Mechanism of nitric oxide regulation of vascular tone in the mesenteric arteries of the cane toad, Bufo marinus

Nitric oxide control of large systemic blood vessels of the cane toad, Bufo marinus is provided by nitrergic nerves. However, the involvement of nitrergic nerves in the regulation of small blood vessels has yet to be determined. This study investigated the nitric oxide (NO) control of the mesenteric arteries (MA) of B. marinus. Immunohistochemistry and NADPH-diaphorase histochemistry demonstrated a dense plexus of nitrergic nerves in the MA of B. marinus. MAs (~ 500–700µm in diameter) were mounted in a myograph and placed under an initial tension equivalent to their normal diameter. MAs were pre-constricted with the thromboxane A2 mimetic, U46619, prior to the addition of putative, vasodilatory chemicals. Acetylcholine caused a vasodilation that was endothelium-independent, because removal of the endothelium had no effect on the dilation. The response to acetylcholine was blocked by the NOS inhibitor, L-NNA, demonstrating that the effect was NO-dependent. Interestingly, nicotine also caused a dilation that was not affected by removal of the endothelium, but was significantly inhibited by L-NNA and the calcitonin gene-related peptide (CGRP) receptor antagonist, CGRP(8–37). These findings indicate that the MA of B. marinus are controlled by NO released from nitrergic nerves. In addition, a component of the response to applied nicotine appears to be mediated CGRP, which is probably released from sensory nerves.

Why is type 2 diabetes such a serious risk factor for coronary heart disease in women?

Women with type 2 diabetes were found to display an altered distribution of body fat, higher resistance to the action of insulin, highly increased levels of tryglycerides and significant elevations in the level of plasminogen activator inhibiter. Concludes that interventions which enhance the action of insulin, such as exercise or drug therapy, should lower the risk of coronary heart disease in these women.

The projected impact of population and high-risk strategies for risk-factor control on coronary heart disease and stroke events

Objective: To model the impact of both population and high-risk strategies on cardiovascular disease (CVD) outcomes.

Design, setting and participants: A CVD risk-factor survey was carried out in rural south-eastern Australia from 2004 to 2006. Using a stratified random sample, data for 1116 participants aged 35–74 years were analysed. Applying the Framingham risk equations to risk-factor data, 5-year probabilities of a coronary heart disease event, stroke and cardiovascular event were calculated. The effect of different changes in risk factors were modelled to assess the extent to which cardiovascular diseases can be prevented by changing the risk factors at a population level (population strategy), among the high-risk individuals (high-risk strategy) or both.

Results: Among men, a population strategy could reduce cardiovascular events by 19.3% (193 per 1000 per 5 years), the high-risk strategy by 12.6% (126 per 1000) and a combined strategy by 24.1% (241 per 1000); and among women, by 21.9% (219 per 1000), 19.0% (190 per 1000) and 28.7% (287 per 1000), respectively.

Conclusions: For prevention of CVD in Australia, it is important both to treat high-risk individuals and to reduce the mean risk-factor levels in the population. We show how risk-factor survey data can be used to set targets for prevention and to monitor progress in line with the recommendations of the National Preventative Health Taskforce.

An index of unhealthy lifestyle is associated with coronary heart disease mortality rates for small areas in England after adjustment for deprivation

Indices of socio-economic deprivation are often used as a proxy for differences in the health behaviours of populations within small areas, but these indices are a measure of the economic environment rather than the health environment. Sets of synthetic estimates of the ward-level prevalence of low fruit and vegetable consumption, obesity, raised blood pressure, raised cholesterol and smoking were combined to develop an index of unhealthy lifestyle. Multi-level regression models showed that this index described about 50% of the large-scale geographic variation in CHD mortality rates in England, and substantially adds to the ability of an index of deprivation to explain geographic variations in CHD mortality rates.

Mechanisms of nitric oxide-mediated neurogenic,vasodilation in mesenteric resistance arteries of toad, Bufo marinus

This study determined the role of nitric oxide (NO) in neurogenic vasodilation in mesenteric resistance arteries of the toad Bufo marinus. NO synthase (NOS) was anatomically demonstrated in perivascular nerves, but not in the endothelium. ACh and nicotine caused TTX-sensitive neurogenic vasodilation of mesenteric arteries. The ACh-induced vasodilation was endothelium-independent and was mediated by the NO/soluble guanylyl cyclase signaling pathway, inasmuch as the vasodilation was blocked by the soluble guanylyl cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one and the NOS inhibitors N^ω- nitro-L-arginine methyl ester and N^ω-nitro-L-arginine. Furthermore, the ACh-induced vasodilation was significantly decreased by the more selective neural NOS inhibitor N⁵-(1-imino-3-butenyl)-L-ornithine. The nicotine-induced vasodilation was endothelium-independent and mediated by NO and calcitonin gene-related peptide (CGRP), inasmuch as pretreatment of mesenteric arteries with a combination of N^ω-nitro-L-arginine and the CGRP receptor antagonist CGRP-(8–37) blocked the vasodilation. Clotrimazole significantly decreased the ACh-induced response, providing evidence that a component of the NO vasodilation involved Ca^2+-activated K⁺ or voltage-gated K⁺ channels. These data show that NO control of mesenteric resistance arteries of toad is provided by nitrergic nerves, rather than the endothelium, and implicate NO as a potentially important regulator of gut blood flow and peripheral blood pressure.

Relative deprivation between neighbouring wards is predictive of coronary heart disease mortality after adjustment for absolute deprivation of wards

Background The aims of this study were to assess whether deprivation inequality at small area level in England is associated with coronary heart disease (CHD) mortality rates and to assess whether this provides evidence of an association between area-level and individual-level risk.

Methods Mortality rates for all wards in England were calculated using all CHD deaths between 2001 and 2006. Ward-level deprivation was measured using the Carstairs Index. Deprivation inequality within local authorities (LAs) was measured by the IQR of deprivation for wards within the LA. Relative deprivation for wards was measured as the modulus of the difference between deprivation for the ward and average deprivation for all neighbouring wards.

Results Deprivation inequality within LAs was positively associated with CHD mortality rates per 100 000 (eg, all men β; 95% CI=2.7; 1.1 to 4.3) after adjustment for absolute deprivation (p<0.001 for all models). Relative deprivation for wards was positively associated with CHD mortality rates per 100 000 (eg, all men 1.4; 0.7 to 2.1) after adjustment for absolute deprivation (p<0.001 for all models). Subgroup analyses showed that relative deprivation was independently associated with CHD mortality rates in both affluent and deprived wards.

Conclusions Rich wards surrounded by poor areas have higher CHD mortality rates than rich wards surrounded by rich areas, and poor wards surrounded by rich areas have worse CHD mortality rates than poor wards surrounded by poor areas. Local deprivation inequality has a similar adverse impact on both rich and poor areas, supporting the hypothesis that income inequality of an area has an impact on individual-level health outcomes.

Contribution of climate and air pollution to variation in coronary heart disease mortality rates in England

There are substantial geographic variations in coronary heart disease (CHD) mortality rates in England that may in part be due to differences in climate and air pollution. An ecological cross-sectional multi-level analysis of male and female CHD mortality rates in all wards in England (1999–2004) was conducted to estimate the relative strength of the association between CHD mortality rates and three aspects of the physical environment - temperature, hours of sunshine and air quality. Models were adjusted for deprivation, an index measuring the healthiness of the lifestyle of populations, and urbanicity. In the fully adjusted model, air quality was not significantly associated with CHD mortality rates, but temperature and sunshine were both significantly negatively associated (p<0.05), suggesting that CHD mortality rates were higher in areas with lower average temperature and hours of sunshine. After adjustment for the unhealthy lifestyle of populations and deprivation, the climate variables explained at least 15% of large scale variation in CHD mortality rates. The results suggest that the climate has a small but significant independent association with CHD mortality rates in England.

Suboptimal management of cardiovascular risk factors in coronary heart disease patients in primary care occurs particularly in women

Background:  Patients with established coronary heart disease (CHD) are at the highest risk of further events. Despite proven therapies, secondary prevention is often suboptimal. General practitioners (GPs) are in an ideal position to improve secondary prevention.

Aim:  To contrast management of cardiovascular risk factors in patients with established CHD in primary care to those in clinical guidelines and according to gender.

Methods:  GPs throughout Australia were approached to participate in a programme incorporating a disease management software (mdCare) program. Participating practitioners (1258 GPs) recruited individual patients whose cardiovascular risk factor levels were measured.

Results:  The mdCare programme included 12 509 patients (58% male) diagnosed with CHD. Their mean age was 71.7 years (intra-quartile range 66–78) for men and 74 years (intra-quartile range 68–80) for women. Low-density-lipoprotein cholesterol was above target levels in 69% (2032) of women compared with 58% (2487) in men (P < 0.0001). There was also a higher proportion of women with total cholesterol above target levels (76%, 3592) compared with men (57%, 3787) (P < 0.0001). In patients who were prescribed lipid-lowering medication, 53% (2504) of men and 72% (2285) of women continued to have a total cholesterol higher than recommended target levels (P < 0.0001). Overall, over half (52%, 6538) had at least five cardiovascular risk factors (55% (2914) in women and 50% (3624) in men, P < 0.0001).

Conclusion:  This study found less intensive management of cardiovascular risk factors in CHD patients, particularly among women, despite equivalent cardiovascular risk. This study has shown that these patients have multiple risk factors where gender also plays a role.

Mortality disparities between geographic regions : results from a risk percentiles model for coronary heart disease

Background: Planning of disease prevention strategies requires information regarding the distribution of absolute risk in the population to allow targeting of people at high disease risk. It is well known that death rates from coronary heart disease (CHD) are higher in remote areas of Australia compared with major cities. Less well understood is the distribution of the absolute risk of CHD death within the different geographic regions. We present a mathematical model of CHD which projects the lifetime risk of death among individuals in different percentiles of CHD risk. We apply this to model the distribution of CHD risk within different geographic regions.

Methods: Using information from the Framingham1, MRFIT2 and AusDiab3 studies, the Australian population was divided into percentiles of CHD risk within age and gender groups by geographic location. Absolute mortality risk was determined at each percentile using current Australian mortality data. Survival curves were generated for each percentile using these risk estimates. Approximate confidence intervals were derived using bootstrap methods.

Conclusions: The difference in life expectancy at age 25 between those in the lowest decile of CHD risk compared to the highest was 5.8 years (95%CI:4.7,6.7) in major cities compared to 8.5 years (95%CI:7.6,9.7) in remote areas. The difference in risk of premature death (before age 75) was 12% (95%CI:10%,14%) in major cities compared to 33% (95%CI:28%,38%) in remote areas.