Changes in fasting plasma glucose and subclinical atherosclerosis: A cohort study from VIPVIZA trial.

BACKGROUND AND AIMS: Studies on the influence of fasting plasma glucose (FPG) on the development of carotid plaque (CP) and intima media thickness (CIMT) mainly focused on single FPG measures. We investigated whether changes in FPG (ΔFPG) are associated with incident CP and CIMT change (ΔCIMT) over time. METHODS: Analyses were based on information from 1896 participants from the VIPVIZA trial (Visualization of asymptomatic atherosclerotic disease for optimum cardiovascular prevention), with baseline and 3-year follow-up data on FPG, ultrasonographic CP (none or ≥1 lesion/s) and CIMT assessments. We studied the association between baseline FPG (prior to intervention) or 3-year ΔFPG (mmol/L) and incident CP (logistic regression) or ΔCIMT (linear regression). Analyses were adjusted for multiple potential confounders. RESULTS: 1896 and 873 individuals, respectively, were included in the analysis on incident CP and ΔCIMT. Participants were 60 years old at baseline and 61% and 54% were females, in the CP and CIMT analyses, respectively. Every mmol/L increase in FPG was associated with an increased odds of incident CP (odds ratio: 1.42, 95% confidence interval [CI]: 1.17, 1.73), but there was no association with ΔCIMT (mean difference: 0.002 mm, 95% CI: -0.003, 0.008) after 3 years. Baseline FPG was not associated with incident CP nor ΔCIMT progression. CONCLUSIONS: In middle-aged individuals with low to moderate risk for cardiovascular diseases, 3-year ΔFPG was positively associated with the risk of incident CP, but not with ΔCIMT. Single measures of FPG may not be sufficient in estimating cardiovascular risk among individuals with low to moderate risk.

COVID-19 Prevention: Vitamin D Is Still a Valid Remedy.

Seven meta-analyses and systematic reviews and three later clinical trials argued that low vitamin D status increased susceptibility to COVID-19 and the risk of greater disease severity and mortality [...].

Obesity Strongly Predicts COVID-19-Related Major Clinical Adverse Events in Coptic Clergy.

BACKGROUND AND AIMS: The Coptic clergy, due to their specific work involving interaction with many people, could be subjected to increased risk of infection from COVID-19. The aim of this study, a sub-study of the COVID-19-CVD international study of the impact of the pandemic on the cardiovascular system, was to assess the prevalence of COVID-19 among Coptic priests and to identify predictors of clinical adverse events. METHODS: Participants were geographically divided into three groups: Group-I: Europe and USA, Group II: Northern Egypt, and Group III: Southern Egypt. Participants' demographic indices, cardiovascular risk factors, possible source of infection, number of liturgies, infection management, and major adverse events (MAEs), comprising death, or mechanical ventilation, were assessed. RESULTS: Out of the 1570 clergy serving in 25 dioceses, 255 (16.2%) were infected. Their mean age was 49.5 ± 12 years and mean weekly number of liturgies was 3.44 ± 1.0. The overall prevalence rate was 16.2% and did not differ between Egypt as a whole and overseas (p = 0.23). Disease prevalence was higher in Northern Egypt clergy compared with Europe and USA combined (18.4% vs. 12.1%, p = 0.03) and tended to be higher than in Southern Egypt (18.4% vs. 13.6%, p = 0.09). Ten priests (3.92%) died of COVID-19-related complications, and 26 (10.2) suffered a MAE. The clergy from Southern Egypt were more obese, but the remaining risk factors were less prevalent compared with those in Europe and USA (p = 0.01). In multivariate analysis, obesity (OR = 4.180; 2.479 to 12.15; p = 0.01), age (OR = 1.055; 0.024 to 1.141; p = 0.02), and systemic hypertension (OR = 1.931; 1.169 to 2.004; p = 0.007) predicted MAEs. Obesity was the most powerful independent predictor of MAE in Southern Egypt and systemic hypertension in Northern Egypt (p < 0.05 for both). CONCLUSION: Obesity is very prevalent among Coptic clergy and seems to be the most powerful independent predictor of major COVID-19-related adverse events. Coptic clergy should be encouraged to follow the WHO recommendations for cardiovascular disease and COVID-19 prevention.

Combined Cardiac Risk Factors Predict COVID-19 Related Mortality and the Need for Mechanical Ventilation in Coptic Clergy.

BACKGROUND AND AIMS: The clinical adverse events of COVID-19 among clergy worldwide have been found to be higher than among ordinary communities, probably because of the nature of their work. The aim of this study was to assess the impact of cardiac risk factors on COVID-19-related mortality and the need for mechanical ventilation in Coptic clergy. METHODS: Of 1570 Coptic clergy participating in the COVID-19-Clergy study, serving in Egypt, USA and Europe, 213 had the infection and were included in this analysis. Based on the presence of systemic arterial hypertension (AH), participants were divided into two groups: Group-I, clergy with AH (n = 77) and Group-II, without AH (n = 136). Participants' demographic indices, cardiovascular risk factors, COVID-19 management details and related mortality were assessed. RESULTS: Clergy with AH were older (p < 0.001), more obese (p = 0.04), had frequent type 2 diabetes (DM) (p = 0.001), dyslipidemia (p = 0.001) and coronary heart disease (CHD) (p = 0.04) compared to those without AH. COVID-19 treatment at home, hospital or in intensive care did not differ between the patient groups (p > 0.05 for all). Clergy serving in Northern and Southern Egypt had a higher mortality rate compared to those from Europe and the USA combined (5.22%, 6.38%, 0%; p = 0.001). The impact of AH on mortality was significant only in Southern Egypt (10% vs. 3.7%; p = 0.01) but not in Northern Egypt (4.88% vs. 5.81%; p = 0.43). In multivariate analysis, CHD OR 1.607 ((0.982 to 3.051); p = 0.02) and obesity, OR 3.403 ((1.902 to 4.694); p = 0.04) predicted COVID-19 related mortality. A model combining cardiac risk factors (systolic blood pressure (SBP) ≥ 160 mmHg, DM, obesity and history of CHD) was the most powerful independent predictor of COVID-19-related mortality, OR 3.991 ((1.919 to 6.844); p = 0.002). Almost the same model also proved the best independent multivariate predictor of mechanical ventilation OR 1.501 ((0.809 to 6.108); p = 0.001). CONCLUSION: In Coptic clergy, the cumulative impact of risk factors was the most powerful predictor of mortality and the need for mechanical ventilation.

The relationship between carotid and coronary calcification in patients with coronary artery disease.

BACKGROUND: Atherosclerosis is a multi-system pathology with heterogeneous involvement. We aimed to investigate the relationship between the presence and severity of carotid and coronary calcification in a group of patients with coronary artery disease. METHODS: Sixty-three patients presenting with unstable angina or positive stress test for myocardial ischaemia were enrolled in this study. All patients underwent CT scanning of the carotid and coronary arteries using the conventional protocol and Agatston scoring system. Risk factors for atherosclerosis were also analyzed for correlation with the extent of arterial calcification. RESULTS: Total coronary artery calcium score (CAC) was several times higher than total carotid calcium score (1274 (1018) vs 6 (124), p = 0·0001, respectively). The left carotid calcium score correlated strongly with the right carotid calcium score (rho = 0·69, p < 0·0001). The total CAC score correlated modestly with the total carotid calcium score (rho = 0·34, p = 0·007), in particular with left carotid score (rho = 0·38, p = 0·002), but not with the right carotid score. The left coronary calcium score correlated with the right coronary calcium score (rho = 0·35, p = 0·004), left carotid calcium score (rho = 0·33, p = 0·007) and left carotid calcium score at the bifurcation (rho = 0·34, p = 0·006). While hypertension correlated with carotid calcium score, diabetes and dyslipidaemia correlated with left CAC score. CONCLUSION: In patients with coronary disease, the carotid calcification pattern appeared to be similar between the right and left system in contrast to that of the coronary arteries. CAC correlated only modestly with the carotid score, despite being significantly higher. Hypertension was related to carotid calcium score while diabetes and dyslipidaemia correlated with coronary calcification.

Sickness behavior may follow fracture as well as infection.

Sickness behavior, induced by pro-inflammatory cytokines in the early stages of an infection, is well known. A case report of three fracture patients, who were not taking analgesic medication, suggests that the initial symptoms experienced, particularly fatigue and mood changes, mirror those of the sickness behavior of infection. A mini-review only found studies investigating one physical, mental or emotional symptom in fracture patients and none drew a parallel with sickness behavior, suggesting that this is a hitherto unrecognised phenomenon which would benefit from further investigation.

Environmental Contaminants and Congenital Heart Defects: A Re-Evaluation of the Evidence.

Congenital heart defects (CHDs) are a common birth defect of largely unknown etiology, with high fetal and neonatal mortality. A review of CHDs and environmental contaminant exposure found that meta-analyses showed only modest associations for smoking, vehicle exhaust components, disinfectant by-products and proximity to incinerators, with stronger results from the newer, larger and better quality studies masked by the typical absence of effect in older studies. Recent studies of exposure to agricultural pesticides, solvents, metals and landfill sites also showed associations. Certain contaminants have been associated with certain CHDs, with septal defects being the most common. Frequent methodological problems include failure to account for potential confounders or maternal/paternal preconception exposure, differences in diagnosing, defining and classifying CHDs, grouping of defects to increase power, grouping of contaminants with dissimilar mechanisms, exclusion of pregnancies that result in death or later life diagnosis, and the assumption that maternal residence at birth is the same as at conception. Furthermore, most studies use measurement estimates of one exposure, ignoring the many additional contaminant exposures in daily life. All these problems can distort and underestimate the true associations. Impaired methylation is a common mechanism, suggesting that supplementary folate may be protective for any birth defect.

Caloric Restriction and Its Effect on Blood Pressure, Heart Rate Variability and Arterial Stiffness and Dilatation: A Review of the Evidence.

Essential hypertension, fast heart rate, low heart rate variability, sympathetic nervous system dominance over parasympathetic, arterial stiffness, endothelial dysfunction and poor flow-mediated arterial dilatation are all associated with cardiovascular mortality and morbidity. This review of randomised controlled trials and other studies demonstrates that caloric restriction (CR) is capable of significantly improving all these parameters, normalising blood pressure (BP) and allowing patients to discontinue antihypertensive medication, while never becoming hypotensive. CR appears to be effective regardless of age, gender, ethnicity, weight, body mass index (BMI) or a diagnosis of metabolic syndrome or type 2 diabetes, but the greatest benefit is usually observed in the sickest subjects and BP may continue to improve during the refeeding period. Exercise enhances the effects of CR only in hypertensive subjects. There is as yet no consensus on the mechanism of effect of CR and it may be multifactorial. Several studies have suggested that improvement in BP is related to improvement in insulin sensitivity, as well as increased nitric oxide production through improved endothelial function. In addition, CR is known to induce SIRT1, a nutrient sensor, which is linked to a number of beneficial effects in the body.

Coronary calcification compromises myocardial perfusion irrespective of luminal stenosis.

AIM: The aim of this study was to evaluate the relationship between coronary artery calcification (CAC) assessed by multi-detector computed tomography (MDCT) and myocardial perfusion assessed by cardiac magnetic resonance imaging (CMR) in a group of symptomatic patients. METHOD: Retrospective analysis of 120 patients (age 65.1 ± 8.9 years, 88 males) who presented with atypical chest pain to Bethanien Hospital, Frankfurt, Germany, between 2007 and 2010 and who underwent CAC scoring using MDCT, CMR, and conventional coronary angiography. Patients were divided into those with high-grade (HG) stenosis (n = 67, age 65.1 ± 9.4 years) and those with no-HG stenosis (n = 53, age 65.1 ± 8.6 years). RESULTS: There were more males with HG stenosis (82.1% vs. 62.3%, p = 0.015), in whom the percentage and number of abnormal perfusion segments were higher at rest (37.3% vs. 17%, p = 0.014) but not different with stress (p = 0.83) from those with no-HG stenosis. Thirty-four patients had myocardial perfusion abnormalities at rest and 26 patients developed perfusion defects with stress. Stress-induced myocardial perfusion defects were 22.4% sensitive and 79.2% specific for detecting HG stenosis. The CAC score was lower in patients with no-HG stenosis compared to those with HG stenosis (p < 0.0001). On the ROC curve, a CAC score of 293 had a sensitivity of 71.6% and specificity of 83% in predicting HG stenosis [(AUC 0.80 (p < 0.0001)]. A CAC score of 293 or the presence of at least 1 segment myocardial perfusion abnormality was 74.6% sensitive and 71.7% specific in detecting HG stenosis, the respective values for the 2 abnormalities combined being 19.4% and 90.6%. The severity of CAC correlated with the extent of myocardial perfusion in the patient group as a whole with stress (r = 0.22, p = 0.015), particularly in those with no-HG stenosis (r = 0.31, p = 0.022). A CAC score of 293 was 31.6% sensitive and 87.3% specific in detecting myocardial perfusion abnormalities. CONCLUSION: In a group of patients with exertional angina, coronary calcification is more accurate in detecting high-grade luminal stenosis than myocardial perfusion defects. In addition, in patients with no stenosis, the incremental relationship between coronary calcium score and the extent of myocardial perfusion suggests coronary wall hardening as an additional mechanism for stress-induced angina other than luminal narrowing. These preliminary findings might have a clinical impact on management strategies of these patients other than conventional therapy.

Diabetes and male sex are key risk factor correlates of the extent of coronary artery calcification: A Euro-CCAD study.

BACKGROUND AND AIMS: Although much has been written about the conventional cardiovascular risk factor correlates of the extent of coronary artery calcification (CAC), few studies have been carried out on symptomatic patients. This paper assesses the potential ability of risk factors to associate with an increasing CAC score. METHODS: From the European Calcific Coronary Artery Disease (Euro-CCAD) cohort, we retrospectively investigated 6309 symptomatic patients, 62% male, from Denmark, France, Germany, Italy, Spain and the USA. All had conventional cardiovascular risk factor assessment and CT scanning for CAC scoring. RESULTS: Among all patients, male sex (OR = 4.85, p<0.001) and diabetes (OR = 2.36, p<0.001) were the most important risk factors of CAC extent, with age, hypertension, dyslipidemia and smoking also showing a relationship. Among patients with CAC, age, diabetes, hypertension and dyslipidemia were associated with an increasing CAC score in males and females, with diabetes being the strongest dichotomous risk factor (p<0.001 for both). These results were echoed in quantile regression, where diabetes was consistently the most important correlate with CAC extent in every quantile in both males and females. To a lesser extent, hypertension and dyslipidemia were also associated in the high CAC quantiles and the low CAC quantiles respectively. CONCLUSION: In addition to age and male sex in the total population, diabetes is the most important correlate of CAC extent in both sexes.

Diabetes and Hypertension Consistently Predict the Presence and Extent of Coronary Artery Calcification in Symptomatic Patients: A Systematic Review and Meta-Analysis.

BACKGROUND: The relationship of conventional cardiovascular risk factors (age, gender, ethnicity, diabetes, dyslipidaemia, hypertension, obesity, exercise, and the number of risk factors) to coronary artery calcification (CAC) presence and extent has never before been assessed in a systematic review and meta-analysis. METHODS: We included only English language studies that assessed at least three conventional risk factors apart from age, gender, and ethnicity, but excluded studies in which all patients had another confirmed condition such as renal disease. RESULTS: In total, 10 studies, comprising 15,769 patients, were investigated in the systematic review and seven studies, comprising 12,682 patients, were included in the meta-analysis, which demonstrated the importance of diabetes and hypertension as predictors of CAC presence and extent, with age also predicting CAC presence. Male gender, dyslipidaemia, family history of coronary artery disease, obesity, and smoking were overall not predictive of either CAC presence or extent, despite dyslipidaemia being a key risk factor for coronary artery disease (CAD). CONCLUSION: Diabetes and hypertension consistently predict the presence and extent of CAC in symptomatic patients.

The effect of statins therapy in aortic stenosis: Meta-analysis comparison data of RCTs and observationals.

Aortic stenosis has been shown to share the same risk factors as atherosclerosis which suggested a potential benefit from statins therapy. Fourteen studies which provided the effect of statins treatment on aortic stenosis (AS) were meta-analyzed, including 5 randomized controlled trials (RCTs) and 9 observational studies. In the RCTs, statins did not have any influence on peak aortic valve velocity, peak valve gradient, mean valve gradient, aortic valve area and aortic calcification compared to controls. In the observational studies, the peak valve velocity, peak gradient and aortic valve area showed less progression in the statins group compared to controls. This article describes data related article title "The effect of statins on valve function and calcification in aortic stenosis: a meta-analysis" (Zhao et al., 2016) [1].

The effect of statins on valve function and calcification in aortic stenosis: A meta-analysis.

BACKGROUND: Aortic calcification has been shown to share the same risk factors as atherosclerosis which suggested a potential benefit from statins therapy. In view of the existing conflicting results, we aimed to provide objective evidence on the effect of statins in aortic stenosis (AS). METHODS AND RESULTS: A meta-analysis of eligible studies that used statins in AS was performed. Fourteen studies were identified, 5 randomized controlled trials (RCTs) and 9 observational studies. In the 14 studies as a whole, no significant differences were found in all cause mortality (OR = 0.98, p = 0.91), cardiovascular mortality (OR = 0.80, P = 0.23) or the need for valve replacement (OR = 0.93, p = 0.45) between the statins and the control groups. LDL-cholesterol dropped in the statins groups in both <24 months and ≥ 24 months follow-up (p < 0.001 for both) but not in controls (p = 0.35 and p = 0.33, respectively). In the <24 months statins group, the annual increase in peak aortic velocity and peak gradient was less (p < 0.0001 and p = 0.004, respectively), but the mean gradient, valve area and calcification score were not different from controls. In the ≥ 24 months statins group, none of the above parameters was different from controls. CONCLUSIONS: Despite the consistent beneficial effect of statins on LDL-cholesterol levels, the available evidence showed no effect on aortic valve structure, function or calcification and no benefit for clinical outcomes.

A review of the effect of diet on cardiovascular calcification.

Cardiovascular (CV) calcification is known as sub-clinical atherosclerosis and is recognised as a predictor of CV events and mortality. As yet there is no treatment for CV calcification and conventional CV risk factors are not consistently correlated, leaving clinicians uncertain as to optimum management for these patients. For this reason, a review of studies investigating diet and serum levels of macro- and micronutrients was carried out. Although there were few human studies of macronutrients, nevertheless transfats and simple sugars should be avoided, while long chain ω-3 fats from oily fish may be protective. Among the micronutrients, an intake of 800 µg/day calcium was beneficial in those without renal disease or hyperparathyroidism, while inorganic phosphorus from food preservatives and colas may induce calcification. A high intake of magnesium (≥380 mg/day) and phylloquinone (500 µg/day) proved protective, as did a serum 25(OH)D concentration of ≥75 nmol/L. Although oxidative damage appears to be a cause of CV calcification, the antioxidant vitamins proved to be largely ineffective, while supplementation of α-tocopherol may induce calcification. Nevertheless other antioxidant compounds (epigallocatechin gallate from green tea and resveratrol from red wine) were protective. Finally, a homocysteine concentration >12 µmol/L was predictive of CV calcification, although a plasma folate concentration of >39.4 nmol/L could both lower homocysteine and protect against calcification. In terms of a dietary programme, these recommendations indicate avoiding sugar and the transfats and preservatives found in processed foods and drinks and adopting a diet high in oily fish and vegetables. The micronutrients magnesium and vitamin K may be worthy of further investigation as a treatment option for CV calcification.

The acid-ash hypothesis revisited: a reassessment of the impact of dietary acidity on bone.

The acid-ash hypothesis states that when there are excess blood protons, bone is eroded to provide alkali to buffer the net acidity and maintain physiologic pH. There is concern that with the typical Western diet, we are permanently in a state of net endogenous acid production, which is gradually reducing bone. While it is clear that a high acid-producing diet generates increased urinary acid and calcium excretion, the effect of diet does not always have the expected results on BMD, fracture risk and markers of bone formation and resorption, suggesting that other factors are influencing the effect of acid/alkali loading on bone. High dietary protein, sodium and phosphorus intake, all of which are necessary for bone formation, were thought to be net acid forming and contribute to low BMD and fracture risk, but appear under certain conditions to be beneficial, with the effect of protein being driven by calcium repletion. Dietary salt can increase short-term markers of bone resorption but may also trigger 1,25(OH)2D synthesis to increase calcium absorption; with low calcium intake, salt intake may be inversely correlated with BMD but with high calcium intake, salt intake was positively correlated with BMD. With respect to the effect of phosphorus, the data are conflicting. Inclusion of an analysis of calcium intake may help to reconcile the contradictory results seen in many of the studies of bone. The acid-ash hypothesis could, therefore, be amended to state that with an acid-producing diet and low calcium intake, bone is eroded to provide alkali to buffer excess protons but where calcium intake is high the acid-producing diet may be protective.

The predictive value of arterial and valvular calcification for mortality and cardiovascular events.

A review of the predictive ability of arterial and valvular calcification has shown an additive effect of calcification in more than 1 location in predicting mortality and coronary heart disease, with mitral annual calcification being a particularly strong predictor. In individual arteries and valves there is a clear association between calcification presence, extent and progression and future cardiovascular events and mortality in asymptomatic, symptomatic and high risk patients, although adjustment for calcification in other arterial beds generally renders associations non-significant. Furthermore, in acute coronary syndrome, culprit plaque is normally not calcified. This would tend to reduce the validity of calcification as a predictor and suggest that the association with cardiovascular events and mortality may not be causal. The association with stroke is less clear; carotid and intracranial artery calcification show little predictive ability, with symptomatic plaques tending to be uncalcified.

Coronary and carotid atherosclerosis: how useful is the imaging?

The recent advancement of imaging modalities has made possible visualization of atherosclerosis disease in all phases of its development. Markers of subclinical atherosclerosis or even the most advanced plaque features are acquired by invasive (IVUS, OCT) and non-invasive imaging modalities (US, MRI, CTA). Determining plaques prone to rupture (vulnerable plaques) might help to identify patients at risk for myocardial infarction or stroke. The most accepted features of plaque vulnerability include: thin cap fibroatheroma, large lipid core, intimal spotty calcification, positive remodeling and intraplaque neovascularizations. Today, research is focusing on finding imaging techniques that are less invasive, less radiation and can detect most of the vulnerable plaque features. While, carotid atherosclerosis can be visualized using noninvasive imaging, such as US, MRI and CT, imaging plaque feature in coronary arteries needs invasive imaging modalities. However, atherosclerosis is a systemic disease with plaque development simultaneously in different arteries and data acquisition in carotid arteries can add useful information for prediction of coronary events.

Arterial calcification: friend or foe?

There is a significant relationship between the presence, extent and progression of coronary artery calcification (CAC) and cardiovascular (CV) events and mortality in both CV and renal patients and CAC scoring can provide improved predictive ability over risk factor scoring alone. There is also a close relationship between CAC presence and atherosclerotic plaque burden, with angiography studies showing very high sensitivity but poor specificity of CAC score for predicting obstructive disease. Nevertheless, there are objections to CAC screening because of uncertainties and lack of studies showing improved outcome. Furthermore, histopathology studies indicate that heavily calcified plaque is unlikely to result in a CV event, while the vulnerable plaque tends to be uncalcified or 'mixed', suggesting that calcification may be protective. This scenario highlights a number of paradoxes, which may indicate that the association between CAC and CV events is spurious, following from the adoption of CAC as a surrogate for high plaque burden, which itself is a surrogate for the presence of vulnerable plaque. Since studies indicate that arterial calcification is a complex, organised and regulated process similar to bone formation, there is no particular reason why it should be a reliable indicator of either the plaque burden or the risk of a future CV event. We suggest that it is time to divorce arterial calcification from atherosclerosis and to view it as a distinct pathology in its own right, albeit one which frequently coexists with atherosclerosis and is related to it for reasons which are not yet fully understood.