Association between high‐sensitivity C‐reactive protein,lipoprotein‐associated phospholipase A2 and carotid atherosclerosis: A cross‐sectional study

High‐sensitivity C‐reactive protein (hs‐CRP) and lipoprotein‐associated phospholipase A2 (Lp‐PLA2) have been reported to be independent predictors of atherosclerosis. However, whether the combination of these two markers can improve the prediction of atherosclerosis is unknown. This study aimed to evaluate the association between combining hs‐CRP and Lp‐PLA2 and predicting carotid atherosclerosis. A total of 1982 participants aged ≥40 years were included in this study. Hs‐CRP and Lp‐PLA2 were measured by a high‐sensitivity nephelometry assay and quantitative sandwich enzyme‐linked immunosorbent assay, respectively. Ultrasonography was performed on the bilateral carotid arteries to evaluate stenosis and plaques. Multivariable logistic regression models were used to analyse the association between the combination of the hs‐CRP and Lp‐PLA2 levels and carotid plaques and stenosis. A total of 1579 (79.7%) and 181 (9.1%) subjects had carotid plaques and carotid stenosis, respectively. The group with high hs‐CRP and Lp‐PLA2 levels had the highest prevalence of carotid plaques (90.6%) and stenosis (20.8%). A significant association was found between high hs‐CRP and Lp‐PLA2 levels and carotid stenosis (adjusted odds ratio [OR]: 2.39; 95% confidence interval [CI]: 1.13‐5.09), but this combination was not associated with carotid plaques (OR: 2.62, 95% CI: 0.93‐7.38). The results suggested that the combination of hs‐CRP and Lp‐PLA2 were better predictors than either protein alone with regard to carotid atherosclerosis.     

Association of Lp-PLA2 Mass and Aysmptomatic Intracranial and Extracranial Arterial Stenosis in Hypertension Patients

Background and Purpose

Intracranial arterial stenosis (ICAS) is a common cause of ischemic stroke in Asians, whereas whites tend to have more extracranial lesions. Lipoprotein-associated phospholipase A₂ (Lp-PLA₂) has been associated with ischemic stroke by a large amount of work. However, there are few studies focusing on the relationship of Lp-PLA₂ and asymptomatic ICAS or extracranial arterial stenosis (ECAS). Wehereby sought to explore the relationship of Lp-PLA₂ and ICAS, ECAS and concurrent stenosis in stroke-free hypertensive patients in Chinese population.

Methods

All the subjects were evaluated for the presence and severity of ICAS and ECAS through computerized tomographic angiography (CTA) covered the whole brain down to the level of aortic arch. Lp-PLA₂ mass was measured by enzyme linked immunoassay. The association of Lp-PLA₂ and vascular stenosis was analyzed through multivariate logistic regression.

Results

Among 414 participants, 163 (39.4%) had no ICAS or ECAS, 63 (15.2%) had ECAS only, 111 (26.8%) had ICAS only and 77 (18.6%) had concurrent extraintracranial stenosis. Lp-PLA₂ mass was significantly associated with isolated ICAS (OR: 2.3; 95% CI: 1.14-4.64), and concurrent stenosis (OR: 3.93; 95% CI: 1.62-9.51), but was not related to isolated ECAS (OR: 1.54; 95% CI: 0.68-3.48). Lp-PLA₂ mass was also associated with moderate to severe ICAS no matter how was the ECAS. Moreover, patients with higher Lp-PLA₂ mass showed more sever ICAS and had more intracranial arterial lesions.

Conclusion

This study revealed the association of Lp-PLA₂ mass with ICAS in stroke-free hypertensive patients in Chinese population. The further long-term cohort study was warranted to elucidate the concrete effect of Lp-PLA₂ on the asymptomatic ICAS.     

Longitudinal association between serum uric acid levels and multiterritorial atherosclerosis

Multiterritorial atherosclerosis has dramatically increased annual risk of adverse cardiovascular events than atherosclerotic disease with single‐artery affected. Serum uric acid (SUA) is an important predictor of stroke and atherosclerosis; however, which is supported by few direct evidence based on cohort studies. A prospective cohort study including 2644 North Chinese adults aged ≥40 years was performed in 2010‐2012 to investigate the association between SUA and multiterritorial vascular stenosis. Hyperuricaemia was defined as SUA levels >6 and >7 mg/dL for males and females, respectively. All participants underwent twice transcranial Doppler (TCD) and bilateral carotid duplex ultrasound to evaluate intracranial artery stenosis (ICAS) and extracranial arterial stenosis (ECAS) and peripheral arterial disease (PAD) was determined by ankle‐brachial index (ABI) on January 2010 and January 2012 based on regular health check‐ups. The cumulative incidence of vascular stenosis was significantly higher in subjects with hyperuricaemia than in those without hyperuricaemia (54.1% vs. 34.7%, P < 0.001). The adjusted odds ratios (ORs) with 95% confidence intervals (CIs) for new on‐set vascular stenosis due to hyperuricaemia and a 1‐mg/dL change in SUA level were 1.75 (1.32‐2.31) and 1.29 (1.21‐1.38), respectively. Furthermore, in the gender‐stratified analysis, the association between SUA levels and ICAS was statistically significant in males (OR: 2.02; 95% CI: 1.18‐3.46), but not females (OR: 0.85, 95% CI: 0.41‐1.76, P for interaction: 0.026).     

Asymptomatic Intracranial Arterial Stenosis and Metabolic Syndrome: The APAC Study

Purpose

The metabolic syndrome (MetS) is a major risk factor for cardiovascular diseases. We investigated potential associations between MetS and asymptomatic intracranial arterial stenosis (ICAS) in a general population.

Methods

The community-based “Asymptomatic Polyvascular Abnormalities in Community Study” examined asymptomatic polyvascular abnormalities in a Chinese population aged 40+ years without history of stroke and coronary heart disease. MetS was defined by the International Diabetes Federation criteria. Asymptomatic ICAS was diagnosed by transcranial color-coded Doppler sonography.

Results

Out of 5393 study participants, asymptomatic ICAS was detected in 713 (13.2%) participants, and MetS in 1323 (24.5%) individuals. Prevalence of asymptomatic ICAS increased significantly from 7.5% to 24.2% with increasing number of MetS components. After adjusting for age, gender, physical activity, body mass index, low-density lipoprotein cholesterol and high-sensitivity C-reactive protein, MetS was significantly associated with asymptomatic ICAS (OR: 1.50; 95%CI: 1.23,1.83). Compared with the subgroup without MetS, the ORs for asymptomatic ICAS increased (P<0.0001) for each of 5 components of MetS from 1.71 (95%CI: 1.27,2.30), to 2.20 (95%CI: 1.63,2.98), 2.79 (95CI: 2.01,3.88), 3.08 (95%CI: 2.11,4.51) and 4.27 (95%CI: 2.22,8.20).

Conclusions

In multivariate analysis, MetS was an independent and additional factor associated with asymptomatic ICAS. Study participants with 5 MetS components had a 4 times higher risk of asymptomatic ICAS than participants with no MetS component.     

Association between Serum Alkaline Phosphatase Level and Cerebral Small Vessel Disease

Background

Serum alkaline phosphatase (ALP) is a marker of vascular calcification. A high serum ALP level is associated with an increase in cardiovascular events, and predicts poor functional outcome in patients with stroke. We investigated whether serum ALP was associated with cerebral small vessel disease (cSVD) and large cerebral artery stenosis (LCAS).

Methods

We evaluated vascular risk factors, brain magnetic resonance images (MRIs), and MR angiograms from 1,011 neurologically healthy participants. The presence of silent lacunar infarction (SLI) and moderate-to-severe cerebral white matter hyperintensities (MS-cWMH) were evaluated as indices of cSVD on brain MRIs. Findings of extracranial arterial stenosis (ECAS) or intracranial arterial stenosis (ICAS) were considered to be indices of LCAS on MR angiograms.

Results

Subjects with SLI (odds ratio [OR]: 2.09; 95% confidence interval [CI]: 1.27–3.42; p = 0.004) and MS-cWMH (OR: 1.48; 95% CI; 1.03–2.13, p = 0.036) were significantly more likely to have ALP levels in the third tertile (ALP ≥ 195 IU/L) than the first tertile (ALP ≤ 155 IU/L), after adjusting for cardiovascular risk factors. The mean serum ALP level was significantly higher in patients with SLI or MS-cWMH compared to patients without those findings. After adjustment for confounding factors, the multivariate model found that the statistical significance of serum ALP remained when the presence of SLI (OR: 1.05 per 10 IU/L increase in ALP; 95% CI: 1.02–1.08; p = 0.003) or MS-cWMH (OR: 1.03 per 10 IU/L increase in ALP; 95% CI: 1.00–1.06; p = 0.025) were added to the model. There were no differences in the proportions of patients with LCAS, ICAS, and ECAS across the serum ALP tertiles.

Conclusions

Our study of neurologically healthy participants found a positive association between serum ALP level and indicators of cSVD, but no association between serum ALP level and the indicators of LCAS.     

Lipoprotein-Associated Phospholipase A2 Is Associated with Atherosclerotic Stroke Risk: The Northern Manhattan Study

Background

Lipoprotein-associated phospholipase A2 (LpPLA2) levels are associated with stroke, though whether this extends to all populations and stroke subtypes is unknown.

Methods

Serum samples from stroke-free community participants in the Northern Manhattan Study were assayed for LpPLA2 mass and activity. Participants were followed annually for stroke. Cox-proportional-hazard models were fitted to estimate hazard-ratios and 95% confidence intervals (HR, 95% CI) for the association of LpPLA2 levels with ischemic stroke (IS), after adjusting for demographic and medical risk factors.

Results

Serum samples were available in 1946 participants, of whom 151 (7.8%) experienced a first IS during median follow-up 11 years. Mean age was 69 (SD 10), 35.6% were men, 20% non-Hispanic Whites, 22% non-Hispanic Blacks, and 55% Hispanics. LpPLA2 mass and activity levels were not associated with overall IS risk.LpPLA2 mass but not activity levels were associated with strokes due to large artery atherosclerosis (LAA; adjusted HR per SD 1.55, 95% CI 1.17–2.04). There was a dose-response relationship with LAA (compared to first quartile, 2nd quartile HR = 1.43, 95% CI 0.23–8.64; 3rd quartile HR = 4.47, 95% CI 0.93–21.54; 4th quartile HR = 5.07, 95% CI 1.07–24.06). The associations between LpPLA2-mass and LAA-stroke risk differed by race-ethnicity (p = 0.01); LpPLA2-mass was associated with increased risk of LAA among non-Hispanic Whites (adjusted HR per SD 1.44, 95% CI 0.98–2.11), but not other race-ethnic groups.

Conclusion

LpPLA2-mass levels were associated with risk of atherosclerotic stroke among non-Hispanic White participants, but not in other race-ethnic groups in the cohort. Further study is needed to confirm these race-ethnic differences and the reasons for them.     

Computational Fluid Dynamics Modeling of Symptomatic Intracranial Atherosclerosis May Predict Risk of Stroke Recurrence

Background

Patients with symptomatic intracranial atherosclerosis (ICAS) of ≥70% luminal stenosis are at high risk of stroke recurrence. We aimed to evaluate the relationships between hemodynamics of ICAS revealed by computational fluid dynamics (CFD) models and risk of stroke recurrence in this patient subset.

Methods

Patients with a symptomatic ICAS lesion of 70–99% luminal stenosis were screened and enrolled in this study. CFD models were reconstructed based on baseline computed tomographic angiography (CTA) source images, to reveal hemodynamics of the qualifying symptomatic ICAS lesions. Change of pressures across a lesion was represented by the ratio of post- and pre-stenotic pressures. Change of shear strain rates (SSR) across a lesion was represented by the ratio of SSRs at the stenotic throat and proximal normal vessel segment, similar for the change of flow velocities. Patients were followed up for 1 year.

Results

Overall, 32 patients (median age 65; 59.4% males) were recruited. The median pressure, SSR and velocity ratios for the ICAS lesions were 0.40 (−2.46–0.79), 4.5 (2.2–20.6), and 7.4 (5.2–12.5), respectively. SSR ratio (hazard ratio [HR] 1.027; 95% confidence interval [CI], 1.004–1.051; P = 0.023) and velocity ratio (HR 1.029; 95% CI, 1.002–1.056; P = 0.035) were significantly related to recurrent territorial ischemic stroke within 1 year by univariate Cox regression, respectively with the c-statistics of 0.776 (95% CI, 0.594–0.903; P = 0.014) and 0.776 (95% CI, 0.594–0.903; P = 0.002) in receiver operating characteristic analysis.

Conclusions

Hemodynamics of ICAS on CFD models reconstructed from routinely obtained CTA images may predict subsequent stroke recurrence in patients with a symptomatic ICAS lesion of 70–99% luminal stenosis.     

Elevated Plasma Total Cholesterol Level Is Associated with the Risk of Asymptomatic Intracranial Arterial Stenosis

Background

Intracranial arterial stenosis (ICAS) is one of the most common causes of stroke, and dyslipidemia was one of the most common risk factors related to ICAS. However, the correlation between the plasma total cholesterol level (PTC) and ICAS, especially asymptomatic ICAS (AICAS) is not clear.

Materials and Methods

5,300 participants were enrolled in this study. The diagnosis of AICAS was made by transcranial Doppler ultrasonography. The participants were then divided into 5 essentially equal-sized groups based on their PTC levels. The multivariate logistic regression was used to analyze the correlation between the PTC level and the prevalence of AICAS.

Results

13.0% of the participants were diagnosed with AICAS. The prevalence of AICAS gradually increased with the increasing PTC level. After adjusted by the possible confounding factors, the Odds Ratios (OR) of the AICAS prevalence between the 1st quintile group and the other 4 groups were 1.13, 1.23, 1.63 and 1.75 with 95% confident intervals (CI) of 0.84–1.52, 0.91–1.66, 1.20–2.22 and 1.23–2.47, respectively. The further subgroup analysis revealed that the PTC level was stronger for males (OR 1.42 95%CI 1.23–1.64), regarding the prevalence of AICAS.

Conclusions

In this large community-based study, the prevalence of AICAS is 13.0%, subjects with higher PTC levels showed a mild increase in the prevalence of AICAS. The PTC level is an independent risk factor of AICAS. Males seem to be significantly more vulnerable to the risk of AICAS.     

Association of Lp‐PLA2 G994T gene polymorphism with risk of ischemic stroke in Chinese population

The association between lipoprotein‐associated phospholipase A2 (Lp‐PLA2) G994T gene polymorphism and the risk of ischemic stroke is unclear. The aim of this study is to investigate the influence of Lp‐PLA2 G994T genetic variant on the pathogenesis of ischemic stroke in Chinese population. A total of 348 patients with a clinical diagnosis of ischemic stroke and 260 gender‐matched control subjects under physical examination were recruited from hospitals and genotyped for G994T gene polymorphism. The results showed that there was a significant difference in the genotype distribution between the two groups and people with GT or TT genotype were associated with the higher risk of ischemic stroke even after adjusting the effects of potential confounding factors. In addition, both ischemic stroke patients and control subjects carrying T allele showed relatively lower Lp‐PLA2 activity and higher oxLDL level. Therefore, Lp‐PLA2 G994T gene polymorphism may be an independent risk factor of ischemic stroke in Chinese population.     

Serum lipoprotein (a) concentrations are inversely associated with T2D,prediabetes, and insulin resistance in a middle-aged and elderly Chinese population

Lipoprotein (a) [Lp(a)], an LDL-like particle, has been proposed as a causal risk factor for CVD among general populations. Meanwhile, both serum Lp(a) and diabetes increase the risk of CVD. However, the relationship between serum Lp(a) and T2D is poorly characterized, especially in the Asian population. Therefore, we conducted a cross-sectional study in 10,122 participants aged 40 years or older in Jiading District, Shanghai, China. Our study found that the prevalence of T2D was decreased from 20.9% to 15.0% from the lowest quartile to the highest quartile of serum Lp(a) concentrations (P for trend <0.0001). Logistic regression analyses showed that the odds ratios and 95% confidence intervals of prevalent T2D for quartiles 2–4 versus quartile 1 were 0.86 (0.73–1.01), 0.88 (0.75–1.04), and 0.76 (0.64–0.90) (P for trend = 0.0002), after adjustment for traditional confounding factors. Moreover, the risks for prevalent prediabetes, insulin resistance, and hyperinsulinemia were also decreased from the lowest to the top quartile. This inverse association between serum Lp(a) and T2D was not appreciably changed after we adjusted hypoglycemic medications or excluded the subjects with hypoglycemic and/or lipid-lowering agents and/or a history of self-reported CVD.     

C-reactive protein modifies the association of plasma leptin with coronary calcium in asymptomatic overweight individuals

Evidence suggests putative interactions of leptin and C‐reactive protein (CRP) in the pathogenesis of adiposity‐related atherosclerotic cardiovascular disease (CVD). Therefore, we investigated whether CRP levels modify the relationship of leptin levels with coronary artery calcium (CAC). We examined 1,460 asymptomatic individuals from two community‐based cross‐sectional studies coordinated at a single, university‐based research center. We focused on subjects who were overweight or obese (BMI ≥25) given greater biologic plausibility in this setting. In multivariable CAC models, we analyzed the interaction of log‐transformed plasma leptin levels with higher CRP levels as defined by three cut‐points: two clinically based (2 mg/l, 3 mg/l) and one dataset specific (sex‐specific upper quartile). The association of plasma leptin with CAC was modified by higher CRP regardless of cut‐point (interaction term P values all <0.01 in fully adjusted models). Leptin levels were associated with CAC in those with high, but not low CRP levels (e.g., tobit ratio for a 1 unit increase in ln(leptin) (95% CI): 2.18 (1.29–3.66) if CRP level ≥3 mg/l; N = 461 vs. 0.94 (0.67–1.31) if CRP levels <3 mg/l; N = 999) in fully adjusted models. No interaction with CRP was present in control analyses with adiponectin, BMI and waist circumference. In conclusion, in asymptomatic overweight and obese adults, increased leptin levels were independently associated with increased CAC in the presence of high, but not low CRP levels, supporting a leptin‐CRP interface in atherosclerosis risk.     

Intake of fruits and vegetables in relation to 10-year weight gain among Spanish adults

Objective: Despite the alarming increase in the prevalence of obesity, epidemiologic studies that prospectively examine the fruit and vegetable consumption and other lifestyle factors in relation to weight gain (WG) are still insufficient. We explored the associations between fruit and vegetable intake and WG over a 10‐year period in an adult Mediterranean population. Methods and Procedures: We performed a 10‐year follow‐up study with healthy participants (n = 206) aged 15–80 years at baseline in 1994, who participated in a nutrition survey in Valencia, Spain. Data on diet, lifestyle factors, and body weight were obtained in 1994 and 2004 using a food frequency questionnaire (FFQ) and direct measurements. Results: The average WG over the study period was 3.41 (s.d. 6.9) kg. In multivariate analyses, participants in the third quartile of fruit intake at baseline in 1994 had lower risk of WG ≥ 3.41 kg compared to those in the lowest quartile (oddsratio (OR) = 0.31, 95% confidence interval (CI), 0.11–0.85; P trend = 0.044). Regarding vegetable intake, the risk of WG was lowest in participants of the fourth quartile (>333 g/day), which had an 84% reduced risk of gaining 3.41 kg weight (OR = 0.18, 95% CI, 0.05–0.66; P trend = 0.017). When the intake of fruits and vegetables was combined, the risk of WG decreased across quartiles, with the lowest risk among those in the fourth quartile (OR = 0.22, 95% CI, 0.06–0.81; P trend = 0.022). Further adjustment for an increased intake of fruits and vegetables over the past 10 years reported by participants in 2004 did not appreciably alter the observed ORs. Discussion: Dietary patterns associated with a high intake of fruits and vegetables in Mediterranean populations may reduce long‐term risk of subsequent WG and obesity among adults.     

Serum tissue inhibitor of metalloproteinase‐1 and risk of cognitive impairment after acute ischaemic stroke

The expression of tissue inhibitor metalloproteinase‐1 (TIMP‐1) significantly increased after acute cerebral ischaemia and involved in neurodegeneration. The purpose was to prospectively investigate the relationship between serum TIMP‐1 with post‐stroke cognitive impairment. Our participants were from an ancillary study of China Antihypertensive Trial in Acute Ischemic Stroke. 598 ischaemic stroke patients from seven participating hospitals were included. Cognitive impairment was evaluated using Mini‐Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) at 3 months. 316 (52.84%) or 384 (64.21%) participants had cognitive impairment according to MMSE or MoCA, respectively. Compared with the first quartile of TIMP‐1, the multivariate‐adjusted odds ratios (95% confidence intervals) for the highest quartile were 1.80 (1.09‐2.97) for cognitive impairment defined by MMSE and 2.55 (1.49‐4.35) by MoCA. Multiple‐adjusted spline regression models showed linear associations between TIMP‐1 concentrations and cognitive impairment (P value for linearity < 0.01). The addition of TIMP‐1 to models including conventional factors improved reclassification for cognitive impairment, as shown by net reclassification index or integrated discrimination improvement (P < 0.05). Participants with both higher TIMP‐1 and matrix metalloproteinase‐9 levels simultaneously had highest risk of cognitive impairment. Higher serum TIMP‐1 levels were associated with increased risk of cognitive impairment after acute ischaemic stroke, independently of established risk factors.     

Cadmium exposure and the risk of prostate cancer among Nigerian men: Effect modification by zinc status

BackgroundProstate cancer (PCa) may result from an interplay between many factors including exposure to trace elements. This study examined the association between cadmium exposure and PCa among Nigerian men and evaluated possible modification of this effect by zinc status.MethodsThis case-control study involved men with histologically confirmed PCa (n = 82), benign prostatic hyperplasia (BPH; n = 93) and controls (n = 98), aged between 40 and 80 years. Study participants were recruited from the main teaching hospital that draws clients from the entire Anambra State in South-Eastern Nigeria. Blood and urine samples were collected from these participants and were analyzed for trace elements using ICP-MS. Statistical models were used to assess the exposure risk for cadmium exposure as well as the mediating effect of zinc status.ResultsAmong men with prostatic disorders (case-case analysis), every 10-fold increase in urinary cadmium was associated with increased risk of PCa (adjusted odds ratios: 2.526; 95% CI: 1.096–5.821). Men in the highest blood zinc quartile had lower odds of PCa compared to the lowest quartile (AOR: 0.19; 95% CI, 0.06–0.54; p-for trend = 0.001). Zinc-specific effect was observed in this group: every 10-fold increase in urinary cadmium was associated with increased risk of PCa among men with creatinine-adjusted urinary zinc levels below the median value (AOR: 8.46; 95% CI: 1.97 –36.39) but not in those above the median value (AOR: 1.55; 95% CI: 0.45 – 5.39).ConclusionHigher exposure to cadmium may be associated with increased risk of PCa in Nigeria and probably other countries with high prevalence of Zn deficiency. These results point to the need to consider co-occurring trace metals in any effort to mitigate the toxicity of Cd in the environment.     

Helicobacter pylori infection reduces the risk of Barrett's esophagus: A meta‐analysis and systematic review

Introduction

The prevalence of Helicobacter pylori infection (HPI) has been decreasing in developed countries, with an increasing prevalence of Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC) at the same time. The aim of our meta‐analysis was to quantify the risk of BE in the context of HPI.

Methods

A systematic search was conducted in 3 databases for studies on BE with data on prevalence of HPI from inception until December 2016. Odds ratios for BE in HPI were calculated by the random effects model with subgroup analyses for geographical location, presence of dysplasia in BE, and length of the BE segment.

Results

Seventy‐two studies were included in the meta‐analysis, including 84 717 BE cases and 390 749 controls. The overall analysis showed that HPI reduces the risk of BE; OR = 0.68 (95% CI: 0.58‐0.79, P < .001). Subgroup analyses revealed risk reduction in Asia OR = 0.53 (95% CI: 0.33‐0.84, P = .007), Australia OR = 0.56 (95% CI: 0.39‐0.80, P = .002), Europe OR = 0.77 (95% CI: 0.60‐0.98, P = .035), and North‐America OR = 0.59 (95% CI: 0.47‐0.74, P < .001). The risk was significantly reduced for dysplastic BE, OR = 0.37 (95% CI: 0.26‐0.51, P < .001) for non‐dysplastic BE, OR = 0.51 (95% CI: 0.35‐0.75, P = .001), and for long segment BE, OR = 0.25 (95% CI: 0.11‐0.59, P = .001) in case of HPI.

Conclusions

This extensive meta‐analysis provides additional evidence that HPI is associated with reduced risk of BE. Subgroup analyses confirmed that this risk reduction is independent of geographical location. HPI is associated with significantly lower risk of dysplastic, non‐dysplastic, and long segment BE.     

Plasma PAF-acetylhydrolase in patients with coronary artery disease: results of a cross-sectional analysis

Inflammation underlies both onset and perpetuation of atherosclerosis. Plasma lipoproteins transport the platelet-activating factor-acetylhydrolase (PAF-AH) with potentially anti-inflammatory activities. Our aim was to determine whether PAF-AH activity was associated with inflammatory markers and with coronary artery disease (CAD). PAF-AH activity and a panel of inflammatory mediators were measured in plasma of 496 patients with CAD and in 477 controls; 276 patients presented with stable angina pectoris and 220 with acute coronary syndrome (ACS). Individuals within the highest quartile of PAF-AH activity had an 1.8-fold increase in CAD risk [95% confidence interval (CI), 1.01 to 3.2; P = 0.048] compared with those in the first quartile (adjusted for clinical and metabolic factors). When excluding individuals receiving statin and angiotensin-converting enzyme-inhibitor medication, individuals within the highest quartile of PAF-AH activity revealed a 3.9-fold increase in CAD risk (95% CI, 2.0 to 7.7; P < 0.0001). In these subjects, the plasma PAF-AH activity increased gradually in stable angina and in ACS both in men (P < 0.0001) and in women (P < 0.001), as compared with controls.No correlation was found between PAF-AH levels and those of common markers of inflammation. This study and the previous ones raise the important issue of whether PAF-AH is simply a marker of risk or directly promotes atherosclerosis.     

Liver enzymes as a predictor for incident diabetes in a Japanese population: the Hisayama study

Objective: We studied the relationship between liver enzymes and the development of diabetes in a general Japanese population. Research Methods and Procedures: A total of 1804 non‐diabetic subjects 40 to 79 years of age were followed‐up prospectively for a mean of 9.0 years. Results: During the follow‐up, 135 subjects developed diabetes. In both sexes, the age‐adjusted cumulative incidence of diabetes increased significantly with elevating quartiles of serum γ‐glutamyltransferase (GGT) and alanine aminotransferase (ALT) levels. This pattern was also observed in aspartate aminotransferase (AST) quartiles for men but not for women. In multivariate analyses after adjusting for comprehensive risk factors and other liver enzymes, the risk of developing diabetes was significantly higher in the highest GGT quartile than in the lowest quartile [odds ratio (OR), 2.54; 95% confidence interval (CI), 1.03 to 6.26 for men; OR, 5.73; 95% CI, 1.62 to 20.19 for women]. Similar results were observed in ALT quartiles (OR, 2.32; 95% CI, 0.91 to 5.92 for men; OR, 4.40; 95% CI, 1.38 to 14.06 for women) but not in AST quartiles in either sex. Significant positive associations of GGT and ALT with diabetes were seen within each stratified category of risk factors, namely fasting insulin, BMI, waist‐to‐hip ratio, high‐sensitivity C‐reactive protein, and alcohol consumption. In receiver operating characteristic analyses, the areas under the receiver operating characteristic curve of GGT and ALT were significantly larger than that of AST, fasting insulin, waist‐to‐hip ratio, or C‐reactive protein. Discussion: Our findings suggest that serum GGT and ALT concentrations are strong predictors of diabetes in the general population, independent of known risk factors.     

Serum zinc and risk of type 2 diabetes incidence in men: The Kuopio Ischaemic Heart Disease Risk Factor Study

ObjectivesZinc may play a role in the development of type 2 diabetes (T2D), because it is involved in antioxidant and anti-inflammatory activities. However, the role of zinc in the etiology of T2D has been poorly investigated. This study was conducted to study the association of serum zinc on T2D risk in middle-aged and older Finnish men.MethodsThis was a 20-year prospective follow-up study on 2220 Finnish men from the Kuopio Ischaemic Heart Disease Risk Factor Study (KIHD) who were 42 to 60 years old at baseline in 1984–1989. The main outcome was incident T2D. Serum zinc, body mass index (BMI), fasting blood glucose (FBG), serum insulin, C-reactive protein (CRP) and, in a subset of 751 participants, insulin-like growth factor-binding protein-1 (IGFBP-1), were measured. Also, the homeostatic model assessment (HOMA) was used to quantify insulin resistance (HOMA-IR), beta-cell function (HOMA-β) and insulin sensitivity (HOMA-IS).ResultsAt baseline, serum zinc was associated with higher BMI, serum insulin, HOMA-IR, HOMA-β and IGFBP-1 and lower HOMA-IS. During the average follow-up of 19.3 years, 416 men developed T2D. Men in the highest quartile of serum zinc had 60% higher risk (95% CI 20–113%; P-trend < 0.001) for incident T2D compared with the men in the lowest quartile, after multivariate adjustments. This association was attenuated after adjustment for BMI (HR = 1.39, 95% CI 1.04–1.85; P-trend = 0.013) or HOMA-IS (HR = 1.38, 95% CI 1.04–1.83; P-trend = 0.015), whereas adjustment for the other factors had only modest impact on the association.ConclusionHigher serum zinc was associated with higher risk of T2D; effects of zinc on BMI and insulin sensitivity may partly explain the association. Further prospective studies are warranted to confirm our results and explore potential mechanisms.