Summary Background Elevated blood pressure and glucose, serum cholesterol, and body mass index (BMI) are risk factors for cardiovascular diseases (CVDs); some of these factors also increase the risk of chronic kidney disease (CKD) and diabetes. We estimated CVD, CKD, and diabetes mortality attributable to these four cardio-metabolic risk factors for all countries and regions between 1980 and 2010. Methods We used data on risk factor exposure by country, age group, and sex from pooled analysis of population-based health surveys. Relative risks for cause-specific mortality were obtained from pooling of large prospective studies. We calculated the population attributable fractions (PAF) for each risk factor alone, and for the combination of all risk factors, accounting for multi-causality and for mediation of the effects of BMI by the other three risks. We calculated attributable deaths by multiplying the cause-specific PAFs by the number of disease-specific deaths from the Global Burden of Diseases, Injuries, and Risk Factors 2010 Study. We propagated the uncertainties of all inputs to the final estimates. Findings In 2010, high blood pressure was the leading risk factor for dying from CVDs, CKD, and diabetes in every region, causing over 40% of worldwide deaths from these diseases; high BMI and glucose were each responsible for about 15% of deaths; and cholesterol for 10%. After accounting for multi-causality, 63% (10.8 million deaths; 95% confidence interval 10.1–11.5) of deaths from these diseases were attributable to the combined effect of these four metabolic risk factors, compared with 67% (7.1 million deaths; 6.6–7.6) in 1980. The mortality burden of high BMI and glucose nearly doubled between 1980 and 2010. At the country level, age-standardised death rates attributable to these four risk factors surpassed 925 deaths per 100,000 among men in Belarus, Mongolia, and Kazakhstan, but were below 130 deaths per 100,000 for women and below 200 for men in some high-income countries like Japan, Singapore, South Korea, France, Spain, The Netherlands, Australia, and Canada. Interpretations The salient features of the cardio-metabolic epidemic at the beginning of the twenty-first century are the large role of high blood pressure and an increasing impact of obesity and diabetes. There has been a shift in the mortality burden from high-income to low- and middle-income countries.

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Despite misclassification, self-reported and measured pre-pregnancy weights were similarly associated with perinatal outcomes in this study population. Our results illustrate the value of the EHR for recording measured pre-pregnancy weight for use in research.

To evaluate the efficacy and safety of leflunomide in the treatment of proliferative lupus nephritis, a prospective multi-centre observational study was conducted. Patients with biopsy proven proliferative lupus nephritis were assigned to receive either leflunomide or cyclophosphamide with concomitant prednisone. Leflunomide was given orally with a loading dose of 1 mg/kg/day for 3 days followed by 30 mg/day. Intravenous cyclophosphamide was administered monthly at a dose of 0.5 g/m2 of body-surface area. A total of 110 patients were enrolled, 70 in the leflunomide group and 40 in the cyclophosphamide group. The complete remission rate in the leflunomide group was 21% and partial remission rate 52%, as compared with 18% and 55%, respectively, in the cyclophosphamide group. Renal parameters and systemic lupus erythematosus disease activity index improved significantly and similarly in both groups. Serum creatinine decreased or stabilized in both treatment groups. No significant difference was noted with respect to clinical outcome between groups. Repeat biopsy also showed a significant reduction of active lesions in kidney pathology after 6 months of leflunomide treatment. Major adverse events, similar in both treatment groups, included infection, alopecia and hypertension. Leflunomide, compared with cyclophosphamide, in combination with prednisone was effective in the induction therapy of proliferative lupus nephritis and was generally well-tolerated.

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