Rationale and design of the SMART Heart study

Left ventricular hypertrophy (LVH) is an independent risk factor for the development of heart failure, coronary heart disease and stroke. LVH develops in response to haemodynamic overload, e.g. hypertension. LVH was originally thought to start as an adaptive and beneficial response required to normalise wall stress. However, this concept has been challenged by recent animal experiments suggesting that any degree of LVH is detrimental for the preservation of cardiac function and survival. If confirmed in humans, these findings imply that an increase in LV mass should be prevented, e.g. by lifestyle or pharmacological interventions. To facilitate and optimise interventions, the SMART Heart study was recently set up to develop a prediction model, also involving single nucleotide polymorphism data, for the identification of subjects at high risk of developing LVH in hypertension. For this purpose 1000 subjects with chronic hypertension will undergo cardiac MR imaging. In addition, this study allows the extrapolation of animal experimental genetic research into the human situation. (Neth Heart J 2007;15:295-8).     

A genomewide linkage study of 1,933 families affected by premature coronary artery disease: The British Heart Foundation (BHF) Family Heart Study

Coronary artery disease (CAD) and its most important complication, myocardial infarction (MI), are the leading cause of premature death in the Western world. CAD has a substantial genetic basis, especially when it occurs early. We investigated the genetic determinants of premature CAD by performing a genomewide linkage analysis of 4,175 affected subjects from 1,933 families recruited throughout the United Kingdom. Each family had at least two available siblings with CAD, with validated onset before age 66 years. Linkage analysis was performed using 416 microsatellite markers. We observed suggestive linkage, for both CAD and MI, to a region on chromosome 2. For CAD, a LOD score of 1.86 was observed at marker D2S2271, which, in an ordered subset analysis, increased to 2.70 in families (n=1,698) with a minimum age at diagnosis of 56 years or younger. For MI, an overlapping peak with a LOD score of 1.15 was observed at marker D2S2216, which increased to 2.1 in families (n=801) with a minimum age at diagnosis of 59 years or younger. Exclusion mapping showed that 100% of the autosomal genome could be excluded for locus-specific sibling relative risks of 1.5 and 1.6 for CAD and MI, respectively. The region identified on chromosome 2 overlaps linked regions observed in two other smaller genome scans for CAD. Together, these findings strongly suggest that there is a locus on chromosome 2 that influences coronary atherosclerosis risk. The exclusion of a common locus that increases risk of CAD to siblings by >50% has important implications for strategies for further defining the genetic basis of CAD.     

Predictors of leptin concentration and association with cardiovascular risk in patients with coronary artery disease: results from the AtheroGene study

Context: Leptin is produced in white adipose tissue, but also in human coronary atherosclerotic lesions.

Objective: The aim of this study is to assess the prognostic value of leptin in patients with proven coronary artery disease (CAD) (N?=?1907).

Methods: AtheroGene is a contemporary CAD cohort study (N?=?3229). Median follow-up time was 3.8 (Quartile 1/3 with 2.8/4.9) years.

Results: Leptin concentration was associated with a hazard ratio (HR) for the fully adjusted model of HR?=?1.32 in women but was not significant in men. The endpoint cardiovascular death and non-fatal myocardial infarction was observed in 167 patients.

Conclusion: In women with known CAD, increased leptin concentration is useful for predicting cardiovascular death and non-fatal myocardial infarction.     

Silent atrial fibrillation in patients with an implantable cardioverter defibrillator and coronary artery disease (INDICO AF) trial: study rationale and design

Background

Timely detection of atrial fibrillation (AF) in implantable cardioverter defibrillator (ICD) patients is clinically important for prevention of AF-related complications and inappropriate shocks. Patients with coronary artery disease (CAD) and a dual or triple chamber ICD show a high incidence of device-detected AF. Whether CAD patients with a single chamber ICD carry a similar risk for device-detected AF remains unknown.

Study design

The INDICO AF trial is an investigator-initiated, multicentre, observational study evaluating the incidence of subclinical AF (SCAF) in CAD patients who will receive a single chamber ICD as primary prevention for sudden cardiac death (SCD). Fifty patients will receive a single chamber ICD with an integrated RR interval based AF detection algorithm. In combination with remote monitoring, rhythm data will be collected monthly. The primary endpoint is the incidence of SCAF at 1 year of follow-up; secondary endpoints include time until 10 and 20% of the patients have a first episode of SCAF. All patients in whom SCAF is detected will be invited for an outpatient visit and will receive adequate anticoagulation treatment when appropriate according to the CHA2DS2-VASc score and current guidelines.

Conclusion

The INDICO AF trial will quantify the incidence of SCAF in patients with an ICD and CAD. The study will underscore the clinical value of SCAF detection in single chamber ICD patients using remote patient monitoring and may improve patient care. This trial is registered at trialregister.nl with trial NTR6910.

     

Clinical implication of coronary tortuosity in patients with coronary artery disease

BackgroundCoronary tortuosity (CT) is a common coronary angiography finding. The exact pathogenesis, clinical implication and long-term prognosis of CT are not fully understood. The purpose of this study is to investigate the clinical characteristics of CT in patients with suspected coronary artery disease(CAD) in a Chinese population.MethodsA total of 1010 consecutive patients underwent coronary angiography with complaints of chest pain or related symptoms were included in the present study (544 male, mean age: 64±11 years). CT was defined by the finding of ≥3 bends (defined as ≥45° change in vessel direction) along main trunk of at least one artery in systole and in diastole. Patients with or without CAD were further divided into CT-positive and CT-negative groups, all patients were followed up for the incidence of major adverse cardiovascular events (MACE) for 2 to 4 years.ResultsThe prevalence of CT was 39.1% in this patient cohort and incidence of CT was significantly higher in female patients than that in male patients (OR = 2.603, 95%CI 1.897, 3.607, P<0.001). CT was positively correlated with essential hypertension (OR = 1.533, 95%CI 1.131, 2.076, P = 0.006) and negatively correlated with CAD (OR = 0.755, 95%CI 0.574, 0.994, P = 0.045). MACE during follow up was similar between CAD patients with or without CT.ConclusionsCT is more often seen in females and positively correlated with hypertension and negatively correlated with coronary atherosclerosis.     

Physical fitness and telomere length in patients with coronary heart disease: findings from the Heart and Soul Study

Background

Short telomere length (TL) is an independent predictor of mortality in patients with coronary heart disease (CHD). However, the relationship between physical fitness and TL has not been explored in these patients.

Methods

In a cross sectional study of 944 outpatients with stable CHD, we performed exercise treadmill testing, assessed self-reported physical activity, and measured leukocyte TL using a quantitative PCR assay. We used generalized linear models to calculate mean TL (T/S ratio), and logistic regression models to compare the proportion of patients with short TL (defined as the lowest quartile), among participants with low, medium and high physical fitness, based on metabolic equivalent tasks achieved (METs).

Results

229 participants had low physical fitness (<5 METS), 334 had moderate physical fitness (5–7 METS), and 381 had high physical fitness (>7 METS). Mean ± T/S ratio ranged from 0.86±0.21 (5349±3781 base pairs) in those with low physical fitness to 0.95±0.23 (5566±3829 base pairs) in those with high physical fitness (p<.001). This association remained strong after adjustment for numerous patient characteristics, including measures of cardiac disease severity and physical inactivity (p = 0.005). Compared with participants with high physical fitness, those with low physical fitness had 2-fold greater odds of having TL in the lowest quartile (OR 2.39, 95% CI 1.60–3.55; p<.001). This association was similar after multivariable adjustment (OR 1.94, 95%CI, 1.18–3.20; p = 0.009). Self-reported physical inactivity was associated with shorter TL in unadjusted analyses, but not after multivariable adjustment.

Conclusions

We found that worse objectively-assessed physical fitness is associated with shorter leukocyte telomere length in patients with CHD. The clinical implications of this association deserve further study.     

Prosthetic valves in adult patients with congenital heart disease: Rationale and design of the Dutch PROSTAVA study

Background

Data on long-term complications in adult patients with congenital heart disease (ACHD) and a prosthetic valve are scarce. Moreover, the influence of prosthetic valves on quality of life (QoL) and functional outcome in ACHD patients with prosthetic valves has not been studied.

Objectives

The primary objective of the PROSTAVA study is to investigate the relation between prosthetic valve characteristics (type, size and location) and functional outcome as well as QoL in ACHD patients. The secondary objectives are to investigate the prevalence and predictors of prosthesis-related complications including prosthesis-patient mismatch.

Methods

The PROSTAVA study, a multicentre cross-sectional observational study, will include approximately 550 ACHD patients with prosthetic valves. Primary outcome measures are maximum oxygen uptake during cardiopulmonary exercise testing and QoL. Secondary outcomes are the prevalence and incidence of valve-related complications including prosthesis-patient mismatch. Other evaluations are medical history, physical examination, echocardiography, MRI, rhythm monitoring and laboratory evaluation (including NT-proBNP).

Implications

Identification of the relation between prosthetic valve characteristics in ACHD patients on one hand and functional outcome, QoL, the prevalence and predictors of prosthesis-related complications on the other hand may influence the choice of valve prosthesis, the indication for more extensive surgery and the indication for re-operation.     

Effect of an intervention to improve the cardiovascular health of family members of patients with coronary artery disease: a randomized trial

Background:

Family members of patients with coronary artery disease (CAD) have higher risk of vascular events. We conducted a trial to determine if a family heart-health intervention could reduce their risk of CAD.

Methods:

We assessed coronary risk factors and randomized 426 family members of patients with CAD to a family heart-health intervention (n = 211) or control (n = 215). The intervention included feedback about risk factors, assistance with goal setting and counselling from health educators for 12 months. Reports were sent to the primary care physicians of patients whose lipid levels and blood pressure exceeded threshold values. All participants received printed materials about smoking cessation, healthy eating, weight management and physical activity; the control group received only these materials. The main outcomes (ratio of total cholesterol to high-density lipoprotein [HDL] cholesterol; physical activity; fruit and vegetable consumption) were assessed at 3 and 12 months. We examined group and time effects using mixed models analyses with the baseline values as covariates. The secondary outcomes were plasma lipid levels (total cholesterol, low-density lipoprotein cholesterol, HDL cholesterol and triglycerides); glucose level; blood pressure; smoking status; waist circumference; body mass index; and the use of blood pressure, lipid-lowering and smoking cessation medications.

Results:

We found no effect of the intervention on the ratio of total cholesterol to HDL cholesterol. However, participants in the intervention group reported consuming more fruit and vegetables (1.2 servings per day more after 3 mo and 0.8 servings at 12 mo; p < 0.001). There was a significant group by time interaction for physical activity (p = 0.03). At 3 months, those in the intervention group reported 65.8 more minutes of physical activity per week (95% confidence interval [CI] 47.0–84.7 min). At 12 months, participants in the intervention group reported 23.9 more minutes each week (95% CI 3.9–44.0 min).

Interpretation:

A health educator–led heart-health intervention did not improve the ratio of total cholesterol to HDL cholesterol but did increase reported physical activity and fruit and vegetable consumption among family members of patients with CAD. Hospitalization of a spouse, sibling or parent is an opportunity to improve cardiovascular health among other family members. Trial registration: clinicaltrials.gov, no {"type":"clinical-trial","attrs":{"text":"NCT00552591","term_id":"NCT00552591"}}NCT00552591.People with a family history of coronary artery disease (CAD) among their first-degree relatives have an increased risk of vascular events.^1–5 This risk is greater if more than 1 relative has heart disease, or if the onset of disease in relatives occurred before age 55.^1–3,5 A concordance of coronary risk factors between patients with heart disease and their spouses has also been reported.^6–10 Although genetic factors are important, familial aggregation of coronary risk factors also plays a role.^9,11,12 Guidelines recommend screening individuals with a positive family history,^13–15 but screening rates are low (< 15%), and interventions are rarely initiated.^16,17 Family members of patients with heart disease may benefit from focused interventions to improve cardiovascular health. Counselling that address physical inactivity and dietary behaviours is central to these interventions; clinical management of risk factors such as tobacco addiction, dyslipidemia, hypertension and dysglycemia are also important. We developed and evaluated a year-long family-based heart-health intervention for the siblings, offspring and spouses of patients admitted to hospital with an acute coronary event.     

Oxypurinol improves coronary and peripheral endothelial function in patients with coronary artery disease

Coronary endothelial dysfunction is a powerful prognostic marker in patients with coronary artery disease (CAD) that is centrally related to oxidative inhibition of nitric oxide (NO)-dependent vascular cell signaling. Xanthine oxidase (XO), which both binds to and is expressed by endothelial cells, generates superoxide and hydrogen peroxide upon oxidation of purines. Whether inhibition of xanthine oxidase activity results in improved coronary vasomotor function in patients with CAD, however, remains unknown. We assessed coronary and peripheral (brachial artery) endothelial function in 18 patients (pts; 65+/-8 years, 86% male) with angiographically documented CAD, preserved left ventricular function, and non-elevated uric acid levels (233+/-10 microM). Patients received incremental doses of intracoronary acetylcholine (ACh; 10(-7) to 10(-5) microM), and minimal lumen diameter (MLD) and coronary blood flow (CBF) were assessed before and after intravenous administration of oxypurinol (200 mg). Oxypurinol inhibited plasma XO activity 63% (0.051+/- 0.001 vs 0.019+/- 0.005 microU/mg protein; p<0.01). In pts who displayed endothelial dysfunction as evidenced by coronary vasoconstriction in response to ACh (n=13), oxypurinol markedly attenuated ACh-induced vasoconstriction (-23+/- 4 vs -15+/- 4% at ACh 10(-5) microM, p<0.05) and significantly increased CBF (16+/-17 vs 62+/-18% at ACh 10(-5) microM, p<0.05), whereas in patients with preserved coronary endothelial function, oxypurinol had no effect on ACh-dependent changes in MLD (+2.8+/- 4.2 vs 5.2+/- 0.7%, p>0.05) or CBF (135+/-75 vs 154+/-61%, p>0.05). Flow-mediated dilation of the brachial artery, assessed in eight consecutive patients, increased from 5.1+/-1.5 before to 7.6+/-1.5% after oxypurinol administration (p < 0.05). Oxypurinol inhibition of XO improves coronary vascular endothelial dysfunction, a hallmark of patients with CAD. These observations reveal that XO-derived reactive oxygen species significantly contribute to impaired coronary NO bioavailability in CAD and that XO inhibition represents an additional treatment concept for inflammatory vascular diseases that deserves further investigation.     

Heart innervation after ligation of the left anterior descending coronary artery (LAD)

Distribution and amount of neuropeptide Y- and synaptophysin-immunoreactive nervous structures within the heart were investigated in dogs 4 days after ligation of the left anterior descending coronary artery (LAD). In the right atrium and posterior left ventricular regions, which were taken as (non-infarcted) control areas, neuropeptide Y-immunoreactive paravascular nerves and a perivascular nerve plexus running within the adventitia of the coronary arteries and their branches down to the arterioles were observed. Morphometric measurements of the area density revealed 0.099 +/- 0.014% for synaptophysin- and 0.037 +/- 0.0072% for neuropeptide Y-immunoreactivity within the posterior wall of the left ventricular myocardium. Four days after ligation of the LAD only single synaptophysin- and neuropeptide Y-immunoreactive nerve fibers were very rarely detected in the infarcted region of the anterior wall of the left ventricle. Above the ligature larger than normal neuropeptide Y-immunoreactive axons within nerves along the LAD indicated a blockage of the axoplasmic transport of this peptide. When investigating this model of experimental myocardial infarction, mechanical traumatization of peri- and paravascular nerves of the LAD by the ligature has to be considered as a major pathogenetic factor, in addition to ischemia leading to denervation of infarcted as well as non-ischemic myocardium.     

Heart innervation after ligation of the left anterior descending coronary artery (LAD)

Summary Distribution and amount of neuropeptide Y- and synaptophysin-immunoreactive nervous structures within the heart were investigated in dogs 4 days after ligation of the left anterior descending coronary artery (LAD). In the right atrium and posterior left ventricular regions, which were taken as (non-infarcted) control areas, neuropeptide Y-immunoreactive paravascular nerves and a perivascular nerve plexus running within the adventitia of the coronary arteries and their branches down to the arterioles were observed. Morphometric measurements of the area density revealed 0.099±0.014% for synaptophysin- and 0.037±0.0072% for neuropeptide Y-immunoreactivity within the posterior wall of the left ventricular myocardium. Four days after ligation of the LAD only single synaptophysin-and neuropeptide Y-immunoreactive nerve fibers were very rarely detected in the infarcted region of the anterior wall of the left ventricle. Above the ligature larger than normal neuropeptide Y-immunoreactive axons within nerves along the LAD indicated a blockage of the axoplasmic transport of this peptide.When investigating this model of experimental myocardial infarction, mechanical traumatization of peri- and paravascular nerves of the LAD by the ligature has to be considered as a major pathogenetic factor, in addition to ischemia leading to denervation of infarcted as well as nonischemic myocardium.This study was supported by the SFB 320 within the Deutsche Forschungsgemeinschaft (DFG)Parts of the results were presented at the 59. Scientific Session of the American Heart Association (1986) and at the Congress of the Deutsche Gesellschaft für Herz- und Kreislaufforschung 1987.     

Psychological and clinical characteristics of female patients with spontaneous coronary artery dissection

Aims

Spontaneous coronary artery dissection (SCAD) is increasingly recognised as a cause of myocardial infarction, but psychological characteristics of patients with SCAD have not yet been extensively investigated. We assessed the prevalence of a broad range of psychological and clinical factors, and their inter-relationships in patients with a history of SCAD. Furthermore, we investigated whether specific clusters of patients with SCAD can be identified.

Methods

Participants were recruited between March and May 2019 from a Dutch SCAD database and completed online questionnaires. Clinical information was verified by review of medical records. Participants were predominantly female (172/183; 94%). Analyses focused on the 172 female patients (mean age 52.0 ± 7.5 years, 37% postmenopausal).

Results

The most common comorbidities of SCAD were migraine (52%), fibromuscular dysplasia (FMD; 29%), chronic pain (29%), and tinnitus (28%). Six women (3%) had pregnancy-associated SCAD. Traditional cardiovascular risk factors were rare (<10%), except for hypertension (31%). Psychological assessment indicated high levels of perceived stress (PSS-10 ≥14; 50%), fatigue (FAS-10 ≥22; 56%), and a frequent history of burnout (25%). The prevalence of depression (9%) and anxiety (12%) was relatively low. Three clusters were identified: (A) FMD and chronic non-ischaemic conditions (tinnitus, chronic pain, and irritable bowel syndrome); (B) migraine; and (C) none of these conditions.

Conclusion

This study shows that perceived stress and fatigue are common in patients with SCAD, in addition to prevalent comorbid FMD, migraine, tinnitus, and non-ischaemic pain conditions. These factors may add to developing tailored rehabilitation programmes for patients with SCAD.

     

Gender differences in plasma levels of lipoprotein (a) in patients with angiographically proven coronary artery disease

The objective of the study was to assess the association between plasma levels of lipoprotein(a) [Lp(a)] and the presence of angiographically defined coronary artery disease (aCAD). Patients (346 men and 184 women) undergoing selective coronary angiography (SCA) were classified into groups with positive [aCAD(+)] and negative [aCAD(-)] findings and their age, body mass index (BMI), waist circumference, blood pressure, smoking, plasma total, LDL-, HDL-cholesterol (TC, LDL-C, HDL-C), triglycerides (TG), apolipoprotein B (apoB), Log(TG/HDL-C) and TC/HDL-C were determined. Concentration of plasma Lp(a) was estimated using the commercial solid phase two-side immunoradiometric assay of apolipoprotein apo(a). The plasma Lp(a) was significantly higher in both women and men with aCAD(+) compared to those with aCAD(-). While there was no significant difference in the Lp(a) level between men and women with aCAD(-) (median 138 vs. 145 units/l), the women with aCAD(+) had almost twice as high Lp(a) levels as men (median 442 vs. 274 units/l, p<0.001). Women with aCAD(+) had also significantly lower HDL cholesterol levels (1.09 vs. 1.20 mmol/l, p<0.05), higher triglycerides (1.82 vs. 1.46 mmol/l, p<0.05) and Log(TG/HDL-C) than women with aCAD(-). The differences in Lp(a) between positive and negative findings remained highly significant (p<0.001 in women, p<0.05 in men) after the adjustment for age, plasma HDL- and LDL-cholesterol and triglycerides in logistic regression analyses. In logistic regression model the Lp(a) and Log(TG/HDL-C) and smoking in women but smoking and age in men were the most powerful predictors of positive aCAD findings. Our findings suggest that Lp(a) is more strongly associated with aCAD+ in women than in men.     

Psychosocial characteristics of patients with bronchial asthma and coronary disease: similarities and differences

The authors compare two groups of subjects: patients with bronchial asthma and those with coronary disease, with regard to some social characteristics, abilities and perception of factors which they conceive are important in the etiology of their disease. Data were obtained by means of a questionnaire based on a known calibrated scale. A group of 100 patients with bronchial asthma and a group of 102 patients with coronary disease were examined. The significance of the difference was tested by chi 2, t-test, Wilcoxon's test and multivariate discriminative analysis. The results showed statistically significant differences between the patients with bronchial asthma and those with coronary disease in some social and psychological characteristics and also with regard to perception of potential etiological factors of their disease. However, no difference was found in life style and habits between the coronary and asthmatic patients.