Arterial endothelial function and wall thickness in familial hypercholesterolemia and familial combined hyperlipidemia and the effect of statins. A systematic review and meta-analysis

BackgroundTo evaluate the impact of familial hypercholesterolemia (FH) and familial combined hyperlipidemia (FCH) on arterial properties and the effects of statins.MethodsWe meta-analyzed 51 studies providing data for 4,057 FH patients and 732 FCH patients with random-effects models, meta-regression analysis and publication bias analysis. The main outcomes of interest were (1) brachial artery flow-mediated dilation (FMD), (2) intima-media thickness (IMT), and (3) change of IMT and FMD after treatment with statins.ResultsCompared to normolipidemic controls, FH patients had lower FMD [pooled mean difference (MD): ?5.31%, 95% CI ?7.09 to ?3.53%, P < 0.001] and higher carotid IMT (pooled MD: 0.12 mm, 95% CI 0.09–0.15 mm, P < 0.001) and femoral IMT (pooled MD: 0.35 mm, 95% CI 0.18–0.51 mm, P < 0.001). FCH patients had lower FMD and increased IMT (pooled MD: ?3.60%, 95% CI ?6.69 to ?0.50%, P = 0.023; and 0.06 mm, 95% CI 0.04–0.08 mm, P < 0.001, respectively). Total and LDL-cholesterol was a significant determinant of FMD and carotid IMT in FCH patients and of FMD and femoral IMT in FH patients. In FH patients, statins improved FMD (pooled MD of change: 5.39%, 95% CI 2.86–7.92%, P < 0.001) and decreased carotid IMT (pooled MD of change: ?0.025 mm, 95% CI ?0.042 to ?0.009 mm, P = 0.003). Changes of both FMD and IMT with statins correlated with the duration × treatment intensity product in FH patients (both P < 0.01). Additionally, statins improved FMD in FCH patients (pooled MD of change: 2.06%, 95% CI 0.43–3.69%, P = 0.013). No significant publication bias was detected.ConclusionArterial properties are impaired in subjects with FH or FCH. Statins improve arterial function and structure in FH patients in a treatment intensity-related manner.     

Effect of folic acid supplementation on the progression of carotid intima-media thickness: a meta-analysis of randomized controlled trials

ObjectivesWe conducted a meta-analysis of relevant randomized trials to assess whether folic acid supplementation reduces the progression of atherosclerosis as measured by carotid intima-media thickness (CIMT).MethodsThis analysis included 2052 subjects from ten folic acid randomized trials with the change in CIMT reported as one of the end points. Summary estimates of weighted mean differences (WMDs) and 95% CIs were obtained by using random-effect models. Meta-regression and subgroup analyses were performed to identify the source of heterogeneity.ResultsOur analysis showed that folic acid supplementation significantly reduces the progression of CIMT (WMD: ?0.04 mm; 95%CI: ?0.07, ?0.02; P < 0.001), particularly in subjects with chronic kidney disease (CKD) (WMD: ?0.16 mm; 95%CI: ?0.26, ?0.07; P = 0.0006) or high cardiovascular disease (CVD) risk (WMD: ?0.05 mm; 95%CI: ?0.11, 0.00; P = 0.06) but not in subjects who were generally healthy with only elevated homocysteine concentrations (WMD:0.00 mm; 95%CI: ?0.01, 0.01; P = 0.35). Furthermore, meta-regression analysis of the data showed that the baseline CIMT levels (P = 0.011) and the percent reduction of homocysteine (P < 0.001) were positively related to the effect size. Consistently, a greater beneficial effect was seen in those trials with baseline CIMT levels ≥0.8 mm (WMD: ?0.14 mm; 95%CI: ?0.19, ?0.08; P < 0.0001), and a reduction in the homocysteine concentration ≥30% (WMD: ?0.22 mm; 95%CI: ?0.38, ?0.06; P = 0.009). In the corresponding comparison groups, the effect sizes were attenuated and insignificant.ConclusionsOur findings indicate that folic acid supplementation is effective in reducing the progression of CIMT, particularly in subjects with CKD or high CVD risk and among trials with higher baseline CIMT levels or a larger homocysteine reduction.     

Effect of thiazolidinediones on in-stent restenosis in patients after coronary stenting: a meta-analysis of randomized controlled trials

BackgroundRecent experimental studies have demonstrated that thiazolidinediones (TZDs) therapy inhibits proliferation and migration of vascular smooth muscle cells, accelerates endothelium reparation and attenuates neointimal hyperplasia. It implies that TZDs therapy may have beneficial effects on in-stent restenosis (ISR). Several small-sample clinical trials have evaluated the effect of TZDs therapy on ISR, however, the results were inconsistent across trials.Methods and resultsWe performed a meta-analysis of all relevant randomized controlled trials to evaluate the effect of TZDs therapy on in-stent restenosis in patients undergoing coronary stenting. Eight trials involving 366 patients were included in this study. TZDs therapy was associated with a significant reduction in the risk of ISR in both diabetic (RR 0.37, 95% CI 0.23–0.59; P < 0.0001) and non-diabetic patients (RR 0.16, 95% CI 0.05–0.45; P = 0.0006). TZDs therapy was associated with a significant reduction in late lumen loss (WMD ?0.54 mm, 95% CI ?0.87 mm, ?0.22 mm; P = 0.001), percent diameter stenosis (WMD ?15.7%, 95% CI ?19.4%, ?12.0%; P < 0.00001), neointimal area/volume (SMD ?0.76, 95% CI ?1.13, ?0.39; P < 0.0001) and target lesion revascularization (RR 0.32, 95% CI 0.18–0.57; P = 0.0001).ConclusionsOur study suggests that TZDs therapy is an effective strategy in preventing ISR in both diabetic and non-diabetic patients undergoing coronary stenting. More studies, especially large multi-centre RCTs, are still warranted to further clarify the anti-restenotic effect of TZDs therapy.     

Vitamin C consumption is associated with less progression in carotid intima media thickness in elderly men: A 3-year intervention study

Background and aimPlant foods may lower the risk of cardiovascular disease.Methods and resultsWe assessed changes in the intima media thickness (IMT) of the carotid artery and diet in elderly men. Men (n = 563) aged 70 ± 5 years were randomly assigned to 1 of 4 groups (dietary intervention, omega-3 supplementation, both or neither) using a 2 × 2 factorial design. B-mode ultrasound of the carotid arteries and calculation of dietary intake were performed at baseline and after 3 years. We previously showed that omega-3 supplementation did not influence the IMT, thus the dietary intervention (n = 233) and no dietary intervention (n = 231) groups were pooled.The dietary intervention group had less progression in the carotid IMT compared with the controls (0.044 ± 0.091 mm versus 0.062 ± 0.105 mm; P = 0.047). This group increased their daily vitamin C intake (P = 0.005) and intake of fruit, berries and vegetables (P ≤ 0.001). Increased intake of vitamin C and of fruit and berries was inversely associated with IMT progression (r = −0.181; P = 0.006 and r = −0.125; P = 0.056, respectively). Multivariate linear regression analysis showed that increased intakes of vitamin C and of fruit and berries were associated with less IMT progression in the intervention group and in the total study population, after adjustment for consumption of dietary cholesterol, cheese, saturated fat and group assignment.ConclusionVitamin C containing foods may protect against the progression of carotid atherosclerosis in elderly men.     

Both long-term HIV infection and highly active antiretroviral therapy are independent risk factors for early carotid atherosclerosis

ObjectiveThere is controversy over whether or not chronic HIV infection contributes to atherosclerosis. We investigated the relationship between HIV infection, antiretroviral medication and ultrasound evidence of early atherosclerosis in the context of vascular risk factors.DesignA case–control design with 292 HIV-positive subjects and 1168 age- and sex-matched controls.MethodsWe assessed vascular risk factors, blood pressure, serum lipids and carotid intima media thickness (IMT) in cases and controls. With multivariate regression models, we investigated the effects of HIV status and antiretroviral medication on IMT.ResultsThe common carotid artery (CCA) IMT value was 5.70% (95% confidence interval [3.08–8.38%], p < 0.0001) or 0.044 mm [0.021–0.066 mm] (p = 0.0001) higher in HIV-positives, adjusted for multiple risk factors. In the carotid bifurcation (BIF), the IMT values were 24.4% [19.5–29.4%] or 0.250 mm [0.198–0.303 mm] higher in HIV patients (p < 0.0001). An investigation of antiretroviral substances revealed higher CCA- and BIF-IMT values in patients receiving combination antiretroviral therapy (HAART).ConclusionsHIV infection and HAART are independent risk factors for early carotid atherosclerosis. Assuming a risk ratio similar to that in large population-based cohorts, the observed IMT elevation suggests that vascular risk is 4–14% greater and the “vascular age” 4–5 years higher in HIV-positive subjects. The underlying mechanisms remain to be clarified.     

Assessment of carotid intima-media thickness in subjects with ischemic cerebrovascular events undergoing endarterectomy

Background and aimIn clinical settings, the degree of lumen stenosis is the parameter used to select patients for carotid surgery. The present study was designed to measure carotid intima–media thickness (IMT), an indicator of atherosclerotic burden, in a sample of consecutive patients with ischemic cerebrovascular events referred for endarterectomy.Methods and resultsCarotid endarterectomy specimens from 55 consecutive patients (age 66 ± 10 years) admitted to hospital with recent documented atherothrombotic ischemic cerebrovascular events were compared with 24 carotid arteries from people (age 68 ± 11 years) who had died from documented causes unrelated to cerebrovascular disease. Measurement of extracranial carotid atherosclerosis was made from three anatomically defined segments, using image-processing software. A total of 426 cross sections was analyzed. Increasing IMT measures were clearly associated with increased risk of an ischemic event. Single maximum IMT values of 2.33 mm (95% CI, 1.69–2.96) for the common carotid, 2.45 mm (95% CI, 1.97–2.93) for the bifurcation, and 2.23 (95% CI, 1.83–2.64) for the internal carotid were associated with a 75% probability of a cerebrovascular ischemic accident. Receiver operator characteristic curve analyses demonstrated that the diagnostic ability of IMT measurements performed at the level of internal carotid artery to separate cases from controls was greater than common carotid artery or bifurcation measurements.ConclusionsThe present pathology study provides data on IMT in patients admitted to hospital for cerebrovascular accidents and referred for carotid endarterectomy.     

Coronary calcification is more predictive of carotid intimal medial thickness in black compared to white middle aged men

BackgroundRace-specific data for the association between coronary artery calcification (CAC) and carotid intimal medial thickness (IMT) are limited. We sought to compare black-white specific associations of these two measures.MethodsWe conducted a population-based study of 379 randomly selected men aged 40–49 years (84 black and 295 white) from Allegheny County, US (2004–2006). Agatston CAC score was evaluated by electron-beam tomography and carotid IMT was evaluated by ultrasonography.ResultsCompared to white men, black men had similar prevalence of CAC (p = 0.56) and higher total carotid IMT (p < 0.001). In black and white men, CAC score had significant positive correlations with total carotid IMT (r = 0.47 and r = 0.24, respectively, p < 0.001 for both) as well as the IMT for the common carotid artery (CCA), internal carotid artery and carotid bulb. The associations of CAC with total and CCA IMT were significantly stronger in black (β = 0.07 and β = 0.05, respectively) than white men (β = 0.03 and β = 0.01, respectively) after adjustment for traditional coronary risk factors (p = 0.046 and p = 0.036, respectively).ConclusionsIn black and white middle aged men, CAC score had significant positive correlations with total and segmental carotid IMT. CAC was more predictive of total and CCA IMT in black than white men independent of coronary risk factors.     

Plasma levels of soluble receptor for advanced glycation end products (sRAGE) and proinflammatory ligand for RAGE (EN-RAGE) are associated with carotid atherosclerosis in patients with peritoneal dialysis

ObjectivesThe soluble receptor for advanced glycation end products (sRAGE) exerts a protective effect on the development of atherosclerotic vascular complications by inhibiting RAGE-mediated inflammatory response. In contrast, extracellular newly identified RAGE-binding protein (EN-RAGE) contributes to increased atherosclerosis as a pro-inflammatory ligand for RAGE. We determined the levels of sRAGE and EN-RAGE in peritoneal dialysis (PD) patients and evaluated their relationship with carotid atherosclerosis.MethodsA cross-sectional study was performed in 91 PD patients and 29 control subjects. Carotid IMT (cIMT) and abdominal aortic vascular calcification score (VCS) were evaluated using high-resolution B-mode ultrasonography and plain radiographic film of the lateral abdomen.ResultsPlasma sRAGE and EN-RAGE levels were more than twice as higher in PD patients compared to controls. EN-RAGE showed a strong positive correlation with serum high-sensitivity CRP (p = 0.007) and IL-6 (p = 0.002), whereas sRAGE was negatively associated with those inflammatory markers (p = 0.001, p = 0.031). Even after adjustments for traditional cardiovascular risk factors, both sRAGE and EN-RAGE were independently associated with cIMT (β = ?0.230, p = 0.037, β = 0.155, p = 0.045) and VCS (β = ?0.205, p = 0.049, β = 0.197, p = 0.156). Multivariate logistic analysis revealed that old age (OR 1.14, 95% CI 1.03–1.25, p = 0.009), presence of diabetes (OR 13.4, 95% CI: 1.20–150.18, p = 0.035) and elevated plasma EN-RAGE (OR 2.26, 95% CI: 1.05–5.11, p = 0.048) were significant predictors for the occurrence of carotid atherosclerosis (cIMT > 1.0 mm and/or plaque formation).ConclusionsOur findings suggest that elevated plasma EN-RAGE and decreased sRAGE level could play a crucial role in systemic inflammation and carotid atherosclerosis in PD patients.     

Recently postmenopausal women have the same prevalence of subclinical carotid atherosclerosis as age and traditional risk factor matched men

ObjectiveTo compare the prevalence of subclinical atherosclerosis between postmenopausal women and men of similar age early after the onset of menopause.MethodsIn the first part of this cross-sectional study 186 non-diabetic young postmenopausal women (n = 101, menopausal age ≤10 years) and men (n = 85) aged 40–60 years without overt CVD were consecutively recruited from the outpatients clinics of an academic hospital. Subclinical carotid atherosclerosis was assessed by high-resolution ultrasonography. The presence of carotid atherosclerosis was defined as either increased carotid intima-media thickness (IMT > 0.9 mm) and/or the presence of plaques. In the second part, 1:1 matching for age and traditional risk factors (hyperlipidemia, smoking, hypertension and BMI) was performed between men and women of this cohort resulting in a matched sub-sample of 76 subjects.ResultsBy multivariate analysis, gender was not an independent determinant of any measure of carotid atherosclerosis. In the matched sub-sample, carotid IMT and the number of segments with atherosclerosis did not significantly differ between women and men (0.734 ± 0.119 mm and 1.47 ± 1.6 versus 0.717 ± 0.138 mm and 1.47 ± 1.5, p = 0.575 and p = 0.999, respectively). Also, the prevalence of increased IMT (60.5% in both genders), carotid plaques and subclinical atherosclerosis (31.6% and 63.2% versus 28.9% and 65.8%, p = 0.803 and p = 0.811, respectively) was similar between men and women.ConclusionsThe prevalence and severity of carotid atherosclerosis was similar between men and young postmenopausal women matched for traditional risk factors. Whether these women may be better risk stratified irrespective of gender should be further assessed in prospective studies.     

Effect of omega-3 fatty acids supplementation on endothelial function: a meta-analysis of randomized controlled trials

ObjectiveInverse association was reported between omega-3 fatty acids (FAs) supplementation and the risk of cardiovascular disease. Identifying the effect of omega-3 FAs on endothelial function may contribute to explain the association. We conducted a meta-analysis to assess the effect of omega-3 FAs supplementation on endothelial function, as measured by flow-mediated dilation (FMD) and endothelium-independent vasodilation (EIV).MethodsRandomized placebo-controlled trials (RCTs) were identified from the databases of PubMed, EMBASE and Cochrane library by two investigators and the pooled effects were measured by weighted mean difference (WMD), together with 95% confidence intervals (CIs). Subgroup and meta-regression analyses were used to explore the source of between-study heterogeneity.ResultsTotally 16 eligible studies involving 901 participants were finally included in meta-analysis. Compared with placebo, omega-3 FAs supplementation significantly increased FMD by 2.30% (95% CI: 0.89–3.72%, P = 0.001), at a dose ranging from 0.45 to 4.5 g/d over a median of 56 days. Subgroup analyses suggested that the effect of omega-3 FAs on FMD might be modified by the health status of the participants or the dose of supplementation. Sensitivity analyses indicated that the protective effect of omega-3 on endothelial function was robust. No significant change in EIV was observed after omega-3 FAs supplementation (WMD: 0.57%; 95% CI: ?0.88 to 2.01%; P = 0.442).ConclusionSupplementation of omega-3 fatty acids significantly improves the endothelial function without affecting endothelium-independent dilation.     

Carotid intima-media thickness is inversely associated with olive oil consumption

BackgroundIntima-media thickness (IMT) is a valid marker for generalized vascular disease whose main risk factors are associated with food habits and lifestyle. A Mediterranean food pattern may have a protective effect on cardiovascular mortality.ObjectiveTo assess the relationship between carotid IMT and olive oil consumption.MethodsOne hundred and ninety nine patients were randomly extracted from 1055 asymptomatic high cardiovascular risk participants at the AP-UNAV recruitment center of the PREDIMED (PREvención con DIeta MEDiterránea) project. Demographic and clinical variables were collected, and a validated semiquantitative food frequency questionnaire (137 items) was administered at the inclusion interview. A B-mode ultrasound imaging technique was used to measure the mean common carotid IMT.ResultsThe mean age was 67.3 years and 53.3% were women. Energy-adjusted olive oil consumption quintiles were assessed as the main exposure after adjusting for potential dietary and non-dietary confounders. Using continuous carotid IMT as the outcome in an ANCOVA analysis, the adjusted IMT means throughout quintiles showed an inverse association with a plateau after the second quintile, with statistical differences when the adjusted IMT mean of the merged four upper quintiles were compared with the lowest quintile (p < 0.05). The averaged (both sides) mean IMT of the common carotid was dichotomised and values above the median (0.804 mm) were used to identify carotid atherosclerotic damage. We also found an inverse association of olive oil consumption with high IMT, throughout the second to the fifth quintile as compared with the lowest quintile. The adjusted OR was of 0.08 (95% confidence interval, CI, of 0.02–0.37; p = 0.001) after merging the four upper quintiles.ConclusionThe inverse association between the olive oil consumption and the carotid IMT could suggest a protective role of olive oil against the development of carotid atherosclerosis in persons at high cardiovascular risk.     

Association between impaired glucose tolerance and carotid atherosclerosis: A study in 64-year-old women and a meta-analysis

Background and aimsImpaired glucose tolerance (IGT) is regarded as a transient metabolic state leading to type-2 diabetes, and is known to predict future risk of cardiovascular disease. This study was designed to investigate if IGT is associated with subclinical atherosclerosis.Methods and resultsIn a population-based cohort of 64-year-old women, a group with IGT determined by repeated oral glucose tolerance tests (n = 205) was compared with healthy women with normal glucose tolerance (NGT, n = 188). Intima-media thickness (IMT) and plaques in the common carotid arteries (CCA) and bulbs were measured by ultrasound. The 95% confidence interval (CI) of the difference between the IGT and NGT groups was −0.03 to 0.03 mm. There was no difference in carotid bulb IMT or in the occurrence, size, and characteristics of plaques between the IGT and NGT groups. A meta-analysis was used to calculate summary measures of 12 reviewed studies showing a difference of 0.030 (95% CI 0.012–0.048) mm in carotid IMT between IGT and NGT groups. Heterogeneity in IMT differences between studies was shown.ConclusionsIn our population-based cohort of 64-year-old women, IGT was not associated with increased occurrence of subclinical atherosclerosis. However, a meta-analysis of 12 studies, including our current study, showed that IGT was associated with a small increase in the CCA IMT.     

Dietary fat, abdominal obesity and smoking modulate the relationship between plasma complement component 3 concentrations and metabolic syndrome risk

ObjectiveChronic inflammation plays a role in the pathogenesis of metabolic syndrome (MetS) and cardiovascular disease (CVD). Complement component 3 (C3) is a novel cardiometabolic risk factor. Whether dietary fat intake modulates MetS risk conferred by elevated C3 concentrations is unknown. Our objective is to investigate the relationship between C3 concentrations and risk of the MetS and its phenotypes, and to further examine whether dietary fat intake modulates these relationships.MethodsBiochemical, dietary and lifestyle measurements were determined in the LIPGENE-SU.VI.MAX study of MetS cases and matched controls (n = 1754).ResultsElevated C3 concentrations (>median) were associated with increased risk of impaired insulin sensitivity [OR 1.78, CI 1.34–2.36, P < 0.0001], insulin resistance [OR 1.73, CI 1.31–2.89, P = 0.0001], abdominal obesity [OR 2.15, CI 1.43–3.24, P = 0.0002] and low HDL cholesterol [OR 1.40, CI 1.05–1.86, P = 0.02] compared to low C3 concentrations. Increased MetS risk conferred by elevated C3 concentrations [OR 3.11, 95% CI 2.52–3.82, P < 0.0001] was further accentuated among high dietary fat consumers [OR 4.80, 95% CI 2.77–8.33, P < 0.0001] (particularly of saturated [OR 4.05, 95% CI 2.33–7.05, P < 0.0001] and monounsaturated fat [OR 4.48, 95% CI 2.62–7.56, P < 0.0001]), and smokers [OR 3.83, 95% CI 2.12–6.94, P < 0.0001], however this effect was abolished in abdominally lean individuals [OR 1.46, 95% CI 0.69–3.14, P = 0.33].ConclusionsDietary fat (intake and composition), abdominal obesity and smoking modulate the relationship between elevated plasma C3 concentrations and MetS risk.     

Single polymorphism nucleotide rs1333049 on chromosome 9p21 is associated with carotid plaques but not with common carotid intima-media thickness in older adults. A combined analysis of the Three-City and the EVA studies

ObjectivesTo address the relationship of rs1333049, the 9p21 variant showing the strongest association with coronary heart disease (CHD), with carotid plaques and plaque-free common carotid artery intima-media thickness (CCA-IMT) in older adults from 2 French population-based cohorts.MethodsWe genotyped for rs1333049, 4097 CHD-free participants including 3191 aged 65–86 years from the Three-City (3C) Study and 906 aged 59–71 years from the Vascular Aging Study (EVA). Plaque-free mean CCA-IMT and the presence of carotid plaques were assessed.ResultsIn multivariate analysis, each C allele copy of rs1333049 was associated with baseline carotid plaques (odds ratio (OR) = 1.24; 95% confidence interval (CI) = 1.13–1.36; p < 0.001) but not with baseline CCA-IMT (p = 0.19). Among the EVA participants, the C allele was associated with 4-year plaques progression (p = 0.04) but not with CCA-IMT progression.ConclusionThe chromosome 9p21 locus might influence CHD risk through carotid plaques development.     

High-density lipoprotein-cholesterol and risk of stroke and carotid atherosclerosis: a systematic review

Background and purposeEpidemiological studies have found no relationship between total cholesterol and stroke risk, but little attention has been paid to high-density lipoprotein-cholesterol (HDL-C).MethodsWe performed a systematic PubMed literature search for epidemiological studies that examined the association between HDL-C level and stroke or carotid intima-media thickness (IMT).ResultsWe identified 18 studies on the relationship between HDL-C and stroke risk and 37 on HDL-C and carotid IMT. Eight of ten prospective cohort studies (n = 238 739) and three of eight case–control studies (n = 3604 cases, 8220 controls) supported an association between elevated HDL-C level and decreased risk of stroke. Prospective cohort studies reporting on relative risk per unit increase in HDL-C showed an 11–15% decreased stroke risk per 10-mg/dl increase in HDL-C. Of 37 studies on carotid IMT, 31 reported cross-sectional, one longitudinal, and five both cross-sectional and longitudinal associations between HDL-C level and carotid IMT. Of 36 cross-sectional studies (n = 51 288), 20 showed an inverse association between HDL-C level and carotid IMT. Of six longitudinal studies (n = 20 065), three showed no association, one showed a weak association in a subgroup of white women and two showed a significant inverse relationship between HDL-C level and carotid IMT. Pooled estimates could not be calculated because of the variation in study designs and analysis.ConclusionsThe weight of evidence in the literature supports an inverse association between HDL-C level and stroke or carotid atherosclerosis, but more data are needed to firmly establish this protective effect.     

Relation of self-reported sleep duration with carotid intima-media thickness in a general population sample

ObjectivesAn association of sleep with cardiovascular disease has been suggested. We analyzed the association of sleep duration with carotid intima-media thickness (IMT) as measure of generalized atherosclerosis.MethodsIMT of the common carotid arteries was measured in 2437 participants of the Study of Health in Pomerania (SHIP). Participants indicated their daily sleep duration as sum of night and afternoon sleep.ResultsThere was a J-shaped association of sleep duration (5 to 11/12 h) with IMT. In this association, IMT values were lowest among subjects with an average sleep duration of 7–8 h (0.76 ± 0.15 and 0.79 ± 0.16 mm, respectively) but increased with shorter and, still more so, with longer sleep duration. Subjects with only 5 h sleep showed age- and sex-adjusted differences of 0.042 mm IMT (95% confidence interval 0.008–0.076 versus 8 h sleep). IMT values were still greater among subjects with 11–12 h sleep (adjusted differences versus 8 h sleep 0.084 mm [0.040–0.128] IMT). Further adjustment for lifestyle indicators, socioeconomic determinants, and biological variables attenuated these differences, but they remained significant.ConclusionsBoth longer and shorter sleep duration is associated with an increased risk of atherosclerosis. These findings support the hypothesis that sleep is related to cardiovascular disease.     

Angiotensin-converting enzyme gene single polymorphism as a genetic biomarker of diabetic peripheral neuropathy: longitudinal prospective study

BackgroundIdentifying patients at risk of developing diabetic peripheral neuropathy (DPN) is of paramount importance in those with type 2 diabetes mellitus (T2DM) to provide and anticipate secondary prevention measures as well as intensify action on risk factors, particularly so in primary care. Noteworthy, the incidence of DPN remains unknown in our environment.Aims(i) To analyze a single angiotensin-converting enzyme (ACE) gene polymorphism (D/I) as a genetic marker of risk of developing DPN, and (ii) to determine the incidence of DPN in our environment.Research design and methodsLongitudinal study with annual follow-up for 3 years involving a group of T2DM (N = 283) randomly selected. ACE gene polymorphism distribution (I = insertion; D = deletion) was determined. DPN was diagnosed using clinical and neurophysiology evaluation.ResultsBaseline DPN prevalence was 28.97% (95% CI, 23.65–34.20). ACE polymorphism heterozygous genotype D/I presence was 60.77% (95% CI, 55.05–66.5) and was independently associated with a decreased risk of DPN (RR, 0.51; 95% CI, 0.30–0.86). DPN correlated with age (P < 0.001) but not with gender (P = 0.466) or time of evolution of T2DM (P = 0.555). Regarding end point, DPN prevalence was 36.4% (95% CI, 30.76–42.04), and accumulated incidence was 10.4% 3 years thereafter. In the final Poisson regression analysis, the presence of heterozygous genotype remained independently associated with a decreased risk of DPN (RR, 0.71; (95% CI, 0.53–0.96). DPN presence remained correlated with age (P = 0.002), but not with gender (P = 0.490) or time of evolution (P = 0.630).ConclusionsIn our series, heterozygous ACE polymorphism (D/I) stands as a protective factor for DPN development. Accumulated incidence of DPN was relevant. Further prospective studies are warranted.     

Markers of atherosclerosis and inflammation and mortality in patients with HIV infection

ObjectiveHIV-infected patients are at increased risk for cardiovascular disease, which may be mediated in part by inflammation. Surrogate marker studies suggest an increased prevalence of vascular abnormalities in HIV infection. We examined the association of all-cause mortality in HIV-infected patients with carotid artery intima-media thickness (cIMT) and high-sensitivity C-reactive protein (hsCRP).Design and methodsBaseline risk factors, cIMT and hsCRP were prospectively measured in 327 HIV-infected participants. Follow-up time with median of 3.1 years was calculated from baseline to death or censored dated 7/31/07. Cox Proportional Hazards models were used to study risk factors associated with mortality.ResultsThirty-eight (11.6%) of participants have died since study enrollment. cIMT was significantly higher in those who died and decedents were significantly more likely to have cIMT above the 75th percentile. Those who died had higher hsCRP than those alive and more had hsCRP values above 3 mg/L. CD4 count was lower and log₁₀ viral load was higher in decedents, but antiretroviral regimens were similar in both groups. cIMT and hsCRP levels were significantly associated with mortality (HR = 2.74, 95% CI 1.26–5.97, p = 0.01; HR = 2.38, 95% CI 1.15–4.9, p = 0.02).ConclusionsOur study demonstrated a strong association of carotid IMT and hsCRP with all-cause death in this HIV-infected population despite being similar with respect to exposure to antiretroviral medications. Together these surrogate markers may be indices of chronic inflammation and unfavorable outcomes in HIV-positive patients.     

ApoB/apoA-I ratio is related to femoral artery plaques in 64-year-old women also in cases with low LDL cholesterol

IntroductionThe apolipoproteinB (apoB)/apolipoproteinA-I (apoA-I) ratio mirrors the number of pro-atherogenic and anti-atherogenic lipoprotein particles. This ratio may carry more information on risk for atherosclerosis than LDL in cohorts with impaired glucose tolerance. The aim was to examine the association between the apoB/apoA-I ratio and ultrasound-assessed atherosclerosis in the carotid and femoral arteries in women with varying degrees of glucose tolerance.MethodsPlaque occurrence, and intima-media thickness in the carotid and femoral arteries were examined by B-mode ultrasound in a random sample of 64-year-old women (n = 646) living in Gothenburg, Sweden, representing different degrees of glucose intolerance (diabetes (n = 234), impaired (n = 212) and normal glucose tolerance (n = 200)). Traditional risk factors and serum concentrations of apolipoproteins were analysed.ResultsFor subjects in the lowest LDL tertile, the risk of having a plaque in the femoral artery was three times greater for subjects in the highest apoB/apoA-I tertile compared to subjects in the lowest tertile (OR: 3.0, 95% CI: 1.2–7.5). A clear increase in the occurrence of femoral plaque was observed already at a cut-off value of 0.63 (OR: 1.8, 95% CI: 1.2–2.6). ApoB/apoA-I was also related to femoral plaque occurrence in women with low HbA1c. ApoB/A-I ratio was associated with carotid and femoral IMT but not carotid plaques.ConclusionThe apoB/apoA-I ratio improved the identification of cases with femoral artery atherosclerosis in a cohort of women with varying degrees of glucose tolerance. Such cases could also be identified in women with normal LDL and HbA1c levels. The results indicate that an apoB/apoA-I ratio above 0.63 should be used as a marker of increased risk.     

Prévalence et facteurs déterminants de l’épaisseur intima-media carotidienne élevée dans une population de 1203 hypertendus noirs africains

ObjectivesTo evaluate the prevalence and determinants of increased carotid intima-media thickness (IMT) in a population of black hypertensive patients and it influence of on the assessment of their overall cardiovascular risk.Patients and methodsThis was a 16-month, cross-sectional study conducted in the outpatient unit of the cardiology department of the Campus teaching hospital of Lome, and included 1203 hypertensive patients, both sexes, aged 35 years and more. Each patient benefited from a carotid IMT measure. Carotid IMT was increased if it was > 0.9 mm and the plaque was defined as a carotid IMT > 1.2 mm.ResultsThe mean age of our patients was 53.3 ± 10.4 years with a sex ratio of 1.6 in favor of women. The duration of hypertension was less than 5 years in 56.7% and hypertension was grade 1 in 47.7% of cases. The mean carotid IMT was 0.89 mm ± 0.20. The prevalence of the increased carotid IMT was 45.8% and that of an atheroma plaque was 15.8%. Carotid IMT was correlated with age (P ˂ 0.0001), duration of arterial hypertension (P = 0.01), history of stroke (P ˂ 0.0001), and presence of left ventricular hypertrophy to cardiac ultrasound (P = 0.01). The overall cardiovascular risk was modified after taking into account the carotid IMT. An increase in cardiovascular risk was observed in 30.5% of hypertensive patients.ConclusionIncreased carotid intima-media thickness is frequent in Togolese hypertension. The determining factors are age, duration of arterial hypertension, left ventricular hypertrophy and stroke. The systematic measurement of the carotid intima-media thickness would better evaluate the overall cardiovascular risk for our patients.