James M. Peacock

Association of C-reactive protein with markers of prevalent atherosclerotic disease

Recent prospective studies have demonstrated that elevated C-reactive protein (CRP) is a marker of increased risk of atherothrombotic clinical events. We examined in a large, cross-sectional family-based study (n = 875 men, 948 women) whether serum CRP was associated with prevalent coronary heart disease (CHD), the ankle/brachial blood pressure index, or carotid intima-media thickness, an indicator of subclinical atherosclerosis as assessed by B-mode ultrasound. CRP was associated with many other cardiovascular risk factors, particularly markers of obesity and insulin resistance, markers of inflammation and acute phase reaction, and hormone replacement therapy. Adjusted for age and family type, there was a weak positive association of CRP with carotid intima-media thickness in both genders and with prevalent CHD in women. However, adjustment for other risk factors completely eliminated the associations. For example, among women, the risk factor-adjusted mean values of intima-media thickness across quartiles of CRP were 0.76, 0.74, 0.75, and 0.76 mm (p >0.5). In men there was a weak inverse association between CRP and ankle/brachial blood pressure index, independent of other risk factors, but no such association in women. Our findings indicate that CRP is not strongly and independently associated with prevalent atherosclerosis. Because CRP has been associated with clinical events, it could be that elevated CRP may be a stronger marker of thrombotic risk than of the degree of atherosclerosis.

Fenofibrate Effect on Triglyceride and Postprandial Response of Apolipoprotein A5 Variants The GOLDN Study

Objective—Apolipoprotein A5 (APOA5) is a key determinant of plasma triglyceride (TG) concentrations. Genetic variation at the APOA5 locus could be responsible for some of the observed differences in response to fenofibrate therapy. Methods and Results—We examined the association between tag SNPs (−1131T>C and 56C>G) at APOA5 and TG and HDL-C response to fenofibrate and a postprandial lipid challenge in 791 men and women participating in the GOLDN study. After 3-week drug treatment, APOA5 56G carriers displayed significant decrease in TG (P=0.006), and increase in HDL-C (P=0.002) levels relative to their basal values in the fasting state when compared with noncarriers (a TG reduction of −35.8±2.8% versus −27.9±0.9% and a HDL-C increase of 11.8±1.3% versus 6.9±0.5%, respectively). In the postprandial lipemia after a fat load, the 56G carriers showed a significant decrease in the area under curve for TG and increase for HDL-C than the noncarriers. These diverse beneficial responses of 56G carriers to fenofibrate were further characterized by a higher increase in large LDL-C concentrations and LDL size. On the other hand, subjects with different APOA5-1131T>C genotypes showed no significant response to fenofibrate intervention. Conclusion—This study suggests that the APOA5 56G carriers benefited more from the fenofibrate treatment than noncarriers in lowering plasma TG and increasing HDL-C levels.

Relationship of serum and dietary magnesium to incident hypertension: The Atherosclerosis Risk in Communities (ARIC) Study

PURPOSE To examine the relationship of serum and dietary magnesium (Mg) with incident hypertension. The setting was the Atherosclerosis Risk in Communities (ARIC) Study, which included a biracial cohort, aged 45-64 years, from four U.S. communities. METHODS This analysis included 7731 participants (4190 women and 3541 men) free of hypertension at baseline and followed six years. Fasting serum Mg was measured, and usual dietary intake was assessed with a food frequency questionnaire. RESULTS After adjustment for age, race, and a number of other risk factors, the odds of incident hypertension across ascending quartiles of serum Mg were 1.0, 0.79, 0.85, and 0.70 in women (p trend = 0.01) and 1.0, 0.87, 0.87, and 0.82 in men (p trend = 0.16). We found no association between dietary Mg intake and incident hypertension. These associations were attenuated after the addition of baseline systolic blood pressure to the models. CONCLUSIONS This study suggests that low Mg may play a modest role in the development of hypertension.

Influence of Apolipoprotein E, Smoking, and Alcohol Intake on Carotid Atherosclerosis National Heart, Lung, and Blood Institute Family Heart Study

Background and Purpose— Apolipoprotein E (apoE) isoforms and lifestyle factors play an important role in the development of coronary heart disease. The association of apoE and carotid atherosclerosis remains controversial. Methods— We investigated the relation of apoE, cigarette smoking, alcohol drinking, and their interaction with carotid atherosclerosis on 544 individuals free of coronary heart disease in the National Heart, Lung, and Blood Institute (NHLBI) Family Heart Study. Atherosclerotic lesions of the carotid arteries were detected through high-resolution ultrasound. Results— Subjects in the apoE4 group had lower blood pressure, lower high-density lipoprotein cholesterol, and higher low-density lipoprotein cholesterol. In a multivariate logistic regression model, apoE isoforms and alcohol consumption were not significantly associated with the prevalence odds of carotid atherosclerosis (P =0.94 and 0.98, respectively, for trend). In contrast, compared with those who never smoked, the prevalence odds ratios for carotid atherosclerosis were 1.7 [95% confidence interval (CI),1.1 to 2.7], 2.8 (95% CI, 1.2 to 6.2), and 1.9 (95% CI, 0.7 to 5.5) for former smokers, current smokers of 1 to 20 cigarettes per day, and current smokers of >20 cigarettes day, respectively (P =0.0018 for trend). We did not find evidence of an interaction between apoE and alcohol consumption. Our data suggested a synergistic effect between the apoE allele &egr;4 and smoking on carotid atherosclerosis: odds ratios were 1.7 (95% CI, 0.8 to 3.6) for smoking alone, 1.0 (95% CI, 0.6 to 1.8) for &egr;4 alone, and 3.7 (95% CI, 1.1 to 3.6) for the joint presence of the apoE allele &egr;4 and smoking. Conclusions— Smoking but not alcohol consumption or ApoE is associated with an increased odds of carotid atherosclerosis. Our data suggest a synergistic effect between the apoE allele &egr;4 and smoking on carotid atherosclerosis.

Utility of Dysphagia Screening Results in Predicting Poststroke Pneumonia

Background and Purpose— Dysphagia screening before oral intake (DS) is a stroke care quality indicator. The value of DS is unproven. Quality adherence and outcome data from the Paul Coverdell National Acute Stroke Registry were examined to establish value of DS. Methods— Adherence to the DS quality indicator was examined in patients with stroke discharged from Paul Coverdell National Acute Stroke Registry hospitals between March 1 and December 31, 2009. Patients were classified as unscreened (US), screened and passed (S/P), and screened and failed. Associations between screening status and pneumonia rate were assessed by logistic regression models after adjustment for selected variables. Results— A total of 18 017 patients with stroke discharged from 222 hospitals in 6 states were included. A total of 4509 (25%) were US; 8406 (47%) were S/P, and 5099 (28%) were screened and failed. Compared with US patients, screened patients were significantly more impaired. Pneumonia rates were: US 4.2%, S/P 2.0%, and screened and failed 6.8%. After adjustment for demographic and clinical features, US patients were at a higher risk of pneumonia (OR, 2.2; 95% CI, 1.7 to 2.7) compared with S/P patients. Conclusions— Data suggest that patients are selectively screened based on stroke severity. Pneumonia rate was higher in US patients compared with S/P patients. Clinical judgment regarding who should be screened is imperfect. S/P patients have a lower pneumonia rate indicating that DS adds accuracy in predicting pneumonia risk. The Joint Commission recently retired DS as a performance indicator for Primary Stroke Center certification. These results suggest the need to implement a DS performance measure for patients with acute stroke.

Serum magnesium and risk of sudden cardiac death in the Atherosclerosis Risk in Communities (ARIC) Study

BACKGROUND We hypothesized that serum magnesium (Mg) is associated with increased risk of sudden cardiac death (SCD). METHODS The Atherosclerosis Risk in Communities Study assessed risk factors and levels of serum Mg in a cohort of 45- to 64-year-old subjects in 1987-1989 (n = 14,232). After an average of 12 years of follow-up, we observed 264 cases of SCD, as determined by physician review of all suspected cases. We used proportional hazards regression to evaluate the association of serum Mg with risk of SCD. RESULTS Individuals in the highest quartile of serum Mg were at significantly lower risk of SCD in all models. This association persisted after adjustment for potential confounding variables, with an almost 40% reduced risk of SCD (hazard ratio 0.62, 95% CI 0.42-0.93) in quartile 4 versus 1 of serum Mg observed in the fully adjusted model. CONCLUSIONS This study suggests that low levels of serum Mg may be an important predictor of SCD. Further research into the effectiveness of Mg supplementation for those considered to be at high risk for SCD is warranted.

Metabolic syndrome and risk of venous thromboembolism: Longitudinal Investigation of Thromboembolism Etiology

Summary.  Background: In a recent case–control study, the odds of metabolic syndrome (MetSyn) among deep vein thrombosis cases were almost twice those among controls. We tested the hypothesis that the incidence of non‐cancer‐related venous thromboembolism (VTE) is higher among adults with MetSyn and further, that associations are stronger for idiopathic than secondary VTE. Methods: A total of 20 374 middle‐aged and elderly adults were followed for over 12 years for incident VTE in the Longitudinal Investigation of Thromboembolism Etiology (LITE). All hospitalizations were identified and VTEs validated by chart review. Baseline MetSyn was defined using ATP III guidelines, including ≥3 of the following components: abdominal obesity, elevated blood pressure, low HDL‐cholesterol, high triglycerides and high glucose. Because sex modified the relation between MetSyn and VTE (pinteraction = 0.001), proportional hazards regression analyses were stratified by sex to assess the associations of MetSyn and its components with risk of incident non‐cancer‐related VTE, adjusting for potential confounders. Results: Incident VTE (n = 358) included 196 idiopathic events. Baseline MetSyn was associated with risk of total VTE (hazard ratio (HR) = 1.84, 95% CI = 1.30, 2.59) and idiopathic VTE (HR = 1.59, 95% CI = 1.02, 2.47) among men, but not women. The association was largely attributable to abdominal obesity (HR of VTE = 2.10, 95% CI = 1.51, 2.93, in men; HR of VTE = 1.70, 95% CI = 1.24, 2.34, in women), with no additional contribution by the other MetSyn components. Conclusion: Although abdominal obesity was associated with increased risk of VTE in both men and women, MetSyn and its other components do not seem important in VTE etiology.

ADIPOQ Polymorphisms, Monounsaturated Fatty Acids, and Obesity Risk : The GOLDN Study

Serum adiponectin levels have been positively associated with insulin sensitivity and are decreased in type 2 diabetes (T2D) and obesity. Genetic and environmental factors influence serum adiponectin and may contribute to risk of metabolic syndrome and T2D. Therefore, we investigated the effect of ADIPOQ single‐nucleotide polymorphisms (SNPs), −11377C>G and −11391G>A, on metabolic‐related traits, and their modulation by dietary fat in white Americans. Data were collected from 1,083 subjects participating in the Genetics of Lipid Lowering Drugs and Diet Network study. Mean serum adiponectin concentration was higher for carriers of the −11391A allele (P = 0.001) but lower for the −11377G allele carriers (P = 0.017). Moreover, we found a significant association with obesity traits for the −11391G>A SNP. Carriers of the −11391A allele had significantly lower weight (P = 0.029), BMI (P = 0.019), waist (P = 0.003), and hip circumferences (P = 0.004) compared to noncarriers. Interestingly, the associations of the −11391G>A with BMI and obesity risk were modified by monounsaturated fatty acids (MUFAs) intake (P‐interaction = 0.021 and 0.034 for BMI and obesity risk, respectively). In subjects with MUFA intake above the median (≥13% of energy intake), −11391A carriers had lower BMI (27.1 kg/m2 for GA+AA vs. 29.1 kg/m2 for GG, P = 0.002) and decreased obesity risk (odds ratio for −11391A = 0.52, 95% confidence interval (CI); 0.28–0.96; P = 0.031). However, we did not detect genotype‐related differences for BMI or obesity in subjects with MUFA intake <13%. Our findings support a significant association between the −11391G>A SNPs and obesity‐related traits and the potential to moderate such effects using dietary modification.

Serum and Dietary Magnesium and Risk of Ischemic Stroke The Atherosclerosis Risk in Communities Study

The authors sought to examine the relation between serum or dietary magnesium and the incidence of ischemic stroke among blacks and whites. Between 1987 and 1989, 14,221 men and women aged 45-64 years took part in the first examination of the Atherosclerosis Risk in Communities Study cohort. The incidence of stroke was ascertained from hospital records. Higher serum magnesium levels were associated with lower prevalence of hypertension and diabetes mellitus at baseline. During the 15-year follow-up, 577 ischemic strokes occurred. Serum magnesium was inversely associated with ischemic stroke incidence. The age-, sex-, and race-adjusted rate ratios of ischemic stroke for those with serum magnesium levels of <or=1.5, 1.6, 1.7, and >or=1.8 mEq/L were 1.0, 0.78 (95% confidence interval (CI): 0.62, 0.96), 0.70 (95% CI: 0.56, 0.88), and 0.75 (95% CI: 0.59, 0.95) (P(trend) = 0.005). After adjustment for hypertension and diabetes, the rate ratios were attenuated to nonsignificant levels. Dietary magnesium intake was marginally inversely associated with the incidence of ischemic stroke (P(trend) = 0.09). Low serum magnesium levels could be associated with increased risk of ischemic stroke, in part, via effects on hypertension and diabetes.

ADIPOQ polymorphisms, monounsaturated fatty acids, and obesity risk

Serum adiponectin levels have been positively associated with insulin sensitivity and are decreased in type 2 diabetes (T2D) and obesity. Genetic and environmental factors influence serum adiponectin and may contribute to risk of metabolic syndrome and T2D. Therefore, we investigated the effect of ADIPOQ single‐nucleotide polymorphisms (SNPs), −11377C>G and −11391G>A, on metabolic‐related traits, and their modulation by dietary fat in white Americans. Data were collected from 1,083 subjects participating in the Genetics of Lipid Lowering Drugs and Diet Network study. Mean serum adiponectin concentration was higher for carriers of the −11391A allele (P = 0.001) but lower for the −11377G allele carriers (P = 0.017). Moreover, we found a significant association with obesity traits for the −11391G>A SNP. Carriers of the −11391A allele had significantly lower weight (P = 0.029), BMI (P = 0.019), waist (P = 0.003), and hip circumferences (P = 0.004) compared to noncarriers. Interestingly, the associations of the −11391G>A with BMI and obesity risk were modified by monounsaturated fatty acids (MUFAs) intake (P‐interaction = 0.021 and 0.034 for BMI and obesity risk, respectively). In subjects with MUFA intake above the median (≥13% of energy intake), −11391A carriers had lower BMI (27.1 kg/m2 for GA+AA vs. 29.1 kg/m2 for GG, P = 0.002) and decreased obesity risk (odds ratio for −11391A = 0.52, 95% confidence interval (CI); 0.28–0.96; P = 0.031). However, we did not detect genotype‐related differences for BMI or obesity in subjects with MUFA intake <13%. Our findings support a significant association between the −11391G>A SNPs and obesity‐related traits and the potential to moderate such effects using dietary modification.