The SYNTAX and Gensini score in combination with clinical variables could be used to predict the cardiovascular prognosis during a long-term follow-up of up to 8 years in CAD patients.

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.

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Keywords asymmetric dimethylarginine, L-arginine, L-homoarginine, nitric oxide, vascular function AIMSLow blood concentrations of the naturally occurring amino acid L-homoarginine (L-hArg) are related to impaired cardiovascular outcome and mortality in humans and animals. L-hArg is a weak substrate of nitric oxide synthase and an inhibitor of arginases in vitro. The aim of our study was to obtain kinetic and dynamic data after oral L-hArg supplementation. METHODSIn a double-blind, randomized, placebo-controlled crossover study, 20 young volunteers received 125 mg L-hArg once daily for 4 weeks. Kinetic parameters (C max , T max and AUC 0-24h ) were calculated after ingestion of single and multiple doses of oral supplementation as primary endpoint. Secondary endpoints that were evaluated were routine laboratory, L-arginine, asymmetric dimethylarginine (ADMA), pulse wave velocity (PWV), augmentation index (AIx), flow-mediated vasodilatation (FMD), corticospinal excitability, i.e. motor threshold (MT), and cortical excitability, i.e. intracortical inhibition (ICI) and facilitation (ICF). RESULTSOne hour after ingestion (T max ), L-hArg increased the baseline L-hArg plasma concentration (2.87 ± 0.91 μmol l À1 , mean ± SD) by 8.74 ± 4.46 [95% confidence intervals 6.65; 10.9] and 17. 3 ± 4.97 [14.9; 19.6] μmol l À1 (C max ), after single and multiple doses, respectively. Once-only and 4 weeks of supplementation resulted in AUCs 0-24h of 63. 5 ± 28.8 [50.0; 76.9] and 225 ± 78.5 [188; 2624] μmol l À1 *h, for single and multiple doses, respectively. Routine laboratory parameters, L-arginine, ADMA, PWV, AIx, FMD, MT, ICI and ICF did not change by L-hArg supplementation compared to baseline. CONCLUSIONOnce daily orally applied 125 mg L-hArg raises plasma L-hArg four-and sevenfold after single dose and 4 weeks of supplementation, respectively, and is safe and well tolerated in young volunteers. British Journal of Clinical Pharmacology WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT• L-Homoarginine (L-hArg) is an amino acid found in pea pulses (Lathyrus sativus and cicera). It is a weak substrate for nitric oxide (NO) synthases (NOS) and an inhibitor of arginases.• In clinical and epidemiological studies, low circulating L-hArg is associated with impaired cerebrovascular and cardiovascular outcome.• Orally administered L-hArg is readily absorbed in rats and pigs with a recovery of >95% of unmetabolized L-hArg in urine. WHAT THIS STUDY ADDS• Our data show that oral supplementation with 125 mg L-hArg raises plasma L-hArg concentrations four-and sevenfold after single and multiple dosing in humans, respectively.• Four weeks of supplementation did not change vascular and neuronal function in young volunteers, nor did any toxic side-effects occur.

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.

In a healthy general population from Finland, sST2 did not improve long-term prediction of cardiovascular events including heart failure or all-cause mortality.

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