Prediction model for hypertension in first decade after pre-eclampsia in initially normotensive women.

OBJECTIVE: To develop a prediction model for the development of hypertension in the decade following pre-eclampsia in women who were normotensive shortly after pregnancy. METHODS: This was a longitudinal cohort study of formerly pre-eclamptic women attending a university hospital in The Netherlands between 1996 and 2019. We developed a prediction model for incident hypertension using multivariable logistic regression analysis. The model was validated internally using bootstrapping techniques. RESULTS: Of 259 women, 185 (71%) were normotensive at the first cardiovascular assessment, at a median of 10 (interquartile range (IQR), 6-24) months after a pre-eclamptic pregnancy, of whom 49 (26%) had developed hypertension by the second visit, at a median of 11 (IQR, 6-14) years postpartum. The prediction model, based on birth-weight centile, mean arterial pressure, total cholesterol, left ventricular mass index and left ventricular ejection fraction, had good-to-excellent discriminative ability, with an area under the receiver-operating-characteristics curve (AUC) of 0.82 (95% CI, 0.75-0.89) and an optimism-corrected AUC of 0.80. The sensitivity and specificity of our model to predict hypertension were 98% and 34%, respectively, and positive and negative predictive values were 35% and 98%, respectively. CONCLUSIONS: Based on five variables, we developed a good-to-excellent predictive tool to identify incident hypertension following pre-eclampsia in women who were normotensive shortly after pregnancy. After external validation, this model could have considerable clinical utility in tackling the cardiovascular legacy of pre-eclampsia. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

The position of renal denervation in treatment of hypertension: an expert consensus statement.

Hypertension is an important risk factor for cardiovascular disease. In the Netherlands, there are approximately 2.8 million people with hypertension. Despite treatment recommendations including lifestyle changes and antihypertensive drugs, most patients do not meet guideline-recommended blood pressure (BP) targets. In order to improve BP control and lower the risk of subsequent cardiovascular events, renal sympathetic denervation (RDN) has been introduced and studied as a non-pharmacological approach. While early data on the efficacy of RDN showed conflicting results, improvements in treatment protocols and study design resulted in robust new evidence supporting the potential of the technology to improve patient care in hypertensive subjects. Recently, 5 randomised sham-controlled trials demonstrated the safety and efficacy of the technology. Modelling studies have further shown that RDN is cost-effective in the Dutch healthcare setting. Given the undisputable disease burden along with the shortcomings of current therapeutic options, we postulate a new, clearly framed indication for RDN as an adjunct in the treatment of hypertension. The present consensus statement summarises current guideline-recommended BP targets, proposed workup and treatment for hypertension, and position of RDN for those patients with primary hypertension who do not meet guideline-recommended BP targets (see central illustration).

The challenge of choosing in cardiovascular risk management.

Cardiovascular disease (CVD) is a major cause of morbidity and mortality worldwide. For many years guidelines have listed optimal preventive therapy. More recently, novel therapeutic options have broadened the options for state-of-the-art CV risk management (CVRM). In the majority of patients with CVD, risk lowering can be achieved by utilising standard preventive medication combined with lifestyle modifications. In a minority of patients, add-on therapies should be considered to further reduce the large residual CV risk. However, the choice of which drug combination to prescribe and in which patients has become increasingly complicated, and is dependent on both the absolute CV risk and the reason for the high risk. In this review, we discuss therapeutic decisions in CVRM, focusing on (1) the absolute CV risk of the patient and (2) the pros and cons of novel treatment options.

Metabolic syndrome and pre-eclampsia.

OBJECTIVE: To evaluate the association between different pre-eclampsia (PE) phenotypes and the development of metabolic syndrome postpartum, in order to identify the subgroup of formerly pre-eclamptic women with a worse cardiovascular risk profile requiring tailored postpartum follow-up. METHODS: This was a cohort study of 1102 formerly pre-eclamptic women in whom cardiovascular and cardiometabolic evaluation was performed at least 3 months postpartum. Women were divided into four subgroups based on PE resulting in delivery before 34 weeks (early-onset (EO)) or at or after 34 weeks (late onset (LO)) of gestation and whether they delivered a small-for-gestational-age (SGA) neonate. Metabolic syndrome was diagnosed as the presence of hyperinsulinemia along with two or more of: body mass index ≥ 30 kg/m2 ; dyslipidemia; hypertension; and microalbuminuria or proteinuria. Data were compared between groups using ANOVA after Bonferroni correction. Odds ratios (OR) were calculated using logistic regression to determine the association between metabolic syndrome and the four subgroups. We constructed receiver-operating characteristics curves and computed the area under the curve (AUC) to quantify the ability of different obstetric variables to distinguish between women who developed metabolic syndrome and those who did not. RESULTS: The prevalence of metabolic syndrome was higher in women with EO-PE and SGA (25.8%) than in those with EO-PE without SGA (14.7%) (OR 2.01 (95% CI, 1.34-3.03)) and approximately five-fold higher than in women with LO-PE with SGA (5.6%) (OR 5.85 (95% CI, 2.60-13.10)). In women with LO-PE, the prevalence of metabolic syndrome did not differ significantly between women with and those without SGA. Multivariate analysis revealed that a history of SGA, a history of EO-PE and systolic blood pressure at the time of screening are the best predictors of developing metabolic syndrome postpartum. The AUC of the model combining these three variables was 74.6% (95% CI, 70.7-78.5%). The probability of the presence of metabolic syndrome was calculated as: P = 1/(1 + e-LP ), where LP is linear predictor = -8.693 + (0.312 × SGA (yes = 1)) + (0.507 × EO-PE (yes = 1)) + (0.053 × systolic blood pressure). CONCLUSIONS: The incidence of metabolic syndrome postpartum was associated more strongly with EO-PE in combination with SGA as compared with LO-PE or EO-PE without SGA. Both time of onset of PE and fetal growth affect the risk of metabolic syndrome after a pre-eclamptic pregnancy. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

Antihypertensive drug concentration measurement combined with personalized feedback in resistant hypertension: a randomized controlled trial.

BACKGROUND: Adherence to antihypertensive drugs (AHDs) is crucial for controlling blood pressure (BP). We aimed to determine the effectiveness of measuring AHD concentrations using a dried blood spot (DBS) sampling method to identify nonadherence, combined with personalized feedback, in reducing resistant hypertension. METHODS: We conducted a multicenter, randomized, controlled trial (RHYME-RCT, ICTRP NTR6914) in patients with established resistant hypertension. Patients were randomized to receive either an intervention with standard of care (SoC) or SoC alone. SoC consisted of BP measurement and DBS sampling at baseline, 3 months (t3), 6 months (t6), and 12 months (t12); AHD concentrations were measured but not reported in this arm. In the intervention arm, results on AHD concentrations were discussed during a personalized feedback conversation at baseline and t3. Study endpoints included the proportion of patients with RH and AHD adherence at t12. RESULTS: Forty-nine patients were randomized to receive the intervention+SoC, and 51 were randomized to receive SoC alone. The proportion of adherent patients improved from 70.0 to 92.5% in the intervention+SoC arm ( P  = 0.008, n  = 40) and remained the same in the SoC arm (71.4%, n  = 42). The difference in adherence between the arms was statistically significant ( P  = 0.014). The prevalence of resistant hypertension decreased to 75.0% in the intervention+SoC arm ( P  < 0.001, n  = 40) and 59.5% in the SoC arm ( P  < 0.001, n  = 42) at t12; the difference between the arms was statistically nonsignificant ( P  = 0.14). CONCLUSION: Personalized feedback conversations based on DBS-derived AHD concentrations improved AHD adherence but did not reduce the prevalence of RH.

The occurrence of cardiovascular disease during 5-year follow-up in patients with idiopathic atrial fibrillation.

AIMS: Idiopathic atrial fibrillation (AF) may be an expression of as yet undetected underlying heart disease. We found it useful for clinical practice to study the long-term development of cardiovascular disease (CVD) in patients diagnosed with idiopathic AF. METHODS AND RESULTS: Forty-one consecutive idiopathic AF patients (56 ± 10 years, 66% male) were compared with 45 healthy control patients in permanent sinus rhythm. Patients were free of hypertension, antihypertensive and antiarrhythmic drugs, diabetes, congestive heart failure, coronary artery or peripheral vascular disease, previous stroke, thyroid, pulmonary and renal disease, and structural abnormalities on echocardiography. Baseline characteristics and echocardiographic parameters were equal in AF cases and controls. During a mean follow-up of 66 ± 11 months, CVD occurred significantly more often in idiopathic AF patients compared with controls (49 vs. 20%, P= 0.006). Patients with idiopathic AF were significantly younger at the time of their first CV event compared with controls (59 ± 9 vs. 64 ± 5 years, P= 0.027), and had more severe disease. Multivariable Cox regression analysis revealed that age, a history of AF, and echocardiographic left ventricular wall width were significant predictors of CVD development. CONCLUSION: Patients originally diagnosed with idiopathic AF develop CVD more often, at younger age, and with a more severe disease profile compared with healthy sinus rhythm control patients. The detection and treatment of CVD in an early stage could improve the prognosis of these patients. At present it seems prudent to regularly check idiopathic AF patients for the insidious development of CVD.

Chest computed tomography in severe bronchopulmonary dysplasia: Comparing quantitative scoring methods.

PURPOSE: Bronchopulmonary dysplasia (BPD) is the most common complication of extreme preterm birth and structural lung abnormalities are frequently found in children with BPD. To quantify lung damage in BPD, three new Hounsfield units (HU) based chest-CT scoring methods were evaluated in terms of 1) intra- and inter-observer variability, 2) correlation with the validated Perth-Rotterdam-Annotated-Grid-Morphometric-Analysis (PRAGMA)-BPD score, and 3) correlation with clinical data. METHODS: Chest CT scans of children with severe BPD were performed at a median of 7 months corrected age. Hyper- and hypo-attenuated regions were quantified using PRAGMA-BPD and three new HU based scoring methods (automated, semi-automated, and manual). Intra- and inter-observer variability was measured using intraclass correlation coefficients (ICC) and Bland-Altman plots. The correlation between the 4 scoring methods and clinical data was assessed using Spearman rank correlation. RESULTS: Thirty-five patients (median gestational age 26.1 weeks) were included. Intra- and inter-observer variability was excellent for hyper- and hypo-attenuation regions for the manual HU method and PRAGMA-BPD (ICCs range 0.80-0.97). ICC values for the semi-automated HU method were poorer, in particular for the inter-observer variability of hypo- (0.22-0.71) and hyper-attenuation (-0.06-0.89). The manual HU method was highly correlated with PRAGMA-BPD score for both hyper- (ρs0.92, p < 0.001) and hypo-attenuation (ρs0.79, p < 0.001), while automated and semi-automated HU methods showed poor correlation for hypo- (ρs < 0.22) and good correlation for hyper-attenuation (ρs0.72-0.74, p < 0.001). Several scores of hyperattenuation correlated with the use of inhaled bronchodilators in the first year of life; two hypoattenuation scores correlated with birth weight. CONCLUSIONS: PRAGMA-BPD and the manual HU method have the best reproducibility for quantification of CT abnormalities in BPD.

Accelerometer-derived physical activity and sedentary time and cardiac biomarkers: The Maastricht Study.

Background: Cardiac troponins and NT-proBNP are biomarkers of cardiac injury that are used clinically in the diagnosis of myocardial infarction and heart failure. It is not known whether the amount, types and patterns of physical activity (PA) and sedentary behaviour are associated with levels of cardiac biomarkers. Methods: In the population-based Maastricht Study (n = 2,370, 51.3% male, 28.3% T2D) we determined cardiac biomarkers hs-cTnI, hs-cTnT, and NT-proBNP. PA and sedentary time were measured by activPAL and divided into quartiles [quartile 1 (Q1) served as reference]. The weekly pattern of moderate-to-vigorous PA (insufficiently active; regularly actives; weekend warriors) and coefficient of variation (CV) was calculated. Linear regression analyses were conducted with adjustment for demographic, lifestyle, and cardiovascular risk factors. Results: There was no consistent pattern between physical activity (different intensities: total, light, moderate-to-vigorous and vigorous) and sedentary time on the one hand and hs-cTnI and hs-cTnT on the other. Those with the highest levels of vigorous intensity PA had significantly lower levels of NT-proBNP. With regard to PA patterns, weekend warriors and regularly actives had lower levels of NT-proBNP but not with hs-cTnI and hs-cTnT (reference:insufficiently actives). A higher weekly moderate-to-vigorous PA CV (indicating more irregular activity) was associated with lower levels of hs-cTnI and higher levels of NT-proBNP, but not with hs-cTnT. Conclusions: In general, there was no consistent association between PA and sedentary time and cardiac troponins. In contrast, vigorous and possibly moderate-to-vigorous intensity PA, especially if done regularly, were associated with lower levels of NT-proBNP.

New diagnostic and treatment strategies in renal artery stenosis: a promising pursuit or disappointment foretold?

Clinical management of renal artery stenosis has seen a major shift, after randomised clinical trials have shown no group benefit of endovascular intervention relative to optimal medical control. However, the inclusion criteria of these trials have been criticised for focusing on a subset of patients with atherosclerotic renal artery stenosis where intervention was unlikely to be beneficial. Moreover, new imaging and computational techniques have become available, which have the potential to improve identification of patients that will respond to interventional treatment. This review addresses the challenges associated with clinical decision making in patients with renal artery stenosis. Opportunities for novel diagnostic techniques to improve patient selection are discussed, along with ongoing Dutch studies and network initiatives that investigate these strategies.

Determinants of DNA yield and purity collected with buccal cell samples.

Buccal cells are an important source of DNA in epidemiological studies, but little is known about factors that influence amount and purity of DNA. We assessed these factors in a self-administered buccal cell collection procedure, obtained with three cotton swabs. In 2,451 patients DNA yield and in 1,033 patients DNA purity was assessed. Total DNA yield ranged from 0.08 to 1078.0 microg (median 54.3 microg; mean 82.2 microg +/- SD 92.6). The median UV 260:280 ratio, was 1.95. Samples from men yielded significantly more DNA (median 58.7 microg) than those from women (median 44.2 microg). Diuretic drug users had significantly lower purity (median 1.92) compared to other antihypertensive drug users (1.95). One technician obtained significantly lower DNA yields. Older age was associated with lower DNA purity. In conclusion, DNA yield from buccal swabs was higher in men and DNA purity was associated with age and the use of diuretics.

Metformin use in type 2 diabetic patients is not associated with lower arterial stiffness: the Maastricht Study.

INTRODUCTION: Type 2 diabetes (T2D) is associated with cardiovascular disease complications such as myocardial infarction and stroke. These complications are at least partially the consequence of diabetes-associated increased arterial stiffness. Metformin, a first choice oral glucose-lowering drug, has been associated with potential cardio-protective effects. However, there are no data on the association between real-life metformin use and arterial stiffness. The objective of the current study is to investigate in a population-based sample of individuals with T2D the association between metformin use and aortic stiffness (i.e. carotid-femoral pulse wave velocity, cfPWV) and carotid stiffness [i.e. carotid distensibility coefficient and Young's elastic modulus (YEM)]. METHODS: We used data from The Maastricht Study, an ongoing observational prospective population-based cohort study (current N = 3451). All participants with T2D, based on pharmacy records (N = 672, 31.3% women, mean age 62.6 ±â€Š7.7), were included in the current study. Linear regression analyses were used to study the association between current metformin use and cfPWV, distensibility coefficient and YEM, as compared with no metformin use. Furthermore, metformin use was stratified by cumulative dose (in grams), continuous duration of use (in days), average daily dose (in grams) and time since first prescription (in years). Regression coefficients of distensibility coefficient were multiplied by -1, consequently, for all arterial stiffness indices, a positive regression coefficient signifies increasing arterial stiffness. RESULTS: Linear regression showed that neither current metformin use was associated with cfPWV [adjusted B: -0.04 (-0.11 to 0.02)] nor metformin use was as stratified by cumulative dose, by continuous duration of use, by average daily dose or by time since first prescription. Metformin use was statistically significantly associated with higher carotid stiffness as assessed by distensibility coefficient [0.12 (0.01 to 0.23)], but not with YEM [0.10 (-0.03 to 0.22)]. However, there was no consistent pattern with the different stratifications of metformin use when further investigating the association with distensibility coefficient. CONCLUSION: We showed that there is no significant association between current metformin use and aortic stiffness, regardless of how metformin use in itself was defined. In addition, metformin use was not associated with a lower carotid stiffness. The present results showed no beneficial effect of metformin use, dosage or duration on arterial stiffness in middle-aged patients with T2D. Alternatively, metformin may exerts its cardio-protective effects via other pathways.

[Practical questions related to self-measurement of blood pressure]. / Praktische vragen bij het zelfmeten van de bloeddruk.

The results of self-measurements of blood pressure predict the risk of developing cardiovascular disease better than those of blood pressure measurements taken at the GP surgery or hospital. In spite of the increasing availability of devices for home measurement, exactly how, by whom, with what and when, blood pressure should be measured at home remains unclear. Self-measurement is to be recommended as a supplement to conventional blood pressure measurement, as, in this way, the white-coat effect and masked hypertension can be recognized. Self-measurement is only useful if it is carried using a validated, automatic, sphygmomanometer and measured in the correct way. It is essential that the patient be clearly instructed on how to do this. A limit for home measurement of 135/85 mmHg should be adhered to. When blood pressure measurements taken at home lead to a different conclusion than those taken at hospital or GP surgery (and if there is no white-coat or masked hypertension), it is recommended that the procedure be repeated. If after this, there is still a discrepancy between the results of these two methods of blood pressure measurement, ambulatory 24-hour blood pressure measurement will perhaps provide the definitive answer to the 'real' level of the patient's blood pressure.

Changes in fibrinolytic activity after angiotensin II receptor blockade in therapy-resistant hypertensive patients.

BACKGROUND: In hypertensive patients, the activated renin-angiotensin system induces a prothrombotic state resulting from imbalance between coagulation and fibrinolysis. Although blood pressure cannot be regulated in therapy-resistant hypertensive patients, they may still be responsive to medication that attenuates the renin-angiotensin system. OBJECTIVE: our objective was to study possible attenuating properties of angiotensin II type 1 receptor blockers (AT1RBs) on the prothrombotic state in therapy-resistant hypertensive patients, focusing on parameters of fibrinolysis and coagulation. METHODS: Fourteen therapy-resistant hypertensive patients received AT1RB eprosartan infusion (45 and 150 microg kg(-1)) (study group), and 33 therapy-resistant hypertensive patients received saline (0.9%) infusion (control group) prior to renal angiography. Baseline values of parameters of coagulation and fibrinolysis were set at 1.00, and relative changes were calculated. RESULTS: Plasminogen activator inhibitor type 1 (PAI-1) antigen showed non-significant decreases in both the study group (arterial 1.00-0.45, venous 1.00-0.42) and control group (arterial 1.00-0.84, venous 1.00-0.88). PAI-1 activity significantly decreased in the study group (arterial 1.00-0.72, venous 1.00-0.71) and control group (arterial 1.00-0.83, venous 1.00-0.94). In the study group, tissue-type plasminogen activator (t-PA) antigen decreased significantly (arterial 1.00-0.62, venous 1.00-0.67), whereas t-PA activity significantly increased (arterial 1.00-6.15, venous 1.00-2.66). In the control group, t-PA antigen remained unchanged. No changes were observed in blood pressure during and after infusion of eprosartan. CONCLUSION: Therapy-resistant hypertensive patients show beneficial changes in fibrinolytic activity after infusion of a non-pressor dose of AT1RB.

The Asp299Gly Toll-like receptor 4 polymorphism in advanced aortic atherosclerosis.

BACKGROUND: Recently, the common Asp299Gly polymorphism of the Toll-like receptor 4 (TLR-4) was found to be associated with a reduced incidence of acute myocardial infarction and carotid atherosclerosis. As TLR-4 signalling is causally involved in atherogenesis, the polymorphism was postulated to impart protection from atherosclerosis. To explore a potential atheroprotective effect, we studied the association between the Asp299Gly polymorphism and atherosclerosis in hypertensive patients undergoing angiography for suspected renovascular disease. METHODS: 140 hypertensive subjects underwent intraarterial digital subtraction angiography, during which the presence of atherosclerotic lesions was assessed at the level of the abdominal aorta and renal arteries. Extensiveness of disease was classified as follows: atherosclerosis confined to the abdominal aorta, unilateral renal artery stenosis or bilateral renal artery stenosis. Subsequently, genotyping for the +896 A>G (Asp299Gly) single nucleotide polymorphism was performed in all patients. In statistical analyses 17 patients were excluded because of incomplete data (n=3) or a diagnosis of fibromuscular disease (n=14). RESULTS: 21 patients were found heterozygous for the 299Gly allele, whereas none of the subjects were 299Gly homozygous (299Gly allele frequency 7.8%). The prevalence of the 299Gly allele in atherosclerotic patients was not different from the prevalence observed in subjects without atherosclerotic lesions (16.9 vs 15.5%, p=0.83). Moreover, 299Gly carriership was not associated with the extensiveness of (advanced) aortic atherosclerosis (p=0.64). CONCLUSION: Our results suggest that the Asp299Gly TLR-4 receptor polymorphism is not associated with the prevalence nor extensiveness of (advanced) aortic atherosclerosis.

Ambulatory blood pressure, asymptomatic cerebrovascular damage and cognitive function in essential hypertension.

Prolonged exposure to elevated blood pressure (BP) can lead to both structural (white matter lesions (WML) or infarctions) and functional changes in the brain. We studied in previously diagnosed essential hypertensive individuals if diurnal BP variation and ambulatory BP (ABP) profile (daytime, night time and 24-h BP averages) were related to evidence of WML, the presence of 'silent' infarcts, and cognitive performance. A group of 86 patients (mean age 57.4+/-10 years, range 40-80) were first screened for hypertension-related organ damage and underwent 24-h ABP monitoring, magnetic resonance imaging (MRI) of the brain, and a comprehensive neurocognitive assessment. Age and ABP profile were related to more periventricular, but not subcortical, WML and to presence of lacunar infarctions on MRI. After correction for demographical group differences, no association was found between night time dipping of BP on the one hand and both WML load and cognitive parameters (verbal memory, sensorimotor speed, cognitive flexibility) on the other. The presence of lacunar infarctions, however, predicted lower performance on verbal memory. Furthermore, daytime and 24-h pulse pressure averages were associated with pWML, whereas systolic BP and mean arterial pressure (MAP) for daytime, night-time and 24-h periods were higher in patients with lacunar infarctions. Notwithstanding the large variability of WML in this sample, the evidence of a connection between diurnal BP variation and early target organ damage in the brain was not convincing. However, the ABP profile may be predictive of cerebral lesion type.

Safety and long-term effects of renal denervation: Rationale and design of the Dutch registry.

BACKGROUND: Percutaneous renal denervation (RDN) has recently been introduced as a treatment for therapy-resistant hypertension. Also, it has been suggested that RDN may be beneficial for other conditions characterised by increased sympathetic nerve activity. There are still many uncertainties with regard to efficacy, safety, predictors for success and long-term effects. To answer these important questions, we initiated a Dutch RDN registry aiming to collect data from all RDN procedures performed in the Netherlands. METHODS: The Dutch RDN registry is an ongoing investigator-initiated, prospective, multicentre cohort study. Twenty-six Dutch hospitals agreed to participate in this registry. All patients who undergo RDN, regardless of the clinical indication or device that is used, will be included. Data are currently being collected on eligibility and screening, treatment and follow-up. RESULTS: Procedures have been performed since August 2010. At present, data from 306 patients have been entered into the database. The main indication for RDN was hypertension (n = 302, 99%). Patients had a mean office blood pressure of 177/100 (±29/16) mmHg with a median use of three (range 0-8) blood pressure lowering drugs. Mean 24-hour blood pressure before RDN was 157/93 (±18/13) mmHg. RDN was performed with different devices, with the Simplicity™ catheter currently used most frequently. CONCLUSION: Here we report on the rationale and design of the Dutch RDN registry. Enrolment in this investigator-initiated study is ongoing. We present baseline characteristics of the first 306 participants.

Low density lipoprotein apheresis improves regional myocardial perfusion in patients with hypercholesterolemia and extensive coronary artery disease. LDL-Apheresis Atherosclerosis Regression Study (LAARS).

OBJECTIVES: In a randomized study we evaluated the effect of biweekly low density lipoprotein (LDL) apheresis plus simvastatin versus medication alone on regional myocardial perfusion. BACKGROUND: In patients with severe hypercholesterolemia, diet and lipid-lowering drugs are often insufficient to achieve optimal LDL cholesterol values. Low density lipoprotein apheresis is a very effective lipid-lowering therapy. Assessment of regional myocardial perfusion enables evaluation of the functional state of the coronary circulation. METHODS: We studied 42 patients with severe hypercholesterolemia and extensive coronary artery disease who were randomized to diet and simvastatin with or without biweekly LDL apheresis. Regional myocardial perfusion was assessed by digital subtraction angiography with videodensitometric calculation of hyperemic mean transit time (HMTT) of contrast medium at baseline and after 2 years of therapy. RESULTS: Low density lipoprotein cholesterol decreased by 63% (to 3.0 mmol/liter) in the LDL apheresis group and by 47% (to 4.1 mmol/liter) in the medication group. Paired HMTT measurements were assessed in 43 regions in the LDL apheresis group and 35 regions in the medication group. In the LDL apheresis group, regional HMTT decreased over 2 years from 3.35 +/- 1.18 (mean +/- SD) to 2.87 +/- 0.82 s (-14%, p = 0.001), whereas no change in the medication group was observed: 2.95 +/- 1.06 to 2.96 +/- 0.90 s (p = NS). In the patient-based comparison, the mean change in HMTT was -0.45 s (-14%, p = 0.01) in the LDL apheresis group and -0.05 s (-2%, p = NS) in the medication group, respectively. Only exercise-induced ischemia improved in the LDL apheresis group. CONCLUSIONS: Biweekly LDL apheresis plus simvastatin decreased time-averaged LDL cholesterol levels by an additional 31% (1.1 mmol/liter) compared with medication alone. After 2 years of therapy, regional myocardial perfusion improved in the LDL apheresis group and remained unchanged in the medication group. Thus, aggressive reduction of LDL cholesterol has a favorable effect on regional myocardial perfusion and alleviates ischemia.

C-reactive protein, atherosclerosis and kidney function in hypertensive patients.

Previous studies have shown a relationship between coronary or carotid atherosclerosis and C-reactive protein (CRP) concentrations. In the present investigation, we evaluated the relationship between high-sensitivity CRP (hsCRP) concentrations and the presence of atherosclerotic lesions in the renal arteries and/or abdominal aorta. In 95 hypertensive patients who underwent intra-arterial DSA on suspicion of renovascular disease, blood was sampled during the procedure for measurement of hsCRP. The presence of atherosclerotic lesions was assessed at the level of the renal arteries and the abdominal aorta. Haemodynamically significant renal artery stenosis was diagnosed when 50% or more stenosis was observed. Patients with fibromuscular disease (n = 8) or incomplete data (n = 4) were excluded from analysis. The results revealed that the median hsCRP concentrations were significantly higher among the 57 patients with atherosclerosis of the aorta and/or renal arteries compared to those in the 26 patients without any angiographic lesions (4.6 vs 1.7 mg/l; P < 0.005). Moreover, in patients with renal artery stenosis, levels of hsCRP were higher when the degree of stenosis exceeded 50%. However, the association between hsCRP and the presence of atherosclerosis appeared to be confounded by serum creatinine, creatinine clearance, age and gender. In the whole group a significant inverse relationship was found between creatinine clearance and hsCRP (P < 0.05). In conclusion, hsCRP concentrations are related to atherosclerotic lesions in the renal arteries and the abdominal aorta. While this supports the view that atherosclerotic renal artery stenosis is part of a systemic inflammatory vascular disease, increased concentrations of CRP may also coincide with decreased renal function.

Regional differences in cardiovascular risk factor profile cannot fully explain differences in cardiovascular morbidity in the Netherlands: a comparison of two urban areas.

BACKGROUND: Our objective was to investigate whether a region in the south of the Netherlands (Heerlen/Kerkrade) had a high burden of cardiovascular disease in comparison with a nearby region (Maastricht) and the average Dutch population, respectively. We also wanted to determine if there are interregional differences in cardiovascular risk factor profile. DESIGN: Cross-sectional study. METHODS: Data from a nationwide registry (CBS) were used to analyse cardiovascular mortality in the two regions and the average in the Netherlands. Data from a primary care morbidity registration network (RNH) were used to compare cardiovascular morbidity and cardiovascular risk factors in both regions. A standardisation procedure was carried out for age and sex. Data were analysed using logistic regression analyses. RESULTS: The overall cardiovascular mortality rate was higher in the Heerlen/Kerkrade region (7.8 per thousand) compared with Maastricht (6.1 per thousand, OR=1.3, 95% CI 1.2-1.5) and the average in the Netherlands (5.7 per thousand). Similarly, most cardiovascular morbidity rates for Heerlen/Kerkrade were more elevated compared with the RNH overall and with Maastricht. Prevalence rates of risk factors such as diabetes mellitus (7.2%, OR=1.5, 95% CI 1.3-1.7) and overweight (10.8%, OR= 2.0, 95% CI 1.8-2.2) were significantly higher in the Heerlen/Kerkrade region compared with Maastricht. There were no differences with regard to hypertension (15.2%, OR=1.0, 95% CI 0.9-1.1). CONCLUSION: Heerlen/Kerkrade is indeed a region with a high burden of cardiovascular disease. Differences in morbidity between Heerlen/Kerkrade and Maastricht cannot be fully explained by differences in cardiovascular risk factor profile.

Effects of brain natriuretic peptide on forearm vasculature: comparison with atrial natriuretic peptide.

OBJECTIVE: The aim of the present study was to determine the vasoactive effects of brain natriuretic peptide (BNP) as compared to those of atrial natriuretic peptide (ANP) in normal man. METHODS: Ten healthy male subjects (median age 21 (20-23) year) were studied twice. In the first study equimolar doses (1, 3, and 10 pmol/dl/min) of both BNP and ANP (in random order and double blind) were infused into the brachial artery of the non-dominant arm with a 1-h wash-out period in between. In the second study two BNP (n = 5) or ANP (n = 5) dose-response curves were performed in order to assess the repeatability of the BNP/ANP infusions. To this end, BNP and ANP were infused in the same equimolar doses as in the first protocol. Forearm blood flow (FBF) was determined by venous occlusion plethysmography before and during infusions. RESULTS: BNP increased the FBF ratio (infused/contralateral arm) by 6%, 17%, and 48%, respectively (p < 0.05), while ANP increased the FBF ratio by 4%, 58%, and 133% (p < 0.001). The slopes of the BNP dose-response curves differed significantly from those of the ANP curves (18.1 versus 43.2; p = 0.022). No differences were observed between the repeated dose-response curves of either BNP or ANP. CONCLUSIONS: The present data demonstrate that BNP induces a dose-dependent vasodilatation in man. On a molar basis, however, this vasodilatation is significantly less than the vasodilatation induced by ANP. These differences may be related to differences in natriuretic-peptide-receptor affinity. Furthermore, our data show that the vasoactive effects of both BNP and ANP are repeatable in time.