Nonatherosclerotic Cardiovascular Disease Research Articles

Association between sleep duration and hypertension: Isfahan Healthy Heart Program, Iran.

BACKGROUNDHypertension (HTN) is an important risk factor for atherosclerotic and non-atherosclerotic cardiovascular disease (CVD). HTN increases risk of stroke and diabetes complications and at the end stage renal disease. Sleep disorders including short sleep duration are involved in pathogenesis of HTN. This study aimed to examine the association between self-reported sleep duration and HTN in a group of adult population in Isfahan City, Iran.METHODSThis cross-sectional survey was performed as part of the Isfahan Healthy Heart Program (IHHP). A total of 12492 individuals aged over 19 years (6110 men and 6382 women) entered the study. Sleep duration was recorded according to subjects’ self-report. HTN was defined as a systolic blood pressure (SBP) of ≥ 140 mmHg, a diastolic blood pressure (DBP) of ≥ 90 mmHg, or use of antihypertensive medication. The relation between sleep hours and HTN was examined using multiple logistic regression in three models, unadjusted, adjusted according to age and sex, and adjusted according to age, sex, body mass index (BMI), and waist circumference (WC).RESULTSSleeping time less than 5 hours, in comparison to sleep duration of 7-8 hours per night,was associated with a higher risk of HTN [odds ratio (OR) = 2.52, 95% confidence interval (CI): 2.17-2.93]. This association remained significant even after adjustment for age, sex, BMI, and WC (OR = 1.38, 95% CI: 1.16-1.64). Sleep duration over 9 hours had a negative association with risk of HTN among those under 60 years old (OR = 0.63, 95% CI: 0.47-0.86).CONCLUSIONSleep duration less than 5 hours is positively associated with HTN. It seems that sleep duration might affect HTN and atherosclerotic CVD.

Incidence of cancers in patients with atherosclerotic cardiovascular diseases

BackgroundTo address a clinical impact of atherosclerotic cardiovascular diseases (CVD) on cancer developments, we investigated an issue whether any difference in an incidence of cancers is present between patients with atherosclerotic CVD and those with non-atherosclerotic CVD. MethodsOf a total of 32,095 consecutive patients with acquired CVD enrolled in the Sakakibara Health Integrative Profile cohort study, we segregated patients based on a presence of atherosclerotic or non-atherosclerotic CVD to investigate an incidence of cancers and mortality. We also evaluated an incidence of cancers in patients with a singular presence versus a plural presence of atherosclerotic CVD. Atherosclerotic CVD included coronary artery diseases, aortic diseases and peripheral artery diseases. Non-atherosclerotic CVD were any acquired CVD except atherosclerotic CVD. ResultsDuring a median follow-up of 1020days (interquartile range, 665–1340days), an incidence of cancers (5% vs. 2%, p=0.0001) and overall mortality (6% vs. 3%, p=0.0001) were more than two-fold higher in 10,592 patients with atherosclerotic CVD than in 21,503 patients with non-atherosclerotic CVD. A presence of atherosclerotic CVD (hazard ratio 1.372 with 95% confidence interval 1.199–1.569) was independently associated with an incidence of cancers. In patients with atherosclerotic CVD, 61 of 640 patients with a plural presence and 470 of 9932 patients with a singular presence developed cancers (9% vs. 5%, p=0.0001). An incremental risk of death was found according to a presence of atherosclerotic CVD, cancers, and both of them (all p=0.0001). ConclusionsA presence of atherosclerotic CVD itself may have a potential risk for cancer developments. Trial registrationClinicalTrials.gov. number, NCT03005834

Metabolic syndrome: pathophysiology, management, and modulation by natural compounds.

Metabolic syndrome (MetS) represents a cluster of metabolic abnormalities that include hypertension, central obesity, insulin resistance, and atherogenic dyslipidemia, and is strongly associated with an increased risk for developing diabetes and atherosclerotic and nonatherosclerotic cardiovascular disease (CVD). The pathogenesis of MetS involves both genetic and acquired factors that contribute to the final pathway of inflammation that leads to CVD. MetS has gained significant importance recently due to the exponential increase in obesity worldwide. Early diagnosis is important in order to employ lifestyle and risk factor modification. Here, we review the epidemiology and pathogenesis of MetS, the role of inflammation in MetS, and summarize existing natural therapies for MetS.

Insights into Cardiovascular Diseases: The Vicious Platelet-Immune System Loop

Cardiovascular disease (CVD) is the leading cause of death today and a burden on a country’s economic growth. Management of this disease continues to depend on dietary control and statins. However, the disease burden refuses to decline. It is probably because treatment regime addresses the effect and not the cause. Augmented LDL level has been traditionally perceived as the major risk factor contributing to the development of atherosclerosis, the main cause of several coronary ailments. Recent research also suggests that pre-existing chronic inflammation leads to oxidation of LDL and thus makes it pathogenic. This inflammatory repertoire, apart from leukocytes, also includes the anucleated cell fragments called platelets. Platelets conventionally associated with clotting phenomenon, also express array of inflammatory mediators creating a crucial link between immune response and thrombotic complications. In this review we will examine the role of inflammation as a primary causative agent of atherosclerotic as well as non-atherosclerotic cardiovascular diseases.

Insights into Cardiovascular Diseases: The Vicious Platelet-Immune System Loop

Cardiovascular disease (CVD) is the leading cause of death today and a burden on a country’s economic growth. Management of this disease continues to depend on dietary control and statins. However, the disease burden refuses to decline. It is probably because treatment regime addresses the effect and not the cause. Augmented LDL level has been traditionally perceived as the major risk factor contributing to the development of atherosclerosis, the main cause of several coronary ailments. Recent research also suggests that pre-existing chronic inflammation leads to oxidation of LDL and thus makes it pathogenic. This inflammatory repertoire, apart from leukocytes, also includes the anucleated cell fragments called platelets. Platelets conventionally associated with clotting phenomenon, also express array of inflammatory mediators creating a crucial link between immune response and thrombotic complications. In this review we will examine the role of inflammation as a primary causative agent of atherosclerotic as well as non-atherosclerotic cardiovascular diseases.

Effects of cinacalcet on atherosclerotic and nonatherosclerotic cardiovascular events in patients receiving hemodialysis: the EValuation Of Cinacalcet HCl Therapy to Lower CardioVascular Events (EVOLVE) trial.

BackgroundPremature cardiovascular disease limits the duration and quality of life on long‐term hemodialysis. The objective of this study was to define the frequency of fatal and nonfatal cardiovascular events attributable to atherosclerotic and nonatherosclerotic mechanisms, risk factors for these events, and the effects of cinacalcet, using adjudicated data collected during the EValuation of Cinacalcet HCl Therapy to Lower CardioVascular Events (EVOLVE) Trial.Methods and ResultsEVOLVE was a randomized, double‐blind, placebo‐controlled clinical trial that randomized 3883 hemodialysis patients with moderate to severe secondary hyperparathyroidism to cinacalcet or matched placebo for up to 64 months. For this post hoc analysis, the outcome measure was fatal and nonfatal cardiovascular events reflecting atherosclerotic and nonatherosclerotic cardiovascular diseases. During the trial, 1518 patients experienced an adjudicated cardiovascular event, including 958 attributable to nonatherosclerotic disease. Of 1421 deaths during the trial, 768 (54%) were due to cardiovascular disease. Sudden death was the most frequent fatal cardiovascular event, accounting for 24.5% of overall mortality. Combining fatal and nonfatal cardiovascular events, randomization to cinacalcet reduced the rates of sudden death and heart failure. Patients randomized to cinacalcet experienced fewer nonatherosclerotic cardiovascular events (adjusted relative hazard 0.84, 95% CI 0.74 to 0.96), while the effect of cinacalcet on atherosclerotic events did not reach statistical significance.ConclusionsAccepting the limitations of post hoc analysis, any benefits of cinacalcet on cardiovascular disease in the context of hemodialysis may result from attenuation of nonatherosclerotic processes.Clinical Trials RegistrationUnique identifier: NCT00345839. URL: ClinicalTrials.gov.

Bioimaging and subclinical cardiovascular disease in low- and middle-income countries.

Cardiovascular disease (CVD) is the leading cause of mortality worldwide and also exerts a significant economic burden, especially in low- and middle-income countries (LMICs). Detection of subclinical CVD, before an individual experiences a major event, may therefore offer the potential to prevent or delay morbidity and mortality, if combined with an appropriate care response. In this review, we discuss imaging technologies that can be used to detect subclinical atherosclerotic CVD (carotid ultrasound, coronary artery calcification) and nonatherosclerotic CVD (echocardiography). We review these imaging modalities, including aspects such as rationale, relevance, feasibility, utilization, and access in LMICs. The potential gains in detecting subclinical CVD may be substantial in LMICs, if earlier detection leads to earlier engagement with the health care system to prevent or delay cardiac events, morbidity, and premature mortality. Thus, dedicated studies examining the feasibility, utility, and cost-effectiveness of detecting subclinical CVD in LMICs are warranted.

LIPID‐LOWERING THERAPY IN CHRONIC KIDNEY DISEASE: IS THERE A ROLE FOR EZETIMIBE?

The use of lipid-lowering therapy (LLT) in chronic kidney disease (CKD) results in a reduction in atherosclerotic cardiovascular events but not mortality. The risk reduction for patients on dialysis appears to be less than in pre-dialysis CKD. These findings may be due to the higher rate of non-atherosclerotic cardiovascular disease found in end-stage disease. Because of this, the role of LLT is less clear in CKD than in the general population. This review outlines the results of recent trials of LLT, particularly Ezetimibe, and implications for patients with CKD. The evidence in favour of lipid lowering in CKD comes largely from the SHARP study. This study used combined simvastatin and Ezetimibe to reduce cholesterol. Though the benefits of statins are well proven, there is no evidence that Ezetimibe independently reduces cardiovascular events in any population. Data which support the use of Ezetimibe show only that it effectively reduces cholesterol. Surrogate end-point data are contentious. Some studies suggest benefit whilst others suggest off-target effects that question the validity of Ezetimibe in the absence of quality cardiovascular outcome data.

Arteriosclerosis and Atherosclerosis

Over the last decade, there has been a dramatic resurgence of interest in large-artery hemodynamics. This has been driven principally by the accumulating evidence that aortic stiffness is an independent predictor of future cardiovascular risk in a variety of populations.1 The current gold-standard measure of aortic stiffness is aortic pulse wave velocity (aPWV). This reflects the fact that it has the most evidence relating to outcome and that it can be reliably assessed between the carotid and femoral arteries, noninvasively.1 However, there continues to be considerable debate about the nature of the relationship between arterial stiffness and cardiovascular disease: is aPWV truly an independent risk factor or simply a marker? A number of hypothetical relationships exist (Figure), as described below. First, aortic stiffening may promote cardiovascular disease independent of other more established cardiovascular risk factors. Data from some of the published outcome studies would support this view, but it is likely that meta-analysis of these data will be required to demonstrate this convincingly. Figure. Proposed mechanisms linking aortic stiffness with atherosclerotic and nonatherosclerotic cardiovascular disease. Arrows numbered 1 to 3 refer to hypothetical relationships discussed in the text (first, second, and third). Second, an alternative suggestion is that aPWV simply represents the integrated effects over time that established risk factors have on the arterial wall and that stiffening of the wall does not in itself cause disease. Nevertheless, aPWV could still be more closely related to future events than a single “snapshot” measure of individual risk factors in isolation. A simple analogy is weight, which represents the integrated relationship between food intake and energy expenditure over an individual’s lifetime and, thus, is a more reliable measure of overall energy balance than a single day’s assessment of energy intake and usage. Third, if the presence of atheroma alters the …

Identification of Unexpected Nonatherosclerotic Cardiovascular Disease With Coronary CT Angiography

The aim of this study was to assess, in a general cardiology cohort screened for obstructive coronary artery disease (CAD), the effectiveness and frequency with which multidetector computed tomography (MDCT) angiography unexpectedly imaged and identified other nonatherosclerotic cardiovascular diseases. MDCT angiography is a novel imaging strategy employed primarily to diagnose CAD that, in the course of these studies, can also potentially identify other important but previously unrecognized cardiovascular abnormalities. Consecutive 64-slice MDCT angiography studies were obtained in 4,543 patients with suspected atherosclerotic CAD at the Minneapolis Heart Institute, over a 29-month period (2005 to 2007). Nonatherosclerotic-related cardiovascular abnormalities judged to be of potential clinical relevance were identified in 201 patients (4.4%). In 50 of these patients (1.1% of 4,543) the abnormality was previously unrecognized despite other imaging studies performed in 40%. Most common among the 50 patients were: congenital coronary artery anomalies (38%; largely right coronary artery from the left aortic sinus); ascending aortic aneurysms > or = 45 mm (22%); hypertrophic cardiomyopathy with apical left ventricular (LV) wall thickening (14%); valvular heart diseases (8%), congenital heart diseases, including ventricular septal defect (6%); pulmonary embolus (6%); as well as LV noncompaction, left atrial myxoma, and LV apical aneurysm (2% each). As a consequence of MDCT angiography findings, new management strategies were instituted in 15 of 50 patients (30%), including surgical correction of coronary artery anomalies of wrong sinus origin, ascending aneurysm graft repair, thrombolytic therapy for pulmonary embolism, and myxoma resection. Approximately 1% of patients undergoing MDCT angiography for suspicion of CAD proved to have otherwise unsuspected, but clinically relevant, cardiovascular abnormalities unrelated to coronary atherosclerosis. Almost one-third of these patients had cardiovascular diseases with major clinical implications for subsequent therapy. These findings underscore the value of MDCT angiography and the importance of careful assessment of scans for the recognition of a variety of cardiovascular abnormalities.

Association between suicide and cardiovascular disease: Time series of 27 years

Despite several proatherogenic characteristics distinguish subjects who commit suicide, it remains unclear whether or not the incidence of suicide and cardiovascular disease are related. Between 1979 and 2005, a total of 3,364,908 deaths were reported from suicide, ischemic heart disease, or stroke of individuals who were 40 years or older. The incidence of deaths from suicide was positively correlated with those from ischemic heart disease ( r = 0.95; p < 0.0001) and stroke ( r = 0.92; p < 0.0001). No such correlation was found between suicides and deaths from other non-cardiovascular or non-atherosclerotic cardiovascular diseases. This study calls attention for the existence of an association between suicide behavior and cardiovascular risk.

Blood glutathione and cysteine changes in cardiovascular disease

The need to investigate aminothiols such as glutathione (GSH), cysteine (Cys), and homocysteine (Hcy) in blood is stimulated by the current interest in hyperhomocysteinemia as a risk factor for atherosclerosis. Our current goal was to determine whether various cardiovascular (CV) diseases altered levels of GSH and Cys in blood and the relationships between these two thiols. Blood samples from 96 patients with atherosclerosis and other CV diseases were analyzed and compared with those from 33 control subjects. In CV patients, GSH levels were normal, but free plasma Cys was significantly higher (P <.0001). In patients with atherosclerosis, bound plasma Cys was 21% higher than that in control subjects (P <.0001), and in patients with other CV diseases it was 14% higher (P =.023). Also, in patients with CV diseases, correlations of free GSH with free Cys (P <.007) and total GSH and Cys with age (P <.04) differed from that in control subjects. There were no differences related to functional disability or duration of disease. A key finding was that these abnormal levels of plasma Cys occurred in both atherosclerotic and non-atherosclerotic CV diseases. These results indicate that high levels of oxidized and bound Cys in CV patients create an oxidative environment that may increase susceptibility to vascular damage. (J Lab Clin Med 2000;135:396-401)

The genomics of cardiovascular disorders: therapeutic implications.

Cardiovascular disease (CVD) is a complicated series of disorders that result from the interaction between genetic predisposing mechanisms and environmental factors. Over the last few years substantial progress has been made in defining the molecular basis of several genetically transmitted non-atherosclerotic CVD such as hypertrophic and dilated cardiomyopathies, long-QT syndrome and essential hypertension. This review represents a summary of the current knowledge about the major gene polymorphisms found to be associated with these CVDs. Moreover, we will discuss how the discovery of disease-associated genes will greatly enhance the ability to formulate advanced diagnoses, to define prophylactic therapeutic strategies to prevent or reduce the progression of the disease and, finally, to proceed to the development of new drugs tailored for the specific cellular or molecular functions altered as consequence of the predisposing genes.

Impact of Laboratory Molecular Diagnosis on Contemporary Diagnostic Criteria for Genetically Transmitted Cardiovascular Diseases: Hypertrophic Cardiomyopathy, Long-QT Syndrome, and Marfan Syndrome

Over the last several years, substantial progress has been achieved in defining the molecular basis for several genetically transmitted, nonatherosclerotic cardiovascular diseases. These advances in molecular biology have enhanced our understanding of the primary defects and basic mechanisms responsible for the pathogenesis of these conditions and their phenotypic expression, and in the process, new perspectives on cardiac diagnosis have been formulated. In the course of this scientific evolution, a certain measure of uncertainty has also arisen regarding the implications of genetic analysis for clinical diagnostic criteria. New subgroups of genetically affected individuals without conventional clinical diagnostic findings have been identified solely by virtue of access to molecular laboratory techniques, creating a number of medical and ethical concerns regarding the possible clinical implications. Indeed, the extent to which such individuals should receive sequential evaluations and/or therapy or be subjected to employment or insurance discrimination, psychological harm, loss of privacy, or unnecessary withdrawal from competitive athletics is uncertain but remains a legitimate source of concern. It is therefore particularly timely and appropriate to analyze these issues in detail, specifically the extent to which molecular biology has revised traditional diagnostic criteria. The role of genetic testing in assessing prognosis and identifying high-risk subgroups or in defining basic disease mechanisms and pathophysiology is, however, largely beyond the scope of this scientific statement. As models for the present critique, we selected the 3 most common familial cardiovascular diseases for which gene defects have been identified, each of which is associated with autosomal dominant inheritance and a risk for sudden cardiac death: hypertrophic cardiomyopathy (HCM), long-QT syndrome (LQTS), and Marfan syndrome (MFS).

775-5 Increased Incidence of Chlamydia Bacteria Detected within Coronary Arteries of Patients with Atherosclerotic Versus Transplant Induced Coronary Artery Disease

Previous work has suggested an association between Chlamydia pneumoniae infection and coronary atherosclerosis, based on the demonstration of increased serologic titers and the detection of bacteria within atherosclerotic tissue. We sought to strengthen a possible etiologic link by comparing the incidence of Chlamydia infection in coronary atherosclerotic tissue to that in coronary arteries of patients with non-atherosclerotic cardiovascular disease. Coronary tissue specimens obtained from 90 consecutive patients (mean age = 57 yrs) with symptomatic coronary artery disease undergoing directional coronary atherectomy were tested for the presence of Chlamydia species by direct immunofluorescence using mouse monoclonal antibody. Immunofluorescence was positive in 68 (76%), equivocal in 5 (6%) and negative in 19 (21 %) of specimens. Polymerase chain reaction confirmed the specific Chlamydia strain TWAR in 2 cases. No clinical factors except the presence of a primary non-testenotic lesion (odds ratio = 3.0, p = 0.057) predicted the detection of Chlamydia. As a control, coronary tissue specimens from 11 patients with previous cardiac transplantation and subsequent transplant-induced coronary artery disease were also tested. Direct immunofluorescence performed on these diseased coronary artery segments was negative for Chlamydia in every case (p = 0.0001 compared with atherosclerotic specimens). This high incidence of Chlamydia detected only in coronary arteries diseased by atherosclerosis suggests an etiologic role for Chlamydia infection in the development of coronary atherosclerosis, which should be further studied.

Degenerative, non-atherosclerotic cardiovascular disease in the elderly: A clinico-pathological survey

Cardiovascular disease, the major cause of death in the elderly, is mostly ascribable to complications of coronary atherosclerosis: angina pectoris, myocardial infarction, and sudden death. However, other degenerative diseases involving several cardiac structures exist, and should be distinguished from age-related cardiac changes. Extensive dystrophic calcification determines aortic stenosis, and may affect either a normally tricuspid or a congenitally bicuspid valve. Surgical valve replacement is now a low risk option, even in elderly persons, whereas the efficacy of balloon valvuloplasty is questionable. Aortic incompetence in adults and aged persons is mostly the consequence of aortic tunica media atrophy with anular ectasia, in the setting of nearly normal aortic leaflets. Mitral valve prolapse is the main cause of mitral incompetence; spontaneous cordal rupture is a late complication in the natural history of this disease, thus warranting prompt surgical valve repair or replacement. The entire spectrum of cardiomyopathies is observed in the elderly: dilated, hypertrophic, restrictive, arrhythmogenic. Cardiac amyloidosis is by far the most frequent secondary form and leads to congestive heart failure by impairing ventricular compliance. Idiopathic fibrosis of the specialized AV junction or dystrophic calcification of central fibrous body are the usual substrates of AV block, which requires pace-maker implantation. Nonrheumatic atrial fibrillation, due to fibro-fatty degeneration of the atrial musculature or dilated left atrium, carries a high risk of thromboembolic complications and cerebral accidents; oral anticoagulants have proven to be effective in preventing stroke. Aortic dissecting aneurysm is a spontaneous laceration, and usually a complication of longstanding systemic hypertension; exceptionally, spontaneous dissection may primarily occur in the coronary arteries. In conclusion, longevity at present is mostly threatened by cardiovascular disease, among which the role of degenerative, non-atherosclerotic disorders may be greater than thought.