One-year outcome and durability of pulmonary vein isolation after prospective use of ablation index for catheter ablation in patients with persistent atrial fibrillation.

BACKGROUND: Radiofrequency (RF) catheter ablation for persistent atrial fibrillation (peAF) is associated with less favorable outcomes than for paroxysmal AF (PAF). Recent studies have shown improved clinical outcomes with use of ablation index (AI) targets for pulmonary vein isolation (PVI) in PAF. AI is a novel ablation quality marker that incorporates contact force (CF), time, and power in a weighted formula. This is a single-arm registry to investigate the 1-year efficacy of AF ablation guided by the AI in patients with peAF, and further to evaluate pulmonary vein reconduction at repeat electrophysiology study in case of recurrent AF. METHODS: In total, 55 consecutive patients (69 ± 10 years, 55% male, median time since first AF diagnosis: 31 months (Q1-Q3: 10-70)) with peAF underwent AIguided PVI using a CF surround-flow catheter. AI targets were 600 for anterior and 450 for roof/posterior/inferior antral segments. Patients were monitored for atrial tachyarrhythmia recurrence using 5-day Holter-ECG recordings at 3, 6, and 12 months. RESULTS: The median procedure time was 173 min (Q1-Q3: 152-204). The median fluoroscopy time was 4 min (Q1-Q3: 3-6) and the median fluoroscopy dose was 2.64 Gy/cm2 (Q1-Q3: 1.04-3.99). The median ablation time was 57 min (Q1-Q3: 47-63). At 12 months, 42% of the patients were in sinus rhythm. AF recurrence was seen in 58% of patients. No major complications occurred. CONCLUSIONS: RF ablation using AI in peAF is a feasible and safe technique. At 1 year, AI-guided ablation was associated with AF recurrence in 58% of the patients.

Air Pollution and Progression of Atherosclerosis in Different Vessel Beds-Results from a Prospective Cohort Study in the Ruhr Area, Germany.

OBJECTIVES: Due to inconsistent epidemiological evidence on health effects of air pollution on progression of atherosclerosis, we investigated several air pollutants and their effects on progression of atherosclerosis, using carotid intima media thickness (cIMT), coronary calcification (CAC), and thoracic aortic calcification (TAC). METHODS: We used baseline (2000-2003) and 5-y follow-up (2006-2008) data from the German Heinz Nixdorf Recall cohort study, including 4,814 middle-aged adults. Residence-based long-term air pollution exposure, including particulate matter (PM) with aerodynamic diameter ≤2.5µm (PM2.5), (PM10), and nitrogen dioxide (NO2) was assessed using chemistry transport and land use regression (LUR) models. cIMT was quantified as side-specific median IMT assessed from standardized ultrasound images. CAC and TAC were quantified by computed tomography using the Agatston score. Development (yes/no) and progression of atherosclerosis (change in cIMT and annual growth rate for CAC/TAC) were analyzed with logistic and linear regression models, adjusting for age, sex, lifestyle variables, socioeconomic status, and traffic noise. RESULTS: While no clear associations were observed in the full study sample (mean age 59.1 (±7.6) y; 53% female), most air pollutants were marginally associated with progression of atherosclerosis in participants with no or low baseline atherosclerotic burden. Most consistently for CAC, e.g., a 1.5 µg/m3 higher exposure to PM2.5 (LUR) yielded an estimated odds ratio of 1.19 [95% confidence interval (CI): 1.03, 1.39] for progression of CAC and an increased annual growth rate of 2% (95% CI: 1%, 4%). CONCLUSION: Our study suggests that development and progression of subclinical atherosclerosis is associated with long-term air pollution in middle-aged participants with no or minor atherosclerotic burden at baseline, while overall no consistent associations are observed. https://doi.org/10.1289/EHP7077.

Investigation of air pollution and noise on progression of thoracic aortic calcification: results of the Heinz Nixdorf Recall Study.

AIMS: Air pollution and noise are potential risk factors for subclinical atherosclerosis. Longitudinal analyses, especially on the interplay of these environmental factors, are scarce and inconsistent. Hence we investigated long-term traffic-related exposure to air pollution and noise with the development and progression of thoracic aortic calcification, a marker of subclinical atherosclerosis. METHODS: We used baseline (2000-2003) and follow-up (2006-2008) data from the German Heinz Nixdorf Recall cohort study, including 4814 middle-aged adults. Residence-based air pollution (PM2.5 (aerodynamic diameter ≤ 2.5 µm), PM10, nitrogen dioxide and particle number), and noise was assessed with dispersion models. Thoracic aortic calcification was quantified from non-contrast enhanced electron beam computed tomography. The presence and extent of thoracic aortic calcification progression were analysed with multiple logistic and linear regression models, respectively, adjusting for age, sex, lifestyle variables, socioeconomic status and respective co-exposure. RESULTS: We observed no association in the full study sample (n = 3155, mean age 59.1 (±7.6) years, 52.8% women). While an interquartile range in particle number and night-time noise yielded odds ratios of 1.20 (1.03, 1.40) and 1.21 (1.00, 1.46) for binary thoracic aortic calcification progression, and 0.02 (-0.01, 0.05) and 0.04 (0.00, 0.07) higher growth rates of thoracic aortic calcification in participants with baseline thoracic aortic calcification less than 10, negative findings were observed in those with baseline thoracic aortic calcification of 10 or greater. Results were similar for other pollutants and daytime noise. CONCLUSION: Our study shows no overall associations. Subgroup analyses suggest independent associations of traffic-related air pollution and noise with the development and progression of subclinical atherosclerosis in participants with no or minor thoracic aortic calcification at baseline, in contrast to negative findings in those with advanced calcification.

Cardiovascular Risk and Atherosclerosis Progression in Hypertensive Persons Treated to Blood Pressure Targets.

Arterial hypertension promotes atherosclerosis and cardiovascular events. We evaluated how cardiovascular risk and atherosclerosis progression are associated with blood pressure, antihypertensive treatment, and treatment efficacy. In 3555 participants of the population-based Heinz Nixdorf Recall study without previous cardiovascular disease (mean±SD; age, 58.9±7.6 years, 46.9% men), we analyzed associations of baseline antihypertensive treatment efficacy (normotension without antihypertensives, normotension with antihypertensives, hypertension without antihypertensives, hypertension with antihypertensives, based on 140/90 mmHg cutoffs) with incident coronary artery calcification (CAC) and CAC progression during 5-year-follow-up and with incident cardiovascular events during 13.5-year-follow-up. We further evaluated associations of incident arterial hypertension and efficacy of new antihypertensive treatment at the 5-year-follow-up with subsequent cardiovascular events. At baseline, 1706 participants had normotension without antihypertensives, 553 normotension with antihypertensives, 786 hypertension without antihypertensives, and 510 hypertension with antihypertensives. Six hundred forty-seven participants experienced rapid CAC progression. One hundred seven, 132, and 249 had incident stroke, coronary event, and cardiovascular event, respectively. Compared with normotensives without antihypertensives, normotensives with antihypertensives had an elevated stroke (hazard ratio, 2.33 [95% CI, 1.19-4.55]), coronary (2.04 [95% CI, 1.20-3.45]), and cardiovascular (2.23 [95% CI, 1.48-3.36]) risk, and increased baseline CAC, but not increased CAC progression. Participants without hypertension at baseline, who were newly hypertensive but achieved normotension with antihypertensives at the 5-year-follow-up, again exhibited elevated stroke (4.80 [95% CI, 1.38-16.70]) and cardiovascular (2.99 [95% CI, 1.25-7.16]) risk, whereas coronary risk was less elevated (2.24 [95% CI, 0.70-7.18]). Normotensives with antihypertensives have an elevated cardiovascular risk. They are characterized by elevated baseline CAC but show no signs of increased CAC progression.

HDAC9 is implicated in atherosclerotic aortic calcification and affects vascular smooth muscle cell phenotype.

Aortic calcification is an important independent predictor of future cardiovascular events. We performed a genome-wide association meta-analysis to determine SNPs associated with the extent of abdominal aortic calcification (n = 9,417) or descending thoracic aortic calcification (n = 8,422). Two genetic loci, HDAC9 and RAP1GAP, were associated with abdominal aortic calcification at a genome-wide level (P < 5.0 × 10-8). No SNPs were associated with thoracic aortic calcification at the genome-wide threshold. Increased expression of HDAC9 in human aortic smooth muscle cells promoted calcification and reduced contractility, while inhibition of HDAC9 in human aortic smooth muscle cells inhibited calcification and enhanced cell contractility. In matrix Gla protein-deficient mice, a model of human vascular calcification, mice lacking HDAC9 had a 40% reduction in aortic calcification and improved survival. This translational genomic study identifies the first genetic risk locus associated with calcification of the abdominal aorta and describes a previously unknown role for HDAC9 in the development of vascular calcification.

Association of progressive thoracic aortic calcification with future cardiovascular events and all-cause mortality: ability to improve risk prediction? Results of the Heinz Nixdorf Recall (HNR) study.

AIMS: Thoracic aortic calcification (TAC) is measured by computed tomography (CT). We investigated the association of TAC-progression with incident cardiovascular (CV) events and all-cause mortality in a population-based cohort and to determine its predictive value for these endpoints. METHODS AND RESULTS: In 3080 participants (45-74 years, 53.6% women), risk factors and TAC via CT were measured at baseline and at a second examination after 5.1 ± 0.3 years. Hard coronary, hard CV events as well as CV events including revascularization and all-cause mortality were recorded during a follow-up time of 7.8 ± 2.2 years after the second CT scan. Cox regression analysis determined the association of TAC-progression with observed endpoints. The predictive value of TAC-progression was assessed using Harrell's C index. We observed 81 hard coronary, 154 hard CV, 231 CV events including revascularization, and 266 deaths. In the crude analysis, event rates increased continuously with the level of TAC-change over 5 years for all endpoints. After adjustment, the significant association of TAC-progression with hard CV events [hazard ratio (HR) 1.28, 95% confidence interval (CI) 1.05-1.57] and all-cause mortality (HR 1.34, 95% CI 1.14-1.58) persisted, per one standard deviation increase in TAC-progression (log(TAC + 1)). Regarding aortic segments separately, HRs were consistently higher for descending thoracic aorta. When adding TAC (baseline and progression) to the model containing classical risk factors and coronary artery calcification (CAC), Harrell's C indices did not increase for any of the observed endpoints. CONCLUSION: TAC-progression is associated with incident hard CV events and all-cause mortality but fails to improve event prediction over CAC.

The BioMonitor 2 insertable cardiac monitor: Clinical experience with a novel implantable cardiac monitor.

INTRODUCTION: Implantable loop recorders (ILR) are leadless subcutaneous devices that allow cardiac monitoring for up to 3 years and are a valuable tool in the diagnosis of arrhythmias, cryptogenic stroke and unexplained syncope. The Biotronik BioMonitor 2 is a novel, insertable ILR allowing long-term continuous monitoring with wireless telemetry options. METHODS: A single-center, prospective, observational study investigating the reliability of sensing quality and detection performance in the BioMonitor 2 ILR, as well as post-implantation patient satisfaction. R-wave amplitude was recorded immediately post implantation and 1 day post implantation, followed by extensive patient instruction. Follow-up was scheduled after 3 months, or after an event. Data from the ILR were retrieved, with documentation of all episodes, R-wave amplitude and noise burden. The anatomical position of the ILR was determined 1 day post implantation and after 3 months. A patient questionnaire was conducted after 3 months. RESULTS: 30 consecutive patients (mean age 71 ±â€¯12 years, 56% male) were analyzed. Indications for ILR implantation were: unexplained syncope (n = 24, 80%), suspected atrial fibrillation (n = 4, 13%), cryptogenic stroke (n = 1, 3%) and palpitations (n = 1, 3%). Median time from skin cut to suture was 8 min. No complications occurred. Mean R-wave amplitude at implantation was 0.84 ±â€¯0.32 mV, at day 1 post implantation 0.96 ±â€¯0.31 mV, and after a mean follow-up of 85 ±â€¯24 days 1.02 ±â€¯0.47 mV (p = 0.01). The mean noise burden was 1.4 ±â€¯2%. CONCLUSION: Implantation of the novel BioMonitor 2 ILR is fast and uncomplicated. Initial sensing values are good and improve over time.

Initial experience of percutaneous left atrial appendage closure using the LAmbre device for thromboembolic prevention.

AIMS: Stroke due to atrial fibrillation has been associated with a high risk of disability and mortality. Percutaneous left atrial appendage (LAA) closure has been established as an alternative strategy for stroke prevention in patients not eligible for oral anticoagulation. The LAmbre is a novel occluder, specifically designed for LAA closure adaptive to various LAA anatomies. The aim of this study was to demonstrate feasibility and initial experience in a nonprescreened patient cohort for LAA occlusion using the novel LAmbre occluder. METHODS: The device was implanted in 11 patients with nonvalvular atrial fibrillation. Follow-up included transesophageal echocardiography and an outpatient visit at 6 weeks and 6 months after implantation. RESULTS: All devices were implanted successfully. Device sizes ranged from 16/22 to 22/34 mm. Patients' mean CHA2DS2-VASc and HAS-BLED scores were 3.3 ±â€Š1.0 and 3.2 ±â€Š1.0, respectively. Two out of 11 patients had previously been rejected for Watchman occluder implantation by reasons of too small LAA. At 6 weeks and 6 months, there were no deaths, strokes, systemic thromboembolism or severe bleeding complications. There was no device-related thrombus or pericardial effusion seen with transesophageal echocardiography. In one out of 11 patients, a minimal peridevice flow (less than 5 mm) was present at 6-week follow-up. CONCLUSION: The LAmbre occluder is a novel LAA-closure device with features that provide many options for LAA-closure to physicians, particularly in patients with challenging anatomies. From our initial experience, implantation is associated with a good success rate and clinical outcome.

Value of Progression of Coronary Artery Calcification for Risk Prediction of Coronary and Cardiovascular Events: Result of the HNR Study (Heinz Nixdorf Recall).

BACKGROUND: Computed tomography (CT) allows estimation of coronary artery calcium (CAC) progression. We evaluated several progression algorithms in our unselected, population-based cohort for risk prediction of coronary and cardiovascular events. METHODS: In 3281 participants (45-74 years of age), free from cardiovascular disease until the second visit, risk factors, and CTs at baseline (b) and after a mean of 5.1 years (5y) were measured. Hard coronary and cardiovascular events, and total cardiovascular events including revascularization, as well, were recorded during a follow-up time of 7.8±2.2 years after the second CT. The added predictive value of 10 CAC progression algorithms on top of risk factors including baseline CAC was evaluated by using survival analysis, C-statistics, net reclassification improvement, and integrated discrimination index. A subgroup analysis of risk in CAC categories was performed. RESULTS: We observed 85 (2.6%) hard coronary, 161 (4.9%) hard cardiovascular, and 241 (7.3%) total cardiovascular events. Absolute CAC progression was higher with versus without subsequent coronary events (median, 115 [Q1-Q3, 23-360] versus 8 [0-83], P<0.0001; similar for hard/total cardiovascular events). Some progression algorithms added to the predictive value of baseline CT and risk assessment in terms of C-statistic or integrated discrimination index, especially for total cardiovascular events. However, CAC progression did not improve models including CAC5y and 5-year risk factors. An excellent prognosis was found for 921 participants with double-zero CACb=CAC5y=0 (10-year coronary and hard/total cardiovascular risk: 1.4%, 2.0%, and 2.8%), which was for participants with incident CAC 1.8%, 3.8%, and 6.6%, respectively. When CACb progressed from 1 to 399 to CAC5y≥400, coronary and total cardiovascular risk were nearly 2-fold in comparison with subjects who remained below CAC5y=400. Participants with CACb≥400 had high rates of hard coronary and hard/total cardiovascular events (10-year risk: 12.0%, 13.5%, and 30.9%, respectively). CONCLUSIONS: CAC progression is associated with coronary and cardiovascular event rates, but adds only weakly to risk prediction. What counts is the most recent CAC value and risk factor assessment. Therefore, a repeat scan >5 years after the first scan may be of additional value, except when a double-zero CT scan is present or when the subjects are already at high risk.

Percutaneous closure of the left atrial appendage in patients with diabetes mellitus.

BACKGROUND: Left atrial appendage closure is a preventive treatment of atrial fibrillation-related thrombo-embolism. Patients with diabetes mellitus have increased risk for a negative outcome in percutaneous cardiac interventions. We assessed whether percutaneous left atrial appendage closure is safe and effective in patients with diabetes mellitus. METHODS: We included 78 patients (mean age of 74.4 ± 8.3 years) with indication for left atrial appendage closure in an open-label observational single-centre study. RESULTS: Patients with diabetes mellitus ( n = 31) were at higher thrombo-embolic and bleeding risk (CHA2DS2-VASc: 4.5 ± 0.9, HAS-BLED: 4.7 ± 0.7) compared to patients without diabetes mellitus ( n = 47, CHA2DS2-VASc: 3.5 ± 1.0, HAS-BLED: 4.1 ± 0.8; p < 0.001 for both). Pre- and periprocedural risk was elevated in patients with diabetes mellitus (Euro II-Score: 6.6 ± 3.7 vs 3.9 ± 1.9, p < 0.01; Society of Thoracic Surgeons (STS)-Score: 4.0 ± 2.5 vs 2.6 ± 1.2, p < 0.01). Procedural success was similar. Periprocedural major adverse cardiac and cerebrovascular events occurred in one patient from the control group (2.1%), whereas patients with diabetes mellitus had no events ( p = 0.672). Follow-up of 6 months revealed no bleeding complication in both groups. No stroke occurred in follow-up, and left atrial appendage flow velocity reduction (55.6 ± 38.6 vs 51.4 ± 19.1 cm/s, p = 0.474) and rate of postinterventional leakage in the left atrial appendage were comparable (0% vs 2.1%, p = 0.672). CONCLUSION: Despite patients with diabetes mellitus are high-risk patients, the outcome of percutaneous left atrial appendage closure is similar to patients without diabetes mellitus.

Aortic Calcification Onset and Progression: Association With the Development of Coronary Atherosclerosis.

BACKGROUND: Thoracic aortic calcification (TAC) and coronary artery calcification (CAC) are markers of subclinical atherosclerosis and are associated with incident major cardiovascular events. We investigated major determinants for incidence and progression of TAC and the association between TAC and CAC incidence and progression. METHODS AND RESULTS: In a population-based cohort study, 3270 participants (aged 45-74 years, 53.1% women) received cardiac computed tomography at baseline and after a mean follow-up of 5.1±0.3 years for quantification of calcification of the ascending (ATAC) and descending thoracic aorta (DTAC) and CAC. Multivariable relative risk regression analysis was used to investigate associations of cardiovascular risk factors with incident TAC, of baseline TAC with incident CAC, and of baseline CAC with incident TAC. Of 1243 participants with baseline TAC of 0, 517 (41.6%) revealed incident TAC after 5 years. Incidence of descending TAC was higher (34.5%) than ascending TAC (23.3%). Incident TAC after 5 years was associated with age (relative risk 1.26 [95% CI 1.21-1.33], per 5 years), blood pressure (relative risk 1.06 [95% CI 1.03-1.10], per 10 mm Hg), low-density lipoprotein cholesterol (relative risk 1.08 [95% CI 1.04-1.12], per 20 mg/dL), and smoking (relative risk 1.28 [95% CI 1.07-1.53]). Among the 1185 participants without CAC at baseline, the risk of developing CAC was 28.3% when baseline TAC was present compared with 22.2% among those without baseline TAC (excess risk 6.1% [95% CI 1.2-11.0%]). The point estimate of excess risk for incident CAC was higher for ascending TAC (10.8% [95% CI 4.8-16.7%]) and low for descending TAC (1.8% [95% CI -3.2% to 6.7%]). Excess risk for developing ascending and descending TAC with present baseline CAC was 16.4% (95% CI 12.7-20.0%) and 15.6% (95% CI 10.8-20.4%), respectively. CONCLUSION: TAC and CAC share similar major determinants for incident calcification. Participants with TAC, especially ascending TAC, are at elevated risk for development of CAC.

CAC Score Improves Coronary and CV Risk Assessment Above Statin Indication by ESC and AHA/ACC Primary Prevention Guidelines.

OBJECTIVES: The aim of this study was to assess the difference in indication for statin therapy by European Society of Cardiology (ESC) versus American Heart Association/American College of Cardiology (AHA/ACC) guidelines and to quantify the potential additional role of coronary artery calcification (CAC) score over updated guidelines in a primary prevention cohort. BACKGROUND: Recently, ESC and AHA/ACC updated the guidelines regarding statin therapy in primary prevention. METHODS: In 3,745 subjects (59 ± 8 years of age, 47% men) from the population based longitudinal Heinz Nixdorf Recall cohort study without cardiovascular disease or lipid-lowering therapy at baseline CAC score was assessed between 2000 and 2003. Subjects remained unaware of their initial CAC score. Statin indication was determined according to 2012 ESC and 2013 AHA/ACC guidelines based on subjects individual baseline characteristics. RESULTS: The frequency of statin recommendation was lower according to ESC compared to AHA/ACC guidelines (34% vs. 56%; p < 0.0001), whereas low CAC score (<100) was common in subjects with statin indication by both guidelines (59% for ESC, 62% for AHA/ACC). During 10.4 ± 2.0 years of follow-up, 131 myocardial infarctions occurred. For ESC recommendations, CAC score differentiated risk for subjects without (1.0 [95% confidence interval (CI): 0.4 to 1.5] vs. 6.5 [95% CI: 4.1 to 8.9] coronary events per 1,000 person-years for CAC 0 vs. ≥100) and with statin indication (2.6 [95% CI: 0.6 to 4.7] vs. 9.9 [95% CI: 7.3 to 12.5] per 1,000 person-years for CAC 0 vs. ≥100). Likewise, CAC score stratified proportions experiencing events subjects with statin indication according to AHA/ACC (2.7 [95% CI: 1.1 to 4.2] vs. 9.1 [95% CI: 7.0 to 11.0] per 1,000 person-years for CAC 0 vs. ≥100), whereas event rate in subjects without statin indication was low (1.1 [95% CI: 0.65 to 1.68] per 1,000 person-years). CONCLUSIONS: Current ESC and AHA/ACC guidelines lead to markedly different recommendation regarding statin therapy in a German primary prevention cohort. Quantification of CAC score in addition to the guidelines improves stratification between subjects at high versus low risk for coronary events, indicating that CAC scoring may help to match intensified risk factor modification to atherosclerotic plaque burden as well as actual risk while avoiding therapy in subjects with low coronary atherosclerosis that have low 10-year event rate.

N-Terminal Pro-B Type Natriuretic Peptide is Associated with Mild Cognitive Impairment in the General Population.

BACKGROUND: N-terminal pro-B type natriuretic peptide (NT-proBNP) is a marker of cardiac stress and is linked with silent cardiac diseases. While associations of cognitive impairment with manifest cardiovascular diseases are established, data on whether subclinical elevation of NT-proBNP levels below clinically established threshold of heart failure is related with cognitive functioning, especially mild cognitive impairment (MCI), is rare. OBJECTIVE: Aim of the present study was to investigate the cross-sectional association of NT-proBNP levels and MCI in a population-based study sample without heart failure. METHODS: We used data from the second examination of the population based Heinz-Nixdorf-Recall-Study. Subjects with overt coronary heart disease and subjects with NT-proBNP levels indicating potential heart failure (NT-proBNP≥300 pg/ml) were excluded from this analysis. Participants performed a validated brief cognitive assessment and were classified either as MCI [subtypes: amnestic-MCI (aMCI), non-amnestic-MCI (naMCI)], or cognitively-normal. RESULTS: We included 419 participants with MCI (63.1±7.4 y; 47% men; aMCI n = 209; naMCI n = 210) and 1,206 cognitively normal participants (62.42±7.1 y; 48% men). NT-proBNP-levels≥125 pg/ml compared to <125 pg/ml were associated with MCI in fully adjusted models (OR 1.65 (1.23;2.23) in the total sample, 1.73 (1.09;2.74) in men and 1.63(1.10;2.41) in women). For aMCI, the fully adjusted OR was 1.53 (1.04;2.25) and for naMCI, the fully adjusted OR was 1.34 (1.09; 166) in the total sample. CONCLUSION: Within normal ranges and without manifest heart failure, higher NT-proBNPlevels are associated with MCI and both MCI subtypes independent of traditional cardiovascular risk factors and sociodemographic parameters.

Accelerated progression of coronary artery calcification in hypertension but also prehypertension.

OBJECTIVE: To determine the role of hypertension for coronary artery calcification (CAC) progression. METHODS: The population-based Heinz Nixdorf Recall study recruited 4814 participants from a German urban population in 2000-2003. CAC was measured using electron-beam computed tomography at baseline and after 5 years. The present analyses refer to 3481 participants with repeat scan (coronary heart disease until 5 years excluded, age at baseline 45-74 years, and 53.1% women). Blood pressure (BP), Framingham risk factors, and antihypertensive medication were recorded at baseline. BP was staged according to Joint National Committee 7 guidelines. Participants under antihypertensive medication were classified as stage 2. CAC at 5 years was predicted from baseline using our dedicated, publicly available algorithm. CAC progression was accordingly classified as slow, expected, or rapid. RESULTS: Normotension was found in 20.5%, prehypertension in 27.2%, stage 1 hypertension in 15.8%, and stage 2 (ST2) in 36.5%. The frequency of rapid progression increases with BP stage (normotension: 16.7% to ST2: 21.1%, P = 0.004). Risk factor adjusted relative risk [RR (95% confidence interval), reference: normotension] of rapid progression was for prehypertension: 1.22 (0.98;1.51), stage 1: 1.29 (1.01;1.65), and ST2: 1.45 (1.17;1.79). Risk factor adjusted measures of CAC progression per 10 mmHg SBP were already elevated in women with BP below 140/90 mmHg: CAC onset, RR = 1.22 (1.07;1.40), rapid progression, RR = 1.17 (1.05;1.31), 5-year CAC progression, 6.7% (0.5;13.4). In men below 140/90 mmHg, only RR of rapid progression was considerably increased [RR = 1.11 (0.96;1.29)]. CONCLUSION: CAC progression, a sign of ongoing target organ damage, is already accelerated in prehypertensive patients, a substantial proportion of our urban population.

Noncoronary Measures Enhance the Predictive Value of Cardiac CT Above Traditional Risk Factors and CAC Score in the General Population.

OBJECTIVES: The aim of this study was to determine whether noncoronary measures from cardiac computed tomography (CT) may enhance the prognostic value of this imaging technology. BACKGROUND: When cardiac CT is performed for quantification of coronary artery calcium (CAC) score, information on other cardiac and thoracic structures is available. METHODS: Participants without known cardiovascular disease from the prospective population based Heinz Nixdorf Recall study underwent noncontrast cardiac CT for CAC score quantification. From CT, epicardial adipose tissue (EAT) volume, left ventricular and left atrial (LA) axial area index, ascending and descending aortic diameters, as well as aortic valve, mitral ring, and thoracic aortic calcification (TAC) were assessed. Incident cardiovascular events included myocardial infarction, stroke, and cardiovascular death. The prognostic value of CT-derived parameters was assessed by Cox regression analysis, receiver operating characteristics, and net reclassification improvement. RESULTS: From 3,630 subjects (59 ± 8 years of age, 46% male), 241 (6.6%) developed a cardiovascular event during 9.9 ± 2.6 years of follow-up. In multivariable Cox regression analysis including Framingham Risk Score, CAC (as log[CAC + 1]), and CT parameters, LA index (hazard ratio [HR]: 1.22 [95% confidence interval [CI]: 1.05 to 1.41] per SD; p = 0.010) and EAT volume (HR: 1.15 [95% CI: 1.01 to 1.30] per SD; p = 0.031) were significantly associated with incident events. In addition, presence of TAC showed an elevated event rate (HR: 1.33 [95% CI: 0.97 to 1.81]; p = 0.08), whereas all other CT-derived parameters showed no relevant association. The LA index, EAT volume, and presence of TAC together improved the prediction of events over Framingham Risk Score and CAC in receiver operating characteristics analysis (area under the curve: 0.749 to 0.764; p = 0.011), and let to a significant net reclassification improvement (HR: 38.0%; 95% CI: 25.1% to 50.8%). CONCLUSION: Assessment of LA index, EAT volume, and TAC from non-contrast-enhanced cardiac CT improves the prediction of incident hard cardiovascular events above CAC and established risk factors, indicating that quantification of these noncoronary measures may improve the prognostic value of this imaging technology.

Association of long-term exposure to local industry- and traffic-specific particulate matter with arterial blood pressure and incident hypertension.

BACKGROUND: Long-term exposure to fine particulate matter (PM2.5) may lead to increased blood pressure (BP). The role of industry- and traffic-specific PM2.5 remains unclear. OBJECTIVE: We investigated the associations of residential long-term source-specific PM2.5 exposure with arterial BP and incident hypertension in the population-based Heinz Nixdorf Recall cohort study. METHODS: We defined hypertension as systolic BP≥140mmHg, or diastolic BP≥90mmHg, or current use of BP lowering medication. Long-term concentrations of PM2.5 from all local sources (PM2.5ALL), local industry (PM2.5IND) and traffic (PM2.5TRA) were modeled with a dispersion and chemistry transport model (EURAD-CTM) with a 1km(2) resolution. We performed a cross-sectional analysis with BP and prevalent hypertension at baseline, using linear and logistic regression, respectively, and a longitudinal analysis with incident hypertension at 5-year follow-up, using Poisson regression with robust variance estimation. We adjusted for age, sex, body mass index, lifestyle, education, and major road proximity. Change in BP (mmHg), odds ratio (OR) and relative risk (RR) for hypertension were calculated per 1µg/m(3) of exposure concentration. RESULTS: PM2.5ALL was highly correlated with PM2.5IND (Spearman's ρ=0.92) and moderately with PM2.5TRA (ρ=0.42). In adjusted cross-sectional analysis with 4539 participants, we found positive associations of PM2.5ALL with systolic (0.42 [95%-CI: 0.03, 0.80]) and diastolic (0.25 [0.04, 0.46]) BP. Higher, but less precise estimates were found for PM2.5IND (systolic: 0.55 [-0.05, 1.14]; diastolic: 0.35 [0.03, 0.67]) and PM2.5TRA (systolic: 0.88 [-1.55, 3.31]; diastolic: 0.41 [-0.91, 1.73]). We found crude positive association of PM2.5TRA with prevalence (OR 1.41 [1.10, 1.80]) and incidence of hypertension (RR 1.38 [1.03, 1.85]), attenuating after adjustment (OR 1.19 [0.90, 1.58] and RR 1.28 [0.94, 1.72]). We found no association of PM2.5ALL and PM2.5IND with hypertension. CONCLUSIONS: Long-term exposures to all-source and industry-specific PM2.5 were positively related to BP. We could not separate the effects of industry-specific PM2.5 from all-source PM2.5. Estimates with traffic-specific PM2.5 were generally higher but inconclusive.

Ankle-Brachial Index but Neither Intima Media Thickness Nor Coronary Artery Calcification is Associated With Mild Cognitive Impairment.

BACKGROUND: Several studies have reported an association of atherosclerosis with mild cognitive impairment (MCI) and dementia independent of cardiovascular risk factors. OBJECTIVE: To compare the cross-sectional association of the ankle-brachial index (ABI), intima media thickness (IMT), and coronary artery calcification (CAC) with MCI and its subtypes, amnestic MCI (aMCI) and non-amnestic MCI (naMCI) in the population-based Heinz Nixdorf Recall cohort study. METHODS: 4,086 participants performed a validated brief cognitive assessment at the first follow-up examination (2006-2008). MCI was diagnosed according to previously published criteria. Prevalence ratio (PR) regression models adjusted for age, gender, education, cardiovascular risk factors, and APOE genotype were used to compare the association of the ABI, the CAC-Agatston score and the IMT with MCI and its subtypes. RESULTS: We identified 490 participants with MCI (mean age 66.1 ± 7.8, 46.9 % male, aMCI n = 249, naMCI n = 241) and 1,242 cognitively normal participants. A decreasing ABI (per 0.1) was significantly associated with a higher MCI prevalence in fully adjusted models (PR 1.06; 95% confidence interval (CI) 1.01-1.11), whereas an increasing CAC (log(CAC+1)) or IMT (per 0.1 mm) were not associated after adjustment. A decreasing ABI was also significantly associated with naMCI in fully adjusted models (PR 1.12; CI 1.03-1.21) but not with aMCI. CONCLUSIONS: Our data show that the degree of generalized atherosclerosis as measured by the ABI is associated with MCI and with naMCI in a population-based cohort.