The Hamburg City Health Study (HCHS) is a large, prospective, long-term, population-based cohort study and a unique research platform and network to obtain substantial knowledge about several important risk and prognostic factors in major chronic diseases. A random sample of 45,000 participants between 45 and 74 years of age from the general population of Hamburg, Germany, are taking part in an extensive baseline assessment at one dedicated study center. Participants undergo 13 validated and 5 novel examinations primarily targeting major organ system function and structures including extensive imaging examinations. The protocol includes validate self-reports via questionnaires regarding lifestyle and environmental conditions, dietary habits, physical condition and activity, sexual dysfunction, professional life, psychosocial context and burden, quality of life, digital media use, occupational, medical and family history as well as healthcare utilization. The assessment is completed by genomic and proteomic characterization. Beyond the identification of classical risk factors for major chronic diseases and survivorship, the core intention is to gather valid prevalence and incidence, and to develop complex models predicting health outcomes based on a multitude of examination data, imaging, biomarker, psychosocial and behavioral assessments. Participants at risk for coronary artery disease, atrial fibrillation, heart failure, stroke and dementia are invited for a visit to conduct an additional MRI examination of either heart or brain. Endpoint assessment of the overall sample will be completed through repeated follow-up examinations and surveys as well as related individual routine data from involved health and pension insurances. The study is targeting the complex relationship between biologic and psychosocial risk and resilience factors, chronic disease, health care use, survivorship and health as well as favorable and bad prognosis within a unique, large-scale long-term assessment with the perspective of further examinations after 6 years in a representative European metropolitan population.

Cerebral small vessel disease (CSVD) is a widespread condition associated to stroke, dementia and depression. To shed light on its opaque pathophysiology, we conducted a neuroimaging study aiming to assess the location of CSVD-induced damage in the human brain network. Structural connectomes of 930 subjects of the Hamburg City Health Study were reconstructed from diffusion weighted imaging. The connectome edges were partitioned into groups according to specific schemes: (1) connection to grey matter regions, (2) course and length of underlying streamlines. Peak-width of skeletonised mean diffusivity (PSMD) - a surrogate marker for CSVD - was related to each edge group’s connectivity in a linear regression analysis allowing localisation of CSVD-induced effects. PSMD was associated with statistically significant decreases in connectivity of most investigated edge groups except those involved in connecting limbic, insular, temporal or cerebellar regions. Connectivity of interhemispheric and long intrahemispheric edges as well as edges connecting subcortical and frontal brain regions decreased most severely with increasing PSMD. In conclusion, MRI findings of CSVD are associated with widespread impairment of structural brain network connectivity, which supports the understanding of CSVD as a global brain disease. The pattern of regional preference might provide a link to clinical phenotypes of CSVD.

Aims Clinical practice guidelines restrict rhythm control therapy to patients with symptomatic atrial fibrillation (AF). The EAST-AFNET 4 trial demonstrated that early, systematic rhythm control improves clinical outcomes compared to symptom-directed rhythm control. Methods and results This prespecified EAST-AFNET 4 analysis compared the effect of early rhythm control therapy in asymptomatic patients (EHRA score I) to symptomatic patients. Primary outcome was a composite of death from cardiovascular causes, stroke, or hospitalization with worsening of heart failure or acute coronary syndrome, analyzed in a time-to-event analysis. At baseline, 801/2633 (30.4%) patients were asymptomatic [mean age 71.3 years, 37.5% women, mean CHA2DS2-VASc score 3.4, 169/801 (21.1%) heart failure]. Asymptomatic patients randomized to early rhythm control (395/801) received similar rhythm control therapies compared to symptomatic patients [e.g. AF ablation at 24 months: 75/395 (19.0%) in asymptomatic; 176/910 (19.3%) symptomatic patients, P = 0.672]. Anticoagulation and treatment of concomitant cardiovascular conditions was not different between symptomatic and asymptomatic patients. The primary outcome occurred in 79/395 asymptomatic patients randomized to early rhythm control and in 97/406 patients randomized to usual care (hazard ratio 0.76, 95% confidence interval [0.6; 1.03]), almost identical to symptomatic patients. At 24 months follow-up, change in symptom status was not different between randomized groups (P = 0.19). Conclusion The clinical benefit of early, systematic rhythm control was not different between asymptomatic and symptomatic patients in EAST-AFNET 4. These results call for a shared decision discussing the benefits of rhythm control therapy in all patients with recently diagnosed AF and concomitant cardiovascular conditions (EAST-AFNET 4; ISRCTN04708680; NCT01288352; EudraCT2010-021258-20).

Cerebral small vessel disease is a common finding in the elderly and associated with various clinical sequelae. Previous studies suggest disturbances in the integration capabilities of structural brain networks as a mediating link between imaging and clinical presentations. To what extent cerebral small vessel disease might interfere with other measures of global network topology is not well understood. Connectomes were reconstructed via diffusion weighted imaging in a sample of 930 participants from a population based epidemiologic study. Linear models were fitted testing for an association of graph‐theoretical measures reflecting integration and segregation with both the Peak width of Skeletonized Mean Diffusivity (PSMD) and the load of white matter hyperintensities of presumed vascular origin (WMH). The latter were subdivided in periventricular and deep for an analysis of localisation‐dependent correlations of cerebral small vessel disease. The median WMH volume was 0.6 mL (1.4) and the median PSMD 2.18 mm2/s x 10−4 (0.5). The connectomes showed a median density of 0.880 (0.030), the median values for normalised global efficiency, normalised clustering coefficient, modularity Q and small‐world propensity were 0.780 (0.045), 1.182 (0.034), 0.593 (0.026) and 0.876 (0.040) respectively. An increasing burden of cerebral small vessel disease was significantly associated with a decreased integration and increased segregation and thus decreased small‐worldness of structural brain networks. Even in rather healthy subjects increased cerebral small vessel disease burden is accompanied by topological brain network disturbances. Segregation parameters and small‐worldness might as well contribute to the understanding of the known clinical sequelae of cerebral small vessel disease.

Background: The randomized EAST-AFNET4 (Early Treatment of Atrial Fibrillation for Stroke Prevention Trial–Atrial Fibrillation Network) demonstrated that early rhythm control (ERC) reduces adverse cardiovascular outcomes in patients with recently diagnosed atrial fibrillation and stroke risk factors. The effectiveness and safety of ERC in patients with multiple cardiovascular comorbidities is not known. Methods: These prespecified subanalyses of EAST-AFNET4 compared the effectiveness and safety of ERC with usual care (UC) stratified into patients with higher (CHA 2 DS 2 -VASc score ≥4) and lower comorbidity burden. Sensitivity analyses ignored sex (CHA 2 DS 2 -VA score). Results: EAST-AFNET4 randomized 1093 patients with CHA 2 DS 2 -VASc score ≥4 (74.8±6.8 years, 61% female) and 1696 with CHA 2 DS 2 -VASc score <4 (67.4±8.0 years, 37% female). ERC reduced the composite primary efficacy outcome of cardiovascular death, stroke, or hospitalization for worsening of heart failure or for acute coronary syndrome in patients with CHA 2 DS 2 -VASc score ≥4 (ERC, 127/549 patients with events; UC, 183/544 patients with events; hazard ratio [HR], 0.64 [0.51–0.81]; P < 0.001) but not in patients with CHA 2 DS 2 -VASc score <4 (ERC, 122/846 patients with events; UC, 133/850 patients with events; HR, 0.93 [0.73–1.19]; P =0.56, P interaction =0.037). The primary safety outcome (death, stroke, or serious adverse events of rhythm control therapy) was not different between study groups in patients with CHA 2 DS 2 -VASc score ≥4 (ERC, 112/549 patients with events; UC, 132/544 patients with events; HR, 0.84 [0.65, 1.08]; P =0.175), but occurred more often in patients with CHA 2 DS 2 -VASc scores <4 randomized to ERC (ERC, 119/846 patients with events; UC, 91/850 patients with events; HR, 1.39 [1.05–1.82]; P =0.019, P interaction =0.008). Life-threatening events or death were not different between groups (CHA 2 DS 2 -VASc score ≥4, ERC, 84/549 patients with event, UC, 96/544 patients with event; CHA 2 DS 2 -VASc scores <4, ERC, 75/846 patients with event, UC, 73/850 patients with event). When female sex was ignored for the creation of higher and lower risk groups (CHA 2 DS 2 -VA score), the P interaction was not significant for the primary efficacy outcome ( P =0.25), but remained significant ( P =0.044) for the primary safety outcome. Conclusions: Patients with recently diagnosed atrial fibrillation and CHA 2 DS 2 -VASc score ≥4 should be considered for ERC to reduce cardiovascular outcomes, whereas those with fewer comorbidities may have less favorable outcomes with ERC. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01288352. URL: https://www.clinicaltrialsregister.eu ; Unique identifier: 2010-021258-20. URL: https://www.isrctn.com/ ; Unique identifier: ISRCTN04708680.

The aim of the study was to investigate the relationship between specific known dietary patterns and the prevalence of periodontal disease in a northern population-based cohort study. We evaluated data from 6209 participants of the Hamburg City Health Study (HCHS). The HCHS is a prospective cohort study and is registered at ClinicalTrial.gov (NCT03934957). Dietary intake was assessed with the food frequency questionnaire (FFQ2). Periodontal examination included probing depth, gingival recession, plaque index, and bleeding on probing. Descriptive analyses were stratified by periodontitis severity. Ordinal logistic regression models were used to determine the association. Ordinal regression analyses revealed a significant association between higher adherence to the DASH diet/Mediterranean diet and lower odds to be affected by periodontal diseases in an unadjusted model (OR: 0.92; 95% CI: 0.87, 0.97; p < 0.001/OR: 0.93; 95% CI: 0.91, 0.96; p < 0.001) and an adjusted model (age, sex, diabetes) (OR: 0.94; 95% CI: 0.89, 1.00; p < 0.0365/OR: 0.97; 95% CI: 0.94, 1.00; p < 0.0359). The current cross-sectional study identified a significant association between higher adherence to the DASH and Mediterranean diets and lower odds to be affected by periodontal diseases (irrespective of disease severity). Future randomized controlled trials are needed to evaluate to which extent macro- and micronutrition can affect periodontitis initiation/progression.

Background Positive and negative influences on oral health are attributed to coffee consumption. The aim of the current study is to evaluate the association between coffee consumption and periodontitis in the general population of Hamburg. Methods A total of 6,209 participants from the Hamburg City Health Study were included in this cross-sectional study. Information on coffee consumption was collected using a food frequency questionnaire. Periodontal examination included assessment of dental care ability via Plaque Index, measurement of pocket depth, gingival recession, and bleeding on probing. Classification was based on the criteria of Eke and Page. Ordinal logistic regression models were performed unadjusted and adjusted for confounding variables. Results Periodontal cohort consists of 6,209 participants, presenting either none/mild (n = 1,453, 39.6% men, 2.4% strong coffee drinkers), moderate (n = 3,580, 49.3% men, 3.3% strong coffee drinkers), or severe (n = 1,176, 60.9% men, 5.0% strong coffee drinkers) periodontitis. There was a significant association between strong coffee consumption (≥ 7or more cups/day) and periodontitis (OR: 1.51; CI: 1.07, 2.12; p > 0.001), compared with low coffee consumption. Conversely, moderate coffee consumption was not associated with periodontitis, compared with low coffee consumption. Conclusion and clinical relevance. In this cross-sectional study of a northern German population, strong coffee consumption was significantly associated with periodontitis. Influence of changes in coffee consumption on periodontal disease etiology/progression should be investigated in future prospective study designs, in order to identify strong coffee consumption as a potential risk factor of periodontitis.

We examined the relationship between white matter hyperintensities (WMH) and cortical neurodegeneration in cerebral small vessel disease (CSVD) by investigating whether cortical thickness is a remote effect of WMH through structural fiber tract connectivity in a population at increased risk of CSVD. We measured cortical thickness on T1-weighted images and segmented WMH on FLAIR images in 930 participants of a population-based cohort study at baseline. DWI-derived whole-brain probabilistic tractography was used to define WMH connectivity to cortical regions. Linear mixed-effects models were applied to analyze the relationship between cortical thickness and connectivity to WMH. Factors associated with cortical thickness (age, sex, hemisphere, region, individual differences in cortical thickness) were added as covariates. Median age was 64 [IQR 46–76] years. Visual inspection of surface maps revealed distinct connectivity patterns of cortical regions to WMH. WMH connectivity to the cortex was associated with reduced cortical thickness ( p = 0.009) after controlling for covariates. This association was found for periventricular WMH ( p = 0.001) only. Our results indicate an association between WMH and cortical thickness via connecting fiber tracts. The results imply a mechanism of secondary neurodegeneration in cortical regions distant, yet connected to subcortical vascular lesions, which appears to be driven by periventricular WMH.