Hyperinsulinaemia: a prospective risk factor for lethal clinical prostate cancer

Previous studies have suggested that hyperinsulinaemia and other components of metabolic syndrome are risk factors for clinical prostate cancer. This prospective study tested the hypothesis that hyperinsulinaemia and other components of metabolic syndrome are risk factors for lethal clinical prostate cancer. The clinical, haemodynamic, anthropometric, metabolic and insulin profile at baseline in men who had died from clinical prostate cancer during follow-up was compared with the profile of men who were still alive at follow-up. If the hypothesis is true, men with an unfavourable prognosis would have a higher profile at baseline than those with a favourable prognosis. A total of 320 patients in whom clinical prostate cancer, stages T2–3, had been diagnosed were consecutively included in the study during 1995–2003. Height, body weight, waist measurement, hip measurement and blood pressure were determined. Body mass index and waist/hip ratio (WHR) were calculated. Blood samples were collected to determine triglycerides, total cholesterol, high-density lipoprotein (HDL)-cholesterol, low-density lipoprotein (LDL)-cholesterol, uric acid, alanine aminotransferase and fasting plasma insulin level. The prostate gland volume was measured using transrectal ultrasound. The annual benign prostatic hyperplasia (BPH) growth rate was calculated. The diagnosis of prostate cancer was established using transrectal ultrasound-guided automatic needle biopsy of the prostate gland. All patients with clinical prostate cancer were followed up until their death or until the study was terminated on 31 December 2003. At follow-up, 54 patients had died from prostate cancer and 219 were still alive. The results showed that the men who died of clinical prostate cancer during the follow-up period were older (P < 0.001), had a larger prostate gland volume (P < 0.001), a faster BPH growth rate (P < 0.001), a higher prevalence of type 2 diabetes (P < 0.035) and treated hypertension (P < 0.023), a higher stage (P < 0.001) and grade (P = 0.028) of clinical prostate cancer, a higher prostate-specific antigen (PSA) level (P < 0.001) and a higher PSA density (P < 0.001) at baseline than men still alive with clinical prostate cancer at follow-up. These men also had a lower HDL-cholesterol level (P = 0.027), a higher fasting plasma insulin level (P = 0.004), a higher WHR (P = 0.097) of borderline significance and a higher uric acid level (P = 0.079) of borderline significance. Eliminating the effect on mortality of higher stage and grade of the clinical prostate cancer and PSA at baseline, the following statistically significant correlations remained: a higher fasting plasma insulin level (P = 0.010) and a lower HDL-cholesterol level of borderline significance (P = 0.065). In conclusion, hyperinsulinaemia and five other previously established components of metabolic syndrome are shown to be prospective risk factors for deaths that can be ascribed to prostate cancer. These findings confirm previous study, which indicate that prostate cancer is a component of metabolic syndrome. Moreover, these data indicate that hyperinsulinaemia and other metabolic disorders precede deaths caused by prostate cancer. Thus, our data support the hypothesis that hyperinsulinaemia is a promoter of clinical prostate cancer. Furthermore, our data suggest that the insulin level could be used as a marker of prostate cancer prognosis and tumour aggressiveness, regardless of the patient’s prostate cancer stage, cancer grade and PSA level.     

Cardiovascular risk factors in rural Kenyans are associated with differential age gradients,but not modified by sex or ethnicity

Abstract

Background: The relationship between metabolic disease and the non-modifiable risk factors sex, age and ethnicity in Africans is not well-established.

Aim: This study aimed to describe sex, age and ethnicity differences in blood pressure (BP) and lipid status in rural Kenyans.

Subjects and methods: A cross-sectional study was undertaken among rural Kenyans. BP and pulse rate (PR) were measured while sitting and fasting blood samples were taken for analysis of standard lipid profile. Standard anthropometric measurements were collected. Physical activity energy expenditure was obtained objectively and lifestyle data were obtained using questionnaires.

Results: In total, 1139 individuals (61.0% women) participated aged 17–68 years. Age was positively associated with BP and plasma cholesterol levels. Sitting PR was negatively associated with age in women only (sex-interaction p?<?0.001). Ethnicity did not modify any of the age-associations with haemodynamic or lipid outcomes. Differences in intercept between women and men were found in all parameters except for diastolic BP (p?=?0.154), with men having lower HDL-C but higher values in all other cardiovascular risk factors.

Conclusion: BP and plasma cholesterol levels increase with age at a similar gradient in men and women, but absolute levels of the majority of the risk factors were higher in men.     

Benefits, challenges, and registerability of the polypill.

Guidelines for the management of cardiovascular disease (CVD) stress the importance of treating global risk, rather than individual risk, factors. Patients at high cardiovascular (CV) risk, for example, benefit from a combination of aspirin, antihypertensive agents, lipid-lowering drugs, and possibly folic acid. As the number of medications that a patient requires increases, adherence and compliance to therapy are likely to decrease. The use of affordable, multiple-target, fixed-combination 'polypills', which concomitantly reduce multiple risk factors without increasing the pill burden or the risk of adverse effects, has the potential to improve CV risk factor management, thereby reducing the incidence of CVD. This review discusses the benefits of the polypill and the challenges and requirements for its success and registerability. Discussions with regulatory bodies are required in order to obtain some 'balance' between an overcautious registration approach and the potentially large public health benefits that are likely to arise from the use of polypills.     

2型糖尿病合并脑梗塞与血脂、血压分析

分析2型糖尿病合并脑梗塞与血脂、血压异常的关系.收集我院2型糖尿病患者100例,其中合并脑梗塞者60例,正常对照组40例.分别测定血脂、血压并进行比较.结果糖尿病合并脑梗塞组血甘油三酯、载脂蛋白B、收缩压明显升高,高密度脂蛋白、载脂蛋白A1显著降低.血甘油三酯、收缩压升高、高密度脂蛋白降低是糖尿病并发脑梗塞的危险因素.     

A comparative study of anti-inflammatory and antidyslipidemic effects of fenofibrate and statins on rheumatoid arthritis

Abstract

We prospectively compared the anti-inflammatory and antidyslipidemic effects of fenofibrate and statins in rheumatoid arthritis (RA) patients. Forty-four RA patients [male (M) = 7, female (F) = 37] with dyslipidemia were enrolled in this 6-month study and randomly allocated to the fenofibrate (2 M + 21 F = 23) or statins (5 M + 16 F = 21) group. We measured blood chemistry (serum lipid profile, sugar, urate, and γ-glutamyl transpeptidase) and blood pressure 2 h after breakfast. Visual analog scale (VAS), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and prednisolone (PSL) dosage were also recorded immediately before and after the study. Fenofibrate, but not statins, significantly decreased serum levels of total cholesterol, low-density lipoprotein–cholesterol, and triglycerides (all p < 0.05). A significant improvement in VAS was observed in both the fenofibrate group (49.1 ± 24.7 → 14.7 ± 11.2; p < 0.0001) and the statins group (47.4 ± 29.7 → 20.2 ± 16.5; p < 0.001). PSL dosage significantly decreased only in the fenofibrate group (3.58 ± 2.68 → 2.00 ± 2.22 mg/day; p < 0.01). Significant correlation was observed between ?VAS and ?CRP in the fenofibrate group (p < 0.05). Fenofibrate showed more anti-inflammatory and antidyslipidemic activity than statins in RA.     

Lipid profile and atherogenic indices in patients with stable chronic obstructive pulmonary disease

Background and aimsLimited number of studies investigated lipid profile in chronic obstructive pulmonary disease (COPD) with inconsistent results. This study aimed to investigate lipid parameters in sera of patients with stable COPD and their associations with disease severity, smoking, comorbidities and therapy.Methods and resultsThe study included 137 COPD patients and 95 controls. Triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) were assessed. Non-HDL-C (NHC), atherogenic coefficient (AC), TG/HDL-C, atherogenic index of plasma (AIP), Castelli's risk index I and II (CRI-I, CRI-II), and monocyte to HDL ratio (MHR) were calculated.HDL-C and MHR were increased, while other lipid parameters and indices were decreased in COPD patients compared to healthy individuals. Smoking did not influence lipid parameters. However, lipid profile was altered only in more severe disease stages. AC, CRI-I and CRI-II showed positive association with lung function parameters in COPD patients, and negative with COPD multicomponent indices (ADO, BODCAT, BODEx, CODEx and DOSE). Combined model that included CRI-II, C-reactive protein, fibrinogen and white blood cells showed great diagnostic performances, and correctly classified 72% of study participants with an AUC of 0.800 (0.742–0.849), P < 0.001. Bronchodilator monotherapy and statins have opposite impact on TC, LDL-C and NHC, while TG, TG/HDL-C and AIP were increased in COPD patients with cardiovascular diseases.ConclusionLipid disbalance is present in COPD, and it seems to occur later as the disease progresses. Further studies are needed to illuminate the underlying mechanism of dyslipidaemia.     

Treatment of Dyslipidaemias in Patients with Established Vascular Disease: A Revival of the Fibrates

Summary

The key ‘statin trials’ focussed on the beneficial effect of lowering the circulating concentrations of low-density lipoprotein cholesterol (LDL). However, epidemiological surveys, mainly based on healthy populations, indicate that other lipid-related variables, such as high-density cholesterol (HDL), triglycerides (TG), dense LDL subfraction distribution, and possibly lipoprotein (a) (Lp(a)), are also predictors of vascular events. Furthermore, TG and HDL levels influenced outcome within some of the statin trials. Plasma fibrinogen levels have also been shown to be powerful predictors of vascular risk in healthy subjects and patients with established ischaemic heart disease. The fibrates exert beneficial effects on all these variables that predict vascular events.

The results from recent trials, the Bezafibrate Infarction Prevention (BIP) study and the Veterans Administration HDL Intervention Trial (VA-HIT) have revived our interest in fibrates. These trials involved bezafibrate and gemfibrozil that have a relatively poor LDL-lowering capacity. Therefore, the benefits reported in BIP and VA-HIT must be attributed to actions on variables other than a reduction in LDL quantity.

Ciprofibrate and fenofibrate have significantly greater LDL-lowering capacity than bezafibrate or gemfibrozil. This advantage may render them more effective, especially since they retain the additional beneficial actions associated with this class of lipidlowering drugs.     

Management of Hypertension and Dyslipidaemia in Patients Presenting with Hyperuricaemia: Case Histories

Summary

A number of studies have shown that hyperuricaemia is associated with an increased incidence of coronary heart disease. It has been proposed that the elevated serum uric acid levels are linked to other risk factors, such as hypertension, dyslipidaemia and diabetes. Hyperuricaemia is commonly encountered in patients with essential hypertension and is considered as a risk factor for morbidity and mortality associated with hypertension. In addition, lipid abnormalities (mainly hypertriglyceridaemia) are also found more frequently in hypertensive patients than in normotensives. There is evidence that the angiotensin II receptor antagonist, losartan, increases urate excretion by reducing reabsorption of urate in the renal proximal tubule. It is also known that fibric acid derivatives (fibrates) have several beneficial actions in addition to their lipidlowering capacity. Fenofibrate administration is associated with a uric acid lowering effect. In this respect, we present two patients with hypertension and dyslipidaemia together with elevated serum uric acid levels. We also discuss (in the format of questions and answers) the pathophysiological mechanisms underlying the association of serum uric acid with cardiovascular disease, and we review the relevant literature to justify an evidence-based decision to choose an antihypetensive agent (losartan) or a lipidlowering drug (fenofibrate) with an additional hypouricaemic effect.     

Dyslipidaemia and insulin resistance in vertically HIV-infected children and adolescents

This cross-sectional study determined the influence of antiretroviral therapy (ART) on the lipid profile and insulin sensitivity of 119 perinatally HIV-infected Brazilian patients aged 6-19 years. Inadequate high-density lipoprotein cholesterol (HDL-c) concentrations were observed in 81.4% of patients. High concentrations of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-c) and triglycerides (TG) were found in 33.9%, 9.7% and 35.6% of patients, respectively. There were statistically significant differences in mean concentrations of TC (P = 0.004), HDL-c (P = 0.015) and LDL-c (P = 0.028) among children (<10 years), early adolescents (10-14 years) and late adolescents (15-19 years). Children presented the highest mean concentrations of TC and LDL-c, and patients in late adolescence presented the lowest concentrations of HDL-c. Insulin sensitivity, assessed by the Homeostasis Model Assessment (HOMA) index, was diagnosed in 16.7% of patients, with a statistically higher proportion (P = 0.034) of insulin-resistant children (33.3%) compared with adolescents (12.5%). There was a statistically significant association between TG concentrations and use of ART regimens containing protease inhibitors (PI) (P = 0.0003). Children presented a higher prevalence of insulin resistance and dyslipidaemia compared with adolescents, suggesting that ART, especially PIs, may lead to metabolic complications.     

Diabetes and other vascular risk factors for dementia: which factor matters most? A systematic review

Vascular risk factors, such as type 2 diabetes, hypertension, obesity and dyslipidaemia often co-occur. Each of these factors has been associated with an increased risk of dementia, but it is uncertain which factor imposes the greatest risk. Moreover, the effect of age at time of exposure may differ across factors. This paper systematically reviews the evidence for the association of each of these risk factors with dementia. Longitudinal population-based studies that assessed the incidence of dementia in relation to diabetes (n=14), hypertension (n=13), dyslipidaemia (n=8) or obesity (n=9) were included. All four risk factors were indeed associated with an increased risk of dementia, but the results of studies on diabetes and obesity were most consistent. The magnitude of the effects was comparable across the risk factors, with odds ratios for 'any dementia' around 1.5. For hypertension, obesity and dyslipidaemia age appeared to modulate the association: the risk of dementia was generally largest in studies that measured the risk factor in midlife (compared to late life) and had a long follow-up time. At midlife, the population attributable risk of dementia was highest for hypertension, up to 30% of cases of late life dementia. Later in life diabetes appears to convey the highest risk of dementia. This review shows that vascular risk factors should be regarded as a major target for preventive measures, but that timing of such measures appears to be critical.