Absence Of Conventional Risk Factors Research Articles

HPV‐related oropharyngeal cancer: preventable and treatable if recognised early

Oncogenic human papilloma virus (HPV) currently accounts for 50% of throat cancer cases in men in the UK. Due to the absence of conventional risk factors for head and neck cancer, many men are diagnosed late. Despite this, cure rates are high. Typically, the treatment is with surgery or chemoradiotherapy. The recently introduced programme of HPV vaccination in boys should, in the long‐term, see a dramatic reduction in this cancer type.

A low-carbohydrate diet in place of SGLT2i therapy in a patient with diabetic cardiomyopathy.

In patients with diabetes mellitus, the toxic milieu caused by abnormal glucose and free fatty acid handling can lead to heart failure (HF). Referred to as diabetic cardiomyopathy (DMCM), this syndrome often exists in the absence of conventional risk factors for HF such as history of myocardial infarction or hypertension. Low-carbohydrate diets (LCDs) have recently been endorsed as an efficacious therapeutic dietary approach to prevent and reverse cardiometabolic disease including type 2 diabetes mellitus (T2DM). LCDs improve systemic insulin resistance (IR), reverses cardiac remodelling in a rodent model and downregulates the expression of sodium-glucose co-transporter 2 (SGLT2) receptors in the kidney. It is therefore conceivable that a lifestyle approach such as adopting an LCD can be offered to patients with DMCM. The reported case is that of a 45-year-old man with a 15-year history of non-ischaemic cardiomyopathy, T2DM and obesity. The patient volunteered to engage in a 16-week low-carbohydrate dietary intervention trial and then self-selected to remain on this diet for 1 year. The whole-food LCD was based on simple 'traffic light' style food lists and not designed to restrict calories, protein, fat or salt. After 1 year, the patient had lost 39 kg and his cardiometabolic markers had significantly improved. LCDs present a potentially beneficial approach for patients with DMCM and could be considered as a lifestyle intervention before SGLT2i therapy is commenced. Diabetic cardiomyopathy (DMCM) is a syndrome precipitated mainly by the detrimental effects of glucose metabolism disorders such as insulin resistance and diabetes. Low-carbohydrate diets (LCD) mimic many effects of sodium-glucose co-transporter 2 inhibitors (SGLT2i). LCDs are a dietary pattern which can have significant and beneficial effects on metabolic and anthropometric markers in patients with DMCM. LCDs and SGLT2i therapy could be combined and may achieve better clinical outcomes for patients with DMCM. Combination therapy may be carried out under close supervision as the real risk for diabetic ketoacidosis remains.

Atherogenic index of plasma predicts coronary artery disease severity and major adverse cardiac events in absence of conventional risk factors.

Various overlapping risk factors lead to coronary artery disease (CAD). The atherogenic index of plasma (AIP) is a marker for CAD severity and progression. However, little is known about its contribution to the residual risk of CAD observed in the absence of all typical risk factors. A prospective cohort study of 366 Indian patients undergoing coronary computed tomography (CT) angiography and diagnosed with stable CAD. Diabetes, hypertension, hypercholesterolemia, smoking, previous CAD, alcohol or lipid-lowering medication intake, renal, liver or thyroid dysfunction were exclusion criteria. Coronary stenosis was graded using the CAD-reporting and data system (CAD-RADS™) system. Lipid profile, HbA1c, uric acid, highly sensitive C-reactive protein (hsCRP) and anthropometric measurements were taken. AIP, triglyceride/high-density lipoprotein cholesterol (HDLc) and total cholesterol (Tc)/HDLc ratios were calculated. Independent predictors of CAD severity and the occurrence of major adverse cardiac events (MACE) during 2.57 (0.52) years of follow-up were identified using logistic regression and Cox proportional hazards regression. Sixty patients experienced a MACE during a cumulative 887.03 person-years. HbA1c, uric acid, hsCRP, Tc/HDLc and AIP were independent predictors of severe coronary lesions (CAD-RADS 4,5) on multivariate analysis with odds ratio 4.52 (2.37-8.61), 1.41 (1.08-1.84), 1.33 (1.09-1.62), 1.76 (1.27-2.44) and 1.29 (1.11-1.50), respectively. Only AIP and Tc/HDLc were independent predictors of MACE with hazard ratios of 1.41 (1.20-1.65) and 1.78 (1.33-2.39) besides patient age and CAD severity. AIP is associated with both the severity of CAD and the occurrence of MACE within 3 years. It could serve as an effective marker of residual risk of CAD in patients devoid of traditional risk factors. Lipid-profile ratios, such as AIP are cost-effective and accessible parameters suitable for low and middle-income settings.

The presence of non-alcoholic fatty liver disease adds to the cardiovascular risk in patients with inflammatory bowel disease.

Background and Aim: Patients with Inflammatory Bowel Disease (IBD) can have an increased risk of developing cardiovascular diseases, even in the absence of conventional risk factors. We compared the Carotid Intima-Media Thickness(CIMT), a surrogate marker for atherosclerosis, of subjects with and without IBD to study the cardiovascular risk. We also looked at whether NAFLD is an important factor affecting CIMT in IBD.

Cardiovascular and systemic determinants of exercise capacity in people with type 2 diabetes mellitus.

The global burden of heart failure (HF) is on the rise owing to an increasing incidence of lifestyle related diseases, predominantly type 2 diabetes mellitus (T2D). Diabetes is an independent risk factor for cardiovascular disease, and up to 75% of those with T2D develop HF in their lifetime. T2D leads to pathological alterations within the cardiovascular system, which can progress insidiously and asymptomatically in the absence of conventional risk factors. Reduced exercise tolerance is consistently reported, even in otherwise asymptomatic individuals with T2D, and is the first sign of a failing heart. Because aggressive modification of cardiovascular risk factors does not eliminate the risk of HF in T2D, it is likely that other factors play a role in the pathogenesis of HF. Early identification of individuals at risk of HF is advantageous, as it allows for modification of the reversible risk factors and early initiation of treatment with the aim of improving clinical outcomes. In this review, cardiac and extra-cardiac contributors to reduced exercise tolerance in people with T2D are explored.

Correlation of hyper-homocysteinemia with coronary artery disease in absence of conventional risk factors among young adults

ObjectiveCoronary artery disease is major cause of mortality and morbidity. Homocysteine has long been postulated as an underlying factor for atherosclerosis leading to coronary artery disease, yet its role in young patients is uncertain. This study was aimed to analyze the correlation between plasma homocysteine and coronary artery disease among young adults in the absence of conventional risk factors. MethodsIt was a case-control study carried out at Rehman Medical Institute, Peshawar, Pakistan from October 1, 2016, to September 30, 2017. Universal sampling technique was adopted and 158 participants were included. A total of 30 participants were in the control group and 128 were in the patient group, who had moderate to severe stenosis in either single or multiple major coronary arteries on coronary angiography and aged <40 years. ResultsCases and controls had similar characteristics but differed significantly in serum homocysteine concentration. In the control group, the mean plasma homocysteine concentration of 6.3 (±2.05) μmol/L and in the patient group a mean plasma homocysteine concentration of 44.5 (±14.01) μmol/L was observed. All the patients with moderate to severe stenosis in single or major coronary arteries had raised plasma homocysteine concentrations. Among 128 patients, 15 (11.7%) had moderate increase, 109 (85.2%) had intermediate increase, and four (3.1%) had severe increase in plasma homocysteine levels. Single vessel coronary artery disease was observed in 118 (92.2%) patients, whereas 10 (7.8%) had more than one major coronary artery involvement. ConclusionHyper-homocysteinemia has positive correlation with coronary artery disease among young adults in the absence of conventional risk factors.

Assessment of subclinical atherosclerosis in psoriatic arthritis patients without clinically overt cardiovascular disease or traditional atherosclerosis risk factors.

Cardiovascular disease (CVD) is more prevalent in almost all patients with chronic inflammatory musculoskeletal diseases than in their healthy counterparts. The aim of this study was to assess the presence of subclinical atherosclerosis in patients with psoriatic arthritis (PsA) in comparison with patients with rheumatoid arthritis (RA) and healthy controls. A total of 30 patients with PsA, 30 patients with RA, and 30 healthy controls were enrolled in this parallel group study. Demographic, clinical, and laboratory data of the groups were recorded. The Disease Activity Score-28 tool was used for joint assessment. The erythrocyte sedimentation rate and C-reactive protein level were measured as acute phase reactants. Flow-mediated dilatation (FMD) and carotid intima media thickness (CIMT) were also measured in all participants. The median duration of disease in patients with PsA was 60 months (range: 8-216 months). A total of 22 of 30 (73.3%) PsA patients had a diagnosis of psoriasis and 13 (48.1%) had active disease. The study groups were similar with regard to age, gender, and body mass index data. In all, 23 (76.7%) of the PsA patients and 5 (16.7%) of the RA patients were using an anti-tumor necrosis factor alpha therapy (p<0.001). The FMD percentage was significantly smaller in both the PsA and the RA patients than in the healthy controls (p<0.001). The median CIMT was greater in the RA patients compared with the PsA patients and the healthy controls (p=0.008). There was no significant difference in FMD or CIMT between patients with and without an active joint lesion. Endothelial functions were impaired in PsA, as in RA, in the absence of conventional risk factors or overt CVD. This finding may show a potential association between PsA, atherosclerosis, and CVD.

Abstract P321: Pregnancy Loss is Associated With Subclinical Cardiovascular Disease in Mexican Women

Introduction: Cardiovascular disease (CVD) in women often develops in the absence of conventional risk factors. Prenatal loss, a common pregnancy outcome, may result in physiologic changes that could affect future risk of myocardial infarction. Little is known about the impact of pregnancy loss on early markers of CVD risk. Hypothesis: Pregnancy loss affects carotid artery intima-media thickness (CIMT). Methods: We conducted a cross-sectional analysis among 1,769 disease-free women from the Mexican Teachers’ Cohort who had been pregnant to evaluate the relation between pregnancy loss and CIMT. In 2008 participants answered a baseline questionnaire on reproductive history, risk factors for chronic disease and medical conditions that was updated in 2011. We defined pregnancy loss as abortion and/or stillbirth. Between 2012 and 2016, CIMT was measured by trained neurologists using ultrasound in three clinical sites. We log-transformed CIMT and defined carotid atherosclerosis as CIMT ≥0.8mm or plaque. We used multivariable linear and logistic regression models to assess the relation between pregnancy loss, CIMT and carotid atherosclerosis. Results: Mean age of participants was 49.8 (SD ± 5.1) years. The prevalence of pregnancy loss was 22% (394 of 1769) , while we observed carotid atherosclerosis in 23% (405 of 1769) of participants. Comparing participants who reported a pregnancy loss to those who did not, the multivariable-adjusted odds ratio for carotid atherosclerosis was 1.52 (95% CI 1.12, 2.06). Women who experienced a stillbirth had 2.32 higher odds (95% CI 1.03, 5.21) of carotid atherosclerosis than those who did not. Mean CIMT appeared to be higher in women who reported a pregnancy loss relative to those who did not, however, in multivariable analyses, pregnancy loss and stillbirth were not significantly associated with CIMT. Conclusions: Abortion and stillbirth may be associated with a higher risk of CVD. Additional investigation on potential underlying mechanisms for this association is required.

Cardiovascular magnetic resonance imaging in hypertrophic cardiomyopathy: Current state of the art.

Hypertrophic cardiomyopathy (HCM) is the most common genetic cardiomyopathy with a prevalence of 1:500 (0.2%) in the general population. Sudden cardiac death (SCD) is the most feared presentation of HCM. Therefore, it is essential to identify individuals at high risk in order to prevent SCD. The absence of conventional risk factors does not nullify the risk of HCM related SCD. Although echocardiography is currently the most widely used imaging modality, cardiac magnetic resonance (CMR) allows detailed characterization of the HCM phenotype, which makes it possible to differentiate HCM from other causes of left ventricular hypertrophy. CMR has the potential to further refine risk stratification. Late gadolinium enhancement (LGE) on CMR is a high-risk feature and there is emerging data to suggest that the presence of LGE should be employed as a marker for major adverse outcomes such as SCD, arrhythmias, systolic and diastolic heart failure. Hence, LGE on CMR may be considered an additional risk factor for SCD in HCM patients and should be incorporated in decision-making for implant-able cardioverter defibrillator implantation to aid primary prevention. Novel markers such as the extent of myocardial fibrosis on CMR must be accounted for comprehensive risk stratifica-tion of HCM patients. The purpose of this review is to discuss the current status and emerging role of CMR in HCM.

Left ventricular hydatid cyst: an uncommon cause of chest pain in young adults

Isolated cardiac involvement in hydatid disease is very rare. We report the case of a young adult male who presented to the emergency department with acute onset of chest pain and was surprisingly detected to have a hydatid cyst in the left ventricular myocardium. The transthoracic echocardiography and cardiac magnetic resonance imaging confirmed the diagnosis. Cardiac hydatid disease should be considered in the differential diagnosis of chest pain in young individuals in the absence of conventional risk factors of atherosclerosis.

Stroke and Cancer

The importance of cancer-associated hypercoagulability as a possible stroke etiology in patients with cancer has received relatively little attention to date. A recent study has suggested that cancer-associated hypercoagulation may be of special importance in the absence of conventional stroke mechanisms. We identified patients with ischemic stroke sequentially admitted to our stroke center with the additional diagnosis of active and malignant cancer from 2002 to 2011. By using our prospectively collected stroke, MRI, and laboratory data banks, the etiology and risk factors of stroke, types of cancer, deep vein thrombosis/pulmonary embolism, d-dimer levels, and diffusion-weighted imaging lesion patterns were compared to an age- and sex-matched control group. Patients with cancer with a conventional stroke etiology and patients with an unidentified and/or cancer-associated stroke etiology were analyzed separately. One hundred forty patients with cancer and 140 control subjects were included. Unidentified stroke (P<0.001) and infarction in multiple vascular territories (P<0.001) were significantly more frequent and d-dimer levels significantly higher (P<0.05) in patients with cancer. Vice versa, risk factors such as hypertension (P<0.05) and hyperlipidemia (P<0.01) were more prevalent in control subjects. Deep vein thrombosis and pulmonary embolism were more frequent (P<0.01) and d-dimer levels higher (P<0.01) in the patients with unidentified and/or cancer-associated stroke etiology compared to the patients with cancer with a conventional stroke etiology. Lung and pancreatic cancer were significantly overrepresented and d-dimer levels higher in these patients compared with other patients with cancer (P<0.01). Our data confirm the concept of cancer-associated hypercoagulation as a widely underestimated important stroke risk factor in patients with cancer, especially in those with severely elevated d-dimer levels and in the absence of conventional risk factors.

Assessment of Visceral Fat Rating Measured By Bioelectrical Impedance Analysis as a Risk Factor for Coronary Artery Diseases (CAD)

Introduction: CAD may occur in absence of conventional risk factors like obesity and abnormal lipid profile. We aim to study a new parameter Visceral Fat Rating (VFR), measuring abdominal fat, and its association in CAD. Methods: 477 subjects were divided into three groups-documented CAD patients (n = 150), CAD risk group (n = 174) and control (n = 153). CAD risk: those with Metabolic Syndrome (based on NCEP-ATPIII) or with Framingham 10 year risk >10%. We measured waist circumference (WC), VFR by bioelectrical impedance using InnerScanV (TANITA Inc., Tokyo) and lipid profile; trigylcerides (TG), total cholesterol (TC), low and high density lipoprotein (LDL, HDL); in all subjects. Groups were compared by one way ANOVA and Tukey's post hoc test. Correlation was seen between VFR, WC and lipid profile. Results: WC was significantly higher in CAD patients and risk group in comparison to control. Mean levels of TG, TC and LDL were highest while HDL was minimum in CAD risk subjects. VFR of CAD patients was significantly higher from risk and control group. VFR was significantly correlated with WC, TG, TC and LDL (r = 0.77, 0.18, 0.19, 0.17, p < 0.001).Tabled 1VariablesControl (n = 153)CAD Risk (n = 174)CAD Patients (n = 150)WC (cm)86.08 ± 0.8096.14 ± 0.80ap<0.05 as compared to Control group.94.73 ± 0.83ap<0.05 as compared to Control group.TG (mg/dl)136.76 ± 5.37204.09 ± 6.63ap<0.05 as compared to Control group.140.63 ± 4.65bp<0.05 as compared to Risk group.TC (mg/dl)158.21 ± 3.42194.19 ± 3.84ap<0.05 as compared to Control group.160.83 ± 3.22bp<0.05 as compared to Risk group.HDL (mg/dl)39.48 ± 0.9731.28 ± 0.87ap<0.05 as compared to Control group.35.65 ± 0.64ap<0.05 as compared to Control group., bp<0.05 as compared to Risk group.LDL (mg/dl)91.38 ± 3.08122.58 ± 3.78ap<0.05 as compared to Control group.97.06 ± 2.83bp<0.05 as compared to Risk group.VFR7.77 ± 0.2610.03 ± 0.23ap<0.05 as compared to Control group.11.30 ± 0.38ap<0.05 as compared to Control group., bp<0.05 as compared to Risk group.a p < 0.05 as compared to Control group.b p < 0.05 as compared to Risk group. Open table in a new tab Conclusion: WC may estimate abdominal obesity erroneously owing to variable amount of subcutaneous fat. VFR estimates visceral fat more correctly and correlates well with abnormal lipid profile. It may be an important risk factor in relation to CAD.

Double or compound sarcomere mutations in hypertrophic cardiomyopathy: A potential link to sudden death in the absence of conventional risk factors

Risk stratification strategies employing sarcomere gene mutational analysis have proved imprecise in identifying high-risk patients with hypertrophic cardiomyopathy (HCM). Therefore, additional genetic risk markers that reliably determine which patients are predisposed to sudden death are needed. The objective of this study was to determine whether multiple disease-causing sarcomere mutations can be regarded as markers for sudden death in the absence of other conventional risk factors. Databases of 3 HCM centers were accessed, and 18 probands with 2 disease-causing mutations in genes encoding proteins of the cardiac sarcomere were identified. Severe disease progression or adverse cardiovascular events occurred in 7 of these 18 patients (39%), including 3 patients (ages 31, 37, and 57 years) who experienced sudden cardiac arrest but also were without evidence of conventional HCM risk factors; 2 survived with timely defibrillation and therapeutic hypothermia and 1 died. These 3 probands carried distinct and heterozygous disease-causing sarcomere mutations (including a man who inherited 1 mutation independently from each of his parents with HCM)-that is, double MYBPC3 and TNNI3 mutations and compound MYBPC3 mutations-as the only predisposing clinical markers evident to potentially explain their unexpected cardiac event. These observations support the emerging hypothesis that double (or compound) mutations detected by genetic testing may confer a gene dosage effect in HCM, thereby predisposing patients to adverse disease progression. In 3 families, multiple sarcomere mutations were associated with a risk of sudden death, even in the absence of conventional risk factors.

The emerging role of telomere biology in cardiovascular disease

A striking variability exists in the susceptibility, age of onset and pace of progression of cardiovascular diseases. This is inadequately explained by the presence or absence of conventional risk factors. Differences in biological aging might provide an additional component of the observed variability. Telomere length provides a potential marker of an individual's biological age, shorter telomeres reflect a more advanced biological age. Telomere length at birth is mainly determined by genetic factors. Telomere attrition occurs as a consequence of cellular replication and can be accelerated by harmful environmental factors such as oxidative stress. When telomeres reach a critical threshold the cell will enter senescence and becomes dysfunctional. Telomeres are remarkably shorter in patients with aging associated diseases, including coronary artery disease and chronic heart failure. In addition, numerous conventional cardiovascular risk factors are associated with shorter telomere length. If telomeres can be proven to be not only associated but also causally involved in the pathogenesis of cardiovascular disease it might provide exciting new avenues for the development of future preventive and therapeutic strategies.

Acute Myeloid Leukemia Associated with Acute Myocardial Infarction and Dural Sinus Thrombosis: The Possible Role of Leukemia-related Hyperhomocysteinemia

The association of acute myeloid leukemia (AML) and acute myocardial infarction (AMI) is rare. We encountered a 40-year-old female with inferior wall myocardial infarction that occurred simultaneously with the diagnosis of AML. She developed subsequent dural sinus thrombosis during chemotherapy for AML. The screen for thrombophilia revealed that she had hyperhomocysteinemia. In the English literature, only 4 cases have been reported previously. Remission induction was not affected by the occurrence of AMI, although anthracyclines were avoided in all cases. In the absence of conventional risk factors for coronary artery disease, AMI can be related to leukemia per se and the role of homocysteine is worth further investigation.

Homocystéine et risque cardiovasculaire: de l'utilité du dosage?

Hyperhomocysteinemia represents an independent risk factor for atherothrombotic disease. Physiopathological mechanisms of accelerated progression of atherosclerosis in presence of hyperhomocysteinemia are complex. Herein we report a clinical case which emphasis the importance of screening elevated homocystein in the absence of conventional risk factors in patients who suffer from premature atherosclerosis.

Cardiovascular News

Cardiovascular News

Dietary fat and gestational hyperglycaemia.

The purpose of this study was to investigate the relation between life-style habits and glucose abnormalities in Caucasian women with and without conventional risk factors for gestational diabetes. A total of 126 pregnant women with gestational diabetes, 84 with impaired glucose tolerance and 294 with normal glucose tolerance, identified by sequential screening, were interviewed to determine their usual weekly food pattern, amount of exercise, smoking habits and alcohol intake. Patients with glucose abnormalities were older and shorter in height and had significantly higher BMI before pregnancy, percentage of diabetic first-degree relatives and higher intake of saturated fat. Patients without known risk factors for gestational diabetes (i. e. younger than 35 years of age, BMI < 25 kg/m2, no first-degree diabetic relatives) included 40 with impaired glucose tolerance or gestational diabetes. In a multiple logistic regression model age, short stature, familial diabetes, BMI and percentages of saturated fat were associated with impaired glucose tolerance or gestational diabetes in all patients, after adjustment for gestational age. In patients without conventional risk factors only percentages of saturated fat (OR = 2.0; 95 %-CI = 1.2-3.2) and polyunsaturated fat (OR = 0.85; 95 %-CI = 0.77-0.92) were associated with gestational hyperglycaemia, after adjustment for age, gestational age and BMI. Saturated fat has an independent role in the development of gestational glucose abnormalities. This role is more important in the absence of conventional risk factors suggesting that glucose abnormalities could be prevented during pregnancy, at least in some groups of women.

Impact of plaque imaging by electron beam tomography on the treatment of dyslipidemias

Current recommendations for the treatment of dyslipidemias are characterized by several critical unresolved questions that potentially limit their utility: 1. Definition of “dyslipidemia”: What exactly defines an abnormal lipid level and which lipids and other established metabolic disorders are considered important enough to be measured and treated? 2. Identification of risk: Is lipid therapy appropriately prescribed for or withheld from people at higher or lower coronary artery disease (CAD) risk? Are the current National Cholesterol Education Program (NCEP) guidelines 1 able to accurately identify patients with subclinical atherosclerosis? 3. Adequacy of lipid treatment: Does the absence of a negative clinical outcome define success, or is there a surrogate that can assess treatment efficacy before death or myocardial infarction heralds treatment failure? The current recommendations are derived from a distillation of evidence-based randomized clinical trials that assess relative risk based on mean lipid values. The efficacy of treatment is measured by reduction in clinical events, accompanied by pharmacologically induced changes in these mean lipid values. The influence of other putative risk factors is incorporated into evaluations such as the Framingham risk score, 2 again based on large population-based mean values of these risk factors and their relative risk. Is it reasonable to extrapolate from mean values in thousands of patients to a single individual in the real world of physician-patient interaction? Perhaps, but, in the absence of objective measurements of the extent of that person’s atherosclerosis, any conclusions would simply be guesswork. A more accurate assessment is offered by electron beam tomography (EBT) measurement of the extent and prematurity of the coronary atherosclerotic plaque burden in individual patients, irrespective of the presence or absence of conventional risk factors. EBT establishes relative risk with a power multiplicative of any risk factors, 3‐5 leads to the identification of other metabolic disorders that may be contributing to atherosclerosis, and provides a surrogate measurement of the efficacy of therapy. Because EBT has the potential to profoundly alter the conventional practice of primary prevention, the level of “evidence-based proof” that is demanded of EBT exceeds that which has been provided to justify almost all of office- and hospital-based medicine. These issues have been debated in many forums, and despite the accelerated pace of publication of favorable peer-reviewed data, EBT has not been approved for large-scale screening. The Society of Atherosclerosis Imaging, after analyzing the rapidly evolving data, has developed practice guideline recommendations6 that are very different from those of the Amer

Case studies in therapeutics: warfarin resistance and inefficacy in a man with recurrent thromboembolism, and anticoagulant‐associated priapism

Case studies in therapeutics: warfarin resistance and inefficacy in a man with recurrent thromboembolism, and anticoagulant‐associated priapism