in cardiovascular disease prevention: A report from the ESC Prevention of CVD Programme led by the European Association of Preventive Cardiology (EAPC) in collaboration with the Acute Cardiovascular Care Association (ACCA) and the Association of Cardiovascular Nursing and Allied Professions (ACNAP).

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.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.

Risk prediction tools in cardiovascular disease prevention: A report from the ESC Prevention of CVD Programme led by the European Association of Preventive Cardiology (EAPC) in collaboration with the Acute Cardiovascular Care Association (ACCA) and the Association of Cardiovascular Nursing and Allied Professions (ACNAP).

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.

Metabolic syndrome and incidence of type 2 diabetes in patients with manifest vascular disease.

Risk reduction in patients with clinically manifest vascular disease focuses on preventing new vascular events and not on prevention of type 2 diabetes. However, given the common pathophysiological pathways involved in the development of atherosclerosis and type 2 diabetes, it is probable that people with atherosclerotic vascular disease have an elevated risk of type 2 diabetes. The present prospective cohort study investigated the incidence of type 2 diabetes and the effect of the presence of metabolic syndrome on the incidence of type 2 diabetes in 4,022 patients with clinically manifest atherosclerosis, included in the study from September 1996 to June 2006. Patients who died (n=456), who were lost to follow-up (n=84) and those with diabetes at baseline (n=558) were excluded, leaving 2,924 patients for analysis. The incidence of diabetes was assessed by questionnaire (self-reported diabetes). During 13,726 person-years of follow-up (median follow-up 4.3 years, range 2.4-7.0 years), there were 152 type 2 diabetes cases (5.2%), corresponding to an incidence rate of 11.1 (95% CI 9.4-13.0) per 1,000 person-years. Patients with metabolic syndrome were at increased risk of incident type 2 diabetes compared to those without metabolic syndrome, with an adjusted hazard ratio of 5.7 (95% CI 3.7-8.9) for Revised National Cholesterol Education Program, 6.0 (4.1-9.0) for National Cholesterol Education Program and 4.0 (2.7-6.1) for International Diabetes Federation definitions of metabolic syndrome. Of all metabolic syndrome components, abdominal obesity was most strongly associated with incident type 2 diabetes (94% higher risk of type 2 diabetes for 1 standard deviation (11.3 cm) increase in waist circumference). In conclusion, patients with manifest atherosclerosis are at high risk of developing type 2 diabetes. Metabolic syndrome identifies those at the highest risk and is an easy to use clinical tool. Abdominal obesity is a strong individual predictor of type 2 diabetes. Patients with manifest atherosclerosis and metabolic syndrome may derive particular benefit from lifestyle interventions focusing on weight reduction.

The relation between body fat distribution, plasma concentrations of adipokines and the metabolic syndrome in patients with clinically manifest vascular disease.

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 (ß 0.247; 95% CI 0.137-0.356) and leptin (ß 0.266; 95% CI 0.207-0.324); the strongest negative relations were between body mass index and plasma amyloid A1 (ß -0.266; 95% CI -0.386 to -0.146) and visceral adipose tissue and adiponectin (ß -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.

SPRINT trial: It's not just the blood pressure!

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.

Relation between cardiovascular disease risk factors and epicardial adipose tissue density on cardiac computed tomography in patients at high risk of cardiovascular events.

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/m2 and 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.

Impact of switching from different treatment regimens to a fixed-dose combination pill (polypill) in patients with cardiovascular disease or similarly high risk.

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.

High ratios of kidney function to kidney size are related to mortality and kidney function decline in high-risk patients.

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, ß -0.34 (95% CI -0.42 to -0.26) and ß -0.55 (95% CI -0.63 to -0.48) ml/min/1.73 m2 per 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.

Adult derived genetic blood pressure scores and blood pressure measured in different body postures in young children.

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.

Uniform data collection in routine clinical practice in cardiovascular patients for optimal care, quality control and research: The Utrecht Cardiovascular Cohort.

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.

Estimated cardiovascular relative risk reduction from fixed-dose combination pill (polypill) treatment in a wide range of patients with a moderate risk of cardiovascular disease.

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.