Federica Barzi

Excess risk of fatal coronary heart disease associated with diabetes in men and women: meta-analysis of 37 prospective cohort studies

Abstract Objective To estimate the relative risk for fatal coronary heart disease associated with diabetes in men and women. Design Meta-analysis of prospective cohort studies. Data sources Studies published between 1966 and March 2005, identified through Embase and Medline, using a combined text word and MESH heading search strategy, in addition to studies from the Asia Pacific Cohort Studies Collaboration. Review methods Studies were eligible if they had reported estimates of the relative risk for fatal coronary heart disease comparing men and women with and without diabetes. Studies were excluded if the estimates were not adjusted at least for age. Results 37 studies of type 2 diabetes and fatal coronary heart disease among a total of 447 064 patients were identified. The rate of fatal coronary heart disease was higher in patients with diabetes than in those without (5.4 v 1.6%). The overall summary relative risk for fatal coronary heart disease in patients with diabetes compared with no diabetes was significantly greater among women than it was among men: 3.50, 95% confidence interval 2.70 to 4.53 v 2.06, 1.81 to 2.34. After exclusion of the eight studies that had adjusted only for age, the difference in risk between the sexes was substantially reduced but still highly significant. The pooled ratio of the relative risks (women: men) from the 29 studies with multiple adjusted estimates was 1.46 (1.14 to 1.88). Conclusions The relative risk for fatal coronary heart disease associated with diabetes is 50% higher in women than it is in men. This greater excess coronary risk may be explained by more adverse cardiovascular risk profiles among women with diabetes, combined with possible disparities in treatment that favour men.

Early Protection Against Sudden Death by n-3 Polyunsaturated Fatty Acids After Myocardial Infarction

Background— Our purpose was to assess the time course of the benefit of n-3 polyunsaturated fatty acids (PUFAs) on mortality documented by the GISSI-Prevenzione trial in patients surviving a recent (<3 months) myocardial infarction. Methods and Results— In this study, 11 323 patients were randomly assigned to supplements of n-3 PUFAs, vitamin E (300 mg/d), both, or no treatment (control) on top of optimal pharmacological treatment and lifestyle advice. Intention-to-treat analysis adjusted for interaction between treatments was carried out. Early efficacy of n-3 PUFA treatment for total, cardiovascular, cardiac, coronary, and sudden death; nonfatal myocardial infarction; total coronary heart disease; and cerebrovascular events was assessed by right-censoring follow-up data 12 times from the first month after randomization up to 12 months. Survival curves for n-3 PUFA treatment diverged early after randomization, and total mortality was significantly lowered after 3 months of treatment (relative risk [RR] 0...

Type-II diabetes and pancreatic cancer: a meta-analysis of 36 studies

Pancreatic cancer is the eighth major form of cancer-related death worldwide, causing 227 000 deaths annually. Type-II diabetes is widely considered to be associated with pancreatic cancer, but whether this represents a causal or consequential association is unclear. We conducted a meta-analysis to examine this association. A computer-based literature search from 1966 to 2005 yielded 17 case–control and 19 cohort or nested case–control studies with information on 9220 individuals with pancreatic cancer. The age and sex-adjusted odds ratio (OR) for pancreatic cancer associated with type-II diabetes was obtained from each study. The combined summary odds ratio was 1.82 (95% confidence interval (95% CI) 1.66–1.89), with evidence of heterogeneity across the studies (P=0.002 for case–control and P=0.05 for cohort studies) that was explained, in part, by higher risks being reported by smaller studies and studies that reported before 2000. Individuals in whom diabetes had only recently been diagnosed (<4 years) had a 50% greater risk of the malignancy compared with individuals who had diabetes for ⩾5 years (OR 2.1 vs 1.5; P=0.005). These results support a modest causal association between type-II diabetes and pancreatic cancer.

Effects of different regimens to lower blood pressure on major cardiovascular events in older and younger adults: meta-analysis of randomised trials.

Objective To quantify the relative risk reductions achieved with different regimens to lower blood pressure in younger and older adults. Design Meta-analyses and meta-regression analyses used to compare the effects on the primary outcome between two age groups (<65 v ≥65 years). Evidence for an interaction between age and the effects of treatment sought by fitting age as a continuous variable and estimating overall effects across trials. Main outcome measures Primary outcome: total major cardiovascular events. Results 31 trials, with 190 606 participants, were included. The meta-analyses showed no clear difference between age groups in the effects of lowering blood pressure or any difference between the effects of the drug classes on major cardiovascular events (all P≥0.24). Neither was there any significant interaction between age and treatment when age was fitted as a continuous variable (all P>0.09). The meta-regressions also showed no difference in effects between the two age groups for the outcome of major cardiovascular events (<65 v ≥65; P=0.38). Conclusions Reduction of blood pressure produces benefits in younger (<65 years) and older (≥65 years) adults, with no strong evidence that protection against major vascular events afforded by different drug classes varies substantially with age.

Coffee, decaffeinated coffee, and tea consumption in relation to incident type 2 diabetes mellitus: a systematic review with meta-analysis.

BACKGROUND Coffee consumption has been reported to be inversely associated with risk of type 2 diabetes mellitus. Similar associations have also been reported for decaffeinated coffee and tea. We report herein the findings of meta-analyses for the association between coffee, decaffeinated coffee, and tea consumption with risk of diabetes. METHODS Relevant studies were identified through search engines using a combined text word and MeSH (Medical Subject Headings) search strategy. Prospective studies that reported an estimate of the association between coffee, decaffeinated coffee, or tea with incident diabetes between 1966 and July 2009. RESULTS Data from 18 studies with information on 457 922 participants reported on the association between coffee consumption and diabetes. Six (N = 225 516) and 7 studies (N = 286 701) also reported estimates of the association between decaffeinated coffee and tea with diabetes, respectively. We found an inverse log-linear relationship between coffee consumption and subsequent risk of diabetes such that every additional cup of coffee consumed in a day was associated with a 7% reduction in the excess risk of diabetes relative risk, 0.93 [95% confidence interval, 0.91-0.95]) after adjustment for potential confounders. CONCLUSIONS Owing to the presence of small-study bias, our results may represent an overestimate of the true magnitude of the association. Similar significant and inverse associations were observed with decaffeinated coffee and tea and risk of incident diabetes. High intakes of coffee, decaffeinated coffee, and tea are associated with reduced risk of diabetes. The putative protective effects of these beverages warrant further investigation in randomized trials.

Serum triglycerides as a risk factor for cardiovascular diseases in the Asia-Pacific region

Background—The importance of serum triglyceride levels as a risk factor for cardiovascular diseases is uncertain. Methods and Results—We performed an individual participant data meta-analysis of prospective studies conducted in the Asia-Pacific region. Cox models were applied to the combined data from 26 studies to estimate the overall and region-, sex-, and age-specific hazard ratios for major cardiovascular diseases by fifths of triglyceride values. During 796 671 person-years of follow-up among 96 224 individuals, 670 and 667 deaths as a result of coronary heart disease (CHD) and stroke, respectively, were recorded. After adjustment for major cardiovascular risk factors, participants grouped in the highest fifth of triglyceride levels had a 70% (95% CI, 47 to 96) greater risk of CHD death, an 80% (95% CI, 49 to 119) higher risk of fatal or nonfatal CHD, and a 50% (95% CI, 29% to 76%) increased risk of fatal or nonfatal stroke compared with those belonging to the lowest fifth. The association between triglycerides and CHD death was similar across subgroups defined by ethnicity, age, and sex. Conclusions—Serum triglycerides are an important and independent predictor of CHD and stroke risk in the Asia-Pacific region. These results may have clinical implications for cardiovascular risk prediction and the use of lipid-lowering therapy.

Ethnic comparisons of the cross‐sectional relationships between measures of body size with diabetes and hypertension

Recent estimates indicate that two billion people are overweight or obese and hence are at increased risk of cardiovascular disease and its comorbidities. However, this may be an underestimate of the true extent of the problem, as the current method used to define overweight may lack sensitivity, particularly in some ethnic groups where there may be an underestimate of risk. Measures of central obesity may be more strongly associated with cardiovascular risk, but there has been no systematic attempt to compare the strength and nature of the associations between different measures of overweight with cardiovascular risk across ethnic groups. Data from the Obesity in Asia Collaboration, comprising 21 cross‐sectional studies in the Asia‐Pacific region with information on more than 263 000 individuals, indicate that measures of central obesity, in particular, waist circumference (WC), are better discriminators of prevalent diabetes and hypertension in Asians and Caucasians, and are more strongly associated with prevalent diabetes (but not hypertension), compared with body mass index (BMI).

Mediterranean diet and all-causes mortality after myocardial infarction: results from the GISSI-Prevenzione trial

Objective: To ascertain whether simple dietary advice to increase the consumption of Mediterranean foods, given in a clinical setting, leads to reduced mortality after a myocardial infarction.Design: Data were used from the GISSI-Prevenzione clinical trial, analysed as a cohort study with adjustment for treatment allocation.Setting: A total of 172 centres in Italy.Subjects: A total of 11 323 men and women with myocardial infarction. All subjects received advice to increase their consumption of fish, fruit, raw and cooked vegetables and olive oil.Measurements: The intakes of the five foods were assessed at baseline, 6, 18 and 42 months. Associations of food intakes, a combined dietary score, and the risk of death over 6.5 y were estimated adjusting for several non-dietary variables, using pooled logistic regression.Results: Subjects generally improved their diet according to the advice given. All foods were associated with a significant reduction in risk of death. Compared with people in the worst dietary score quarter, the odds ratio for those in the best score quarter was 0.51 (95% CI 0.44–0.59). A good diet had a protective effect in sub-groups defined by age, sex, smoking, randomized treatment and concomitant drug therapy.Conclusions: Myocardial infarction patients can respond positively to simple dietary advice, and this can be expected to lead to a substantial reduction in the risk of early death. Regardless of any drug treatment prescribed, clinicians should routinely advise patients with myocardial infarction to increase their frequency of consumption of Mediterranean foods.

Body-mass index and cancer mortality in the Asia-Pacific Cohort Studies Collaboration: pooled analyses of 424 519 participants

BACKGROUND Excess bodyweight is an established risk factor for several types of cancer, but there are sparse data from Asian populations, where the proportion of overweight and obese individuals is increasing rapidly and adiposity can be substantially greater for the same body-mass index (BMI) compared with people from Western populations. METHODS We examined associations of adult BMI with cancer mortality (overall and for 20 cancer sites) in geographic populations from Asia and from Australia and New Zealand (ANZ), within the Asia-Pacific Cohort Studies Collaboration, by use of Cox regression analysis. Pooled data from 39 cohorts (recruitment 1961-99, median follow-up 4 years) were analysed for 424,519 participants (77% Asian; 41% female; mean recruitment age 48 years) with individual data on BMI. FINDINGS After excluding those with follow-up of less than 3 years, 4872 cancer deaths occurred in 401,215 participants. Hazard ratios for cancer sites with increased mortality risk in obese (BMI > or = 30 kg/m(2)) compared with normal weight participants (BMI 18.5-24.9 kg/m(2)) were: 1.21 (95% CI 1.09-1.36) for all-cause cancer (excluding lung and upper aerodigestive tract), 1.50 (1.13-1.99) for colon, 1.68 (1.06-2.67) for rectum, 1.63 (1.13-2.35) for breast in women 60 years or older, 2.62 (1.57-4.37) for ovary, 4.21 (1.89-9.39) for cervix, 1.45 (0.97-2.19) for prostate, and 1.66 (1.03-2.68) for leukaemia (all after left censoring at 3 years). The increased risk associated with a 5-unit increase in BMI for those with BMI of 18.5 kg/m(2) or higher was 1.09 (95% CI 1.04-1.14) for all cancers (excluding lung and upper aerodigestive tract). There was little evidence of regional differences in relative risk of cancer with higher BMI, apart from cancers of the oropharynx and larynx, where the association was inverse in ANZ and absent in Asia. INTERPRETATION Overweight and obese individuals in populations across the Asia-Pacific region have a significantly increased risk of mortality from cancer. Strategies to prevent individuals from becoming overweight and obese in Asia are needed to reduce the burden of cancer that is expected if the obesity epidemic continues. FUNDING National Health and Medical Research Council of Australia, Health Research Council of New Zealand, and Pfizer Inc.

The Relationship between Proteinuria and Coronary Risk: A Systematic Review and Meta-Analysis

Background Markers of kidney dysfunction such as proteinuria or albuminuria have been reported to be associated with coronary heart disease, but the consistency and strength of any such relationship has not been clearly defined. This lack of clarity has led to great uncertainty as to how proteinuria should be treated in the assessment and management of cardiovascular risk. We therefore undertook a systematic review of published cohort studies aiming to provide a reliable estimate of the strength of association between proteinuria and coronary heart disease. Methods and Findings A meta-analysis of cohort studies was conducted to obtain a summary estimate of the association between measures of proteinuria and coronary risk. MEDLINE and EMBASE were searched for studies reporting an age- or multivariate-adjusted estimate and standard error of the association between proteinuria and coronary heart disease. Studies were excluded if the majority of the study population had known glomerular disease or were the recipients of renal transplants. Two independent researchers extracted the estimates of association between proteinuria (total urinary protein >300 mg/d), microalbuminuria (urinary albumin 30–300 mg/d), macroalbuminuria (urinary albumin >300 mg/d), and risk of coronary disease from individual studies. These estimates were combined using a random-effects model. Sensitivity analyses were conducted to examine possible sources of heterogeneity in effect size. A total of 26 cohort studies were identified involving 169,949 individuals and 7,117 coronary events (27% fatal). The presence of proteinuria was associated with an approximate 50% increase in coronary risk (risk ratio 1.47, 95% confidence interval [CI] 1.23–1.74) after adjustment for known risk factors. For albuminuria, there was evidence of a dose–response relationship: individuals with microalbuminuria were at 50% greater risk of coronary heart disease (risk ratio 1.47, 95% CI 1.30–1.66) than those without; in those with macroalbuminuria the risk was more than doubled (risk ratio 2.17, 1.87–2.52). Sensitivity analysis indicated no important differences in prespecified subgroups. Conclusion These data confirm a strong and continuous association between proteinuria and subsequent risk of coronary heart disease, and suggest that proteinuria should be incorporated into the assessment of an individuals cardiovascular risk.