Impact of Cardiovascular Risk Factors on Arterial Stiffness in a Countryside Area of Switzerland: Insights from the Swiss Longitudinal Cohort Study.

INTRODUCTION: Cardiovascular disease is the leading cause of morbidity and mortality. Besides traditional cardiovascular risk factors, arterial stiffness is a recognized predictor of cardiovascular risk. METHODS: We investigated the relationship between traditional cardiovascular risk factors, sex, and aortic pulse wave velocity in subjects living in a countryside area of Southern Switzerland. For this aim, we performed a cross-sectional analysis of data from adult participants of the Swiss Longitudinal Cohort Study, which, initiated in 2015, follows health status and disease risk factors in a Swiss countryside cohort at least 6 years of age. RESULTS: A total of 387 people (205 women and 182 men) were included. Hyperlipidemia, overweight, and obesity were more common (p ≤ 0.001) and LDL-cholesterol, triglycerides, and hemoglobin A1c were higher (p < 0.03) in men than women. Systolic and diastolic brachial and aortic blood pressures were higher in men (p < 0.02), whereas aortic pulse wave velocity and aortic pulse pressure were higher in women (p < 0.05). The aortic pulse wave velocity was significantly higher in subjects with hypertension, hyperlipidemia, diabetes, and obesity, and significantly increased with age (p < 0.0001). Multiple linear regression analysis showed a significant correlation between pulse wave velocity and age, female sex, brachial systolic blood pressure, and heart rate (p < 0.005). CONCLUSION: Also in a countryside area, the aortic pulse wave velocity is higher in subjects with hypertension, hyperlipidemia, diabetes and obesity, and significantly increases with age. Furthermore, with advancing age, aortic pulse wave velocity is higher in women than men. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT02282748.

The Central Nervous System and Psychosocial Factors in Primary Microvascular Angina.

Patients diagnosed with ischemia without obstructive coronary artery disease (INOCA) comprise the group of patients with primary microvascular angina (MVA). The pathophysiology underlying ischemia and angina is multifaceted. Differences in vascular tone, collateralization, environmental and psychosocial factors, pain thresholds, and cardiac innervation seem to contribute to clinical manifestations. There is evidence suggesting potential interactions between the clinical manifestations of MVA and non-cardiac conditions such as abnormal function of the central autonomic network (CAN) in the central nervous system (CNS), pain modulation pathways, and psychological, psychiatric, and social conditions. A few unconventional non-pharmacological and pharmacological techniques targeting these psychosocial conditions and modulating the CNS pathways have been proposed to improve symptoms and quality of life. Most of these unconventional approaches have shown encouraging results. However, these results are overall characterized by low levels of evidence both in observational studies and interventional trials. Awareness of the importance of microvascular dysfunction and MVA is gradually growing in the scientific community. Nonetheless, therapeutic success remains frustratingly low in clinical practice so far. This should promote basic and clinical research in this relevant cardiovascular field investigating, both pharmacological and non-pharmacological interventions. Standardization of definitions, clear pathophysiological-directed inclusion criteria, crossover design, adequate sample size, and mid-term follow-up through multicenter randomized trials are mandatory for future study in this field.

[Cascade genetic testing of familial hypercholesterolemia A new opportunity for prevention]. / Dépistage génétique en cascade de l'hypercholestérolémie familiale - Une nouvelle opportunité pour la prévention cardiovasculaire.

Familial hypercholesterolemia (FH) is a genetic disorder associated with an increased risk of early-onset cardiovascular events. Because lifestyle interventions and lipid-lowering drugs can strongly reduce cardiovascular risk, the early diagnosis of FH is important. Indeed, given the autosomal dominant transmission of the pathogenic variant, a genetic cascade screening program of first-degree relatives from an index case could identify patients at high cardiovascular risk. In Switzerland, genetic testing for FH is rarely used, because it is not reimbursed by health insurance companies. To test the usefulness of cascade genetic testing for FH, the CATCH study is currently ongoing in all linguistic part of Switzerland.

L'hypercholestérolémie familiale (HF) est une maladie génétique associée à un risque augmenté d'événements cardiovasculaires précoces. Étant donné que les adaptations du style de vie et les traitements hypolipémiants peuvent réduire fortement le risque cardiovasculaire, le diagnostic précoce de l'HF est important. À cette fin, en raison de la transmission autosomique dominante du variant pathogène, un dépistage génétique en cascade des apparentés du premier degré organisé autour du cas index permettrait d'identifier précocement les patients à risque cardiovasculaire élevé. Cependant, le test génétique est très peu utilisé en Suisse, car il n'est pas remboursé par les caisses-maladie. Afin de tester l'utilité du dépistage génétique en cascade de l'HF, l'étude CATCH est en cours actuellement dans les trois régions linguistiques de Suisse.

Prevalence of ideal cardiovascular health in a community-based population - results from the Swiss Longitudinal Cohort Study (SWICOS).

AIMS OF THE STUDY: The American Heart Association (AHA) developed a concept to measure cardiovascular health in populations. We aimed to analyse participants in the Swiss Longitudinal Cohort Study (SWICOS) according to the AHA concept. METHODS: We analysed cardiovascular health according to the AHA concept in all 474 participants of the prospective, population-based SWICOS study who were 18 years or older. The AHA concept uses seven health metrics of known cardiovascular risk factors (blood pressure, total cholesterol, blood glucose, smoking, body weight, physical activity and diet), and classifies each health metric according to three levels (ideal, intermediate and poor) using pre-defined cut-offs. RESULTS: Ideal cardiovascular health for three or more of the seven health metrics was found in 259 participants (54.9%; 95% confidence interval [CI] 50.1-59.4%), but a relevant number of participants (n = 213, 45.1%, 95% CI 40.6-49.7%) showed ideal cardiovascular health for only two or fewer of the seven health metrics. Poor cardiovascular health for three or more of the seven health metrics was found in 40 participants (8.5%; 95% CI 6.1-11.4%); a majority of 432 participants (91.5%; 95% CI 88.6-93.9%) showed a poor level for only two or fewer of the seven health metrics. CONCLUSIONS: Overall, we found favourable results for cardiovascular health in the population-based SWICOS cohort. Nevertheless, we see the need for further health prevention campaigns given the fact that a relevant proportion of the participants could optimise their cardiovascular health.

Age-Dependency of Cardiometabolic Risk and Protective Factors in Females Living in a Countryside Area of Switzerland.

We investigated the effect of age on cardiometabolic risk and protective factors in females living in a countryside area of Switzerland. For this cross-sectional analysis, data from 268 female adults, who live in two neighboring countryside villages in Italian-speaking Switzerland were retained. 89 study participants were premenopausal, 82 climacteric and 97 postmenopausal. Television viewing time, short duration of sleep, overweight, blood pressure, levels of atherogenic lipids and glycated hemoglobin significantly increased with age. Walking time also significantly increased with age. Tobacco smoking was more common among premenopausal women. It is concluded that in these countryside villages climacteric and postmenopausal women generally have an unfavorable cardiometabolic risk profile. On the other side, low physical activity and smoking are, compared to premenopausal and climacteric women, less prevalent in postmenopausal women.

Role of the central autonomic nervous system intrinsic functional organisation and psychosocial factors in primary microvascular angina and Takotsubo syndrome.

INTRODUCTION AND OBJECTIVE: Dysfunctional central autonomic nervous system network (CAN) at rest may result in aberrant autonomic responses to psychosocial stressors. We hypothesised that patients with primary microvascular angina (MVA) or Takotsubo syndrome (TTS) would exhibit a peculiar functional organisation of the CAN, potentially associated with psychological patterns. METHODS: Patients underwent a psychosocial evaluation: a clinical diagnostic interview, Millon Clinical Multiaxial Inventory III, State-Trait Anxiety Inventory form Y and Short Form 36 Health Survey (SF-36). The strength of intrinsic functional connectivity (FC) between various nodes of the CAN was investigated using cerebral resting state functional MRI (RS-fMRI). RESULTS: We evaluated 50 (46 women) stable patients: 16 patients with MVA, 17 patients with TTS and 17 patients with previous acute myocardial infarction (AMI). Compared with AMI, patients with MVA showed a lower (higher impairment) SF-36 Body-Pain score (p 0.046) and a higher SF-36 Mental-Health score (p 0.039). Patients with TTS showed the strongest FC between two nodes of the CAN (sympathetic midcingulate cortex and parasympathetic primary motor area) (F 6.25, p 0.005) using RS-fMRI. CONCLUSIONS: The study implements an innovative collaborative research among cardiologists, neuroscientists and psychiatrists ('Neuro-psycho-heart Team'). MVA showed a discrepancy between the highest level of self-reported body pain and the best mental health score, which might suggest a mechanism of somatisation. TTS exhibited an increased functional integration between two areas of the CAN involved in interoceptive pain awareness and negative emotional status. We implemented an innovative research collaboration among cardiologists, neuroscientists and psychiatrists. These data are hypothesis generating and suggest potential prospective investigations on pathophysiology and implementation of psychotherapy and stress-reducing techniques as therapeutic strategies. TRIAL REGISTRATION NUMBER: NCT02759341.

Intractable coronary fibromuscular dysplasia leading to end-stage heart failure and fatal heart transplantation.

Coronary fibromuscular dysplasia is uncommon, and even rarer its unstable and recurrent course. We present the unique case of a 52-year-old woman who underwent in total 12 coronary angiographies and three percutaneous coronary intervention within 24 months because of repetitive acute coronary syndromes due to refractory spasm, dissection, restenosis all leading to end-stage heart failure, and heart transplantation. The patient died 12 days after the heart transplantation complicated by intraoperative acute thrombotic occlusion of left anterior descending artery of the graft despite normal pretransplant coronary angiography. Autopsy of the recipient heart confirmed coronary fibromuscular dysplasia with massive intimal hyperplasia and restenosis.

Imaging of Carotid Plaque Neovascularization by Contrast-Enhanced Ultrasound and Dynamic Contrast-Enhanced Magnetic Resonance Imaging.

BACKGROUND: Carotid plaque neovascularization (vasa vasorum [VV]) may be useful for detecting high-risk atherosclerotic plaques. Contrast-enhanced ultrasound (CEUS) and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) are 2 commonly used techniques for imaging VV of the carotid plaque, yet the relationship between their measurements remains unknown. OBJECTIVES: We aimed to blindly evaluate the correlation between CEUS and DCE-MRI in measuring carotid plaque VV. METHODS: We recruited subjects with asymptomatic carotid stenosis (≥50%). VV was graded by CEUS, based on richness of contrast signal, according to 3 different methods named CEUS_A, CEUS_B and CEUS_C on different point scales (the higher the values, the higher the estimated VV). A 3.0 T MRI scanner was used for VV quantification by DCE-MRI using gadolinium contrast kinetic modelling for computing the fractional plasma volume (vp) and transfer constant (Ktrans). RESULTS: The analysis included 30 patients. A significant correlation between CEUS and DCE-MRI findings was observed when CEUS_C was used for neovessel grading and DCE-MRI was used to determine adventitial (r = 0.460, p = 0.010) and plaque (r = 0.374, p = 0.042) Ktrans values. CEUS_B (r = 0.416, p = 0.022) and CEUS_C (r = 0.443, p = 0.014) grading showed a significant correlation with regard to the maximal Ktrans. CONCLUSIONS: We found a positive but weak correlation and a moderate diagnostic agreement between neovessels as visually graded by CEUS and adventitial neovessels assessed by DCE-MRI Ktrans in carotid atherosclerosis. These findings may help in understanding how VV density, flow, and permeability influence in vivo measurements by CEUS and DCE-MRI as well as in selecting the most appropriate variables and imaging method in future research and potentially in clinical settings. Further confirmative studies are necessary to confirm our results.

Cardiovascular Imaging and Theranostics in Cardiovascular Pharmacotherapy.

Imaging plays a pivotal role in the diagnostic and prognostic assessment of cardiovascular diseases. During the past two decades, there has been an expansion of the available imaging techniques, some of which are now part of routine clinical practice. Cardiovascular imaging of atherosclerosis is a useful instrument, and it can corroborate and expand pathophysiological evidence on cardiovascular disease, providing proof of concept for medical therapy and can predict its responsiveness, and it may be able to be used as surrogate endpoints for clinical trials. Theranostics is an emerging therapy that combines imaging and therapeutic functions, using imaging-based therapeutic delivery systems. Theranostics could partially overcome current imaging limitations and translate experimental evidence and large-scale trials assessing clinical endpoints, rationalising cardiovascular drug development and paving the way to personalised medicine. The medical community cannot overlook the use of cardiovascular imaging as a complementary and supportive adjunct to trials investigating clinical endpoints, which remain the mainstay for investigating the efficacy and safety of cardiovascular pharmacotherapy.

The Growing Field of Imaging of Atherosclerosis in Peripheral Arteries.

In the past decades, peripheral arteries have represented a model for the comprehension of atherosclerosis as well as for the development of new diagnostic imaging modalities and therapeutic strategies. Peripheral arteries may represent a window to study atherosclerosis. Pathology has prominently contributed to move the clinical and research attention from the arterial lumen stenosis and angiography to morphological and functional imaging techniques. Evidence from large and prospective cohort or randomized controlled studies is still modest. Nevertheless, several emerging imaging investigations represent a potential tool for a comprehensive "in vivo" evaluation of the entire natural history of peripheral atherosclerosis. This constitutes a demanding assignment, as it would be desirable to obtain both single-lesion focused and extensive arterial system views to achieve the most accurate prognostic information. Our narrative review rests upon the fundamental pathological evidence, summarizing the rapidly growing field of imaging of atherosclerosis in peripheral arteries and presenting a selection of both currently available and emerging imaging techniques.

Long-term Outcomes of a Telementoring Program for Distant Teaching of Endovascular Aneurysm Repair.

PURPOSE: To prospectively evaluate the long-term outcomes after a telementoring program for distant teaching of endovascular aneurysm repair (EVAR) and the degree of EVAR procedure assimilation into routine practice. METHODS: A telementoring protocol using stepwise introduction of EVAR was implemented between a university care center and a remote vascular health care site; from March 1999 to October 2003, 49 EVAR patients (mean age 72 years; 48 men) were treated during telementoring at the remote center. After the telementoring period, 86 patients (mean age 71 years; 77 men) underwent EVAR procedures carried out at the secondary care center from November 2003 to July 2011. The long-term outcomes were compared between the EVAR procedures performed during telementoring with the procedures performed independently thereafter. RESULTS: No significant difference was appreciated between telementored and not telementored procedures either in 30-day mortality (4.1% vs 2.3%, p=0.621) or in the initial technical success (93.9% vs 97.7%, p=0.353). The telementored group showed no significant difference in overall aneurysm-related mortality (6.1% vs 2.3%, p=0.353) or in the overall complication rates (p=0.985). The reintervention rate was significantly lower among the unmentored procedures (11.6% vs 32.7%, p=0.004). In particular, significantly fewer patients underwent late endovascular procedures (1.2% vs 12.2%, p=0.009) and late percutaneous interventions (7.0% vs 20.4%, p=0.027) after telementoring ceased. CONCLUSION: The telementoring program followed here allowed excellent EVAR skill assimilation into the routine practice of a remote health care site. Telementoring is a feasible strategy to support skill introduction in remote medical facilities.

First in-human radiation dosimetry of 68Ga-NODAGA-RGDyK.

BACKGROUND: Integrin-targeting radiopharmaceuticals have potential broad applications, spanning from cancer theranostics to cardiovascular diseases. We have previously reported preclinical dosimetry results of 68Ga-NODAGA-RGDyK in mice. This study presents the first human dosimetry of 68Ga-NODAGA-RGDyK in the five consecutive patients included in a clinical imaging protocol of carotid atherosclerotic plaques. Five male patients underwent whole-body time-of-flight (TOF) PET/CT scans 10, 60 and 120 min after tracer injection (200 MBq). Quantification of 68Ga activity concentration was first validated by a phantom study. To be used as input in OLINDA/EXM, time-activity curves were derived from manually drawn regions of interest over the following organs: brain, thyroid, lungs, heart, liver, spleen, stomach, kidneys, red marrow, pancreas, small intestine, colon, urinary bladder and whole body. A separate dosimetric analysis was performed for the choroid plexuses. Female dosimetry was extrapolated from male data. Effective doses (EDs) were estimated according to both ICRP60 and ICRP103 assuming 30-min and 1-h voiding cycles. RESULTS: The body regions receiving the highest dose were urinary bladder, kidneys and choroid plexuses. For a 30-min voiding cycle, the EDs were 15.7 and 16.5 µSv/MBq according to ICRP60 and ICRP103, respectively. The extrapolation to female dosimetry resulted in organ absorbed doses 17% higher than those of male patients, on average. The 1-h voiding cycle extrapolation resulted in EDs of 19.3 and 19.8 µSv/MBq according to ICRP60 and ICRP103, respectively. A comparison is made with previous mouse dosimetry and with other human studies employing different RGD-based radiopharmaceuticals. CONCLUSIONS: According to ICRP60/ICRP103 recommendations, an injection of 200 MBq 68Ga-NODAGA-RGDyK leads to an ED in man of 3.86/3.92 mSv. For future therapeutic applications, specific attention should be directed to delivered dose to kidneys and potentially also to the choroid plexuses. TRIAL REGISTRATION: Clinical trial.gov, NCT01608516.

Associations of sodium, potassium and protein intake with blood pressure and hypertension in Switzerland.

BACKGROUND: Nutritional factors play an important role in the regulation of blood pressure and in the development of hypertension. In this analysis, we explored the associations of 24-hour urinary Na+, K+ and urea excretion with blood pressure levels and the risk of hypertension in the Swiss population, taking regional linguistic differences into account. METHODS: The Swiss Survey on Salt is a population based cross-sectional study that included 1336 subjects from the three main linguistic regions (French, German and Italian) of Switzerland. Blood pressure was measured with a validated oscillometric Omron HEM 907 device. Hypertension was defined as current antihypertensive treatment or a mean systolic blood pressure >140 mm Hg and/or diastolic >90 mm Hg, based on eight blood pressure measurements performed at two visits. Na+, K+ and urea excretion were assessed in 24-hour urine collections. We use multiple logistic/linear regressions to explore the associations of urine Na+, K+ and urea with blood pressure / hypertension, taking into account potential confounders and effect modifiers. RESULTS: The prevalence of hypertension was 30%, 26% and 17% in the German-, French- and Italian- speaking regions respectively, (p-value across regions <0.001). In the Swiss adult population, besides age, sex, and body mass index, urinary Na+ excretion was positively associated with systolic blood pressure and hypertension. Urinary K+ excretion tended to be negatively associated with blood pressure but this was not significant (p = 0.08). Hypertensive people had a higher 24-hour urinary Na+/K+ ratio than normotensive people (p = 0.003). Urinary urea excretion was associated with neither blood pressure nor hypertension. Participants from the German-speaking region had a higher likelihood of having a high systolic blood pressure. CONCLUSIONS: We confirm a high prevalence of elevated blood pressure in Swiss adults, including regional differences. In Switzerland, urinary Na+ excretion is associated positively with blood pressure and hypertension, independently of urinary K+ and urea excretion. The observed differences in blood pressure levels across linguistic regions are independent of the urinary Na+, K+ and urea excretion.

Protocol of the Swiss Longitudinal Cohort Study (SWICOS) in rural Switzerland.

INTRODUCTION: Increased longevity and consequent major changes in demographics and population lifestyles necessitate new approaches to reduce the burden of ageing-related diseases (including cardiovascular disease) and maintain an optimal quality of life. This study aims to examine and longitudinally follow health status and disease risk factors in a Swiss rural cohort, evaluating all health-related research and practice disciplines to assure development of new implementable and successful preventive strategies for healthy ageing. METHODS AND OBJECTIVES: Small Swiss villages with low migration rates will be selected for this study. 2 villages (Cama/Lostallo) have already been selected as initial study sites. All residents (age ≥6 years, no upper age limit) are eligible. The target enrolment number per village is 300. Examinations and measurements encompass medical history, anthropometry, cardiac and vascular health, pulmonary function, physical performance, nutritional, mental and emotional status, biochemical and molecular analyses. Follow-up examinations (identical to baseline) will be performed after 5 and 10 years, and in 10-year intervals thereafter. The major objective is to assess, and observe change in, health status over time in a prospective manner. Secondary objectives are to: (1) identify 'hidden' (asymptomatic and/or unrecognised) health problems which enhance risk for chronic diseases; (2) identify barriers to accessing healthcare and adapting health behaviours; (3) evaluate efficacy of present preventive strategies and recommendations; (4) evaluate knowledge and attitude towards ongoing health programmes and public health recommendations; (5) monitor change and progress towards the national health objectives; (6) formulate new preventive strategies and recommendations based on the findings and knowledge base of the past 10 years; (7) formulate models for successful prevention of chronic diseases and for healthy ageing. ETHICS AND DISSEMINATION: The Ethics Committee of Nordwest-und Zentralschweiz approved this study (EKNZ 2014-209). It is registered at ClinicalTrials.gov (NCT02282748). Findings will be disseminated through scientific articles/presentations and public events.