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.

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.

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.

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.

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.

CYP2C19*2 genetic polymorphism and incidence of in-stent restenosis in patients on clopidogrel: a matched case-control study.

OBJECTIVES: The cytochrome P450 2C19*2 (CYP2C19*2) genetic polymorphism is associated with reduced clopidogrel bioactivation, increasing the risk of atherothrombotic complications after percutaneous coronary intervention (PCI). In-stent restenosis (ISR) is a complication that limits the long-term prognosis of PCI. The aim was to investigate the association between presence of the CYP2C19*2 allele and ISR within one-year after PCI in patients prescribed dual antiplatelet therapy with aspirin and clopidogrel. METHODS: Sixty patients with angiographically-confirmed drug eluting stent (DES)-ISR within 12 months post-PCI when on DAPT with aspirin and clopidogrel were retrospectively identified (Cases). Another 60 patients with no documented ISR post-PCI in the study period (Controls) were case-matched for age, gender, ethnicity, diabetes mellitus and estimated glomerular filtration rate value, and were invited for CYP2C19*2 genotyping. The association between presence of the CYP2C19*2 allele and ISR was analysed using the Fisher's exact test and binary logistic regression. RESULTS: Twenty-six (43.3%) cases and 5 (8.3%) controls were carriers of one or two CYP2C19*2 alleles. As to non-carrier status of the CYP2C19*2 allele, 34 (56.7%) cases and 55 (91.7%) controls were identified. The association between CYP2C19*2 carrier status and DES-ISR within one-year post-PCI was statistically significant (p<0.001) in both the univariate and multivariate analysis. CONCLUSIONS: The proportion of patients who were carriers of one or two CYP2C19*2 alleles who presented with DES-ISR within one-year post-PCI while on clopidogrel was significantly higher compared to patients with no documented ISR.

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.

Relationship of Hyperglycaemia, Hypoglycaemia, and Glucose Variability to Atherosclerotic Disease in Type 2 Diabetes.

OBJECTIVE: Type 2 diabetes mellitus (T2DM) is known to be associated with increased cardiovascular risk. The aim of this study was therefore to investigate the independent effects of hyperglycaemia, hypoglycaemia, and glucose variability on microvascular and macrovascular disease in T2DM. METHODS: Subjects with T2DM of <10 years duration and on stable antiglycaemic treatment underwent carotid intima-media thickness (CIMT), ankle-brachial index (ABI), albumin-creatinine ratio (ACR), and HbA1c measurement, as well as 72-hour continuous glucose monitoring. Macrovascular disease was defined as one or more of the following: history of ischaemic heart disease (IHD), cerebrovascular accident (CVA), ABI < 0.9, or abnormal CIMT. RESULTS: The study population comprised 121 subjects with T2DM (89 males : 32 females). The mean age was 62.6 years, and the mean DM duration was 3.7 years. Macrovascular disease was present in 71 patients (58.7%). In multivariate logistic regression analysis, body surface area (BSA) (OR 18.88 (95% CI 2.20-156.69), p = 0.006) and duration of blood glucose (BG) < 3.9 mmol/L (OR 1.12 (95% CI 1.014-1.228), p = 0.024) were independent predictors of macrovascular disease. BSA (OR 12.6 (95% CI 1.70-93.54), p = 0.013) and duration of BG < 3.9 mmol/L (OR 1.09 (95% CI 1.003-1.187), p = 0.041) were independent predictors of abnormal CIMT. Area under the curve for BG > 7.8 mmol/L (ß = 15.83, p = 0.005) was the sole independent predictor of albuminuria in generalised linear regression. CONCLUSIONS: This study demonstrates that hypoglycaemia is associated with the occurrence of atherosclerotic disease while hyperglycaemia is associated with microvascular disease in a Caucasian population with T2DM of recent duration.

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.

Comparison of a rapid point-of-care and two laboratory-based CYP2C19*2 genotyping assays for personalisation of antiplatelet therapy.

BACKGROUND: A quick CYP2C19*2 genotyping assay can be useful in personalised antiplatelet-therapy. OBJECTIVE: To apply a rapid point-of-care (POC) CYP2C19*2 genotyping assay for personalisation of antiplatelet therapy in patients undergoing percutaneous coronary intervention (PCI) and to compare this POC assay to two laboratory-based CYP2C19*2 genotyping assays. SETTING: Cardiac Catheterisation Suite and Molecular Diagnostics Unit in a general hospital. METHODS: A buccal sample was collected for POC CYP2C19*2 genotyping with the Spartan™ RX system (Spartan Bioscience). A whole blood sample was collected from the same patients for laboratory-based CYP2C19*2 genotyping with a TaqMan® allelic discrimination assay (Life Technologies) using real-time quantitative PCR and with the GenID® reverse dot-blot hybridisation assay (Autoimmun Diagnostika GmbH). Each patient was genotyped as a non-carrier of CYP2C19*2 (*1/*1), a carrier of one CYP2C19*2 allele (*1/*2), or a carrier of two CYP2C19*2 alleles (*2/*2). Genotyping, interpretation and communication of genotype results (*1/*2, *2/*2) to the consultant cardiologist was undertaken by a clinical pharmacist researcher. Quantitative and qualitative comparison between the three assays was carried out. MAIN OUTCOME MEASURES: Application of a rapid POC CYP2C19*2 genotyping assay for antiplatelet therapy individualisation; comparison of the POC CYP2C19*2 genotyping assay to two laboratory-based assays. RESULTS: The total sample consisted of 34 Caucasian patients. With the POC assay, 21 patients were genotyped as non-carriers of CYP2C19*2, 12 patients as carriers of one CYP2C19*2 allele and one patient as a carrier of two CYP2C19*2 alleles. With both laboratory-based assays, the same 21 patients were genotyped as non-carriers of CYP2C19*2, however 13 patients were genotyped as carriers of one CYP2C19*2 allele and no patients were genotyped as carriers of two CYP2C19*2 alleles. Agreement in genotype results was 97 % (κ = 0.939) between the POC assay and both laboratory-based assays and 100 % (κ = 1.000) between the two laboratory-based assays. CONCLUSION: Compared to both laboratory-based genotyping assays, the POC assay is accurate and reliable, provides rapid results, can process single samples, is portable and more operator-friendly, however the tests are more expensive.

Non-dipping heart rate and microalbuminuria in type 2 diabetes mellitus.

OBJECTIVES: The aim of this study was to identify factors which are independently associated with non-dipping heart rate (HR) in a type 2 diabetic population at high risk of cardiovascular disease. METHODS: The study recruited 179 type 2 diabetic subjects with a mean diabetes duration of 18.3 years and with proliferative retinopathy. All underwent 24-hour blood pressure and HR monitoring, and were assessed for markers of inflammation, insulin resistance, albuminuria, presence of peripheral neuropathy and peripheral vascular disease. Subjects whose night-time HR did not decrease by more than 10% as compared to daytime readings were classified as non-dippers. RESULTS: Univariate analysis revealed that non-dippers had significantly higher logarithmic albumin-creatinine ratio (ACR; p = 0.001) and higher platelet count (p = 0.014). Also, non-dippers were more likely to be on ß-blockers (p = 0.037). Binary logistic regression analysis showed that logarithmic ACR (p = 0.001) and platelet count (p = 0.026) were independent predictors of non-dipping HR, even when correcting for ß-blocker use. CONCLUSIONS: In this high-risk type 2 diabetic population, non-dipping HR was independently associated with ACR and platelet count, suggesting that non-dipping HR might give an indication of underlying generalised atherosclerosis in diabetic patients. Also, non-dipping HR may represent a novel mechanism explaining the association of nephropathy with cardiovascular events. This merits further study.

Stress echocardiography vs nuclear stress imaging in clinical cardiology.

Stress echocardiography and nuclear stress imaging are important non-invasive tools in clinical cardiology. This review discusses the uses, strengths and limitations of these imaging modalities and looks at whether stress echocardiography can actually replace nuclear stress imaging.