Effects of blood pressure lowering on cardiovascular risk according to baseline body-mass index: a meta-analysis of randomised trials.

BACKGROUND: The cardiovascular benefits of blood pressure lowering in obese people compared with people of normal weight might depend on choice of drug. We compared the effects of blood pressure-lowering regimens on cardiovascular risk in groups of patients categorised by baseline body-mass index (BMI). METHODS: We used individual patient data from trials included in the Blood Pressure Lowering Treatment Trialists' Collaboration to compare the effects of different classes of blood pressure-lowering regimens for the primary outcome of total major cardiovascular events (stroke, coronary heart disease, heart failure, and cardiovascular death). We used meta-analyses and meta-regressions to assess interactions between treatment and BMI when fitted as either a categorical variable (<25 kg/m(2), 25 to <30 kg/m(2), and ≥30 kg/m(2)) or a continuous variable. FINDINGS: Analyses were based on 135,715 individuals from 22 trials who had 14,353 major cardiovascular events. None of the six primary comparisons showed evidence that protection varied by drug class across the three BMI groups (all p for trend >0·20). When analysed as a continuous variable, angiotensin-converting-enzyme inhibitors gave slightly greater protection for each 5 kg/m(2) higher BMI than did calcium antagonists (hazard ratio 0·93, 95% CI 0·89-0·98; p=0·004) or diuretics (0·93, 0·89-0·98; p=0·002). The meta-regressions showed no relation between BMI category and the risk reduction for a given fall in systolic blood pressure. By contrast with a previous report, we noted no relation between BMI and the efficacy of calcium antagonists compared with diuretics. INTERPRETATION: We found little evidence that selection of a particular class of blood pressure-lowering drug will lead to substantially different outcomes for individuals who are obese compared with those who are lean. FUNDING: None.

Women's reproductive health factors and body adiposity: findings from the UK Biobank.

OBJECTIVE: To conduct a comprehensive examination of the association between women's reproductive health factors and measures of body adiposity in a contemporary Western population. METHODS: A cross-sectional analysis of 502 664 individuals from the UK Biobank was conducted. Multivariable linear regression models were used to examine the association of age at menarche, age at first birth, parity and age at menopause with measures of general and central body adiposity, adjusted for age, smoking and socioeconomic status. The association between number of children and body adiposity in men was also assessed. RESULTS: Age at menarche was inversely associated with body mass index (BMI); adjusted mean BMI was 29.0 kg m(-2) in women with menarche before the age of 12 years, compared with 26.5 kg m(-2) in those who had menarche after 14 years of age. Age at first birth was linearly and inversely associated with BMI: 0.16 kg m(-2) lower BMI per year increase in age of first birth. Each additional live birth or child fathered was associated with a 0.22 kg m(-2) higher BMI in women and a 0.14 kg m(-2) higher BMI in men. There was no evidence for an association between age at menopause and BMI. Corresponding associations for other markers of general or abdominal adiposity were similar to those for BMI. Findings were broadly similar in analyses stratified by age, smoking status, socioeconomic status, ethnic background, and history of diabetes or cardiovascular disease. CONCLUSIONS: In women from a contemporary Western population, earlier age at menarche and age at first birth, and higher number of total live births were associated with higher levels of body adiposity. Prospective evaluations of the association between reproductive health factors, adiposity and the onset of cardiometabolic diseases are needed to assess causality, and to explore the mechanisms involved.

Age at menarche and risk of type 2 diabetes among African-American and white women in the Atherosclerosis Risk in Communities (ARIC) study.

AIMS/HYPOTHESIS: We examined race differences in the association between age at menarche and type 2 diabetes before and after adjustment for adiposity. METHODS: We analysed baseline and 9-year follow-up data from 8,491 women (n = 2,505 African-American, mean age 53.3 years; n = 5,986 white, mean age 54.0 years) in the Atherosclerosis Risk in Communities (ARIC) study. Stratifying by race, we used logistic regression to estimate the OR for prevalent diabetes at baseline, and Cox proportional hazard models to estimate the HR for incident diabetes over follow-up according to age at menarche category (8-11, 12, 13, 14 and 15-18 years). RESULTS: Adjusting for age and centre, we found that early age at menarche (8-11 vs 13 years) was associated with diabetes for white, but not African-American women in both the prevalent (white OR 1.72, 95% CI 1.32, 2.25; African-American OR 1.13, 95% CI 0.84, 1.51; interaction p = 0.043) and incident models (white HR 1.43, 95% CI 1.08, 1.89; African-American HR 1.20, 95% CI 0.87, 1.67; interaction p = 0.527). Adjustment for adiposity and lifestyle confounders attenuated associations for prevalent (white OR 1.41, 95% CI 1.05, 1.89; African-American OR 0.94, 95% CI 0.68, 1.30; interaction p = 0.093) and incident diabetes (white HR 1.22, 95% CI 0.92, 1.63; African-American HR 1.11, 95% CI 0.80, 1.56; interaction p = 0.554). CONCLUSIONS/INTERPRETATION: Early menarche was associated with type 2 diabetes in white women, and adulthood adiposity attenuated the relationship. We did not find a similar association in African-American women. Our findings suggest that there may be race/ethnic differences in the influence of developmental factors in the aetiology of type 2 diabetes, which merit further investigation.

Associations of diabetes mellitus with site-specific cancer mortality in the Asia-Pacific region.

BACKGROUND: Owing to the increasing prevalence of obesity and diabetes in Asia, and the paucity of studies, we examined the influence of raised blood glucose and diabetes on cancer mortality risk. MATERIALS AND METHODS: Thirty-six cohort Asian and Australasian studies provided 367, 361 participants (74% from Asia); 6% had diabetes at baseline. Associations between diabetes and site-specific cancer mortality were estimated using time-dependent Cox models, stratified by study and sex, and adjusted for age. RESULTS: During a median follow-up of 4.0 years, there were 5992 deaths due to cancer (74% Asian; 41% female). Participants with diabetes had 23% greater risk of mortality from all-cause cancer compared with those without: hazard ratio (HR) 1.23 [95% confidence interval (CI) 1.12, 1.35]. Diabetes was associated with mortality due to cancer of the liver (HR 1.51; 95% CI 1.19, 1.91), pancreas (HR 1.78; 95% CI 1.20, 2.65), and, less strongly, colorectum (HR 1.32; 95% CI 0.98, 1.78). There was no evidence of sex- or region-specific differences in these associations. The population attributable fractions for cancer mortality due to diabetes were generally higher for Asia compared with non-Asian populations. CONCLUSION: Diabetes is associated with increased mortality from selected cancers in Asian and non-Asian populations.

Adult height and cancer mortality in Asia: the Asia Pacific Cohort Studies Collaboration.

BACKGROUND: The observation that taller people experience an increased risk of selected cancers is largely restricted to Caucasian cohorts. These associations may plausibly differ in Asian populations. For the first time, we make direct comparison in the same analyses of the associations between height and a series of malignancies in Australasian (Caucasian) and Asian populations. METHODS: Analyses were based on the Asia Pacific Cohort Studies Collaboration of 506 648 study participants (408 381 Asia, 98 267 Australasia) drawn from 38 population-based cohort studies. Cox proportional hazards regression was used to estimate the relationship between height and cancer rates. RESULTS: A total of 3 272 600 person-years of follow-up gave rise to 7497 cancer deaths (4415 in Asia; 3082 in Australasia). After multiple adjustments and left censoring, taller individuals experienced increased rates of carcinoma of the intestine (men and women); all cancers, liver, lung, breast, 'other' malignancies (all women); and cancers of the prostate and bladder (men). No consistent regional (Asia versus Australasia) or sex differences were observed. CONCLUSIONS: In the present study, taller men and women had an elevated risk of selected malignancies. These associations did not differ appreciably between Asian and Caucasian populations.

The hazards and benefits associated with smoking and smoking cessation in Asia: a meta-analysis of prospective studies.

OBJECTIVE: To provide the most reliable evidence as to the nature of the associations between smoking and cause-specific illness, as well as the expected benefits from quitting smoking, in studies conducted in Asia, where smoking remains popular among men. DATA SOURCES: Studies published between January 1966 and October 2008, identified in the Medline search strategy with medical subject headings, in addition to studies from the Asia Pacific Cohort Studies Collaboration. STUDY SELECTION: Studies were considered to be relevant if they were prospective studies, in an Asian setting that reported on the association between smoking, quitting and cause-specific illness. DATA EXTRACTION: Two reviewers independently screened all identified articles for possible inclusion and extracted data. DATA SYNTHESIS: The pooled relative risks (RRs) for incidence or mortality, comparing current to never smokers were always significantly higher than unity; the highest was for lung cancer: 3.54 (95% confidence interval 3.00 to 4.17). The pooled RRs for former smokers (compared to never smokers) were also always significantly higher than unity, and were lower than in current smokers, for coronary heart disease, stroke, lung and upper aero-digestive tract cancer. Only for respiratory disease was the RR for former smokers higher than that for current smokers. CONCLUSIONS: This meta-analysis has shown that, despite the relative immaturity of the smoking epidemic in Asia, smoking is unquestionably a major contributor to ill health and death. However, the beneficial effects of quitting are not yet always apparent, most probably because quitting is a consequence of ill health and the relative unpopularity of smoking cessation in many Asian populations.

Obesity and overweight in relation to liver disease mortality in men: 38 year follow-up of the original Whitehall study.

Obesity has been implicated in the aetiology of liver disease. However, to date, evidence is largely drawn from cross-sectional studies, where interpretation is hampered by reverse causality, and from studies on clinical populations that have limited generalisability. In this prospective cohort study, data on body mass index (BMI) and covariates were collected at baseline on 18 863 male government employees (aged 40-69 years). Respondents were then followed up for a maximum of 38 years of age. Mortality surveillance gave rise to 13 129 deaths, 122 of which were due to liver disease (57 cancers; 65 non-cancers). In age-adjusted analyses, BMI was positively related to total liver disease mortality (hazards ratio per 1 s.d. increase in BMI; 95% confidence interval (CI): 1.36; 1.14, 1.62) in a graded fashion across the weight categories (P-value for trend: 0.01). The magnitude of this association was somewhat stronger for non-cancer liver disease deaths (1.47; 1.16, 1.86) than for cancer liver disease deaths (1.25; 0.96, 1.62). Excluding deaths in the first 10 years of follow-up somewhat strengthened the BMI-non-cancer liver disease association. Adjustment for socioeconomic position, other candidate confounders and mediating factors led to the modest attenuation of these associations. Further investigation in prospective cohort studies with more detailed data on liver disease, for instance using biochemical tests of liver function or hepatic ultrasonography, is warranted.

Association of smoking and smoking cessation with major causes of mortality in the Asia Pacific Region: the Asia Pacific Cohort Studies Collaboration.

BACKGROUND: Although the dangers of smoking, and the benefits of quitting, are well established and understood in the West, smoking remains popular among Asian men. We investigated the associations between smoking (including ex-smoking) and major causes of mortality in Asian men and women, and compared with Australians and New Zealanders (ANZ). METHODS: An overview of 34 cohort studies in the Asia Pacific region involving 512 676 individuals (81% from Asia), followed up for a median of 6.7 years (20 804 deaths). RESULTS: Mortality rates for cause-specific and all causes of mortality were systematically higher for current compared with never smokers. Hazard ratios (HR) for overall and cause-specific mortality comparing current-smokers with never smokers, ex- smokers with current-smokers and comparing numbers of cigarettes smoked per day, were higher for ANZ than Asia (p<0.001). For overall mortality, the HR (95% CI) comparing current-smoking with not was 1.37 (1.23 to 1.53) and 1.33 (1.26 to 1.40) in Asian men and women respectively. The corresponding figures in ANZ were 1.95 (1.81 to 2.09) and 1.85 (1.69 to 2.02). The HR for quitting in ANZ was 0.67 (0.63 to 0.71) and 0.66 (0.58 to 0.74) in men and women respectively. Quitting smoking had a significant benefit among Asian men, the HR was 0.88 (0.81 to 0.97) after ignoring the first 3 years of follow-up. There was no evidence of benefit for Asian women, for whom ex-smoking is rare. CONCLUSIONS: Allowing for the recent uptake of smoking in Asia, its effects are comparable to those observed in ANZ. Stringent tobacco control measures and smoking cessation strategies are urgently required in Asia.

The role of lifestyle risk factors on mortality from colorectal cancer in populations of the Asia-Pacific region.

Although colorectal cancer is one of the leading malignancies worldwide, there are few data on aetiological relationships from the Asia-Pacific region. Therefore, a collaborative study was conducted involving over half a million subjects from 33 cohort studies in the region. Age-adjusted death rates from colorectal cancer, over an average of 6.8 years follow-up, were 12 and 14 per 100,000 person-years among Asian women and men, respectively; corresponding values in Australasia were 31 and 41. Height was strongly associated with death from colorectal cancer: an extra 5 cm of height was associated with 10% (95%confidence interval, 3% - 18% additional risk, after adjustment for other factors. Smoking increased risk by 43% (9% - 88%), although no significant dose-response relationship was discerned (p>0.05). Other significant (p <0.05) risk factors were body mass index and lack of physical activity. There was no significant effect on colorectal cancer mortality for alcohol consumption, waist circumference, fasting blood glucose or diabetes, although the latter conferred a notable 26% additional risk. Height may be a biomarker for some currently unknown genetic, or environmental, risk factors that are related both to skeletal growth and mutanogenesis. Understanding such mechanisms could provide opportunities for novel preventive and therapeutic intervention.

The impact of modifiable risk factors on mortality from prostate cancer in populations of the Asia-Pacific region.

Mortality from cancer of the prostate is increasing in the Asia-Pacific, when much of this region is undergoing a transition to a Western lifestyle. The role that lifestyle factors play in prostate cancer appears limited, but existing data mainly are from the West. We conducted an individual participant data analysis of 24 cohort studies involving 320,852 men (83% in Asia). Cox proportional hazard models were used to quantify associations between risk factors and mortality from prostate cancer. There were 308 deaths from prostate cancer (14% in Asia) during 2.1 million person-years of follow-up. The age-adjusted hazard ratio (95% confidence interval; CI) for men with body mass index (BMI) 28 kg/m2 or more, compared with below 25, was 1.55 (1.12 - 2.16); no such significant relationship was found for height or waist circumference. The BMI result was unchanged after adjustment for other variables, was consistent between Asia and Australia/New Zealand (ANZ) and did not differ with age. There was no significant relationship with diabetes, glucose or total cholesterol (p > or = 0.18). Smoking, alone, showed different effects in the two regions, possibly due to the relative immaturity of the smoking epidemic in Asia. In ANZ, the multiple-adjusted hazard ratio for an extra 5 cigarettes per day was 1.12 (95%CI: 1.03 - 1.22), whereas in Asia it was 0.77 (0.56 - 1.05). Body size is an apparently important determinant of prostate cancer in the Asia-Pacific. Evidence of an adverse effect of smoking is conclusive only in the predominantly Caucasian parts of the region.

The fraction of ischaemic heart disease and stroke attributable to smoking in the WHO Western Pacific and South-East Asian regions.

BACKGROUND: Tobacco will soon be the biggest cause of death worldwide, with the greatest burden being borne by low and middle-income countries where 8/10 smokers now live. OBJECTIVE: This study aimed to quantify the direct burden of smoking for cardiovascular diseases (CVD) by calculating the population attributable fractions (PAF) for fatal ischaemic heart disease (IHD) and stroke (haemorrhagic and ischaemic) for all 38 countries in the World Health Organization Western Pacific and South East Asian regions. DESIGN AND SUBJECTS: Sex-specific prevalence of smoking was obtained from existing data. Estimates of the hazard ratio (HR) for IHD and stroke with smoking as an independent risk factor were obtained from the approximately 600,000 adult subjects in the Asia Pacific Cohort Studies Collaboration (APCSC). HR estimates and prevalence were then used to calculate sex-specific PAF for IHD and stroke by country. RESULTS: The prevalence of smoking in the 33 countries, for which relevant data could be obtained, ranged from 28-82% in males and from 1-65% in females. The fraction of IHD attributable to smoking ranged from 13-33% in males and from <1-28% in females. The percentage of haemorrhagic stroke attributable to smoking ranged from 4-12% in males and from <1-9% in females. Corresponding figures for ischaemic stroke were 11-27% in males and <1-22% in females. CONCLUSIONS: Up to 30% of some cardiovascular fatalities can be attributed to smoking. This is likely an underestimate of the current burden of smoking on CVD, given that the smoking epidemic has developed further since many of the studies were conducted.

Risk of fatal stroke in patients with treated familial hypercholesterolemia: a prospective registry study.

BACKGROUND AND PURPOSE: Although it is recognized that in heterozygous familial hypercholesterolemia, large extracranial carotid vessels are affected by atherosclerosis, the risk of fatal stroke after treatment with cholesterol-lowering therapy remains uncertain. The goal of this study was to determine the risk of fatal stroke in patients with treated familial hypercholesterolemia. METHODS: A cohort of 1405 men and 1466 women with definite or possible heterozygous familial hypercholesterolemia was recruited from 21 outpatient lipid clinics in the United Kingdom. Patients were followed up prospectively from 1980 to 1998 for 22 992 person-years for a median duration of 7.9 years (interquartile range, 4.9 to 12.0 years). The mortality rate was calculated, and the standardized mortality ratio for men and women 20 to 79 years of age was derived from the ratio of the observed deaths to the number expected in the general population of England and Wales (standardized mortality ratio=100 for the standard population). RESULTS: A total of 169 deaths occurred; 9 (5.3%) were a result of stroke. The mortality rate from stroke was 0.39 per 1000 person-years (95% confidence interval, 0.18 to 0.74), and the standardized mortality ratio for fatal stroke was nonsignificantly lower than in the general population (79; 95% CI, 36 to 150). CONCLUSIONS: The results suggest that patients with treated familial hypercholesterolemia are not at increased risk of fatal stroke. However, the possibility cannot be excluded that untreated individuals are at increased risk, which would be consistent with the evidence that familial hypercholesterolemia is a panvascular disease.

Effects of a perindopril-based blood pressure-lowering regimen on the risk of recurrent stroke according to stroke subtype and medical history: the PROGRESS Trial.

BACKGROUND AND PURPOSE: The Perindopril Protection Against Recurrent Stroke Study (PROGRESS) showed that blood pressure lowering reduced stroke risk in patients with a history of cerebrovascular events. Here, we report the consistency of treatment effects across different stroke subtypes and among major clinical subgroups. METHODS: PROGRESS was a randomized, double-blind trial among 6105 people with a prior history of cerebrovascular events. Participants were assigned to active treatment (perindopril for all participants and indapamide for those with neither an indication for nor a contraindication to a diuretic) or matching placebo(s). RESULTS: During a mean of 3.9 years of follow-up, active treatment reduced the absolute rates of ischemic stroke from 10% to 8% (relative risk reduction [RRR], 24%; 95% confidence interval [CI], 10 to 35) and the absolute rates of intracerebral hemorrhage from 2% to 1% (RRR, 50%; 95% CI, 26 to 67). The relative risk of any stroke during follow-up was reduced by 26% (95% CI, 12 to 38) among patients whose baseline cerebrovascular event was an ischemic stroke and by 49% (95% CI, 18 to 68) among those whose baseline event was an intracerebral hemorrhage. There was no evidence that treatment effects were modified by other drug therapies (antiplatelet or other antihypertensive agents), residual neurological signs, atrial fibrillation, or the time since the last cerebrovascular event. CONCLUSIONS: Beneficial effects of a perindopril-based treatment regimen were observed for all stroke types and all major clinical subgroups studied. These data suggest that effective blood pressure-lowering therapy should be routinely considered for all patients with a history of cerebrovascular events.

Comparison of the risk of fatal coronary heart disease in treated xanthomatous and non-xanthomatous heterozygous familial hypercholesterolaemia: a prospective registry study.

BACKGROUND: A clinical diagnosis of familial hypercholesterolaemia (FH) is often made in the absence of tendon xanthomata (TX), which are not usually present before the fourth decade of life. The prognosis of treated non-xanthomatous (TX-) FH is uncertain and the objective of this study was to compare mortality from coronary heart disease (CHD) in patients with treated TX+ (definite) and TX- (possible) heterozygous FH. METHODS: A diagnosis of definite or possible FH was based on raised cholesterol levels (>7.5 mmol/l) and a family history of premature CHD or hypercholesterolaemia. Patients were recruited from 21 outpatient lipid clinics in the UK from 1980 to 1998. The cohort of 1569 patients with TX+ FH were followed for 12754 person years and the cohort of 1302 patients with TX- FH for 10238 person years. The standardised mortality ratio (SMR) was calculated from the ratio of the number of deaths observed to the number expected in the general population of England and Wales (SMR=100 for reference population). FINDINGS AND DISCUSSION: CHD accounted for 64 (63%) of the 102 deaths in the TX+ cohort and 38 (57%) of the 67 deaths in the TX- cohort with the SMR for a fatal coronary event being, respectively, 294 (95% confidence interval 228, 380, P<0.00001) and 205 (95% CI 145, 282, P=0.0001). The similarly elevated CHD mortality risk suggests that, in adulthood, both groups of patients should be treated equally aggressively with HMG Co A reductase inhibitors (statins).

Left ventricular functional alterations at rest and during submaximal exercise in patients with recent myocardial infarction.

Submaximal exercise testing with radionuclide ventriculography was performed in 117 patients prior to hospital discharge 16.7 +/- 6.7 days (SD) following acute myocardial infarction. The hypothesis tested in this study was that patients with different locations and types of infarction have different functional responses to submaximal exercise prior to discharge. The distribution of the myocardial infarctions were anterior transmural in 33, inferior transmural in 39, anterior nontransmural in 23, inferior nontransmural in 19, and indeterminant in three. Patients with transmural infarction generally had significantly larger resting left ventricular volumes at end-diastole and end-systole and lower ejection fractions and systolic blood pressure/end-systolic volume indexes than patients with nontransmural infarctions (p less than 0.05). During submaximal exercise, the change in end-systolic volume was significantly different in these two groups. When patients were separated further into anterior and inferior transmural subgroups, the patients with anterior transmural infarction had significantly lower left ventricular ejection fractions and higher right ventricular ejection fractions than the group with inferior transmural infarction (p less than 0.05). In response to exercise, the group with anterior transmural infarction had a significant decrease in left ventricular ejection fraction and a blunted systolic blood pressure/left ventricular end-systolic volume index, in comparison to patients with inferior myocardial infarction (p less than 0.05); this was the only group to have a significant increase in end-systolic volume. The group variance for the parameters studied was large, particularly during exercise when the individual responses were frequently directionally opposite from the group means. The group with anterior transmural infarction was the most homogeneous, with 26 of 33 having a directionally abnormal response to submaximal exercise. It was concluded that the group with anterior transmural infarction generally displayed the most abnormal left ventricular function. However, despite significant group differences in resting ventricular function with different infarcts, the intragroup variability at rest and in response to exercise was too great to permit an accurate prediction of the subject's resting ventricular performance or to permit a prediction of exercise response based solely on location of the infarct.

The role of size at birth and postnatal catch-up growth in determining systolic blood pressure: a systematic review of the literature.

OBJECTIVE: To conduct a systematic review in order to (i) summarize the relationship between birthweight and blood pressure, following numerous publications in the last 3 years, (ii) assess whether other measures of size at birth are related to blood pressure, and (iii) study the role of postnatal catch-up growth in predicting blood pressure. DATA IDENTIFICATION: All papers published between March 1996 and March 2000 that examined the relationship between birth weight and systolic blood pressure were identified and combined with the papers examined in a previous review. SUBJECTS: More than 444,000 male and female subjects aged 0-84 years of all ages and races. RESULTS: Eighty studies described the relationship of blood pressure with birth weight The majority of the studies in children, adolescents and adults reported that blood pressure fell with increasing birth weight, the size of the effect being approximately 2 mmHg/kg. Head circumference was the only other birth measurement to be most consistently associated with blood pressure, the magnitude of the association being a decrease in blood pressure by approximately 0.5 mmHg/cm. Skeletal and non-skeletal postnatal catch-up growth were positively associated with blood pressure, with the highest blood pressures occurring in individuals of low birth weight but high rates of growth subsequently. CONCLUSIONS: Both birth weight and head circumference at birth are inversely related to systolic blood pressure. The relationship is present in adolescence but attenuated compared to both the pre- and post-adolescence periods. Accelerated postnatal growth is also associated with raised blood pressure.

Prognostic value of resting and submaximal exercise radionuclide ventriculography after acute myocardial infarction in high-risk patients with single and multivessel disease.

In patients who survive the acute phase of myocardial infarction, those with multivessel coronary artery disease generally have a worse prognosis than those with single-vessel disease. However, some patients with significant multivessel stenoses have a good prognosis, whereas some with a significant single-vessel stenosis have a poor prognosis. Thus, although definition of coronary anatomy may be helpful, it is a not a fail-safe prognosticator. In this retrospective analysis, the association of abnormalities at rest and during submaximal exercise testing with radionuclide ventriculography after acute myocardial infarction with major cardiac complications (death, recurrent infarction, severe angina or congestive heart failure) in the ensuing 6 months was assessed in patients with single and multivessel disease. Coronary angiography and submaximal exercise testing with radionuclide ventriculography were performed within 3 months of each other in 42 patients. Eleven of the 16 patients with single-vessel coronary stenosis had major cardiac complications. The subsequent course of these 16 patients was correctly predicted by left ventricular ejection fraction (LVEF) less than or equal to 0.40 in 8 patients, by LVEF less than 0.55 in 7 patients, by failure of LVEF to increase by 0.05 units in 13 patients, and by an increase in left ventricular end-systolic volume index (LVESVI) during exercise greater than 5% above baseline in 11 patients. Of the 26 patients with multivessel coronary artery disease, 24 had major cardiac complications. The subsequent course of these 26 patients was correctly predicted in 13 by LVEF less than or equal to 0.40, in 20 by LVEF less than 0.55, in 25 by a failure of LVEF to increase by 0.05 units during exercise, and in 20 by an increase in LVESVI by greater than 5% during exercise. Thus, submaximal exercise testing with radionuclide ventriculography may provide valuable prognostic information concerning the occurrence of major cardiac events after myocardial infarction not only in patients with multivessel disease, but also in those with single-vessel disease. Exercise-induced abnormalities of left ventricular function may have greater prognostic importance than the delineation of coronary arterial anatomy or the assessment of residual left ventricular function at rest.

Detection of acute right ventricular infarction by right precordial electrocardiography.

The value of 0.1 mV or greater of S-T segment elevation in at least one right precordial lead (V4R to V6R) in defining right ventricular myocardial infarction was assessed prospectively in 43 subjects (33 consecutive patients with enzymatically confirmed infarction of varying type and location, 4 patients with unstable angina and 6 healthy volunteers). Patients with acute myocardial infarction were studied with radionuclide ventriculography and technetium-99m stannous pyrophosphate myocardial scintigraphy 18.2 +/- 14.3 (mean +/- standard deviation) and 85.1 +/- 18.0 hours after the onset of symptoms, respectively. Eleven patients (Group A: 9 patients with transmural inferior infarction, 1 with transmural inferolateral infarction and 1 with transmural anteroseptal infarction) demonstrated right precordial S-T segment elevation and 22 patients (Group B: 6 patients with transmural inferior infarction, 2 with transmural posterior infarction, 3 with transmural inferolateral infarction, 3 with transmural anteroseptal infarction, 3 with transmural extensive anterior infarction, 4 with subendocardial anterior infarction and 1 with unclassified infarction) did not. Right ventricular ejection fraction was significantly lower in Group A (0.47 +/- 0.11) than in Group B (0.60 +/- 0.12) (p less than 0.01). Right ventricular total wall motion score was 63.8 +/- 15.6 percent of normal in Group A versus 94.3 +/- 8.5 percent in Group B (p less than 0.001). Technetium-99m pyrophosphate uptake (2+ or greater) over the right ventricle occurred in nine patients (81.8 percent) in Group A and in one patient (4.5 percent) in Group B (p less than 0.001). No patient with unstable angina and no healthy volunteer had S-T segment elevation in a right precordial lead. S-T segment elevation of 0.1 mV or greater in one or more of leads V4R to V6R is both highly sensitive (90 percent) and specific (91 percent) in identifying acute right ventricular infarction.

Nausea and vomiting in early pregnancy: its role in placental development.

Nausea and emesis in early pregnancy is a common phenomenon affecting between 50% and 70% of pregnant women, but little is known about the etiology and possible function of this common and often incapacitating condition. Morning sickness has been reported to have a positive effect on pregnancy outcome and is associated with a decreased risk of miscarriage, preterm birth, low birth weight (LBW), and perinatal death. Both human and animal studies have shown that reduced energy intakes in early pregnancy are associated with increased placental weight. Based on evidence from the literature, a hypothesis is proposed that suggests a functional role for the nausea and emesis of pregnancy in stimulating early placental growth. It is suggested that morning sickness, resulting from secretion of hCG and thyroxine, reduces maternal energy intake. As a result, maternal levels of the anabolic hormones, insulin, and insulin growth factor-1 (IGF-1) are lowered. By suppressing maternal tissue synthesis in early pregnancy, we propose that nausea and vomiting in pregnancy helps ensure that nutrient partitioning favors the developing placenta. Evidence is also presented that suggests there may be a positive relationship between morning sickness and preconceptional body mass index (BMI), such that women who are underweight will experience less severe symptoms of morning sickness compared with women with normal preconceptional BMIs.

The relation between dietary flavonol intake and coronary heart disease mortality: a meta-analysis of prospective cohort studies.

OBJECTIVE: To assess the association of dietary flavonol intake with the subsequent risk of coronary heart disease (CHD) mortality. DESIGN: Meta-analysis of prospective cohort studies published before September 2001. Studies were identified by MEDLINE and EMBASE searches and by scanning relevant reference lists. The following information was extracted from published reports: size of cohort, mean age, mean duration of follow-up, number of fatal CHD events, mean flavonol intake, main sources of flavonol intake, degree of adjustment for potential confounders, and the relation of CHD mortality to dietary flavonol intake measured at baseline. RESULTS: Seven prospective cohorts of men and women were identified including a total of 2087 fatal CHD events. Comparison of individuals in the top third with those in the bottom third of dietary flavonol intake yielded a combined risk ratio of 0.80 (95% CI 0.69-0.93) after adjustment for known CHD risk factors and other dietary components. CONCLUSION: This overview of prospective cohort studies indicates that high dietary intake of flavonols from a small number of fruits and vegetables, tea and red wine may be associated with a reduced risk from CHD mortality in free-living populations.