Blerim Mujaj

Association of office and ambulatory blood pressure with blood lead in workers before occupational exposure

In view of decreasing lead exposure and guidelines endorsing ambulatory above office blood pressure (BP) measurement, we reassessed association of BP with blood lead (BL) in 236 newly employed men (mean age, 28.6xa0years) without previous lead exposure not treated for hypertension. Office BP was the mean of five auscultatory readings at one visit. Twenty-four-hour BP was recorded at 15- and 30-minute intervals during wakefulness and sleep. BL was determined by inductively coupled plasma mass spectrometry. Systolic/diastolic office BP averaged 120.0/80.7xa0mm Hg, and the 24-hour, awake, and asleep BP 125.5/73.6, 129.3/77.9, and 117.6/65.0xa0mm Hg, respectively. The geometric mean of blood lead was 4.5xa0μg/dL (interquartile range, 2.60-9.15xa0μg/dL). In multivariable-adjusted analyses, effect sizes associated with BL doubling were 0.79/0.87xa0mm Hg (Pxa0=xa0.11/.043) for office BP and 0.29/-0.25, 0.60/-0.10, and -0.40/-0.43xa0mm Hg for 24-hour, awake, and asleep BP (Pxa0≥xa0.33). Neither office nor 24-hour ambulatory hypertension was related to BL (Pxa0≥xa0.14). A clinically relevant white coat effect (WCE; office minus awake BP, ≥20/≥10xa0mm Hg) was attributable to exceeding the systolic or diastolic threshold in 1 and 45 workers, respectively. With BL doubling, the systolic/diastolic WCE increased by 0.20/0.97xa0mm Hg (Pxa0=xa0.57/.046). Accounting for the presence of a diastolic WCE, reduced the association size of office diastolic BP with BL to 0.39xa0mm Hg (95% confidence interval, -0.20 to 1.33; Pxa0=xa0.15). In conclusion, a cross-sectional analysis of newly hired workers before lead exposure identified the WCE as confounder of the association between office BP and BL and did not reveal any association between ambulatory BP and BL.

Associations of Endogenous Estradiol and Testosterone Levels with Plaque Composition and Risk of Stroke in Subjects with Carotid Atherosclerosis

Rationale: Sex steroids may play a role in plaque composition and in stroke incidence. Objectives: To study the associations of endogenous estradiol and testosterone with carotid plaque composition in elderly men and postmenopausal women with carotid atherosclerosis, as well as with risk of stroke in this population. Methods and Results: Data of 1023 postmenopausal women and 1124 men (≥45 years) with carotid atherosclerosis, from prospective population-based RS (Rotterdam Study), were available. At baseline, total estradiol (TE) and total testosterone (TT) were measured. Carotid atherosclerosis was assessed by ultrasound, whereas plaque composition (presence of calcification, lipid core, and intraplaque hemorrhage) was assessed by magnetic resonance imaging. TE and TT were not associated with calcified carotid plaques in either sex. TE was associated with presence of lipid core in both sexes (in women odds ratio, 1.48 [95% confidence interval [CI], 1.02–2.15]; in men odds ratio, 1.23 [95% CI, 1.03–1.46]), whereas no association was found between TT and lipid core in either sex. Higher TE (odds ratio, 1.58 [95% CI, 1.03–2.40]) and lower TT (odds ratio, 0.82 [95% CI, 0.68–0.98]) were associated with intraplaque hemorrhage in women but not in men. In women, TE was associated with increased risk of stroke (hazard ratio, 1.98 [95% CI, 1.01–3.88]), whereas no association was found in men. TT was not associated with risk of stroke in either sex. Conclusions: TE was associated with presence of vulnerable carotid plaque as well as increased risk of stroke in women, whereas no consistent associations were found for TT in either sex.

Comparison of CT and CMR for detection and quantification of carotid artery calcification: the Rotterdam Study

BackgroundCarotid artery atherosclerosis is an important risk factor for stroke. As such, quantitative imaging of carotid artery calcification, as a proxy of atherosclerosis, has become a cornerstone of current stroke research. Yet, population-based data comparing the computed tomography (CT) and cardiovascular magnetic resonance (CMR) for the detection and quantification of calcification remain scarce.MethodsA total of 684 participants from the population-based Rotterdam Study underwent both a CT and CMR of the carotid artery bifurcation to quantify the amount of carotid artery calcification (mean interscan interval: 4.9u2009±u20091.2xa0years). We investigated the correlation between the amount of calcification measured on CT and CMR using Spearman’s correlation coefficient, Bland-Altman plots, and linear regression. In addition, using logistic regression modeling, we assessed the association of CT and CMR based calcification volumes with a history of stroke.ResultsWe found a strong correlation between CT and CMR based calcification volumes (Spearman’s correlation coefficient:0.86, p-value ≤0.01). Bland-Altman analyses showed a good agreement, though CT based calcification volumes were systematically larger. Finally, calcification volume assessed with either imaging modality was associated with a history of stroke with similar effect estimates (odds ratio (OR) per 1-SD increase in calcification volume: 1.52 (95% CI:1.00;2.30) for CT, and 1.47 (95% CI:1.01;2.14) for CMR.ConclusionCT based and CMR based volumes of carotid artery calcification are highly correlated, but CMR based calcification is systematically smaller than those obtained with CT. Despite this difference, both provide comparable information with regard to a history of stroke.

Urinary Proteomics in Predicting Heart Transplantation Outcomes (uPROPHET)-Rationale and database description

Objectives Urinary Proteomics in Predicting Heart Transplantation Outcomes (uPROPHET; NCT03152422) aims: (i) to construct new multidimensional urinary proteomic (UP) classifiers that after heart transplantation (HTx) help in detecting graft vasculopathy, monitoring immune system activity and graft performance, and in adjusting immunosuppression; (ii) to sequence UP peptide fragments and to identify key proteins mediating HTx-related complications; (iii) to validate UP classifiers by demonstrating analogy between UP profiles and tissue proteomic signatures (TP) in diseased explanted hearts, to be compared with normal donor hearts; (iv) and to identify new drug targets. This article describes the uPROPHET database construction, follow-up strategies and baseline characteristics of the HTx patients. Methods HTx patients enrolled at the University Hospital Gasthuisberg (Leuven) collected mid-morning urine samples. Cardiac biopsies were obtained at HTx. UP and TP methods and the statistical work flow in pursuit of the research objectives are described in detail in the Data supplement. Results Of 352 participants in the UP study (24.4% women), 38.9%, 40.3%, 5.7% and 15.1% had ischemic, dilated, hypertrophic or other cardiomyopathy. The median interval between HTx and first UP assessment (baseline) was 7.8 years. At baseline, mean values were 56.5 years for age, 25.2 kg/m2 for body mass index, 142.3/84.8 mm Hg and 124.2/79.8 mm Hg for office and 24-h ambulatory systolic/diastolic pressure, and 58.6 mL/min/1.73 m2 for the estimated glomerular filtration rate. Of all patients, 37.2% and 6.5% had a history of mild (grade = 1B) or severe (grade ≥ 2) cellular rejection. Anti-body mediated rejection had occurred in 6.2% patients. The number of follow-up urine samples available for future analyses totals over 950. The TP study currently includes biopsies from 7 healthy donors and 15, 14, and 3 patients with ischemic, dilated, and hypertrophic cardiomyopathy. Conclusions uPROPHET constitutes a solid resources for UP and TP research in the field of HTx and has the ambition to lay the foundation for the clinical application of UP in risk stratification in HTx patients.

Statin use is associated with carotid plaque composition: The Rotterdam Study

BACKGROUNDnStatins represent a key treatment for cardiovascular disease. Nevertheless, the direct effects of statin treatment on the composition of atherosclerotic plaques remain elusive.nnnOBJECTIVESnWe aimed to investigate the association of statin treatment with the presence of different plaque components located in the carotid arteries within a population-based setting.nnnMETHODSnFrom the population-based Rotterdam Study, 1740 participants with carotid atherosclerosis (mean age 72.9u202fyears, 46% women) underwent MRI of the carotid arteries to determine the presence of calcification, lipid core, and intraplaque hemorrhage. Information for the duration and dosage of statin use was obtained from pharmacy records for all participants. We used logistic regression models to study the association of statin use with the presence of plaque components.nnnRESULTSnStatin treatment was associated with a higher presence of calcification (OR: 1.73 [95% CI: 1.22-2.44]). Longer duration of use strengthened this association (OR: 1.82 [95% CI: 1.00-3.33] for 10 to 48u202fmonths, and OR 1.74 [95% CI: 1.09-2.77] for >48u202fmonths, compared to OR: 1.65 [95% CI: 0.94-2.89] for ≤10u202fmonths). Current statin treatment was also associated with a lower presence of lipid core (OR: 0.66 [95% CI: 0.42-1.04]), but only when using statins for 10u202fmonths or less. Any dosage of statins was associated with a higher presence of calcification, whilst only high dosages (DDDu202f>u202f1.33) were associated with a lower presence of lipid core.nnnCONCLUSIONSnActive, high-dosage statin use seems to beneficially influence the composition of carotid atherosclerosis by shifting the composition from vulnerable plaque with a lipid core to more stable calcified plaque.

Antithrombotic treatment is associated with intraplaque haemorrhage in the atherosclerotic carotid artery: a cross-sectional analysis of The Rotterdam Study

Abstract Aims Antithrombotic treatment plays a key role in stroke prevention, but their direct effects on the composition of carotid artery atherosclerotic plaques are unknown. To investigate the association of antithrombotic treatment with carotid artery plaque composition, with a specific focus on an intraplaque haemorrhage (IPH). Methods and results From the population-based Rotterdam Study, 1740 participants with carotid atherosclerosis on ultrasound (mean age 72.9u2009years, 46.0 women) underwent magnetic resonance imaging of the carotid arteries to assess plaque composition. Information on the use of oral anticoagulants [vitamin K antagonists (VKA)] and antiplatelet agents (salicylates), including duration of use and dosage, was obtained from pharmacy records for all participants. We used logistic regression models to assess the association between the use of anticoagulants and antiplatelet agents, and the different plaque components adjusting for confounders. Current and past use of VKA [adjusted odds ratio (OR): 1.88, 95% confidence interval (CI): 0.74–4.75 and OR 1.89, 95% CI: 0.91–3.93] and antiplatelet agents (OR: 1.22, 95% CI: 0.91–1.62), and (OR: 1.23, 95% CI: 0.86–1.75) showed positive trend with a higher presence of IPH. Also, a longer duration of use was associated with a higher frequency of IPH (OR: 3.15, 95% CI: 1.23–8.05) for the use of VKA, and longer duration of the use for antiplatelet agents showed a positive trend (OR: 1.21, 95% CI: 0.88–1.67). We also found that higher levels of international normalized ratio above 2.97 for VKA (OR: 1.48, 95% CI: 1.03–2.15) and higher daily defined dosage than 1.0 for antiplatelet agents (OR: 1.50, 95% CI: 1.21–1.87) were related to a higher frequency of IPH. We found no association with lipid core or calcification. Conclusions The use of antithrombotic treatment relates to a higher frequency of IPH in carotid atherosclerotic plaques.

ECG Voltage in Relation to Peripheral and Central Ambulatory Blood Pressure

Abstract BACKGROUND The heart ejects in the central elastic arteries. No previous study in workers described the diurnal profile of central blood pressure (BP) or addressed the question whether electrocardiogram (ECG) indexes are more closely associated with central than peripheral BP. METHODS In 177 men (mean age, 29.1 years), we compared the associations of ECG indexes with brachial and central ambulatory BP, measured over 24 hours by the validated oscillometric Mobil-O-Graph 24h PWA monitor. RESULTS From wakefulness to sleep, as documented by diaries, systolic/diastolic BP decreased by 11.7/13.1 mm Hg peripherally and 9.3/13.6 mm Hg centrally, whereas central pulse pressure (PP) increased by 4.3 mm Hg (P < 0.0001). Over 24 hours and the awake and asleep periods, the peripheral-minus-central differences in systolic/diastolic BPs averaged 11.8/–1.6, 12.7/–1.8, and 10.3/–1.2 mm Hg, respectively (P < 0.0001). Cornell voltage and index averaged 1.18 mV and 114.8 mV·ms. Per 1-SD increment in systolic/diastolic BP, the Cornell voltages were 0.104/0.086 mV and 0.082/0.105 mV higher in relation to brachial 24-hour and asleep BP and 0.088/0.90 mV and 0.087/0.107 mV higher in relation to central BP. The corresponding estimates for the Cornell indexes were 9.6/8.6 and 8.2/10.5 mV·ms peripherally and 8.6/8.9 and 8.8/10.7 mV·ms centrally. The regression slopes (P ≥ 0.067) and correlation coefficients (P ≥ 0.088) were similar for brachial and central BP. Associations of ECG measurements with awake BP and PP were not significant. CONCLUSIONS Peripheral and central BPs run in parallel throughout the day and are similarly associated with the Cornell voltage and index.

Inactive matrix Gla protein is a novel circulating biomarker predicting retinal arteriolar narrowing in humans

Active matrix Gla protein (MGP), a potent inhibitor of calcification in large arteries, protects against macrovascular complications. Recent studies suggested that active MGP helps maintaining the integrity of the renal and myocardial microcirculation, but its role in preserving the retinal microcirculation remains unknown. In 935 randomly recruited Flemish participants (mean age, 40.9 years; 50.3% women), we measured plasma desphospho-uncarboxylated MGP (dp–ucMGP), a marker of poor vitamin K status using an ELISA-based assay at baseline (1996–2010) and retinal microvascular diameters using IVAN software (Vasculomatic ala Nicola, version 1.1) including the central retinal arteriolar (CRAE) and venular (CRVE) equivalent and the arteriole-to-venule ratio (AVR) at follow-up (2008–2015). CRAE (Pu2009=u20090.005) and AVR (Pu2009=u20090.080) at follow-up decreased across tertiles of the dp–ucMGP distribution. In unadjusted models, for a doubling of dp–ucMGP at baseline, CRAE and AVR at follow-up respectively decreased by 1.40u2009µm (95% confidence interval [CI], 0.32 to 2.48; Pu2009=u20090.011) and 0.006 (CI, 0.001 to 0.011; Pu2009=u20090.016). In multivariable-adjusted models accounting for sex, baseline characteristics and follow-up duration, these estimates were −1.03u2009µm (CI, −1.96 to −0.11; Pu2009=u20090.028) and −0.007 (CI, −0.011 to −0.002; Pu2009=u20090.007). Additional adjustment for changes from baseline to follow-up in major baseline characteristics yielded as estimates −0.91u2009µm (CI, −1.82 to −0.01; Pu2009=u20090.048) and −0.006 (95% CI, −0.011 to −0.001; Pu2009=u20090.014), respectively. Circulating inactive dp–ucMGP is a long-term predictor of smaller retinal arteriolar diameter in the general population. Our observations highlight the possibility that vitamin K supplementation might promote retinal health.

Renal function in relation to low-level environmental lead exposure

Abstract Background Numerous studies suggested that occupational or environmental exposure to lead adversely affects renal function. However, most studies lost relevance because of the substantially lower current environmental lead exposure and all relied on serum creatinine to estimate glomerular filtration. We investigated the association of estimated glomerular filtration rate (eGFR), estimated from serum creatinine, cystatin C or both, with blood lead (BPb) using the baseline measurements of the ongoing Study for Promotion of Health in Recycling Lead (SPHERL; NCT02243904) in newly hired workers prior to significant occupational lead exposure. Methods Among 447 men (participation rate, 82.7%), we assessed the association of eGFR and the urinary albumin-to-creatinine ratio (ACR) with BPb across thirds of the BPb distribution using linear regression analysis. Fully adjusted models accounted for age, blood pressure, body mass index, the waist-to-hip ratio, smoking, the total-to-high-density-lipoprotein ratio, plasma glucose, serum γ-glutamyltransferase and antihypertensive drug treatment. Results Age averaged 28.7 (SD, 10.2) years (range, 19.1–31.8). Geometric mean BPb concentration was 4.34 μg/dL (5th–95th percentile interval, 0.9–14.8). In unadjusted and adjusted analyses, eGFR estimated from serum creatinine [mean (SD), 105.26 (15.2) mL/min/1.73 m2], serum cystatin C [mean (SD), 127.8 (13.8) mL/min/1.73 m2] or both [mean (SD), 111.9 (14.8) mL/min/1.73 m2] was not associated with BPb (P u2009≥ u20090.36), whereas ACR [geometric mean, 4.32u2009mg/g (5th–95th percentile interval, 1.91–12.50)] was lower with higher BPb. Conclusions At the BPb levels observed in this study, there was no evidence for an association between renal function and lead exposure.

The rationale and design of reduction of uncontrolled hypertension by Remote Monitoring and Telemedicine (REMOTE) study

Abstract Purpose: Although self-measurement of home blood pressure (HBP) is common in Japan and HBP telemonitoring via the Internet is possible, whether telemonitoring improves HBP control better than conventional practice remains unclear. Furthermore, hypertension care with online communication using telemonitored HBP is feasible, whereas the efficacy and safety of such telemedicine have not been established. We aim to compare traditional care, care with office visits using HBP telemonitoring, and antihypertensive telemedicine based on HBP telemonitoring. Methods and design: In total, 444 patients with uncontrolled hypertension will be recruited and randomly assigned to three groups: (1) control: usual care with office visits and HBP self-report, (2) telemonitoring: weekly assessment of transmitted HBP by physicians and treatment adjustment upon office visits, or (3) telemedicine: online communication instead of office visits to adjust medication using telemonitored HBP. Primary outcome is the time to control of HBP, and secondary outcomes include achieved HBP levels, adherence, treatment intensity, adverse events, patient satisfaction and cost-effectiveness. Discussion: Hypertension care with telemonitoring and telemedicine are expected to require shorter time to achieve HBP control compared to usual care. Combining HBP telemonitoring with telemedicine may lower the hurdles for starting and persisting to hypertension treatment and eventually reduce cardiovascular events.