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.

WHAT'S KNOWN ON THIS SUBJECT:Attention-deficit/ hyperactivity disorder agents increase systolic and diastolic blood pressure and heart rate. Case reports of sudden death in children and adolescents receiving these agents have led to the concern that they might increase the risk of cardiovascular events. WHAT THIS STUDY ADDS:Low rates of validated cardiovascular events and of all-cause death, nonsuicide, and non-accidental death were found in children and adolescents receiving attention-deficit/ hyperactivity disorder medications.abstract OBJECTIVE: The objective of this study was to compare the rate of severe cardiovascular events and death in children who use attentiondeficit/hyperactivity disorder (ADHD) medications versus nonusers. PATIENTS AND METHODS:We performed a large cohort study using data from 2 administrative databases. All children aged 3 to 17 years with a prescription for an amphetamine, atomoxetine, or methylphenidate were included and matched with up to 4 nonusers on the basis of data source, gender, state, and age. Cardiovascular events were validated using medical records. Proportional hazards regression was used to calculated hazard ratios. RESULTS: We identified 241 417 incident users (primary cohort) CONCLUSIONS:The rate of cardiovascular events in exposed children was very low and in general no higher than that in unexposed control subjects. Because of the low number of events, we have limited ability to rule out relative increases in rate.

The objective of this study was to determine whether two vitamin K epoxide reductase complex 1 (VKORC1) polymorphisms contribute to the variability in warfarin response, particularly in African Americans. The effect of the VKORC1 1173C/T and -1639G/A polymorphisms was examined in a prospective cohort study of 338 warfarin users. Subjects carrying an 1173T allele had a lower warfarin maintenance dose compared with subjects with the CC genotype in African Americans (-12.10 mg/week+/-4.93; P=0.02) and Caucasians (-14.41 mg/week+/-3.28; P<0.001). Before reaching maintenance dose, only Caucasians with the T allele had significantly increased risk of international normalized ratio >3 (odds ratio=3.10; 95% confidence interval: 1.73-5.55) compared with Caucasians with the CC genotype. Polymorphisms in the VKORC1 gene are associated with warfarin maintenance dose requirements among both African Americans and Caucasians. However, these polymorphisms may not be as useful in predicting over-anticoagulation among African Americans.

Although initiation of methylphenidate was associated with a 1.8-fold increase in risk of sudden death or ventricular arrhythmia, the lack of a dose-response relationship suggests that this association may not be a causal one.

Objectives-The objective of this study was to determine whether clinical, environmental, and genetic factors can be used to develop dosing algorithms for Caucasians and African Americans that perform better than giving empirical 5 mg/day. Methods-From April 2002 through December 2005, 259 warfarin initiators were prospectively followed until they reached maintenance dose.Results-The Caucasian algorithm included 11 variables (R 2 =0.43). This model (51% within 1 mg) performed better compared with 5 mg/day (29% within 5±1 mg). The African American algorithm included 10 variables (R 2 =0.28). This model predicted 37% of doses within 1 mg of the observed dose; a small improvement compared with 5 mg/day (34%). These results were similar to the results we obtained from testing other (published) algorithms.Conclusions-The dosing algorithms in Caucasians explained <45% of the variability and the algorithms in African Americans performed only marginally better than giving 5 mg empirically.