Arterial Stiffness and its Impact on Cardiovascular Health.

PURPOSE OF REVIEW: Cardiovascular diseases are the leading cause of mortality globally. Identifying patients at risk is important to initiate preventive strategies. Over the last few decades, the role of the endothelium and its impact on arterial stiffness have been recognised as playing a pivotal role in cardiovascular disease. This review will focus on the effect of arterial stiffness in different patient cohorts with regard to cardiovascular morbidity and mortality, as well as its use in clinical practice. RECENT FINDINGS: Arterial stiffness is associated with a range of cardiovascular risk factors and is an independent predictor of cardiovascular mortality. The gold standard for evaluating arterial stiffness is pulse wave velocity. Recently, cardio-ankle vascular index has been implemented as an easy and highly reproducible measure of arterial stiffness. Moreover, certain pharmacologic agents may modify arterial stiffness and alter progression of cardiovascular disease. The endothelium plays an important role in cardiovascular disease. Implementing assessment of arterial stiffness in clinical practice will improve stratification of patients at risk of cardiovascular disease and help modify disease progression.

Metabolic Health and Carotid Intima-Media Thickness: Association of Different Definitions in Women.

The concept of metabolic health and the metabolic syndrome is to identify subjects at a higher cardiovascular risk. However, many definitions are currently in use, and it is uncertain which is the best in identifying at-risk subjects. We performed a cross-sectional study whereby women were invited to participate and were assessed for several anthropometric and biochemical parameters. Carotid intima-media thickness (CIMT) was measured in both common carotid arteries in each participant. The study cohort consisted of 203 white premenopausal women with a mean age of 38.3 ± 5.4 years. The prevalence of the metabolically unhealthy varied from 7.3% to 61.6%, according to the definition used. The prevalence of the metabolic syndrome, as defined by the International Diabetes Federation, was 20.7%. Women with a metabolically unhealthy phenotype had a higher referent CIMT for all definitions of metabolic health. Defining metabolically unhealthy phenotype as having <2 abnormalities using the National Cholesterol Education Program Expert Panel on Detection, Evaluation, And Treatment of High Blood Cholesterol In Adults (NCEP-ATPIII) cutoffs had the highest odds ratio for an abnormal CIMT. In conclusion, we found that in a contemporary cohort of middle-aged women, the NCEP-ATPIII definition of the metabolic syndrome was more strongly associated with atherosclerosis as determined by the CIMT than the International Diabetes Federation definition or other definitions of metabolic health; it was also more strongly associated than body mass index or waist circumference. Our results need to be validated by other investigators in other populations.

Sleep measures and cardiovascular disease in type 2 diabetes mellitus.

OBJECTIVE: The objective of this study was to assess whether poor sleep is independently associated with cardiovascular disease in people with type 2 diabetes mellitus (T2DM). METHODS: A cross-sectional study was performed in subjects with T2DM aged between 40 and 80 years. Sleep assessment was achieved by actigraphy and Pittsburgh Sleep Quality Index (PSQI) score. RESULTS: The study population comprised 108 subjects with T2DM. The mean age was 64.9 years, the median diabetes duration was 6 years and 73.1% were men. No association was shown between sleep parameters as assessed by actigraphy and T2DM-associated micro- and macrovascular complications. However, sleep quality as assessed by PSQI was significantly associated with macrovascular disease in univariate analysis. Multivariate logistic regression analysis showed red blood cell distribution width (RDW) (odds ratio (OR) 1.79, p=0.018) and good sleep quality (OR 0.35, p=0.017) to be independently associated. Binary logistic regression analysis revealed that body mass index (BMI) (OR 1.11, p=0.024), RDW (OR 1.95, p=0.007) and Center for Epidemiologic Studies Depression score (OR 1.06, p=0.012] were independently associated with abnormal carotid intima-media thickness (CIMT). CONCLUSIONS: Poor sleep quality and higher RDW levels are associated with macrovascular disease in a T2DM population. Increased BMI as well as depression also appear to have an independent role in subclinical atherosclerosis, as assessed by CIMT.

Sleep measures and cardiovascular disease in type 2 diabetes mellitus.

OBJECTIVE: The objective of this study was to assess whether poor sleep is independently associated with cardiovascular disease in people with type 2 diabetes mellitus (T2DM). METHODS: A cross-sectional study was performed in subjects with T2DM aged between 40 and 80 years. Sleep assessment was achieved by actigraphy and Pittsburgh Sleep Quality Index (PSQI) score. RESULTS: The study population comprised 108 subjects with T2DM. The mean age was 64.9 years, the median diabetes duration was 6 years and 73.1% were men. No association was shown between sleep parameters as assessed by actigraphy and T2DM-associated micro- and macrovascular complications. However, sleep quality as assessed by PSQI was significantly associated with macrovascular disease in univariate analysis. Multivariate logistic regression analysis showed red blood cell distribution width (RDW) (odds ratio (OR) 1.79, p=0.018) and good sleep quality (OR 0.35, p=0.017) to be independently associated. Binary logistic regression analysis revealed that body mass index (BMI) (OR 1.11, p=0.024), RDW (OR 1.95, p=0.007) and Center for Epidemiologic Studies Depression score (OR 1.06, p=0.012] were independently associated with abnormal carotid intima-media thickness (CIMT). CONCLUSIONS: Poor sleep quality and higher RDW levels are associated with macrovascular disease in a T2DM population. Increased BMI as well as depression also appear to have an independent role in subclinical atherosclerosis, as assessed by CIMT.

Predictors of subclinical atherosclerosis and microalbuminuria in middle-aged women: a cross-sectional study.

BACKGROUND: Cardiovascular disease is of increasing concern in women. The aim was to assess the role of clinical and anthropometric measures in the development of subclinical atherosclerosis. METHODS: A cross-sectional study in 203 Europid females to determine the prevalence of abnormal carotid intima-media thickness (CIMT) and associated clinical parameters. RESULTS: The study population had a mean age of the 38.3±5.4 years, a median Body Mass Index of 29.25 (IQR 25.06-36.11) kg/m2 and median waist index (WI) of 1.15 (IQR 1.06-1.34). Increased CIMT was present in 169 (83.25%) participants. Linear regression analysis revealed WI to be the sole predictor of increased CIMT (ß=24.387, P<0.001). Post-hoc ROC analysis revealed a WI of 1.12 has 62% sensitivity and 53% specificity for predicting increased CIMT (AUC 0.63, 95% CI 0.55-0.72, P=0.016). The median urinary albumin-creatinine ratio (ACR) was 4.4 mg/g, and the prevalence of microalbuminuria was 8.9%; serum triglycerides were the only independent predictor of ACR. CONCLUSIONS: Atherosclerosis, as detected by abnormal CIMT, is very prevalent in middle-aged women. Waist index is the major predictor of subclinical atherosclerosis in a contemporary premenopausal female population. A WI of 1.12 exhibits relatively good sensitivity and specificity in predicting the presence of atherosclerosis in this patient population.

Long COVID Syndrome: A Case-Control Study.

BACKGROUND: Acute coronavirus disease 2019 (COVID-19) causes various cardiovascular complications. However, it is unknown if there are cardiovascular sequelae in the medium and long-term. The aim of this study was dual. Firstly, we wanted to investigate symptomatology and health-related quality of life (HRQoL) at medium-term follow-up (6 months post-COVID). Secondly, we wanted to assess whether history of COVID-19 and persistent shortness of breath at medium-term follow-up are associated with ongoing inflammation, endothelial dysfunction, and cardiac injury. METHODS: A case-control study was performed. Virologically proven COVID-19 cases and age- and gender-matched controls were interviewed to assess symptoms and HRQoL. Biochemical tests were also performed. RESULTS: The study comprised 174 cases and 75 controls. The mean age of the participants was 46.1±13.8 years. The median follow-up was 173.5 days (interquartile range 129-193.25 days). There was no significant difference in the demographics between cases and controls. At follow-up, cases had a higher frequency of shortness of breath, fatigue, arthralgia, abnormal taste of food (P <.001), and anosmia. Cases also exhibited worse scores in the general health and role physical domains of the Short Form Survey-36. High-sensitivity C-reactive protein (hsCRP) was significantly higher in the cases, and there was a positive correlation of hsCRP with time. Significant determinants of shortness of breath were age, female gender and white cell count, troponin I, and lower hemoglobin levels at follow-up. CONCLUSION: Post-COVID-19 patients have persistent symptomatology at medium-term follow-up. Higher hsCRP in cases and the positive association of hsCRP with time suggest ongoing systemic inflammation in patients persisting for months after COVID-19.

BEAT-IT: A de-novo cardiac screening programme in Maltese adolescents.

AIMS: Sudden cardiac death (SCD) in young individuals is often unexpected, provoking substantial emotional stress for family and friends of the deceased. Cardiac screening may identify individuals who harbour disorders linked to SCD. The feasibility and diagnostic yield of a nationwide cardiac screening programme in adolescents has never been explored. METHODS: All individuals eligible for cardiac screening (students aged 15 years) were systematically invited to enrol. Students were provided with a health questionnaire. ECGs were acquired at school. A physician led consultation was carried out on site. Participants with an abnormal screen were then referred for secondary evaluation to the nation's tertiary centre. Feasibility criteria included a) participation rate >60%, b) adherence to secondary evaluation >80%, and c) cost per individual screened equating to <€100. The diagnostic yield was also evaluated. RESULTS: At the end of enrolment, 2708 students gave consent (mean 15 years, 50.4% male), equating to 67.9% of the eligible cohort. Overall, 109 participants (4.0%) were referred for further evaluation. An abnormal electrocardiogram (ECG) was the most common reason for referral (3.7%). Fifteen individuals (0.6%) were diagnosed with a cardiac condition. Nine (0.3%) had a condition linked to SCD (n = 1 Long-QT syndrome, n = 1 Hypertrophic Cardiomyopathy, n = 5 Wolff-Parkinson White, n = 2 coronary anomalies). The yield was similar in athletes and non-athletes (p = 0.324). The cost per cardiac individual screened equated to €51.15. CONCLUSION: A nationwide systematic cardiac screening programme for adolescent athletes and non-athletes is feasible and cost-efficient, provided that responsible centres have the appropriate infrastructure.

The juvenile ECG pattern in adolescent athletes and non-athletes in a national cardiac screening program (BEAT-IT).

BACKGROUND: Anterior T wave inversion (TWI) is frequent in healthy adolescent individuals (juvenile ECG pattern), normalising after puberty. Its clinical implications are uncertain. AIM: This study assessed a) national prevalence of anterior TWI, b) ST segment morphology, c) proportion of individuals with a juvenile ECG pattern whose ECG normalises and d) factors predicting TWI persistence >16 years. METHODS: Adolescents (mean 15y) in Malta were systematically invited to enrol in a cardiac screening program. Subjects completed a health questionnaire and an ECG at their school. Participants with TWI were labelled as TWI in V1-V2 or extended TWI (V1-V3/4). The latter were followed at 1 year with a repeat ECG. Those with persistent extended anterior TWI were offered evaluation and surveillance. RESULTS: The prevalence of isolated anterior TWI was 5.0%, commoner in females (6.3%) independent of athletic ability. Extended TWI was commoner in female athletes (4.2%, non-athletes 2.1%). Females often had shallow TWI without overt ST segment abnormalities. Deep TWI and ST segment changes were more frequent in males. Only 0.2% of cases persisted ≥16 years of age. ST segment characteristics were not able to predict T wave normalisation. No events took place during follow up (40 ± 9 months). CONCLUSION: Anterior TWI is a frequent phenomenon in adolescents, especially in females. Female athletes are also more likely to have extended anterior TWI. Only 0.2% of cases have persistent anterior TWI at 16 years of age. Chest wall anatomy may explain this phenomenon in females. It is uncommon in males, hence why surveillance is more prudent.

Six Months After the Patients Stayed Home: A Nationwide Study of Cardiac Mortality and Readmissions Following the First Wave of the COVID-19 Pandemic in Malta.

Background The first COVID-19 wave resulted in a significant decline in acute cardiac admissions (ACAs) and delays to hospital presentation in Malta, as well as an excess of out-of-hospital cardiac arrests. The aim was to investigate the impact of the observed delays in presentation in 2020 on mortality and cardiac readmissions at six months. Methods All ACAs between 28th February and 30th April 2020 (first wave of COVID-19 in Malta) were included, and the corresponding 2019 period was used as a control. ACA was defined as an unplanned admission of an adult (aged ≥16 years) under the care of a cardiologist. Outcomes over the six months following the index ACA included death, cardiac readmission, and planned cardiac intervention at discharge. The term 'death' referred to all-cause mortality. Cardiac readmissions referred to unplanned admissions for acute cardiac pathology following the index ACA. During sub-analyses, ACAs were divided into acute coronary syndrome (ACS) and non-ACS. A first analysis compared the frequency of deaths, cardiac readmissions, and planned interventions between the 2019 and 2020 cohorts. A second analysis investigated differences in six-month survival and freedom from readmission between the two cohorts. Both analyses were followed by a sub-analysis. Results There were 330 ACAs among the 2019 cohort and 220 in 2020. There were no significant differences between the 2019 and 2020 cohorts in all-cause mortality (2019, 8.8% vs 2020, 8.2%, p=0.466) and Kaplan-Meier survival estimates at a six-month follow-up (2019, 169.06 days (95% CI 164.95-173.17) vs 2020, 168.27 days (95% CI 162.82-173.72), p=0.836), including subgroup analysis for non-ACS (2019, 168.52 days (95% CI 163.08-173.96) vs 168.11 days (95% CI 160.93-175.30), p=0.952) and ACS patients (169.81 days (95% CI 163.54-176.09) in 2019 vs 168.45 days (95% CI 160.17-176.73) in 2020, p=0.739). A significantly higher number of patients from the 2019 cohort (75/319, 23.5%) required readmission compared to 2020 (32/212; 15.1%) (p=0.02). Similarly, there was shorter freedom from cardiac readmission among 2019 patients (mean 150.98 days (95% CI 144.63-157.33)) compared to 2020 patients (mean 158.66 days (95% CI 151.58-165.74, p=0.024). During sub-analysis, the difference in freedom from readmission was significant only for non-ACS patients (mean of 145.45 days (95% CI 136.58-154.32) in 2019 vs 158.92 days (95% CI 149.19-168.64) in 2020, p=0.018). Analysis of cardiac interventions during the six months post-index ACA discharge showed significantly more planned cardiac interventions in 2019 (52/319; 16.3%) compared to 2020 (20/212; 9.4%) (p=0.027). Conclusions A delay in presentation of ACAs during COVID-19 in Malta resulted in lower readmission rates and increased freedom from readmissions, with no excess in all-cause mortality at a six-month follow-up. The reasons for the optimistic outcomes of patients admitted during the first wave of COVID-19 may be multifactorial. Reasons may include ongoing fear of hospital presentation, a more holistic approach to patients' in-hospital care during 2020 aimed at reducing further hospital contact post-discharge, and a selection bias secondary to an excess of out-of-hospital cardiac arrests during the initial wave of COVID-19. Further studies will be required to truly assess the collateral impact of non-COVID-19-related illness. Public education on cardiovascular health is vital and must be emphasized during the pandemic.

When the patients stayed home: the impact of the COVID-19 pandemic on acute cardiac admissions and cardiac mortality in Malta.

Aim: This study aimed to investigate the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection on all types of acute cardiac admissions (ACAs) and cardiac mortality in Malta. Methods: Number, characteristics and delay to presentation of ACAs to our institution during the study period (28 February-30 April 2020) were compared with the corresponding 2019 period. Non-parametric correlation analyses between daily SARS-CoV-2 cases in Malta, Italy and the UK and daily ACAs were performed. Differences in cardiac death distribution (community vs. in-hospital) during the two periods were analysed. Results: There was a significant decline in daily ACAs in 2020 (median 3 [IQR 3]) vs. 2019 (median 5 [IQR 4]), p < 0.001. Patient characteristics were comparable. Delay to presentation for 2020 ACAs was significantly higher across all categories (ST-elevation myocardial infarction [STEMI] median: 2019 [1 h, IQR 1] vs. 2020 [4 h, IQR 43.8], p = 0.009; non-ST-elevation-acute coronary syndrome [NSTE-ACS] median: 2019 [4 h, IQR 71] vs. 2020 [48 h, IQR 199], p = 0.001; non-ACS median: 2019 [24 h, IQR 95] vs. 2020 [84 h, IQR 499.8], p < 0.001). There was a significant negative correlation between ACAs and daily Malta SARS-CoV-2 infection cases (r s = -0.298, p = 0.018) but not with cases in Italy and the UK when controlling for Malta cases. Significantly more cardiac deaths occurred in the community in 2020 (107, 61.8%) compared to 2019 (87, 46.8%) (p = 0.004). Conclusion: Fear of SARS-CoV-2 infection led to a significant avoidance of acute cardiac care with an accompanying rise in community cardiac deaths, suggesting a need for better public education on recognising and addressing cardiovascular symptoms.

Clinical outcomes at medium-term follow-up of COVID-19.

BACKGROUND: The long coronavirus disease 2019 (COVID-19) syndrome is defined as persistent physical, cognitive and/or psychological symptoms that continue for more than 12 weeks following the acute illness. METHODS: In all, 2,646 patients were randomly selected from all individuals who were diagnosed with COVID-19. They were interviewed so as to assess the persistence of symptoms and health-related quality of life. Blood investigations were also taken. RESULTS: The median (interquartile range (IQR)) age was 44 (31-55) years and 48.6% were males. Five per cent had been hospitalised. Follow-up was for a median of 142 days (IQR: 128-161). Twenty-two per cent of the participants claimed that they were feeling worse than they felt before COVID-19. The most common symptoms were anosmia, ageusia, fatigue, shortness of breath, headaches and myalgia. The Short Form-36 questionnaire revealed that 16.4% felt that they were somewhat worse than in the previous year and that hospitalised patients fared worse in all domains except for role-emotional. New-onset diabetes was similar to the rate of undiagnosed diabetes in the background population. Hospitalised patients had significantly higher liver transaminases, fasting plasma glucose, glycated haemoglobin, uric acid, red cell distribution width, mean platelet volume, triglyceride levels and troponin levels but lower estimated glomerular filtration rate and high-density lipoprotein-cholesterol at follow-up. DISCUSSION: A significant proportion of patients were symptomatic at a median follow-up of 142 days and felt worse than 1 year previously. Hospitalised patients had more biochemical and haematological abnormalities compared to non-hospitalised ones, suggesting ongoing inflammation in subjects who were more severely affected by the disease.

Gestational Glycemic Parameters and Future Cardiometabolic Risk at Medium-Term Follow Up.

OBJECTIVES: Gestational diabetes is known to be associated with increased risk for future maternal cardiovascular disease. However, it is not known which gestational glycemic parameters mediate this risk. The study's aim was to assess the relationship between gestational glycemic parameters and gestational diabetes with future cardiometabolic status. METHODS: This cohort study comprised subjects who underwent assessment for gestational diabetes by means of a 75 g oral glucose tolerance test at Mater Dei Hospital, Malta, during 2009. These patients were consequently followed up through January 2018. Carotid intima-media thickness was assessed as a marker of subclinical atherosclerosis in both common carotid arteries. RESULTS: The mean age of the study population was 38.3±5.4 years. Of the 203 participants, 43 (21.2%) had gestational diabetes. Gestational diabetes and individual glycemic parameters of intrapregnancy oral glucose tolerance tests were associated with higher glycated hemoglobin, fasting plasma glucose, low-density-cholesterol and lower high-density-cholesterol levels and with the presence of the metabolic syndrome in both univariate and multivariate analyses after a median follow up of 8 years. Neither gestational diabetes nor individual glycemic parameters of intrapregnancy oral glucose tolerance tests was associated with current carotid intima-media thickness. CONCLUSIONS: Our results suggest that there is no threshold of glycemic parameters for predicting future cardiometabolic status. Our data also suggest that the known association between gestational diabetes and cardiovascular disease is mediated, at least in part, by higher postpregnancy glycemia and worse lipid profiles, even though these metabolic parameters often remain within the normal range.

A case report of desmoid tumour-a forgotten aspect of FAP?

INTRODUCTION: Desmoid tumours are locally aggressive tumours which are common in Familial Adenomatous Polyposis (FAP). PRESENTATION OF CASE: A 20-year old Familial Adenomatous Polyposis (FAP) patient presented with abdominal pain and distention. Abdominal imaging showed small bowel obstruction and hydronephrosis due to a pelvic mass. This mass showed significant enlargement on repeat imaging, and a diagnostic biopsy confirmed desmoid tumour. The mass was deemed unresectable and he was initially started on sulindac and raloxifene. Repeat imaging however showed further enlargement of the tumour, and therefore vinblastine+methotrexate chemotherapy was commenced, with a good response. DISCUSSION: FAP is an autosomal dominant condition caused by a germline mutation in the adenomatous polyposis coli (APC) gene. Gardner's syndrome is also caused by a mutation in the APC gene, and is now considered a different phenotypic presentation of FAP. Desmoid tumours are initially kept under observation while their size remains stable. Treatment options for enlarging desmoids tumours include surgery (first-line), radiotherapy, and systemic therapy with non-cytotoxic and cytotoxic therapy. CONCLUSION: FAP patients should be examined regularly post-panprocotocolectomy, since desmoid tumours may arise. The presence of epidermal cysts in this FAP patient suggests a diagnosis of Gardner's syndrome.

Female gender and cardiovascular disease.

Despite a generalized belief that women are protected from cardiovascular disease, this remains the leading cause of death in women. This review focuses on differences in symptomatology, diagnostic modalities and therapeutic strategies in women with regard to cardiovascular disease.