Perioperative Psychological Interventions in Heart Surgery­Opportunities and Clinical Benefit.

BACKGROUND: Heart surgery is a source of high levels of emotional distress for the patient. If the stress experience is not adequately compensated, it can have a negative impact on postoperative recovery, as can untreated comorbid mental disorders. METHODS: A selective literature review on emotional distress and mental comorbidities in heart surgery patients and a scoping review on the spectrum and effectiveness of perioperative psychological interventions to compensate and reduce the stress experience. RESULTS: Mental factors such as depressive symptoms or anxiety disorders are associated with an elevated risk of postoperative morbidity and mortality in patients treated for heart disease. Mental comorbidities occur more frequently in these patients than in the general population. Following the manifestation of chronic heart disease (CHD), for example, 15-20% of the patients display severe depressive disorders. A few psychotherapeutic interventions to reduce anxiety and depression, emotional distress, consumption of analgesics, and extubation time have been found effective, with low to moderate evidence quality. Many different psychological interventions have proved useful in clinical practice, including multimodal, multiprofessional interventions incorporating medications, education, sports, and exercise as well as psychosocial therapy including stress management. Individual psychotherapy during the period of acute inpatient treatment after myocardial infarction is also effective. CONCLUSION: Because psychosocial factors are important, the current guidelines recommend systematic screening for mental symptoms and comorbidities in advance of heart transplantation or the implantation of ventricular assist devices (VAD). Acute psychotherapeutic interventions to reduce mental symptoms can be offered in the perioperative setting.

Patients with ventricular assist device and cerebral entrapment-Supporting skullcap reimplantation.

Effects of cranioplasty (CP) and skullcap reimplantation after decompressive craniectomy (DC) for cerebral hemorrhage or malignant brain infarction in patients with left ventricular assist device (LVAD) support as bridge to transplantation has not been surveyed yet. The aim of this study was to evaluate outcome and management after CP when aiming for transplantation. Data were collected from our prospective institutional database including all patients undergoing LVAD implantation between 2010 and 2019. Six patients needed CP procedures and were included. Our analysis focused on postoperative outcome, survival, and facilitation of heart transplantation. Study endpoints included also all-cause mortality. From a total of 1010 LVAD implantations during analysis period in our center, six bridge-to-transplantation LVAD patients [median age at LVAD implantation: 32.5 years (IQR: 24.8-39.5 years); four male, HVAD, n = 3; HM II, n = 1; HM 3, n = 2] underwent CP with imminent entrapment secondary to cerebral hemorrhage or malignant infarction. Primary heart failure etiology was myocarditis (n = 2), dilated (n = 2), or ischemic (n = 2). Median INTERMACS class was 1.5 (IQR; 1.0-2.8). Median time on LVAD support to DC procedure was 33 months (IQR: 16-48 months). The indication for DC was intraparenchymal hemorrhage (n = 4), subdural hematoma (n = 1), and malignant middle cerebral artery infarction (n = 1). After a median time of 4 months (IQR: 3.3-4.0 months, range; 2.0-10 months) post DC procedure, CP was subsequently performed without profound neurologic disabilities in all patients. After median time of 26 months (IQR: 21-42 months) follow-up, three patients successfully received heart transplantation, one patient could undergo LVAD explantation for myocardial recovery, and the remaining two patients are still on the list awaiting heart transplantation. CP procedure with skullcap reimplantation is feasible and can be safely performed in LVAD patients, which subsequently may even be eligible for heart transplantation with beneficial prognosis.

Clustering of cardiovascular risk factors and carotid intima-media thickness: The USE-IMT study.

BACKGROUND: The relation of a single risk factor with atherosclerosis is established. Clinically we know of risk factor clustering within individuals. Yet, studies into the magnitude of the relation of risk factor clusters with atherosclerosis are limited. Here, we assessed that relation. METHODS: Individual participant data from 14 cohorts, involving 59,025 individuals were used in this cross-sectional analysis. We made 15 clusters of four risk factors (current smoking, overweight, elevated blood pressure, elevated total cholesterol). Multilevel age and sex adjusted linear regression models were applied to estimate mean differences in common carotid intima-media thickness (CIMT) between clusters using those without any of the four risk factors as reference group. RESULTS: Compared to the reference, those with 1, 2, 3 or 4 risk factors had a significantly higher common CIMT: mean difference of 0.026 mm, 0.052 mm, 0.074 mm and 0.114 mm, respectively. These findings were the same in men and in women, and across ethnic groups. Within each risk factor cluster (1, 2, 3 risk factors), groups with elevated blood pressure had the largest CIMT and those with elevated cholesterol the lowest CIMT, a pattern similar for men and women. CONCLUSION: Clusters of risk factors relate to increased common CIMT in a graded manner, similar in men, women and across race-ethnic groups. Some clusters seemed more atherogenic than others. Our findings support the notion that cardiovascular prevention should focus on sets of risk factors rather than individual levels alone, but may prioritize within clusters.

Race/Ethnic Differences in the Associations of the Framingham Risk Factors with Carotid IMT and Cardiovascular Events.

BACKGROUND: Clinical manifestations and outcomes of atherosclerotic disease differ between ethnic groups. In addition, the prevalence of risk factors is substantially different. Primary prevention programs are based on data derived from almost exclusively White people. We investigated how race/ethnic differences modify the associations of established risk factors with atherosclerosis and cardiovascular events. METHODS: We used data from an ongoing individual participant meta-analysis involving 17 population-based cohorts worldwide. We selected 60,211 participants without cardiovascular disease at baseline with available data on ethnicity (White, Black, Asian or Hispanic). We generated a multivariable linear regression model containing risk factors and ethnicity predicting mean common carotid intima-media thickness (CIMT) and a multivariable Cox regression model predicting myocardial infarction or stroke. For each risk factor we assessed how the association with the preclinical and clinical measures of cardiovascular atherosclerotic disease was affected by ethnicity. RESULTS: Ethnicity appeared to significantly modify the associations between risk factors and CIMT and cardiovascular events. The association between age and CIMT was weaker in Blacks and Hispanics. Systolic blood pressure associated more strongly with CIMT in Asians. HDL cholesterol and smoking associated less with CIMT in Blacks. Furthermore, the association of age and total cholesterol levels with the occurrence of cardiovascular events differed between Blacks and Whites. CONCLUSION: The magnitude of associations between risk factors and the presence of atherosclerotic disease differs between race/ethnic groups. These subtle, yet significant differences provide insight in the etiology of cardiovascular disease among race/ethnic groups. These insights aid the race/ethnic-specific implementation of primary prevention.

Prediction of asymptomatic carotid artery stenosis in the general population: identification of high-risk groups.

BACKGROUND AND PURPOSE: Because of a low prevalence of severe carotid stenosis in the general population, screening for presence of asymptomatic carotid artery stenosis (ACAS) is not warranted. Possibly, for certain subgroups, screening is worthwhile. The present study aims to develop prediction rules for the presence of ACAS (>50% and >70%). METHODS: Individual participant data from 4 population-based cohort studies (Malmö Diet and Cancer Study, Tromsø Study, Carotid Atherosclerosis Progression Study, and Cardiovascular Health Study; totaling 23 706 participants) were pooled. Multivariable logistic regression was performed to determine which variables predict presence of ACAS (>50% and >70%). Calibration and discrimination of the models were assessed, and bootstrapping was used to correct for overfitting. RESULTS: Age, sex, history of vascular disease, systolic and diastolic blood pressure, total cholesterol/high-density lipoprotein ratio, diabetes mellitus, and current smoking were predictors of stenosis (>50% and >70%). The calibration of the model was good confirmed by a nonsignificant Hosmer and Lemeshow test for moderate (P=0.59) and severe stenosis (P=0.07). The models discriminated well between participants with and without stenosis, with an area under the receiver operating characteristic curve corrected for over optimism of 0.82 (95% confidence interval, 0.80-0.84) for moderate stenosis and of 0.87 (95% confidence interval, 0.85-0.90) for severe stenosis. The regression coefficients of the predictors were converted into a score chart to facilitate practical application. CONCLUSIONS: A clinical prediction rule was developed that allows identification of subgroups with high prevalence of moderate (>50%) and severe (>70%) ACAS. When confirmed in comparable cohorts, application of the prediction rule may lead to a reduction in the number needed to screen for ACAS.

Prevalence of asymptomatic carotid artery stenosis in the general population: an individual participant data meta-analysis.

BACKGROUND AND PURPOSE: In the discussion on the cost-effectiveness of screening, precise estimates of severe asymptomatic carotid stenosis are vital. Accordingly, we assessed the prevalence of moderate and severe asymptomatic carotid stenosis by age and sex using pooled cohort data. METHODS: We performed an individual participant data meta-analysis (23 706 participants) of 4 population-based studies (Malmö Diet and Cancer Study, Tromsø, Carotid Atherosclerosis Progression Study, and Cardiovascular Health Study). Outcomes of interest were asymptomatic moderate (> or =50%) and severe carotid stenosis (> or =70%). RESULTS: Prevalence of moderate asymptomatic carotid stenosis ranged from 0.2% (95% CI, 0.0% to 0.4%) in men aged <50 years to 7.5% (5.2% to 10.5%) in men aged > or =80 years. For women, this prevalence increased from 0% (0% to 0.2%) to 5.0% (3.1% to 7.5%). Prevalence of severe asymptomatic carotid stenosis ranged from 0.1% (0.0% to 0.3%) in men aged <50 years to 3.1% (1.7% to 5.3%) in men aged > or =80. For women, this prevalence increased from 0% (0.0% to 0.2%) to 0.9% (0.3% to 2.4%). CONCLUSIONS: The prevalence of severe asymptomatic carotid stenosis in the general population ranges from 0% to 3.1%, which is useful information in the discussion on the cost-effectiveness of screening.

Fractalkine receptor/ligand genetic variants and carotid intima-media thickness.

BACKGROUND AND PURPOSE: The fractalkine ligand/receptor (CX3CL1/CX3CR1) complex is important in inflammatory responses and has been associated with vascular disease. We determined whether genetic variants in CX3CL1 and CX3CR1 are associated with carotid atherosclerosis in 2 large European populations. METHODS: 18 polymorphisms in CX3CL1 and CX3CR1 were genotyped in 2763 German community individuals (CAPS). Positive results were tested for replication on 6049 French community individuals (3C Study). RESULTS: In CAPS we found associations of common carotid artery (CCA)-IMT with 2 CX3CL1 (rs170364, rs614230) and 1 CX3CR1 (rs3732378) variants, and significant interactions of CX3CR1 rs11129820, rs3732378, and rs614230 variants with smoking and alcohol consumption in relation with CCA-IMT. None of these were replicated in 3C. In 3C only there was a borderline significant association of rs3732378 with carotid plaques. CONCLUSIONS: In almost 9000 subjects, we found no replicable associations of CX3CL1 and CX3CR1 polymorphisms with CCA-IMT or plaque.

The interdisciplinary treatment of unruptured intracranial aneurysms.

INTRODUCTION: The purpose of this article is to present the results of microsurgical clipping or endovascular coil obliteration of unruptured intracranial aneurysms (UIA), in a single cerebrovascular center with regard to successful obliteration and periprocedural complications. METHODS: Data concerning patients with UIA were recorded in the neurovascular database of the neurosurgical department at the University of Frankfurt. The outcome of treatment was assessed with the modified Rankin Scale. RESULTS: 126 patients were treated by open surgery and 74 patients by endovascular coil obliteration. After treatment, the rate of new, mostly transient neurological deficits was 5%, and there were no deaths related to any treatment in this series. The outcome was good in 124 (98.4%) of the surgically treated patients and 73 (98.6%) of the endovascularly treated patients, and only 3 patients (1.5%) had a treatment-related unfavorable outcome. 98% of the treated aneurysms were satisfactorily obliterated. Seven endovascularly treated patients required retreatment because of coil compaction leading to recanalization of the aneurysm. CONCLUSIONS: The majority of patients with unruptured intracranial aneurysms, even complex ones, can be treated by microsurgery or endovascular aneurysm obliteration with very good clinical results and a very low percentage of unfavorable outcomes. With careful patient selection and individualized assignment of the best form of treatment to each patient, we were able to achieve a low overall complication rate and a very high rate of obliteration in our specialized neurovascular center.

Toll receptor polymorphisms and carotid artery intima-media thickness.

BACKGROUND AND PURPOSE: Inflammation is a key mechanism in atherosclerosis. Variation in genes encoding inflammatory responses may therefore influence atherosclerosis risk possibly through interaction with chronic infections and proinflammatory environmental risk factors such as smoking, diabetes, and obesity. The Toll-like receptor family (TLRs) genes TLR2 and TLR4, both involved in the inflammatory process, are potential candidates and TLR-4 has been previously associated with cardiovascular disease, although other studies have failed to confirm this. METHODS: A total of 3000 individuals from the prospective community-based Carotid Atherosclerosis Progression Study (CAPS) were genotyped for single nucleotide polymorphisms: TLR2 (Arg753Gln, -16934 A/T) and TLR4 (D299G, T399I). Associations were determined with common carotid artery intima-media thickness (IMT) at baseline and also progression of IMT over the 3-year follow-up period. Gene-environment interactions with high sensitive C-reactive protein, smoking, body mass index, and diabetes were determined. RESULTS: There was no association between single nucleotide polymorphisms or haplotypes in either TLR4 or TLR2 and either baseline IMT or progression of IMT over the 3-year follow up. There were no interactions among the three proinflammatory risk factors. No genotype or haplotype was associated with high sensitive C-reactive protein. CONCLUSIONS: In this large community population, we found no evidence for genetic variation in these two TLRs being risk factors for increased IMT either directly or through interaction with proinflammatory risk factors. We were unable to confirm associations with the TLR4 polymorphisms reported in previous smaller studies.

Atherosclerotic carotid stenosis and occlusion.

Ultrasonic techniques can determine both the presence and degree of atherosclerotic lesions around the internal carotid artery bifurcation with a high degree of accuracy. Carried out by experienced sonographers, who are aware of the relevant limitations and the most common pitfalls, noninvasive ultrasound can serve as a screening tool, supply the vascular surgeon or interventionalist with sufficient information for determining treatment, and is an optimal tool for follow-up examinations. In this context, it will be of importance that ultrasound also facilitates the delineation of blood flow in a stented internal carotid artery. This will open up the possibility of using ultrasound to detect restenosis after endovascular treatment.

Inflammatory gene load is associated with enhanced inflammation and early carotid atherosclerosis in smokers.

BACKGROUND AND PURPOSE: Smoking acts as a pro-inflammatory stimulus. Inflammation may provide a key mechanism by which smoking causes atherosclerosis. If so, then the degree to which an individual mounts an inflammatory response is likely to influence atherosclerosis severity. This study examined the impact of inflammatory gene polymorphisms and gene-smoking interactions on common carotid artery intima-media thickness (IMT), a measure of early atherosclerosis. METHODS: In a community population (n=1000), mean IMT was determined using ultrasound. This population was genotyped for 6 polymorphisms in 4 inflammatory genes: IL-6-174, IL-6-572, and IL-6-597; IL-1-beta-31; IL-1 receptor antagonist VNTR and CD14-159. Serum IL-6 levels were measured in the first 500 subjects. Genotypes/haplotypes associated with higher IL-6 levels were designated "inflammatory haplotypes." A gene load score was calculated, in which 2 represented individuals homozygous for > or =2 inflammatory genotypes/haplotypes and 0 was homozygous for none. RESULTS: Increasing gene load of inflammatory genotypes was associated with a linear increase in serum IL-6 levels (P=0.018) and increased carotid artery IMT (P=0.003). There was a significant interaction between gene load and smoking status on carotid IMT (P for interaction=0.002). Specifically, in smokers, carriers of inflammatory haplotypes had significantly increased age- and sex-adjusted IMT (IL-6-174C/IL-6-572G/IL-6-597A, P=0.005; IL-1-beta-31T/IL-1RN*2,P=0.04; CD14-159CC, P=0.028). CONCLUSIONS: These findings support the hypothesis that inflammation and cytokine responses provide a key mechanism by which smoking causes atherogenesis. Secondly, they highlight the importance of gene-environment, and gene-gene-environment interactions in the pathogenesis of atherosclerosis.

Functional impairment, disability, and quality of life outcome after decompressive hemicraniectomy in malignant middle cerebral artery infarction.

OBJECT: Whether decompressive hemicraniectomy is an appropriate treatment for space-occupying middle cerebral artery (MCA) infarction is still a controversial issue. Previous studies are in agreement on a reduction of the mortality rate, but the reported functional outcome was highly variable. The authors sought to determine functional impairment, disability, and health-related quality of life (QOL) outcome in long-term survivors who had undergone this procedure, and tried to identify factors related to functional outcome. METHODS: The study included 36 consecutive patients (mean age 58.8 +/- 12.7 years, 20 men and 16 women) who underwent decompressive hemicraniectomy for treatment of malignant MCA infarction (29 on the right and seven on the left side; mean time to surgery 37.8 +/- 20 hours). The survival rate was determined at 6 months: 13.7 +/- 6.7 months after the stroke, a cross-sectional personal investigation of survivors was performed to assess functional impairment, disability, and health-related QOL. Survival rates were 78% at 6 months and 64% at the time of the follow-up investigation; one patient was lost to follow up. Sixteen of 22 long-term survivors lived at home. The median Barthel Index (BI) was 45 (25th and 75th percentile 19 and 71) and the BI correlated negatively with patient age (r = -0.58, p = 0.005). Three patients reached a BI of at least 90. Older age, more severe neurological deficit on admission, and longer duration of intensive care treatment and mechanical ventilation were significantly associated with worse disability (BI < 50). The health-related QOL was considerably impaired in the subscales of mobility, household management, and body care. CONCLUSIONS: Decompressive hemicraniectomy improves survival in patients with malignant MCA infarction when compared with earlier reports of conservative treatment alone. Functional outcome and QOL remain markedly impaired, especially among elderly patients and in those with a severe neurological deficit at admission.

Serum S100B predicts a malignant course of infarction in patients with acute middle cerebral artery occlusion.

BACKGROUND AND PURPOSE: Early predictors of infarct volume may improve therapeutic decisions in patients with acute cerebral ischemia. We investigated whether measurements of serum astroglial protein S100B can predict a malignant course of infarction in acute middle cerebral artery (MCA) occlusion. METHODS: We included 51 patients (24 women, mean age 69.1+/-12.4 years) admitted within 6 hours after stroke symptom onset caused by proximal MCA occlusion, as shown by magnetic resonance angiography (n=39), intra-arterial angiography (n=4), or transcranial duplex sonography (n=8). Blood samples were drawn at hospital admission and 8, 12, 16, 20, and 24 hours after symptom onset. Serum S100B concentrations were determined using a fully automated immunoluminometric assay. A malignant course of infarction was defined as the occurrence of clinical signs of cerebral herniation within the first 7 days of treatment or the clinical decision to perform decompressive hemicraniectomy caused by critical space-occupying swelling as detected by repeated neuroimaging. RESULTS: Sixteen patients developed malignant infarction (31%). Beginning with the 12-hour value, mean S100B serum concentrations were significantly higher in patients with a malignant course compared with those without (12 hours 1.23+/-1.24 versus 0.29+/-0.45 microg/L; 16 hours 1.80+/-1.65 versus 0.38+/-0.53 microg/L; 20 hours 1.90+/-1.53 versus 0.44+/-0.48 microg/L; and 24 hours 2.41+/-1.59 versus 0.57+/-0.66 microg/L; all P<0.001). A 12-hour S100B value >0.35 microg/L predicted malignant infarction with 0.75 sensitivity and 0.80 specificity. A 24-hour value >1.03 microg/L provided 0.94 sensitivity and 0.83 specificity. CONCLUSIONS: The serum marker S100B can predict a malignant course of infarction in proximal MCA occlusion. This finding may improve the identification and monitoring of patients at particularly high risk for herniation.

Rates and determinants of site-specific progression of carotid artery intima-media thickness: the carotid atherosclerosis progression study.

BACKGROUND AND PURPOSE: Carotid intima-media thickness (IMT) progression rates are increasingly used as an intermediate outcome for vascular risk. The carotid bifurcation (BIF) and internal carotid artery (ICA) are predilection sites for atherosclerosis. IMT measures from these sites may be a better estimate of atherosclerosis than common carotid artery (CCA) IMT. The study aim was to evaluate site-specific IMT progression rates and their relationships to vascular risk factors compared with baseline IMT measurements. METHODS: In a community population (n=3383), ICA-IMT, BIF-IMT, CCA-IMT, and vascular risk factors were evaluated at baseline and at 3-year follow-up. RESULTS: Mean (SD) IMT progression was significantly greater at the ICA (0.032 [0.109] mm/year) compared with the BIF (0.023 [0.108] mm/year) and the CCA (0.001 [0.040] mm/year) (P<0.001). Only ICA-IMT progression significantly correlated with baseline vascular risk factors (age, male gender, hypertension, diabetes, and smoking). Change in risk factor profile over follow-up, estimated using the Framingham risk score, was a predictor of IMT progression only. For all arterial sites, correlations were stronger, by a factor of 2 to 3, for associations with baseline IMT compared with IMT progression. CONCLUSIONS: Progression rates at the ICA rather than the CCA yield greater absolute changes in IMT and better correlations with vascular risk factors. Vascular risk factors correlate more strongly with baseline IMT than with IMT progression. Prospective data on IMT progression and incident vascular events are required to establish the true value of progression data as a surrogate measure of vascular risk.

Promoter polymorphism in the endotoxin receptor (CD14) is associated with increased carotid atherosclerosis only in smokers: the Carotid Atherosclerosis Progression Study (CAPS).

BACKGROUND AND PURPOSE: The risk of atherosclerosis from endotoxemia is increased in smokers. Endotoxin is a potent mediator of inflammation, and smokers have elevated plasma levels of endotoxin. The endotoxin receptor CD14 can enhance the endotoxin-neutralization capacity of plasma. A functional polymorphism in the promoter region of the CD14 gene (CD14 -159C/T) was studied to determine its impact on common carotid artery (CCA) intima-media thickness (IMT) and any interactions with environmental inflammatory stimuli. METHODS: A community population (n=992; aged 50 to 65 years) underwent genotypic examination for the CD14 -159 polymorphism by restriction fragment length polymorphism analysis. RESULTS: The CC genotype was associated with increased CCA IMT. The age- and sex-adjusted odds ratio for IMT above the 75th percentile was 1.63 (95% CI, 1.19 to 2.24; P=0.002) and 1.70 (95% CI, 1.18 to 2.44; P=0.004) after additional adjustment for conventional risk factors. This gene effect was found only in current smokers and ex-smokers. Multivariate analysis in this group (n=503) increased the odds ratio to 2.02 (95% CI, 1.23 to 3.34; P=0.006). No significant interactions were found in nonsmokers or with alcohol consumption. CONCLUSIONS: The CD14 -159 polymorphism is associated with increased CCA IMT in smokers from a general population. CD14 may modulate the inflammatory effects of smoking in atherogenesis.

Interleukin-6 promoter polymorphism modulates the effects of heavy alcohol consumption on early carotid artery atherosclerosis: the Carotid Atherosclerosis Progression Study (CAPS).

BACKGROUND AND PURPOSE: A J-shaped relationship has been demonstrated between alcohol and both clinical cardiovascular events and carotid atherosclerosis. A similar J-shaped relationship has been found between alcohol intake and inflammatory markers. If inflammation were on the intermediate causal pathway between alcohol intake and atherosclerosis, then genetic determinants of enhanced inflammation would be expected to modify this relationship. METHODS: In a large community population (n=1000; age, 50 to 65 years), we studied the effects of the interleukin-6 (IL-6)-174 polymorphism and gene-alcohol interactions on common carotid artery intima-media thickness (CCA-IMT) and carotid plaque. RESULTS: The CC genotype was associated with significantly higher IL-6 levels; the odds ratio (OR) for IL-6 in the top quartile was 2.07 (95% CI, 1.16 to 3.72; P=0.014). Interactions were seen between genotype and alcohol consumption for both IL-6 levels and CCA-IMT. In individuals who drank >30 g/d of alcohol, the CC genotype was associated with higher IL-6 levels, elevated CCA-IMT (P=0.001), and increased risk of carotid plaque (OR, 3.64; 95% CI, 1.15 to 11.54; P=0.028). The J-shaped relationship between alcohol intake and IMT was seen only for the CC genotype. CONCLUSIONS: These data suggest that the IL-6-174 promotor polymorphism may modulate the effects of alcohol on carotid atherosclerosis. These data support the hypothesis that inflammation forms part of the intermediate causal pathway between alcohol intake and atherosclerosis.

C-reactive protein and carotid intimal medial thickness in a community population.

BACKGROUND: C-reactive protein (CRP) has been linked to cardiovascular disease and atherosclerosis. Large-scale epidemiological studies have shown a correlation of CRP level with risk of stroke, myocardial infarction and peripheral arterial disease. Nevertheless, the question whether serum CRP itself is an independent indicator of the atherosclerotic process remains unanswered. METHODS: In a community-based sample free of advanced atherosclerotic disease (n = 1018; mean age +/- SD, 54.1 +/- 12.0 years; 49.7% women) we examined the relationship between carotid intimal medial thickness (IMT), conventional vascular risk factors (that is, smoking, obesity, elevated blood pressure, diabetes mellitus, hypercholesterolaemia) and serum CRP. RESULTS: We found an association between increasing IMT values with increasing CRP values for all sites within the carotid system (for example, common carotid artery [CCA-] IMT, beta = 0.174, P < 0.001). The relationship was weakened after accounting for the above-mentioned conventional risk factors (linear regression), particularly body mass index, but remained significant (for example, mean CCA-IMT beta = 0.02, P = 0.042). Including fibrinogen in the regression made the relationship no longer significant (mean CCA-IMT beta = 0.01, P = 0.277). CONCLUSION: It is unlikely that CRP per se is a major independent cause of early arteriosclerosis. Elevations of CRP, or less specifically chronic inflammation, may mediate the effect of certain conventional risk factors on promoting atherogenesis, especially obesity.

Helicobacter pylori infection, the cytotoxin gene A strain, and carotid artery intima-media thickness.

BACKGROUND: Chronic Helicobacter pylori infection has been implicated as a risk factor for stroke and other cardiovascular disease. It has been suggested that it acts by promoting atherogenesis. A particular strain of H. pylori, the cytotoxin gene A strain (CagA strain), which has been associated with increased inflammation, has been reported to account for much of this relationship. An early estimate of atherosclerosis can be obtained by ultrasonic imaging of the carotid artery to determine intima-media thickness (IMT). We determined whether H. pylori infection, and particularly the CagA strain, is associated with increased IMT. METHODS: In 983 normal population individuals we measured common carotid artery (CCA) IMT. From serum samples we determined H. pylori and CagA status. RESULTS: There was no significant association between H. pylori seropositivity and CCA IMT after controlling for age and gender. There were significant relationships between H. pylori seropositivity and a number of conventional cardiovascular risk factors (age, systolic and diastolic blood pressure, body mass index, smoking) and after controlling for these the magnitude of the regression coefficient was reduced by a further half. Amongst H. pylori seropositives the CagA strain was associated with increased IMT after controlling for age and gender (B = 0.0256, 95% CI 0.001-0.050, P = 0.038). The relationship was no longer significant after controlling for other cardiovascular risk factors. (B = 0.0194, 95% CI -0.004-0.042, P = 0.098). CONCLUSIONS: H. pylori and the CagA strain are not major risk factors for early arteriosclerosis as assessed by carotid artery intima-media thickness.