Racial differences in the burden of coronary artery calcium and carotid intima media thickness between Blacks and Whites

Background

Identification of racial differences in the burden and correlates of carotid intima media thickness (CIMT) and coronary artery calcium (CAC) may provide the basis for the development of race-specific cardiovascular disease (CVD) risk prediction algorithms.

Methods

In the Heart Strategies Concentrating on Risk Evaluation (Heart SCORE) study, CIMT was measured by carotid ultrasonography in 792 individuals (35 % Black). CIMT >1 mm was considered significant. CAC was quantified by electron beam computed tomography in 776 individuals (46 % Black). CAC was considered significant if the Agatston score was >100. Cross-sectional associations between race, CIMT and CAC were assessed using logistic regression models.

Results

Blacks had greater CIMT (mean difference 0.033 mm, 95 % CI 0.005–0.06 mm; p = 0.02) and 1.5-fold (95 % CI 1.0–2.3) higher odds of having significant CIMT than Whites. Blacks had less CAC than Whites (mean Agatston score difference 66, [11–122]; p = 0.02) and 50 % lower odds of a significant CAC score compared with Whites (0.5 [0.3–0.7]). These associations were virtually unchanged after adjustment for CVD risk factors. Of the novel CVD risk markers assessed, small-dense low-density lipoprotein was independently associated with increased odds of significant CIMT, with the association being similar among Blacks and Whites (odds ratio [95 % CI]: 1.7 [1.2–2.5] and 1.4 [1.0–1.8] per 1-SD higher level, respectively). Interleukin-6 was significantly associated with CAC among Blacks (1.4 [1.0–2.0]).

Conclusion

Black race is independently associated with greater CIMT but less CAC than White race. CVD risk stratification strategies that incorporate these measures of subclinical atherosclerosis should consider race-specific algorithms.

Electronic supplementary material

The online version of this article (doi:10.1007/s12471-014-0610-4) contains supplementary material, which is available to authorized users.     

Adiponectin Provides Additional Information to Conventional Cardiovascular Risk Factors for Assessing the Risk of Atherosclerosis in Both Genders

Background

This study evaluated the relation between adiponectin and atherosclerosis in both genders, and investigated whether adiponectin provides useful additional information for assessing the risk of atherosclerosis.

Methods

We measured serum adiponectin levels and other cardiovascular risk factors in 1033 subjects (454 men, 579 women) from the Korean Genomic Rural Cohort study. Carotid intima–media-thickness (CIMT) was used as measure of atherosclerosis. Odds ratios (ORs) with 95% confidence intervals (95% CI) were calculated using multiple logistic regression, and receiver operating characteristic curves (ROC), the category-free net reclassification improvement (NRI) and integrated discrimination improvement (IDI) were calculated.

Results

After adjustment for conventional cardiovascular risk factors, such as age, waist circumference, smoking history, low-density and high-density lipoprotein cholesterol, triglycerides, systolic blood pressure and insulin resistance, the ORs (95%CI) of the third tertile adiponectin group were 0.42 (0.25–0.72) in men and 0.47 (0.29–0.75) in women. The area under the curve (AUC) on the ROC analysis increased significantly by 0.025 in men and 0.022 in women when adiponectin was added to the logistic model of conventional cardiovascular risk factors (AUC in men: 0.655 to 0.680, p = 0.038; AUC in women: 0.654 to 0.676, p = 0.041). The NRI was 0.32 (95%CI: 0.13–0.50, p<0.001), and the IDI was 0.03 (95%CI: 0.01–0.04, p<0.001) for men. For women, the category-free NRI was 0.18 (95%CI: 0.02–0.34, p = 0.031) and the IDI was 0.003 (95%CI: −0.002–0.008, p = 0.189).

Conclusion

Adiponectin and atherosclerosis were significantly related in both genders, and these relationships were independent of conventional cardiovascular risk factors. Furthermore, adiponectin provided additional information to conventional cardiovascular risk factors regarding the risk of atherosclerosis.     

The Age-Specific Quantitative Effects of Metabolic Risk Factors on Cardiovascular Diseases and Diabetes: A Pooled Analysis

Background

The effects of systolic blood pressure (SBP), serum total cholesterol (TC), fasting plasma glucose (FPG), and body mass index (BMI) on the risk of cardiovascular diseases (CVD) have been established in epidemiological studies, but consistent estimates of effect sizes by age and sex are not available.

Methods

We reviewed large cohort pooling projects, evaluating effects of baseline or usual exposure to metabolic risks on ischemic heart disease (IHD), hypertensive heart disease (HHD), stroke, diabetes, and, as relevant selected other CVDs, after adjusting for important confounders. We pooled all data to estimate relative risks (RRs) for each risk factor and examined effect modification by age or other factors, using random effects models.

Results

Across all risk factors, an average of 123 cohorts provided data on 1.4 million individuals and 52,000 CVD events. Each metabolic risk factor was robustly related to CVD. At the baseline age of 55–64 years, the RR for 10 mmHg higher SBP was largest for HHD (2.16; 95% CI 2.09–2.24), followed by effects on both stroke subtypes (1.66; 1.39–1.98 for hemorrhagic stroke and 1.63; 1.57–1.69 for ischemic stroke). In the same age group, RRs for 1 mmol/L higher TC were 1.44 (1.29–1.61) for IHD and 1.20 (1.15–1.25) for ischemic stroke. The RRs for 5 kg/m² higher BMI for ages 55–64 ranged from 2.32 (2.04–2.63) for diabetes, to 1.44 (1.40–1.48) for IHD. For 1 mmol/L higher FPG, RRs in this age group were 1.18 (1.08–1.29) for IHD and 1.14 (1.01–1.29) for total stroke. For all risk factors, proportional effects declined with age, were generally consistent by sex, and differed by region in only a few age groups for certain risk factor-disease pairs.

Conclusion

Our results provide robust, comparable and precise estimates of the effects of major metabolic risk factors on CVD and diabetes by age group.     

Hypokalemia,Its Contributing Factors and Renal Outcomes in Patients with Chronic Kidney Disease

Background

In the chronic kidney disease (CKD) population, the impact of serum potassium (sK) on renal outcomes has been controversial. Moreover, the reasons for the potential prognostic value of hypokalemia have not been elucidated.

Design, Participants & Measurements

2500 participants with CKD stage 1–4 in the Integrated CKD care program Kaohsiung for delaying Dialysis (ICKD) prospective observational study were analyzed and followed up for 2.7 years. Generalized additive model was fitted to determine the cutpoints and the U-shape association between sK and end-stage renal disease (ESRD). sK was classified into five groups with the cutpoints of 3.5, 4, 4.5 and 5 mEq/L. Cox proportional hazard regression models predicting the outcomes were used.

Results

The mean age was 62.4 years, mean sK level was 4.2±0.5 mEq/L and average eGFR was 40.6 ml/min per 1.73 m². Female vs male, diuretic use vs. non-use, hypertension, higher eGFR, bicarbonate, CRP and hemoglobin levels significantly correlated with hypokalemia. In patients with lower sK, nephrotic range proteinuria, and hypoalbuminemia were more prevalent but the use of RAS (renin-angiotensin system) inhibitors was less frequent. Hypokalemia was significantly associated with ESRD with hazard ratios (HRs) of 1.82 (95% CI, 1.03–3.22) in sK <3.5mEq/L and 1.67 (95% CI,1.19–2.35) in sK = 3.5–4 mEq/L, respectively, compared with sK = 4.5–5 mEq/L. Hyperkalemia defined as sK >5 mEq/L conferred 1.6-fold (95% CI,1.09–2.34) increased risk of ESRD compared with sK = 4.5–5 mEq/L. Hypokalemia was also associated with rapid decline of renal function defined as eGFR slope below 20% of the distribution range.

Conclusion

In conclusion, both hypokalemia and hyperkalemia are associated with increased risk of ESRD in CKD population. Hypokalemia is related to increased use of diuretics, decreased use of RAS blockade and malnutrition, all of which may impose additive deleterious effects on renal outcomes.     

Does High C-reactive Protein Concentration Increase Atherosclerosis? The Whitehall II Study

Background

C-reactive protein (CRP), a marker of systemic inflammation, is associated with risk of coronary events and sub-clinical measures of atherosclerosis. Evidence in support of this link being causal would include an association robust to adjustments for confounders (multivariable standard regression analysis) and the association of CRP gene polymorphisms with atherosclerosis (Mendelian randomization analysis).

Methodology/Principal Findings

We genotyped 3 tag single nucleotide polymorphisms (SNPs) [+1444T>C (rs1130864); +2303G>A (rs1205) and +4899T>G (rs 3093077)] in the CRP gene and assessed CRP and carotid intima-media thickness (CIMT), a structural marker of atherosclerosis, in 4941 men and women aged 50–74 (mean 61) years (the Whitehall II Study). The 4 major haplotypes from the SNPs were consistently associated with CRP level, but not with other risk factors that might confound the association between CRP and CIMT. CRP, assessed both at mean age 49 and at mean age 61, was associated both with CIMT in age and sex adjusted standard regression analyses and with potential confounding factors. However, the association of CRP with CIMT attenuated to the null with adjustment for confounding factors in both prospective and cross-sectional analyses. When examined using genetic variants as the instrument for serum CRP, there was no inferred association between CRP and CIMT.

Conclusions/Significance

Both multivariable standard regression analysis and Mendelian randomization analysis suggest that the association of CRP with carotid atheroma indexed by CIMT may not be causal.     

Homocysteine and Carotid Plaque Stability: A Cross-Sectional Study in Chinese Adults

Background and Purpose

This study aimed to explore the possible association of plasma total homocysteine with carotid plaque stability.

Methods

A cross-sectional study was conducted from 2010 to 2011. A stratified random sample of 2,919 Chinese participants aged 40 years or older was enrolled. Plasma total homocysteine levels were measured and carotid plaques were evaluated by ultrasonography. Logistic regression model was used to analyze the association of homocysteine levels to the progression of carotid plaque development, while adjusting for demographics and vascular risk factors.

Results

The mean level of plasma homocysteine in the subjects was 14.9 µmol/l. Along with increase in homocysteine level, the risk of advanced carotid plaque elevated (odds ratio = 1.28; 95% confidence interval = 1.09–1.51) after adjusting for age, sex, and other potential confounders. Stratified by sex, higher homocysteine level was strongly associated with advanced carotid plaque in men (OR = 1.41; 95% confidence interval = 1.17–1.70), but not in women.

Conclusion

The findings suggest that plasma level of homocysteine may be associated with advanced carotid plaque, which constitutes high risks of stroke, in male Chinese adults.     

Relationship between adult height and body weight and risk of carotid atherosclerosis assessed in terms of carotid intima-media thickness: The Nagasaki Islands study

Background

Previous studies have reported an inverse association between height and risk of cardiovascular disease. However, evidence is limited for the association between risk of atherosclerosis and height. Further, although the association between atherosclerosis and body mass index (BMI) is reportedly positive, there have been no reports of studies on associations between height and atherosclerosis in relation to BMI.

Methods

We conducted a cross-sectional study of Japanese men aged 30 to 89 years undergoing general health check-ups.

Results

Of the 1,337 men, 312 were diagnosed with carotid atherosclerosis (carotid intima-media thickness (CIMT) ≥ 1.1 mm), but no significant association was found between height and carotid atherosclerosis for the entire study group. Stratification by BMI status of those analytical findings disclosed a significant inverse association between height and carotid atherosclerosis among overweight (BMI ≥ 25 kg/m²) but not among non-overweight (BMI < 25 kg/m²) men. The classical cardiovascular risk factors-adjusted odds ratio (OR) and 95% confidence interval (CI) of carotid atherosclerosis for an increment of one SD (standard deviation) in height (6.70 cm) were 0.71 (0.54 to 0.94) for overweight (BMI ≥ 25 kg/m²) and 1.05 (0.87 to 1.27) for non-overweight (BMI < 25 kg/m²) men.

Conclusion

Independent from classical cardiovascular risk factors, height was found to be inversely associated with carotid atherosclerosis for overweight but not for non-overweight men.     

Association between hemoglobin A1c and carotid atherosclerosis in rural community-dwelling elderly Japanese men

Background

Recent studies have reported an association between both higher and lower levels of hemoglobin A1c (HbA1c) and higher mortality of diabetes patients. Like diabetes, carotid atherosclerosis is a well known lifestyle-related disease. However, no studies have yet reported an association between HbA1c levels and carotid atherosclerosis.

Methods

We conducted a cross-sectional study of 1,150 Japanese elderly men aged ≥60 years who were undergoing general health checkups. Carotid atherosclerosis was defined as a carotid intima-media thickness (CIMT) ≥1.1 mm. Since body mass index (BMI) is regarded as a cardiovascular risk factor that exerts a strong influence on both HbA1c levels and carotid atherosclerosis, we performed a stratified analysis of this risk based on BMI.

Results

Using the intermediate HbA1c quintile as a reference group, the groups in the lowest HbA1c quintiles showed a significantly higher risk of carotid atherosclerosis in patients with low BMI (≤23 kg/m²) vs. no increased risk in those with high BMI (>23 kg/m²). The association of HbA1c with carotid atherosclerosis became slightly stronger when these analyses were limited to subjects who were not taking glucose-lowering medications or medications for hyperlipidemia and cardiovascular disease. After adjusting for classical cardiovascular risk factors, adjusted odds ratios (ORs) for carotid atherosclerosis were 1.36 (0.84 to 2.20) for total subjects, 2.29 (1.12 to 4.66) for low-BMI groups, and 0.68 (0.33 to 1.41) for high-BMI groups.

Conclusions

Lower HbA1c level is a significant risk factor for carotid atherosclerosis in rural community-dwelling elderly Japanese men with low, but not high BMI, particularly in those not taking glucose-lowering medication.     

Risk of Cerebral Palsy among the Offspring of Immigrants

Background

Cerebral palsy (CP) has a multifactorial etiology, and placental vascular disease may be one major risk factor. The risk of placental vascular disease may be lower among some immigrant groups. We studied the association between immigrant status and the risk of CP.

Methods

We conducted a population-based retrospective cohort study of all singleton and twin livebirths in Ontario between 2002–2008, and who survived ≥28 days after birth. Each child was assessed for CP up to age 4 years, based on either a single inpatient or ≥2 outpatient pediatric diagnoses of CP. Relative to non-immigrants (n = 566,668), the risk of CP was assessed for all immigrants (n = 177,390), and further evaluated by World region of origin. Cox proportional hazard ratios (aHR) were adjusted for maternal age, income, diabetes mellitus, obesity, tobacco use, Caesarean delivery, year of delivery, physician visits, twin pregnancy, preterm delivery, as well as small- and large-for-gestational age birthweight.

Results

There were 1346 cases of CP, with a lower rate among immigrants (1.45 per 1000) than non-immigrants (1.92 per 1000) (aHR 0.77, 95% confidence interval [CI] 0.67 to 0.88). Mothers from East Asia and the Pacific (aHR 0.54, 95% CI 0.39 to 0.77) and the Caribbean (aHR 0.58, 95% CI 0.37 to 0.93) were at a significantly lower risk of having a child with CP. Whether further adjusting for preeclampsia, gestational hypertension, placental abruption or placental infraction, or upon using a competing risk analysis that further accounted for stillbirth and neonatal death, these results did not change.

Conclusions

Immigration and ethnicity appear to attenuate the risk of CP, and this effect is not fully explained by known risk factors.     

Lower Intensified Target LDL-c Level of Statin Therapy Results in a Higher Risk of Incident Diabetes: A Meta-Analysis

Background

A recent meta-analysis has reported that intensive-dose statin drug increases the risk of incident diabetes. However, doubling of the statin dose generates only a further 6% decrease in low-density lipoprotein cholesterol (LDL-c) on average. This study aimed to determine whether statin therapy with lower intensive-target LDL-c level contributes to higher risk of new-onset diabetes.

Methods

Medline, Embase, and the Cochrane Central Register of Controlled Trials were searched for randomized controlled endpoint trials of statins conducted from 1966 to 2012. We included trials with more than 1000 participants who were followed up for at least 2 years. The included trials were stratified by the target LDL-c level. I ² statistic was used to measure heterogeneity between trials. We further calculated risk estimates with random-effect meta-analysis. Meta-regression was used to identify the potential risk factors of statin-induced diabetes.

Results

Fourteen trials with a total of 95 102 non-diabetic participants were included. The risks elevated by 33% [odds ratio (OR) = 1.33; 95% confidence interval (CI) 1.14–1.56; I ² = 7.7%] and 16% (OR = 1.16; 95% CI 1.06–1.28; I ² = 0.0%) when the intensified target LDL-c levels were ≤1.8 mmol/L and 1.8–2.59 mmol/L, respectively. The risk of incident diabetes did not increase when the target LDL-c level was ≥2.59 mmol/L. Apart from age, female, and baseline level of total cholesterol, meta-regression analysis showed that the target and baseline levels of LDL-c and relative LDL-c reduction were predictors of statin-induced diabetes.

Conclusion

A lower intensified target LDL-c level of statin therapy resulted in a higher risk of incident diabetes.     

Effects of Neck Radiation Therapy on Extra-Cranial Carotid Arteries Atherosclerosis Disease Prevalence: Systematic Review and a Meta-Analysis

Introduction

Radiation arteritis following neck irradiation as a treatment for head and neck malignancy has been well documented. The long-term sequelae of radiation exposure of the carotid arteries may take years to manifest clinically, and extra-cranial carotid artery (ECCA) stenosis is a well-recognised vascular complication. These carotid lesions should not be regarded as benign and should be treated in the same manner as standard carotid stenosis. Previous studies have noted increased cerebrovascular events such as stroke in this cohort of patients because of high-grade symptomatic carotid stenosis resulting in emboli.

Aim

To evaluate the effect of radiation therapy on ECCA atherosclerosis progression.

Methods

Online search for case-control studies and randomised clinical trials that reported on stenosis in extra-cranial carotid arteries in patients with neck malignancies who received radiation therapy (RT) comparing them to patients with neck malignancies who did not receive RT.

Results

Eight studies were included in the final analysis with total of 1070 patients – 596 received RT compared to 474 in the control group. There was statistically significant difference in overall stenosis rate (Pooled risk ratio  =  4.38 [2.98, 6.45], P  =  0.00001) and severe stenosis (Pooled risk ratio  =  7.51 [2.78, 20.32], P <0.0001), both being higher in the RT group. Pooled analysis of the five studies that reported on mild stenosis also showed significant difference (Pooled risk ratio  =  2.74 [1.75, 4.30], 95% CI, P  =  0.0001).

Conclusion

The incidence of severe ECCA stenosis is higher among patients who received RT for neck malignancies. Those patients should be closely monitored and screening programs should be considered in all patients who receive neck RT.     

SSRIs Increase Risk of Blood Transfusion in Patients Admitted for Hip Surgery

Background

Recent studies have shown that an increased bleeding tendency can be caused by Selective Serotonin Reuptake Inhibitors (SSRI) use. We aimed to investigate the occurrence and risk of blood transfusion in SSRI users compared to non-SSRI users in a cohort of patients admitted for hip-surgery.

Methods

We conducted a retrospective cohort study of patients who underwent planned or emergency hip surgery from 1996 to 2011 in the Academic Medical Center in Amsterdam. Primary outcome measure was risk of blood transfusion. Secondary outcome measures were pre- and postoperative hemoglobin level. Multivariate logistic regression was used to adjust for potential confounders.

Results

One-hundred and fourteen SSRI users were compared to 1773 non-SSRI users. Risk of blood transfusion during admission was increased for SSRI users in multivariate analyses (OR 1.7 [95% CI 1.1–2.5]). Also, pre-operative hemoglobin levels were lower in SSRI users (7.8±1.0 mmol/L) compared to non-SSRI users (8.0±1.0 mmol/L) (p = 0.042)), as were postoperative hemoglobin levels (6.2±1.0 mmol/L vs. 6.4±1.0 mmol/L respectively) (p = 0.017)).

Conclusions

SSRI users undergoing hip surgery have an increased risk for blood transfusion during admission, potentially explained by a lower hemoglobin level before surgery. SSRI use should be considered as a potential risk indicator for increased blood loss in patients admitted for hip surgery. These results need to be confirmed in a prospective study.     

Gender Differences in the Association between Socioeconomic Status and Subclinical Atherosclerosis

Objectives

This study explored the pattern of associations between socioeconomic status (SES) and atherosclerosis progression (as indicated by carotid intima media thickness, CIMT) across gender.

Design

Cross-sectional analysis of a sample of 5474 older persons (mean age 73 years) recruited between 1999 and 2001 in the 3C study (France). We fitted linear regression models including neighborhood SES, individual SES and cardiovascular risk factors.

Results

CIMT was on average 24 µm higher in men (95% CI: 17 to 31). Neighborhood SES was inversely associated with CIMT in women only (highest versus lowest tertiles: −12.2 µm, 95%CI −22 to −2.4). This association persisted when individual SES and risk factors were accounted for. High individual education was associated with lower CIMT in men (−21.4 µm 95%CI −37.5 to −5.3) whereas high professional status was linked to lower CIMT among women (−15.7 µm 95%CI: −29.2 to −2.2). Adjustment for cardiovascular risk factors resulted in a slightly more pronounced reduction of the individual SES-CIMT association observed in men than in women.

Conclusion

In this sample, neighborhood and individual SES displayed different patterns of associations with subclinical atherosclerosis across gender. This suggests that the causal pathways leading to SES variations in atherosclerosis may differ among men and women.     

Trend in Annual Risk of Tuberculous Infection in North India

Setting

Six selected districts in Northern India.

Objectives

To find out the trend in Annual risk of tuberculous infection (ARTI) in north India.

Study Design

Two rounds of community level surveys were conducted during 2000–2001 and 2009–10 respectively. Representative samples of children 1–9 years of age were tuberculin tested and maximum transverse diameter of induration was recorded in mm at about 72 hours. ARTI was computed from the estimated Prevalence of infection using mirror-image technique and anti-mode method.

Results

ARTI was found to decline from 1.9% (confidence interval: 1.7–2.1) at round I to 1.1% (confidence interval: 0.8–1.3) at round II at the rate of 8% per year during the intervening period.

Conclusion

A significant reduction in the risk of tuberculous infection among children was observed between two rounds of surveys carried out at an interval of about 9 years.     

Regional Differences of Undiagnosed Type 2 Diabetes and Prediabetes Prevalence Are Not Explained by Known Risk Factors

Background

We have previously found regional differences in the prevalence of known type 2 diabetes between northeastern and southern Germany. We aim to also provide prevalence estimates for prediabetes (isolated impaired fasting glucose (i-IFG), isolated glucose intolerance (i-IGT), combined IFG and IGT) and unknown type 2 diabetes for both regions.

Methods

Prevalence (95%CI) of prediabetes (i-IFG: fasting glucose 5.6–6.9 mmol/l; i-IGT: 2 h postchallenge gluose 7.8–11.0 mmol/l, oral glucose tolerance test (OGTT), ≥8 h overnight fasting) and unknown diabetes were analyzed in two regional population-based surveys (age group 35–79 years): SHIP-TREND (Study of Health in Pomerania (northeast), 2008–2012) and KORA F4 (Cooperative Health Research in the region of Augsburg (south), 2006–2008). Both studies used similar methods, questionnaires, and identical protocols for OGTT. Overall, 1,980 participants from SHIP-TREND and 2,617 participants from KORA F4 were included.

Results

Age-sex-standardized prevalence estimates (95%CI) of prediabetes and unknown diabetes were considerably higher in the northeast (SHIP-TREND: 43.1%; 40.9–45.3% and 7.1%; 5.9–8.2%) than in the south of Germany (KORA F4: 30.1%; 28.4–31.7% and 3.9%; 3.2–4.6%), respectively. In particular, i-IFG (26.4%; 24.5–28.3% vs. 17.2%; 15.7–18.6%) and IFG+IGT (11.2%; 9.8–12.6% vs. 6.6%; 5.7–7.5%) were more frequent in SHIP-TREND than in KORA. In comparison to normal glucose tolerance, the odds of having unknown diabetes (OR, 95%CI: 2.59; 1.84–3.65) or prediabetes (1.98; 1.70–2.31) was higher in the northeast than in the south after adjustment for known risk factors (obesity, lifestyle).

Conclusions

The regional differences of prediabetes and unknown diabetes are in line with the geographical pattern of known diabetes in Germany. The higher prevalences in the northeast were not explained by traditional risk factors.     

Two Years after Molecular Diagnosis of Familial Hypercholesterolemia: Majority on Cholesterol-Lowering Treatment but a Minority Reaches Treatment Goal

Background

The risk of premature cardiovascular disease in patients with familial hypercholesterolemia (FH) can be profoundly reduced by cholesterol-lowering therapy, and current guidelines for FH advocate ambitious low-density lipoprotein cholesterol (LDL-C) goals. In the present study, we determined whether these goals are reflected in current clinical practice once FH has been diagnosed.

Methodology/Principal Findings

In 2008, we sent questionnaires to all subjects (aged 18–65 years) who were molecularly diagnosed with FH in the year 2006 through the screening program in the Netherlands. Of these 1062 subjects, 781 completed the questionnaire (46% males; mean age: 42±12 years; mean LDL-C at molecular diagnosis (baseline): 4.1±1.3 mmol/L). The number of persons that used cholesterol-lowering therapy increased from 397 (51%) at baseline to 636 (81%) after diagnosis. Mean treated LDL-C levels decreased significantly to 3.2±1.1 mmol/L two years after diagnosis. Only 22% achieved the LDL-C target level of ≤2.5 mmol/L.

Conclusions/Significance

The proportion of patients using cholesterol-lowering medication was significantly increased after FH diagnosis through genetic cascade screening. The attained LDL-C levels were lower than those reported in previous surveys on medication use in FH, which could reflect the effect of more stringent lipid target levels. However, only a minority of the medication users reached the LDL-C target.     

HDL Size is More Accurate than HDL Cholesterol to Predict Carotid Subclinical Atherosclerosis in Individuals Classified as Low Cardiovascular Risk

Background

Misclassification of patients as low cardiovascular risk (LCR) remains a major concern and challenges the efficacy of traditional risk markers. Due to its strong association with cholesterol acceptor capacity, high-density lipoprotein (HDL) size has been appointed as a potential risk marker. Hence, we investigate whether HDL size improves the predictive value of HDL-cholesterol in the identification of carotid atherosclerotic burden in individuals stratified to be at LCR.

Methods and Findings

284 individuals (40–75 years) classified as LCR by the current US guidelines were selected in a three-step procedure from primary care centers of the cities of Campinas and Americana, SP, Brazil. Apolipoprotein B-containing lipoproteins were precipitated by polyethylene glycol and HDL size was measured by dynamic light scattering (DLS) technique. Participants were classified in tertiles of HDL size (<7.57; 7.57–8.22; >8.22 nm). Carotid intima-media thickness (cIMT) <0.90 mm (80^th percentile) was determined by high resolution ultrasonography and multivariate ordinal regression models were used to assess the association between cIMT across HDL size and levels of lipid parameters. HDL-cholesterol was not associated with cIMT. In contrast, HDL size >8.22 nm was independently associated with low cIMT in either unadjusted and adjusted models for age, gender and Homeostasis Model Assessment 2 index for insulin sensitivity, ethnicity and body mass index (Odds ratio 0.23; 95% confidence interval 0.07–0.74, p = 0.013).

Conclusion

The mean HDL size estimated with DLS constitutes a better predictor for subclinical carotid atherosclerosis than the conventional measurements of plasma HDL-cholesterol in individuals classified as LCR.     

Predictors of the Extent of Carotid Atherosclerosis in Patients Treated with Radiotherapy for Nasopharyngeal Carcinoma

Objective

To determine the predictors of the extent of carotid atherosclerosis in patients treated with radiotherapy (RT) for nasopharyngeal carcinoma (NPC).

Methods

The present study investigated 129 post-RT NPC patients. Carotid atherosclerotic parameters, such as carotid intima-media thickness, carotid arterial stiffness and carotid plaque burden (plaque score, the presence of plaque and ≥50% stenosis) were assessed using ultrasonography. The association between carotid atherosclerotic parameters and nine potential predictors, including age, gender, post-RT duration, radiation dose, chemotherapy, diabetes mellitus, hypertension, hypercholesterolemia, and smoking, were determined using multiple regression. The cutoff values of age, post-RT duration and number of cardiovascular risk factors for the presence of carotid plaque or ≥50% carotid stenosis were analyzed using receiver operating characteristic (ROC) curve analysis. Multiple testing was corrected using Benjamini-Hochberg false discovery rate.

Results

Age, post-RT duration and number of cardiovascular risk factors were significantly associated with carotid plaque burden (corrected P value, P_cor<0.05). Age of 44.5 years (sensitivity = 99.2% and specificity = 50%, P_cor<0.01) and post-RT duration of 8.5 years (sensitivity = 75.7% and specificity = 64.3%, P_cor<0.001) were the cutoff values for detecting carotid plaque, while post-RT duration of 13.5 years (sensitivity = 66.7% and specificity = 71.6%, P_cor<0.001) and 1.5 cardiovascular risk factors (sensitivity = 40.7% and specificity = 84.3%, P_cor<0.05) were the cutoff values for screening ≥50% carotid stenosis.

Conclusions

Age, post-RT duration and number of cardiovascular risk factors are significant predictors of carotid atherosclerosis in post-RT NPC patients. Post-RT NPC patients, who are at least 45 years old, with post-RT duration of 9 years or above, and/or have ≥2 cardiovascular risk factors, are more susceptible to carotid atherosclerosis.     

Differential Impact of Statin on New-Onset Diabetes in Different Age Groups: A Population-Based Case-Control Study in Women from an Asian Country

Background

Statins reduce cardiovascular risks but increase the risk of new-onset diabetes (NOD). The aim of this study is to determine what effect, if any, statins have on the risk of NOD events in a population-based case-control study. An evaluation of the relationship between age and statin-exposure on NOD risks was further examined in a female Asian population.

Method

In a nationwide case-controlled study, the authors assessed 1065 female NOD patients and 10650 controls with matching ages, genders and physician visit dates. The impact of statin-exposure on NOD was examined through multiple logistic regression models. Subgroup analysis for exploring the risk of NOD and statin-exposure in different age groups was performed.

Results

Statin-exposure was statistically significantly associated with increased new-onset diabetes risks using multivariate analysis. Interaction effect between age and statin-exposure on NOD risk was noted. For atorvastatin, the risk of cDDDs>60 was highest among the 55–64 year-olds (adjusted odds ratio [OR], 8.0; 95% confidence interval [CI], 2.57–24.90). For rosuvastatin, the risk of cDDDs>60 was highest among the 40–54 year-olds (adjusted OR, 14.8; 95% CI, 2.27–96.15). For simvastatin, the risk of cDDDs>60 was highest among the 55–64 year-olds (adjusted OR, 15.8; 95% CI, 5.77–43.26). For pravastatin, the risk of cDDDs>60 was highest among the 55–64 year-olds (adjusted OR, 14.0; 95% CI, 1.56–125.18).

Conclusions

This population-based study found that statin use is associated with an increased risk of NOD in women. The risk of statin-related NOD was more evident for women aged 40–64 years compared to women aged 65 or more, and was cumulative-dose dependent. The use of statins should always be determined by weighing the clinical benefits and potential risks for NOD, and the patients should be continuously monitored for adverse effects.     

Undercarboxylated osteocalcin as a biomarker of subclinical atherosclerosis in non-dialysis patients with chronic kidney disease

Background

Studies in recent years have shown that undercarboxylated osteocalcin (uOC) not only maintains bone mineralization, but is also involved in the regulation of atherosclerosis. However, a correlation between uOC and carotid atherosclerosis in non-dialysis patients with chronic kidney disease (CKD) has not been investigated.A total of 240 non-dialysis patients with CKD were included in the study. For these patients, the median estimated glomerular filtration rate (eGFR) was 20.05 (12.43–49.32) ml/min/1.73m². Serum uOC levels were measured using enzyme-linked immunosorbent assay (ELISA). Carotid ultrasonography was performed to assess carotid atherosclerotic plaques and intima–media thickness (IMT) in an attempt to analyze the relationship between uOC level and carotid atherosclerosis.

Results

The uOC levels of non-dialysis patients with CKD were significantly lower than those of healthy controls [28.16 (21.40–45.85) ng/mL vs. 36.42 (28.05–49.28) ng/mL, P < 0.01]. The uOC levels gradually decreased as CKD progressed (P < 0.01). The uOC levels were significantly lower in patients with carotid plaques than in patients without carotid plaques [25.98 (20.14–31.35) ng/mL vs. 31.02 (25.86–36.40) ng/mL, P < 0.01]. uOC level showed significant negative correlation with IMT (r = -0.33, P < 0.01). Logistic regression analysis revealed that after adjustment for various confounding factors, decreased uOC levels were shown to indicate increased possibility of carotid atherosclerotic plaque development in non-dialysis patients with CKD (on every 1 SD decrease in the uOC level, odds ratio 1.70, 95 % confidence interval 1.24–2.98, P < 0.01). Multivariate stepwise regression analysis demonstrated that decreased uOC level (β = -0.163, P < 0.05) was an independent risk factor for increased carotid IMT in non-dialysis patients with CKD.

Conclusion

Serum uOC levels in non-dialysis patients with CKD are significantly lower than those in healthy individuals, and uOC is closely associated with subclinical atherosclerosis in CKD patients.