Mortality from coronary heart disease and stroke in relation to degree of glycaemia: the Whitehall study.

In the Whitehall study of 18 403 male civil servants aged 40-64 years the 10 year mortality rates from coronary heart disease and stroke showed a non-linear relation to two hour blood glucose values, with a significantly increased risk for glucose intolerant subjects with concentrations above the 95th centile point (5.4-11.0 mmol/l; 96-199 mg/100 ml) and for diabetics (blood glucose greater than or equal to 11.1 mmol/l; greater than or equal to 200 mg/100 ml). Multiple logistic analysis showed that between one half and three quarters of the relative risks for deaths from coronary heart disease and stroke were "unexplained" by between group differences in risk factors such as age, blood pressure, obesity, smoking, cholesterol concentration, and electrocardiographic abnormalities. Within the glucose intolerant and diabetic groups the risk factors most strongly related to subsequent death from coronary heart disease were age and blood pressure, with less consistent relations for smoking, cholesterol concentration, and obesity. This study confirms the importance of hypertension as a cardiovascular risk factor in groups with glucose intolerance and diabetes, and this may have important preventive implications.     

Weight and mortality in the Whitehall Study.

Ten-year mortality rates in men aged 40-64 years in the Whitehall Study were analysed in relation to weight and height at the initial examination. At ages 40-49 "all-causes" mortality increased with increasing body mass index; but this simple relation disappeared at older ages, where there was an increased mortality in the lowest quintile of body mass index. The "all-ages" relation was "J"-shaped, and this could not be explained by the confounding effects of blood pressure, cholesterol values, and cigarette smoking. Some, but not all, of the J shape was due to a high short-term mortality in thin men from cancers (presumably already present at examination). At younger ages mortality from coronary heart disease was positively related to body mass index, but this depended on its association with other risk factors. Mortality from causes other than cancers or coronary heart disease was highest in the lowest quintile of body mass index.     

Survival in treated hypertension: follow up study after two decades

Objective: To compare survival and cause specific mortality in hypertensive men with non-hypertensive men derived from the same random population, and to study mortality and morbidity from cardiovascular diseases in the hypertensive men in relation to effects on cardiovascular risk factors during 22-23 years of follow up. Design: Prospective, population based observational study. Subjects and methods: 686 hypertensive men aged 47-55 at screening compared with 6810 non-hypertensive men. The hypertensive men were having stepped care treatment with either β adrenergic blocking drugs, thiazide diuretics, or combination treatment. Mortality, morbidity, and adverse effects were registered at yearly examinations and from death certificates. Main outcome measures: All cause mortality and cause specific mortality. Results: Treated hypertensive men had significantly impaired probability of total survival as well as survival from coronary heart disease and stroke. All cause mortality as well as coronary heart disease and stroke mortality were very similar in hypertensive men and normotensive men during the first decade, but increased steadily thereafter despite continuous good blood pressure control. Smoking, signs of target organ damage, and high serum cholesterol levels, but not blood pressure at screening, were significantly related to the incidence of coronary heart disease during follow up. In time dependent Cox’s regression analysis, the incidence of coronary heart disease was significantly related only to serum cholesterol concentrations in the study. Cancer mortality was almost similar in treated hypertensive men (61/686, 8.9%) and non-hypertensive men (732/6810, 10.8%). Conclusion: Treated hypertensive men had impaired survival and increased mortality from cardiovascular disease compared with non-hypertensive men of similar age. These differences were observed during the second decade of follow up. During an observation period of 22-23 years—about 15 000 patient years—hypertensive men receiving diuretics and β blockers had no increased risk of cancer or non-cardiovascular disease.

Key messages

• Hypertension is a prevalent (10-20%) and important risk factor for cardiovascular disease.
• In controlled trials over 3-5 years drug treatment for hypertension prevents these complications, but little is known about long term prognosis
• During 20-22 years treated hypertensive men had a significantly increased mortality, especially from coronary heart disease, compared with non-hypertensive men from the same population
• The high incidence of myocardial infarction was related to organ damage, smoking, and cholesterol at the time of entry to the study, and to achieved serum cholesterol concentrations during follow up
• The poor prognosis for mortality from coronary heart disease is dependent upon strict monitoring of serum cholesterol concentrations

     

The antioxidant hypothesis of cardiovascular disease: epidemiology and mechanisms

Plasma levels of major essential antioxidants were determined in representative random samples of middle-aged men from 16 European study populations which differed up to 6-fold in age-specific mortality from ischaemic heart disease (IHD). In 12 study populations having total plasma cholesterol in the medium range (5.7-6.2 mmol/l) and usual blood pressure, both these classical risk factors lacked a significant correlation to IHD mortality, whereas the absolute level of vitamin E (alpha-tocopherol) showed a strong inverse correlation (r2 = 0.63, P = 0.002). On evaluation of all study populations, cholesterol and diastolic blood pressure had a moderate direct association with IHD, but their importance still remained inferior to that of vitamin E as an inversely associated, presumably protective factor. In stepwise regression and multiple regression analysis, the IHD mortality of the study populations was predictable to 62% by lipid-standardized vitamin E, to 79% by vitamin E and total cholesterol, to 83% after inclusion of lipid-standardized vitamin A (retinol) and to 87% by all the above parameters plus diastolic blood pressure. In conclusion, in the present study the plasma status of vitamin E is the most important factor to explain cross-cultural differences of IHD mortality. This finding is consistent with the hypothesis of the prevention of arteriosclerosis by antioxidant protection against peroxidative lipoprotein modification, but does not exclude additional effects of antioxidant vitamins, e.g. on the cellular or immunological level.     

Lipoprotein (a) and ischemic heart diseases in patients with type 2 diabetes

Lipoprotein (a) is a new independent coronary risk factor, but the role of lipoprotein (a) in type 2 diabetes remains controversial. The objective of this study was to demonstrate the relationship between the level of lipoprotein (a) and the coronary artery diseases (CAD) in type 2 diabetes. Recruitment was carried out in 3 groups of patients: Group 1: 110 control subjects, Group 2: 115 diabetics (D), Group 3: 105 diabetics with CAD (DC). The mean age was, 51 + 7; 52 + 6; 56 + 6 respectively. Total cholesterol, triglyceride, HDL-C, LDL-C, Apo A-I, Apo B and lipoprotein (a) were measured for the patients. The Lp (a) level was significantly higher in the diabetic groups as compared to the controls (p < 0.05), but this level was different between D and DC: 312 + 232 vs 347.8 + (NS). However, when the Lp (a) level is higher than 300 mg/ml, there is a significant difference between DC and D (53% vs 42% p = 0.05). There is no correlation between Lp level and total cholesterol; however, there is a significant variation of Lp (a) level with LDL-C (r = -0.14, P = 0.01). There is a negative correlation between Lp (a) and HDL-C (r = -0.13, p = 0.03), Lp (a) and ApoA-I (r = - 0.11, p = 0.05); but there is a positive correlation between Lp (a) and ApoB (r = 0.14, p = 0.02). Lp(a) level higher than 300 mg/L constitutes a coronary risk factor in type 2 diabetes. This contributes, with the other lipid disorders, to the increase of the coronary risk factors in diabetes.     

The efficacy and safety of intensive statin therapy: a meta-analysis of randomized trials

Background

Recent lipid guidelines recommend aggressive low-density lipoprotein (LDL) cholesterol lowering in patients with coronary artery disease. To clarify the evidence for this recommendation, we conducted a meta-analysis of randomized controlled trials that compared different intensities of statin therapy.

Methods

We searched electronic databases (MEDLINE, EMBASE, Cochrane Central Registery of Controlled Trials, Web of Science) for randomized controlled trials published up to July 19, 2007, that compared statin regimens of different intensities in adults with coronary artery disease and that reported cardiovascular events or mortality. Data were pooled using random-effects models to calculate odds ratios (OR).

Results

A total of 7 trials (29 395 patients) were included. Compared with less intensive statin regimens, more intensive regimens further reduced LDL levels (0.72 mmol/L reduction, 95% confidence interval [CI] 0.60–0.84 mmol/L), and reduced the risk of myocardial infarction (OR 0.83, 95% CI 0.77–0.91) and stroke (OR 0.82, 95% CI 0.71–0.95). Although there was no effect on mortality among patients with chronic coronary artery disease (OR 0.96, 95% CI 0.80–1.14), all-cause mortality was reduced among patients with acute coronary syndromes treated with more intensive statin regimens (OR 0.75, 95% CI 0.61–0.93). Compared with lower intensity regimens, more intensive regimens were associated with small absolute increases in rates of drug discontinuation (2.5%), elevated levels of aminotransferases (1%) and myopathy (0.5%), and there was no difference in noncardiovascular mortality. All 7 trials reported events by randomization arm rather than by LDL level achieved. About half of the patients treated with more intensive statin therapy did not achieve an LDL level of less than 2.0 mmol/L, and none of the trials tested combination therapies.

Interpretation

Our analysis supports the use of more intensive statin regimens in patients with established coronary artery disease. There is insufficient evidence to advocate treating to particular LDL targets, using combination lipid-lowering therapy to achieve these targets or for using more intensive regimens in patients without established coronary artery disease.Dyslipidemia is the most important modifiable risk factor for myocardial infarction worldwide,¹ and serum cholesterol levels are directly related to mortality from coronary artery disease in all populations studied.^2–4 Over the past decade, randomized controlled trials enrolling a wide variety of patients have confirmed that for every 1-mmol/L reduction in serum low-density lipoprotein (LDL) cholesterol achieved by statin therapy, the relative risks of cardiovascular events and mortality are reduced (by 21% and 12% respectively).⁵Statins exert their beneficial effects primarily by reducing the level of LDL cholesterol,⁶ and the reductions in the relative risk of cardiovascular events achieved by statin therapy appears to be similar regardless of baseline cholesterol levels.⁵ As a result, attention has increasingly focused on defining optimal target LDL levels, particularly in patients at highest risk (i.e., those with coronary artery disease). Based on the observational studies mentioned above,^2,3 the apparent lack of a lower threshold for statin benefit in the randomized controlled trials, and recent trials reporting greater benefits with more intensive statin regimens (compared with less intensive regimens), Canadian⁷ and American⁸ guidelines for secondary prevention now recommend target LDL levels below 2.0 mmol/L in patients with coronary artery disease. On the other hand, European guidelines specify a target LDL of 2.5 mmol/L in these patients.⁹ Questions have been raised about the safety and incremental benefits of more intensive statin regimens.^10–12We performed a systematic review and meta-analysis to critically examine the evidence for the safety, efficacy (LDL lowering) and clinical effectiveness from trials comparing more intensive statin therapy with less intensive statin therapy in patients with coronary artery disease.     

Non-fasting serum triglyceride concentration and mortality from coronary heart disease and any cause in middle aged Norwegian women.

OBJECTIVE--To study the association between non-fasting serum triglyceride concentrations and mortality in women from coronary and cardiovascular disease and all causes. DESIGN--Follow up by ambulatory teams of men and women who underwent cardiovascular screening for a mean of 14.6 years. SETTING--National health screening service in Norway. SUBJECTS--25,058 men and 24,535 women aged 35-49 years. MAIN OUTCOME MEASURE--Predictive value of non-fasting serum triglyceride concentrations. RESULTS--At initial screening total serum cholesterol concentration, serum triglyceride concentration, blood pressure, height, and weight were measured, and self reported information about smoking habits, physical activity, and time since last meal were recorded. During subsequent follow up 108 women died from coronary heart disease, 238 from cardiovascular diseases, and 931 from all causes. In women mortality increased steadily with increasing triglyceride concentration for all three causes of death. With the proportional hazards model and adjustment for age, systolic blood pressure, total cholesterol concentration, time since last meal, and number of cigarettes a day the relative risk between triglyceride concentration > or = 3.5 mmol/l and < 1.5 mmol/l was 4.7 (95% confidence interval 2.5 to 8.9) for deaths from coronary heart disease, 3.0 (1.9 to 4.8) for deaths from cardiovascular disease, 2.3 (1.8 to 2.9) for total deaths in all women. CONCLUSIONS--A raised non-fasting concentration of triglycerides is an independent risk factor for mortality from coronary heart disease, cardiovascular disease, and any cause mortality among middle aged Norwegian women in contrast to what is seen in men.     

Cholesterol and mortality in New Zealand Maoris.

The relation between serum cholesterol concentration and mortality was studied prospectively over 11 years in 630 New Zealand Maoris aged 25-74. Serum cholesterol concentration was measured at initial examination in 1962-3 in 94% of the subjects and whether each was dead or alive was determined in 1974. The causes of death were divided into three categories: cancer, cardiovascular disease, and "other." The Mantel-Haenszel method of analysis of survivorship data showed a significant inverse relation between serum cholesterol concentration and overall mortality in men (x 2/2 = 11.6; p = 0.003) and women (x 2/2 = 7.6; p = 0.02) with odds ratios of 2.3 and 1.9 respectively. Similar significant inverse relations were found for cancer and "other" causes of death. These relations remained significant when baseline age, systolic blood pressure, and the Quetelt index were controlled in Cox''s proportional hazards regression model. The results of this study provide evidence for a potentially deleterious effect of low serum cholesterol concentration. Hence, further research is needed before indiscriminate efforts are made to lower serum cholesterol concentrations in New Zealand Maoris.     

冠状动脉狭窄对血流量的影响

在22条开胸犬上观察了冠脉狭窄对血流量(CBF)的影响。用一可调节的微米缩窄器定量调节左旋支缩窄程度,测量了主动脉平均压(Pa)、冠脉远端小动脉平均压(Pc)和狭窄端压力降(ΔP)。冠脉狭窄程度与血流量变化曲线显示:在冠脉狭窄程度小于85％时,CBF相对稳定;随着狭窄程度的进一步增加,CBF急剧下降;而在狭窄程度大于95％后,CBF又缓慢下降。冠状动脉狭窄程度与CBF下降的曲线可用下列方程式表达: CBF=1.48×10~(10)e~(-27.6A)(A=冠脉狭窄程度) 冠脉狭窄程度大于50％时,狭窄程度与Pc呈负相关:Pc=159.1—1.36A(r=-0.73,P<0.01)。Pc与CBF呈正相关;Pc=16.9 1.3CBF(r=0.74,P<0.01)     

Evaluation of blood pressure changes and heart rate in young health men based on results of a 24-hour monitoring of pressure]

Systolic and diastolic blood pressures and heart rate were monitored in a group of 20 young healthy men for 24 hours. Period of time between 8 o'clock a.m. and 10 o'clock p.m. was treated as waking state whereas period of time from 12 p.m. to 6 a.m. as sleep phase. Mean value of systolic blood pressure for waking state was 124.6 +/- 7.6 mm Hg, and for sleep phase 110.4 +/- 11.5 mm Hg. (p < .001). Mean diastolic blood pressures were also significantly different (76.5 +/- 5.9 mm Hg and 63.8 +/- 7.7 mm Hg, respectively), the same concerns heart rate (79.6 +/- 6.4 and 63.0-7.2 min-1, respectively). In both cases p < .001. To evaluate dependence of heart rate on systolic blood pressure in waking state the following calculation was made: HR = 0.230 x systolic blood pressure +51.4 (r = 0.24; p < .001) whereas for sleep phase r did not reach a level of statistical significance (HR = 0.074 x systolic blood pressure + 53.9; r = 0.094). Single or even multiple measurements of the arterial blood pressure are not sufficient to evaluate circadian changes.     

Autoregulation of coronary vessels following the acute blood loss and its combination with preexisting immobilization stress]

A 6-hour immobilization stress and a 2-hour posthaemorrhagic hypotension caused elevation of the coronary flow, deterioration of coronary autoregulation, decreasing of the coronary dilation reserve, and diminishing of the left ventricular pressure. In the "stress + haemorrhage" group, the changes of the coronary vessels autoregulation ability were less obvious. Concentration of NO3-/NO2- in the blood serum was elevated after stress. Inhibition of the NO-synthase decreased the coronary flow. Thereupon, a pre-existing immobilization stress alters the coronary vessels tone.     

Differential effects of the changes of LDL cholesterol and systolic blood pressure on the risk of carotid artery atherosclerosis

ABSTRACT: BACKGROUND: The effects of baseline and changes in blood pressure and low density lipoprotein (LDL) cholesterol on the carotid intima media thickness (IMT) have not been well documented. METHODS: A total of 2572 adults (mean age 53.8 years, 54.6% women) in a Taiwanese community undertook three blood pressure and LDL cholesterol examinations over 6 years. Latent growth curve modeling was used to investigate the effects of baseline and change in blood pressure and LDL cholesterol on IMT. RESULTS: Greater baseline LDL and blood pressure were associated with an increase in IMT (0.005 +/- 0.002 mm per 1 mg/dL [p = 0.006] and 0.041 +/- 0.004 mm mmHg [p <0.0001], respectively. Change in blood pressure was associated with a significant increase in IMT (0.047+/-0.016, P = 0.004), whilst the association between change in LDL and change in IMT was not statistically significant (0.008+/-0.006, P = 0.20). CONCLUSIONS: Carotid IMT was associated with baseline blood pressure and LDL cholesterol, yet only changes of blood pressure, not LDL cholesterol, were related to carotid IMT during the 6- year observation.     

高血压患者血压控制水平、血脂水平及颈动脉斑块与冠脉病变的关系

目的:探讨血压控制水平、血脂水平和颈动脉斑块与高血压患者冠脉病变程度和病变支数的关系。方法:回顾性分析2014年01月至2016年05月收住于南京中医药大学附属江苏省中西医结合医院心血管科的原发性高血压患者273例,按血压控制水平分为达标组和未达标组。按颈动脉超声结果判断有无斑块,冠状动脉造影结果使用Gensini评分和病变支数表示,并检测血脂指标。结果:血压控制达标者130人(47.61%),颈动脉有斑块者193例(70.70%)。与血压控制达标患者相比,血压控制不达标者冠脉病变支数及冠脉狭窄程度得分均明显增加(P0.05)。血压不达标合并斑块患者冠脉病变支数和狭窄程度与血压达标无斑块、血压达标合并斑块及血压不达标无斑块患者相比均明显增加(P0.001)。患者HDL-C水平与冠状动脉狭窄程度呈负相关(r=-0.139,P=0.022),AI与冠状动脉狭窄程度呈正相关(r=0.136,P=0.025),LDL/HDL-C和AI与冠脉病变支数均呈正相关,分别为(r=0.128,P=0.035)和(r=0.137,P=0.023)。结论:血压控制不佳,高血脂和颈动脉斑块形成可增加高血压患者冠脉病变的严重程度。     

Impact of cardiovascular risk factors on coronary heart disease and mortality among middle aged diabetic men: a general population study.

OBJECTIVE--To investigate the effect of cardiovascular risk factors on coronary heart disease and all cause mortality in middle aged diabetic men. DESIGN--Prospective population study based on data collected from second screening (from 1974 to 1977) in the multifactor primary prevention trial and follow up until March 1983. SETTING--Gothenburg, Sweden. SUBJECTS--6897 Men aged 51 to 59, of whom 232 were self reported diabetics and 6665 were non-diabetic; none had a history of myocardial infarction. MAIN OUTCOME MEASURES--Incidences of coronary heart disease and mortality from all causes. RESULTS--Diabetic men with a serum cholesterol concentration greater than 7.3 mmol/l had a significantly higher incidence of coronary heart disease during follow up than those with a concentration less than or equal to 5.5 mmol/l (28.3% v 5.4%; p = 0.020); corresponding figures for non-diabetic men were 9.4% and 2.4% respectively. In multivariate logistic regression analyses serum cholesterol concentration and smoking habit were independent predictors of coronary heart disease (odds ratio serum cholesterol concentration 6.1 (95% confidence interval 2.1 to 17.6) current smoking 2.9 (1.1 to 7.5)) and of all cause mortality (3.2 (1.3 to 7.9), 3.0 (1.4 to 6.7) respectively) in diabetic men whereas systolic blood pressure, body mass index, family history, marital state, and alcohol abuse were not. Low occupational class was an independent predictor of mortality (2.4 (1.01 to 5.5)), but not of coronary heart disease, in diabetic men. CONCLUSIONS--Middle aged diabetic men with hypercholesterolaemia are at very high risk of developing coronary heart disease and of dying prematurely. Lowering serum cholesterol concentration in such subjects seems to be warranted.     

Plasma cholesterol,coronary heart disease,and cancer in the Renfrew and Paisley survey.

The relation between plasma cholesterol concentration and mortality from coronary heart disease, incidence of and mortality from cancer, and all cause mortality was studied in a general population aged 45-64 living in the west of Scotland. Seven thousand men (yielding 653 deaths from coronary heart disease, 630 new cases of cancer, and 463 deaths from cancer) and 8262 women (322 deaths from coronary heart disease, 554 new cases of cancer, and 395 deaths from cancer) were examined initially in 1972-6 and followed up for an average of 12 years. All cause mortality was not related to plasma cholesterol concentration. This was largely a consequence of a positive relation between cholesterol values and mortality from coronary heart disease being balanced by inverse relations between cholesterol and cancer and between cholesterol and other causes of death. These changes were highly significant for coronary heart disease and cancer in men and significant for coronary heart disease and other causes of death in women. The inverse association between cholesterol concentration and cancer in men was strongest for lung cancer, was not merely a function of the age at which a subject died, was present for the incidence of cancer as well as mortality from cancer, and persisted when new cases or deaths occurring within the first four years of follow up were excluded from the analysis.     

Coronary collaterals provide a constant scaffold effect on the left ventricle and limit ischemic left ventricular dysfunction in humans

Coronary collaterals preserve left ventricular (LV) function during coronary occlusion by reducing myocardial ischemia and may directly influence LV compliance. We aimed to re-evaluate the relationship between coronary collaterals, measured quantitatively with a pressure wire, and simultaneously recorded LV contractility from conductance catheter data during percutaneous coronary intervention (PCI) in humans. Twenty-five patients with normal LV function awaiting PCI were recruited. Pressure-derived collateral flow index (CFI(p)): CFI(p) = (P(w) - P(v))/(P(a) - P(v)) was calculated from pressure distal to coronary balloon occlusion (P(w)), central venous pressure (P(v)), and aortic pressure (P(a)). CFI(p) was compared with the changes in simultaneously recorded LV end-diastolic pressure (ΔLVEDP), end-diastolic volume, maximum rate of rise in pressure (ΔLVdP/dt(max); systolic function), and time constant of isovolumic relaxation (ΔLV τ; diastolic function), measured by a LV cavity conductance catheter. Measurements were recorded at baseline and following a 1-min coronary occlusion and were duplicated after a 30-min recovery period. There was significant LV diastolic dysfunction following coronary occlusion (ΔLVEDP: +24.5%, P < 0.0001; and ΔLV τ: +20.0%, P < 0.0001), which inversely correlated with CFI(p) (ΔLVEDP vs. CFI(p): r = -0.54, P < 0.0001; ΔLV τ vs. CFI(p): r = -0.46, P = 0.0009). Subjects with fewer collaterals had lower LVEDP at baseline (r = 0.33, P = 0.02). CFI(p) was inversely related to the coronary stenosis pressure gradient at rest (r = -0.31, P = 0.03). Collaterals exert a direct hemodynamic effect on the ventricle and attenuate ischemic LV diastolic dysfunction during coronary occlusion. Vessels with lesions of greater hemodynamic significance have better collateral supply.     

Plasma cholesterol concentration and death from coronary heart disease: 10 year results of the Whitehall study.

Ten year mortality from coronary heart disease in 17,718 middle aged men was related to their initial plasma cholesterol concentrations. The relative risk of death from coronary heart disease declined with age, but the absolute excess risk did not. The risk gradient was continuous over the whole range of cholesterol concentrations, the lowest mortality being among men with concentrations below the lowest decile. It seems that, as with blood pressure, the average cholesterol concentration in the blood pressure, the average cholesterol concentration in the population is too high: lowest concentrations are prognostically the best. A quarter of all deaths from coronary heart disease related to cholesterol occurred among men with concentrations above the top decile, but 55% occurred among men with concentrations in the middle three fifths of the distribution; this figure of 55% could be reduced only by a policy aimed at lowering concentrations in the whole population.     

Systolic and diastolic blood pressures as predictors of coronary heart disease mortality in the Whitehall study.

Systolic and diastolic blood pressures were compared as predictors of death due to coronary heart disease using data on the 10 year mortality outcome from the 18 403 male civil servants, aged 40-64, in the Whitehall study. There were 727 deaths due to coronary heart disease. At entry to the study the systolic pressure in these men was significantly higher than the diastolic pressure, and a standardised index of relative risk for death from coronary heart disease was greater for systolic blood pressure. After adjustment for age the top quintile of systolic pressure (greater than 151 mm Hg) identified 5% more men at risk of death from coronary heart disease than for the top diastolic quintile (greater than 95 mm Hg). The findings suggested that clinicians should pay more attention to systolic levels as a criterion for making diagnostic and therapeutic decisions.     

Coffee consumption and death from coronary heart disease in middle aged Norwegian men and women.

OBJECTIVE--To study the association between number of cups of coffee consumed per day and coronary death when taking other major coronary risk factors into account. DESIGN--Men and women attending screening and followed up for a mean of 6.4 years. SETTING--Cardiovascular survey performed by ambulatory teams from the National Health Screening Service in Norway. PARTICIPANTS--All middle aged people in three counties: 19,398 men and 19,166 women aged 35-54 years who reported neither cardiovascular disease or diabetes nor symptoms of angina pectoris or intermittent claudication. MAIN OUTCOME MEASURE--Predictive value of number of cups of coffee consumed per day. RESULTS--At initial screening total serum cholesterol concentration, high density lipoprotein cholesterol concentration, blood pressure, height, and weight were measured and self reported information about smoking history, physical activity, and coffee drinking habits was recorded. Altogether 168 men and 16 women died of coronary heart disease during follow up. Mean cholesterol concentrations for men and women were almost identical and increased from the lowest to highest coffee consumption group (13.1% and 10.9% respectively). With the proportional hazards model and adjustment for age, total serum and high density lipoprotein cholesterol concentrations, systolic blood pressure, and number of cigarettes per day the coefficient for coffee corresponded to a relative risk between nine or more cups of coffee and less than one cup of 2.2 (95% confidence interval 1.1 to 4.5) for men and 5.1 (0.4 to 60.3) for women. For men the relative risk varied among the three counties. CONCLUSIONS--Coffee may affect mortality from coronary heart disease over and above its effect in raising cholesterol concentrations.     

Splenic baroreceptors control splenic afferent nerve activity

Stenosis of either the portal or splenic vein increases splenic afferent nerve activity (SANA), which, through the splenorenal reflex, reduces renal blood flow. Because these maneuvers not only raise splenic venous pressure but also reduce splenic venous outflow, the question remained as to whether it is increased intrasplenic postcapillary pressure and/or reduced intrasplenic blood flow, which stimulates SANA. In anesthetized rats, we measured the changes in SANA in response to partial occlusion of either the splenic artery or vein. Splenic venous and arterial pressures and flows were simultaneously monitored. Splenic vein occlusion increased splenic venous pressure (9.5 +/- 0.5 to 22.9 +/- 0.8 mmHg, n = 6), reduced splenic arterial blood flow (1.7 +/- 0.1 to 0.9 +/- 0.1 ml/min, n = 6) and splenic venous blood flow (1.3 +/- 0.1 to 0.6 +/- 0.1 ml/min, n = 6), and increased SANA (1.7 +/- 0.4 to 2.2 +/- 0.5 spikes/s, n = 6). During splenic artery occlusion, we matched the reduction in either splenic arterial blood flow (1.7 +/- 0.1 to 0.7 +/- 0.05, n = 6) or splenic venous blood flow (1.2 +/- 0.1 to 0.5 +/- 0.04, n = 5) with that seen during splenic vein occlusion. In neither case was there any change in either splenic venous pressure (-0.4 +/- 0.9 mmHg, n = 6 and +0.1 +/- 0.3 mmHg, n = 5) or SANA (-0.11 +/- 0.15 spikes/s, n = 6 and -0.05 +/- 0.08 spikes/s, n = 5), respectively. Furthermore, there was a linear relationship between SANA and splenic venous pressure (r = 0.619, P = 0.008, n = 17). There was no such relationship with splenic venous (r = 0.371, P = 0.236, n = 12) or arterial (r = 0.275, P = 0.413, n = 11) blood flow. We conclude that it is splenic venous pressure, not flow, which stimulates splenic afferent nerve activity and activates the splenorenal reflex in portal and splenic venous hypertension.