Automatic risk evaluation in elderly patients based on Autonomic Nervous System assessment

Dysfunction of Autonomic Nervous System (ANS) is a typical feature of chronic heart failure and other cardiovascular disease. As a simple non-invasive technology, heart rate variability (HRV) analysis provides reliable information on autonomic modulation of heart rate. The aim of this thesis was to research and develop automatic methods based on ANS assessment for evaluation of risk in cardiac patients. Several features selection and machine learning algorithms have been combined to achieve the goals. Automatic assessment of disease severity in Congestive Heart Failure (CHF) patients: a completely automatic method, based on long-term HRV was proposed in order to automatically assess the severity of CHF, achieving a sensitivity rate of 93% and a specificity rate of 64% in discriminating severe versus mild patients. Automatic identification of hypertensive patients at high risk of vascular events: a completely automatic system was proposed in order to identify hypertensive patients at higher risk to develop vascular events in the 12 months following the electrocardiographic recordings, achieving a sensitivity rate of 71% and a specificity rate of 86% in identifying high-risk subjects among hypertensive patients. Automatic identification of hypertensive patients with history of fall: it was explored whether an automatic identification of fallers among hypertensive patients based on HRV was feasible. The results obtained in this thesis could have implications both in clinical practice and in clinical research. The system has been designed and developed in order to be clinically feasible. Moreover, since 5-minute ECG recording is inexpensive, easy to assess, and non-invasive, future research will focus on the clinical applicability of the system as a screening tool in non-specialized ambulatories, in order to identify high-risk patients to be shortlisted for more complex investigations.

Plasma homocysteine and cardiovascular risk in heart failure with and without cardiorenal syndrome

Plasma homocysteine (Hcy) has been associated with an increased cardiovascular (CV) risk in patients with chronic heart failure (CHF). Thus, we investigated whether Hcy has a prognostic impact on CV events in CHF-patients with and without cardiorenal syndrome (CRS).

Periodontitis: a future risk of acute coronary syndrome? A follow-up study over 3 years

BACKGROUND: Periodontitis has been associated with cardiovascular disease. We assess if the recurrence of acute coronary syndrome (ACS) could be predicted by preceding medical and periodontal conditions. METHODS: A total of 165 consecutive subjects with ACS and 159 medically healthy, matched control subjects were examined and followed for 3 years. Periodontitis was defined by alveolar bone loss. Subgingival microbial samples were studied by the checkerboard DNA-DNA hybridization method. RESULTS: The recurrence of ACS was found in 66 of 165 (40.0%) subjects, and a first ACS event was found in seven of 159 (4.4%) subjects among baseline control subjects. Subjects who later had a second ACS event were older (P <0.001). Significantly higher serum levels of high-density lipoprotein (P <0.05), creatinine (P <0.01), and white blood cell (WBC) counts (P <0.001) were found in subjects with future ACS. Periodontitis was associated with a first event of ACS (crude odds ratio [OR]: 10.3:1; 95% confidence interval [CI]: 6.1 to 17.4; P <0.001) and the recurrence of ACS (crude OR: 3.6:1; 95% CI: 2.0 to 6.6; P <0.001). General linear modeling multivariate analysis, controlling for age and the prediction of a future ACS event, identified that WBC counts (F = 20.6; P <0.001), periodontitis (F = 17.6; P <0.001), and serum creatinine counts (F = 4.5; P <0.05) were explanatory of a future ACS event. CONCLUSIONS: The results of this study indicate that recurrent ACS events are predicted by serum WBC counts, serum creatinine levels, and a diagnosis of periodontitis. Significantly higher counts of putative pathogens are found in subjects with ACS, but these counts do not predict future ACS events.

Regular physical activity moderates cardiometabolic risk in Alzheimer's caregivers

Dementia caregivers have an increased risk of cardiovascular disease, and it is possible that metabolic disturbances contribute to this risk. Regular physical exercise reduces cardiometabolic risk, but caregivers may have less opportunity to engage in such activity. We hypothesized that regular physical activity would moderate cardiometabolic risk in dementia caregivers.

All cause and disease specific mortality in patients with knee or hip osteoarthritis: population based cohort study

Objective To examine all cause and disease specific mortality in patients with osteoarthritis of the knee or hip. Design Population based cohort study. Setting General practices in the southwest of England. Participants 1163 patients aged 35 years or over with symptoms and radiological confirmation of osteoarthritis of the knee or hip. Main outcome measures Age and sex standardised mortality ratios and multivariable hazard ratios of death after a median of 14 years’ follow-up. Results Patients with osteoarthritis had excess all cause mortality compared with the general population (standardised mortality ratio 1.55, 95% confidence interval 1.41 to 1.70). Excess mortality was observed for all disease specific causes of death but was particularly pronounced for cardiovascular (standardised mortality ratio 1.71, 1.49 to 1.98) and dementia associated mortality (1.99, 1.22 to 3.25). Mortality increased with increasing age (P for trend <0.001), male sex (adjusted hazard ratio 1.59, 1.30 to 1.96), self reported history of diabetes (1.95, 1.31 to 2.90), cancer (2.28, 1.50 to 3.47), cardiovascular disease (1.38, 1.12 to 1.71), and walking disability (1.48, 1.17 to 1.86). However, little evidence existed for increased mortality associated with previous joint replacement, obesity, depression, chronic inflammatory disease, eye disease, or presence of pain at baseline. The more severe the walking disability, the higher was the risk of death (P for trend <0.001). Conclusion Patients with osteoarthritis are at higher risk of death compared with the general population. History of diabetes, cancer, or cardiovascular disease and the presence of walking disability are major risk factors. Management of patients with osteoarthritis and walking disability should focus on effective treatment of cardiovascular risk factors and comorbidities, as well as on increasing physical activity.

A multifactorial analysis of obesity as CVD risk factor: use of neural network based methods in a nutrigenetics context

Obesity is a multifactorial trait, which comprises an independent risk factor for cardiovascular disease (CVD). The aim of the current work is to study the complex etiology beneath obesity and identify genetic variations and/or factors related to nutrition that contribute to its variability. To this end, a set of more than 2300 white subjects who participated in a nutrigenetics study was used. For each subject a total of 63 factors describing genetic variants related to CVD (24 in total), gender, and nutrition (38 in total), e.g. average daily intake in calories and cholesterol, were measured. Each subject was categorized according to body mass index (BMI) as normal (BMI ≤ 25) or overweight (BMI > 25). Two artificial neural network (ANN) based methods were designed and used towards the analysis of the available data. These corresponded to i) a multi-layer feed-forward ANN combined with a parameter decreasing method (PDM-ANN), and ii) a multi-layer feed-forward ANN trained by a hybrid method (GA-ANN) which combines genetic algorithms and the popular back-propagation training algorithm.

Distress related to myocardial infarction and cardiovascular outcome: a retrospective observational study

Background During acute coronary syndromes patients perceive intense distress. We hypothesized that retrospective ratings of patients' MI-related fear of dying, helplessness, or pain, all assessed within the first year post-MI, are associated with poor cardiovascular outcome. Methods We studied 304 patients (61 ± 11 years, 85% men) who after a median of 52 days (range 12-365 days) after index MI retrospectively rated the level of distress in the form of fear of dying, helplessness, or pain they had perceived at the time of MI on a numeric scale ranging from 0 ("no distress") to 10 ("extreme distress"). Non-fatal hospital readmissions due to cardiovascular disease (CVD) related events (i.e., recurrent MI, elective and non-elective stent implantation, bypass surgery, pacemaker implantation, cerebrovascular incidents) were assessed at follow-up. The relative CVD event risk was computed for a (clinically meaningful) 2-point increase of distress using Cox proportional hazard models. Results During a median follow-up of 32 months (range 16-45), 45 patients (14.8%) experienced a CVD-related event requiring hospital readmission. Greater fear of dying (HR 1.21, 95% CI 1.03-1.43), helplessness (HR 1.22, 95% CI 1.04-1.44), or pain (HR 1.27, 95% CI 1.02-1.58) were significantly associated with an increased CVD risk without adjustment for covariates. A similarly increased relative risk emerged in patients with an unscheduled CVD-related hospital readmission, i.e., when excluding patients with elective stenting (fear of dying: HR 1.26, 95% CI 1.05-1.51; helplessness: 1.26, 95% CI 1.05-1.52; pain: HR 1.30, 95% CI 1.01-1.66). In the fully-adjusted models controlling for age, the number of diseased coronary vessels, hypertension, and smoking, HRs were 1.24 (95% CI 1.04-1.46) for fear of dying, 1.26 (95% CI 1.06-1.50) for helplessness, and 1.26 (95% CI 1.01-1.57) for pain. Conclusions Retrospectively perceived MI-related distress in the form of fear of dying, helplessness, or pain was associated with non-fatal cardiovascular outcome independent of other important prognostic factors.

Non-fatal cardiovascular outcome in patients with posttraumatic stress symptoms caused by myocardial infarction

Objectives Posttraumatic stress disorder (PTSD) prospectively increases the risk of incident cardiovascular disease (CVD) independent of other risk factors in otherwise healthy individuals. Between 10% and 20% of patients develop PTSD related to the traumatic experience of myocardial infarction (MI). We investigated the hypothesis that PTSD symptoms caused by MI predict adverse cardiovascular outcome. Methods We studied 297 patients (61 ± 10 years, 83% men) who self-rated PTSD symptoms attributable to a previous index MI. Non-fatal CVD-related hospital readmissions (i.e. recurrent MI, elective and non-elective intracoronary stenting, bypass surgery, pacemaker implantation, cardiac arrhythmia, cerebrovascular event) were assessed at follow-up. Cox proportional hazard models controlled for demographic factors, coronary heart disease severity, major CVD risk factors, cardiac medication, and mental health treatment. Results Forty-three patients (14.5%) experienced an adverse event during a mean follow-up of 2.8 years (range 1.3–3.8). A 10 point higher level in the PTSD symptom score (mean 8.8 ± 9.0, range 0–47) revealed a hazard ratio (HR) of 1.42 (95% CI 1.07–1.88) for a CVD-related hospital readmission in the fully adjusted model. A similarly increased risk (HR 1.45, 95% CI 1.07–1.97) emerged for patients with a major or unscheduled CVD-related readmission (i.e. when excluding patients with elective stenting). Conclusions Elevated levels of PTSD symptoms caused by MI may adversely impact non-fatal cardiovascular outcome in post-MI patients independent of other important prognostic factors. The possible importance of PTSD symptoms as a novel prognostic psychosocial risk factor in post-MI patients warrants further study.

Cardiovascular safety of non-steroidal anti-inflammatory drugs: network meta-analysis

Objective To analyse the available evidence on cardiovascular safety of non-steroidal anti-inflammatory drugs. Design Network meta-analysis. Data sources Bibliographic databases, conference proceedings, study registers, the Food and Drug Administration website, reference lists of relevant articles, and reports citing relevant articles through the Science Citation Index (last update July 2009). Manufacturers of celecoxib and lumiracoxib provided additional data. Study selection All large scale randomised controlled trials comparing any non-steroidal anti-inflammatory drug with other non-steroidal anti-inflammatory drugs or placebo. Two investigators independently assessed eligibility. Data extraction The primary outcome was myocardial infarction. Secondary outcomes included stroke, death from cardiovascular disease, and death from any cause. Two investigators independently extracted data. Data synthesis 31 trials in 116 429 patients with more than 115 000 patient years of follow-up were included. Patients were allocated to naproxen, ibuprofen, diclofenac, celecoxib, etoricoxib, rofecoxib, lumiracoxib, or placebo. Compared with placebo, rofecoxib was associated with the highest risk of myocardial infarction (rate ratio 2.12, 95% credibility interval 1.26 to 3.56), followed by lumiracoxib (2.00, 0.71 to 6.21). Ibuprofen was associated with the highest risk of stroke (3.36, 1.00 to 11.6), followed by diclofenac (2.86, 1.09 to 8.36). Etoricoxib (4.07, 1.23 to 15.7) and diclofenac (3.98, 1.48 to 12.7) were associated with the highest risk of cardiovascular death. Conclusions Although uncertainty remains, little evidence exists to suggest that any of the investigated drugs are safe in cardiovascular terms. Naproxen seemed least harmful. Cardiovascular risk needs to be taken into account when prescribing any non-steroidal anti-inflammatory drug.

Relationship between chronic stress and carotid intima-media thickness (IMT) in elderly Alzheimer's disease caregivers

The stress associated with providing care for a spouse diagnosed with Alzheimer's disease can have adverse effects on cardiovascular health. One potential explanation is that chronic caregiving stress may contribute to the development of atherosclerosis. The purpose of this study was to determine whether the duration that one has provided care is associated with the degree of atherosclerotic burden, as measured by carotid artery intima-media thickness (IMT). One hundred and ten Alzheimer caregivers [mean age 74 ± 8 (SD) years, 69% female] underwent in-home assessment of carotid artery IMT via B-mode ultrasonography. Data regarding medical history, blood pressure, and multiple indicators of caregiving stress were also collected. Multiple regression indicated that duration of care was positively associated with IMT measured in the internal/bifurcation segments of the carotid artery (β = 0.202, p = 0.044) independent of risk factors such as age, gender, body mass index, smoking history, sleep quality, hypertension status, and caregiving stressors. Duration of care was positively associated with IMT in the common carotid artery, but the relationship was not significant. These findings provide more evidence of the link between chronic caregiving stress and cardiovascular disease and indicate that enduring the experience of caregiving over a period of years might be associated with atherosclerotic burden.

Resting heart rate and incident heart failure and cardiovascular mortality in older adults: role of inflammation and endothelial dysfunction: the PROSPER study

Resting heart rate is a promising modifiable cardiovascular risk marker in older adults, but the mechanisms linking heart rate to cardiovascular disease are not fully understood. We aimed to assess the association between resting heart rate and incident heart failure (HF) and cardiovascular mortality, and to examine whether these associations might be attributable to systemic inflammation and endothelial dysfunction.

Proteomics in cardiovascular surgery

Proteomics describes, analogous to the term genomics, the study of the complete set of proteins present in a cell, organ, or organism at a given time. The genome tells us what could theoretically happen, whereas the proteome tells us what does happen. Therefore, a genomic-centered view of biologic processes is incomplete and does not describe what happens at the protein level. Proteomics is a relatively new methodology and is rapidly changing because of extensive advances in the underlying techniques. The core technologies of proteomics are 2-dimensional gel electrophoresis, liquid chromatography, and mass spectrometry. Proteomic approaches might help to close the gap between traditional pathophysiologic and more recent genomic studies, assisting our basic understanding of cardiovascular disease. The application of proteomics in cardiovascular medicine holds great promise. The analysis of tissue and plasma/serum specimens has the potential to provide unique information on the patient. Proteomics might therefore influence daily clinical practice, providing tools for diagnosis, defining the disease state, assessing of individual risk profiles, examining and/or screening of healthy relatives of patients, monitoring the course of the disease, determining the outcome, and setting up individual therapeutic strategies. Currently available clinical applications of proteomics are limited and focus mainly on cardiovascular biomarkers of chronic heart failure and myocardial ischemia. Larger clinical studies are required to test whether proteomics may have promising applications for clinical medicine. Cardiovascular surgeons should be aware of this increasingly pertinent and challenging field of science.

INFLUENCE OF 24-HOUR SLEEP DEPRIVATION ON CARDIOVASCULAR AND NEURAL CONTROL AT REST AND DURING ACUTE STRESS IN HUMANS

Recent epidemiological studies report a consistent association between short sleep and incidence of hypertension, as well as short sleep and cardiovascular disease-related mortality. While the association between short sleep and hypertension appears to be stronger in women than men, the mechanisms underlying the relations between sleep deprivation, stress, risks of cardiovascular diseases, and sex remain unclear. We conducted two studies to investigate the underlying neural mechanisms of these relations. In study 1, we examined sympathetic neural and blood pressure responses to experimentally-induced sleep deprivation in men and women. We further investigated the influence of sleep deprivation on cardiovascular reactivity to acute stress. In study 2, we examined the neural and cardiovascular function throughout the ovarian cycle in sleep deprived women. Twenty-eight young healthy subjects (14men and 14 women) were tested twice in study 1, once after normal sleep (NS) and once after 24-h total sleep deprivation (TSD). We measured the blood pressure, heart rate (HR), muscle sympathetic nerve activity (MSNA) and forearm blood flow (FBF) during 10min baseline, 5min of mental stress (MS) and 2 min cold pressor test (CPT). We demonstrated that TSD increased resting arterial blood pressure to a similar extent in both men and women, but MSNA decreased only in men following TSD. This MSNA response was associated with altered baroreflex function in women and divergent testosterone responses to TSD between men and women. Regarding TSD and cardiovascular reactivity, TSD elicited augmented HR reactivity and delayed recovery during both MS and CPT in men and women, and responses between sexes were not statistically different. Fourteen young healthy women participated in study 2. Subjects were tested twice, once during their early follicular (EF) phase after TSD, once during their mid-luteal (ML) phase after TSD. Blood pressure, HR, MSNA, and FBF were recorded during 10min baseline, 5 min MS, and 2 min CPT. We observed an augmented resting supine blood pressure during EF compared to ML in sleep deprived women. In contrast, resting MSNA, as well as cardiovascular responses to stressors, were similar between EF and ML after TSD. In conclusion, we observed sex differences in MSNA responses to TSD that demonstrate reductions of MSNA in men, but not women. TSD elicited augmented HR reactivity and delayed HR recovery to acute stressors similarly in men and women. We also reported an augmented supine blood pressure during EF compared to ML in sleep deprived women. These novel findings provide new and valuable mechanistic insight regarding the complex and poorly understood relations among sleep deprivation, sex, stress, and risk of cardiovascular disease.

Effects of gender and dementia severity on Alzheimer's disease caregivers' sleep and biomarkers of coagulation and inflammation

BACKGROUND: Being a caregiver for a spouse with Alzheimer's disease is associated with increased risk for cardiovascular illness, particularly for males. This study examined the effects of caregiver gender and severity of the spouse's dementia on sleep, coagulation, and inflammation in the caregiver. METHODS: Eighty-one male and female spousal caregivers and 41 non-caregivers participated (mean age of all participants 70.2 years). Full-night polysomnography (PSG) was recorded in each participants home. Severity of the Alzheimer's disease patient's dementia was determined by the Clinical Dementia Rating (CDR) scale. The Role Overload scale was completed as an assessment of caregiving stress. Blood was drawn to assess circulating levels of D-dimer and Interleukin-6 (IL-6). RESULTS: Male caregivers who were caring for a spouse with moderate to severe dementia spent significantly more time awake after sleep onset than female caregivers caring for spouses with moderate to severe dementia (p=.011), who spent a similar amount of time awake after sleep onset to caregivers of low dementia spouses and to non-caregivers. Similarly, male caregivers caring for spouses with worse dementia had significantly higher circulating levels of D-dimer (p=.034) than females caring for spouses with worse dementia. In multiple regression analysis (adjusted R(2)=.270, p<.001), elevated D-dimer levels were predicted by a combination of the CDR rating of the patient (p=.047) as well as greater time awake after sleep onset (p=.046). DISCUSSION: The findings suggest that males caring for spouses with more severe dementia experience more disturbed sleep and have greater coagulation, the latter being associated with the disturbed sleep. These findings may provide insight into why male caregivers of spouses with Alzheimer's disease are at increased risk for illness, particularly cardiovascular disease.