Age-related clonal hematopoiesis associated with adverse outcomes.

BACKGROUND: The incidence of hematologic cancers increases with age. These cancers are associated with recurrent somatic mutations in specific genes. We hypothesized that such mutations would be detectable in the blood of some persons who are not known to have hematologic disorders. METHODS: We analyzed whole-exome sequencing data from DNA in the peripheral-blood cells of 17,182 persons who were unselected for hematologic phenotypes. We looked for somatic mutations by identifying previously characterized single-nucleotide variants and small insertions or deletions in 160 genes that are recurrently mutated in hematologic cancers. The presence of mutations was analyzed for an association with hematologic phenotypes, survival, and cardiovascular events. RESULTS: Detectable somatic mutations were rare in persons younger than 40 years of age but rose appreciably in frequency with age. Among persons 70 to 79 years of age, 80 to 89 years of age, and 90 to 108 years of age, these clonal mutations were observed in 9.5% (219 of 2300 persons), 11.7% (37 of 317), and 18.4% (19 of 103), respectively. The majority of the variants occurred in three genes: DNMT3A, TET2, and ASXL1. The presence of a somatic mutation was associated with an increase in the risk of hematologic cancer (hazard ratio, 11.1; 95% confidence interval [CI], 3.9 to 32.6), an increase in all-cause mortality (hazard ratio, 1.4; 95% CI, 1.1 to 1.8), and increases in the risks of incident coronary heart disease (hazard ratio, 2.0; 95% CI, 1.2 to 3.4) and ischemic stroke (hazard ratio, 2.6; 95% CI, 1.4 to 4.8). CONCLUSIONS: Age-related clonal hematopoiesis is a common condition that is associated with increases in the risk of hematologic cancer and in all-cause mortality, with the latter possibly due to an increased risk of cardiovascular disease. (Funded by the National Institutes of Health and others.).

Body mass index and cancer incidence: the FINRISK study.

The relation between body mass index (BMI) and risk of cancer incidence is controversial. Cancer incidence during 1972-2008 in relation to BMI was investigated in a prospective cohort of 54,725 Finns aged 24-74 years and free of cancer at enrollment. Over a mean follow-up of 20.6 years, 8,429 (15.4%) incident cancers were recorded, 4,208 (49.9%) from men. Both parametric and nonparametric approaches were used to evaluate the shape of the relationship between BMI and incidence of cancer. BMI had a linear positive association with incidence of cancers of the colon, liver, kidney, bladder and all sites combined in men, and of cancers of the stomach, colon, gallbladder and ovary in women, an inverse association with incidence of cancers of the lung in men and the lung and breast in women, a J-shaped association with incidence of all cancers combined in women. High BMI in women was associated with an increased overall cancer risk in never smokers but a reduced risk in smokers. Elevated BMI was associated with an increased risk of incidence of cancers of certain sites.

The diabetes-cardiovascular risk paradox: results from a Finnish population-based prospective study.

AIMS: To assess changes in coronary heart disease (CHD) event rates and CHD mortality rates among diabetic and non-diabetic individuals between two large study cohorts with baseline assessments 10 years apart and followed up for 10 years. METHODS AND RESULTS: Four population surveys were carried out in 1972, 1977, 1982, and 1987 in a randomly selected independent population in Finland. For the analyses, we combined the 1972 and 1977 cohorts (cohort 1) and similarly also the 1982 and 1987 cohorts (cohort 2). A total of 16 779 men and 18 235 women were followed up for 10 years. Whereas the risk of first cardiovascular disease event in women did not change between the two cohorts, the risk in diabetic men aged 25-49 years and men of all age groups with incidence diabetes during the follow-up decreased compared with the earlier cohort. The relative risk of CHD mortality in men with baseline diabetes or incident diabetes compared with non-diabetic individuals increased (from 1.67 to 1.75 and 1.00 to 1.92, respectively). CHD event rates and CHD mortality rates decreased among non-diabetic individuals between the two study cohorts. CONCLUSION: Special attention should be given to prevent the onset of diabetes in the population and to intensify the management of patients with diabetes.

Coronary heart disease incidence and mortality, and all-cause mortality among diabetic and non-diabetic people according to their smoking behavior in Finland.

BACKGROUND: As type 2 diabetes (T2D) patients have a high risk for coronary heart disease (CHD) and all-cause mortality and smoking is a major single risk factor for total and CHD mortality, it is important to understand the impact of smoking to the outcome events in comparison to people without T2D. Studies of excess risk of CHD incidence and mortality, and all-cause mortality in T2D patients related to smoking are controversial. We aimed to assess the risk of CHD incidence and mortality, and all-cause mortality in a large Finnish population cohort consisting of people with and without T2Daccording to smoking status. METHODS: Prospective follow-up of 28 712 men and 30 700 women aged 25-64 years living in eastern and south-western Finland. The data on mortality were obtained from the nationwide death register using the unique national personal identification number. Follow-up information regarding CHD was based on the Finnish Hospital Discharge Register for non-fatal outcomes. The Cox proportional hazards models were used to estimate the association between diabetes and smoking subgroups and the risk for total and CHD mortality. RESULTS: T2D patients who were smoking had higher all-cause mortality in both men (HR 3.76; 95% CI 2.95-4.78) and women (HR 4.51; 95% CI 2.91-7.00) than non-smoking diabetic men (HR 2.03; 95% CI 1.51-2.74) and women (HR 2.11; 95% CI 1.71-2.59). The CHD mortality risk for smoking men with T2D was higher (HR 6.15; 95% CI 4.22-8.96) than in non-smoking diabetic men (HR 2.62; 95% CI 1.60-4.29). Similar results were found in women revealing corresponding HR for CHD mortality of 6.92 (95% CI 2.79-17.19) for smoking, T2D women and 4.06 (95% CI 2.83-5.82) for non-smoking T2D women, respectively. Even though the risk of CHD incidence in T2D patients who had stopped smoking was statistically significantly higher than in their non-smoking non-diabetic counterparts, their CHD incidence was lower than in smoking T2D patients (HR in men 3.00; HR in women 2.80). CONCLUSION: It is important to address tobacco consumption in T2D patients, especially during primary health care contacts in order to reduce their high risk of CHD and all-cause mortality.

Trends in the prevalence, awareness, treatment and control of hypertension: the WHO MONICA Project.

OBJECTIVE: To describe the secular changes in the prevalence, awareness, treatment and control of hypertension. DESIGN: Two independent cross-sectional population surveys using standardized methods conducted between the early 1980s and mid-1990s. SETTING: Twenty-four geographically defined populations of the WHO MONICA Project. PARTICIPANTS: Randomly selected men and women aged 35-64 years. The total number of participants was 69 907. MAIN OUTCOME MEASURES: Two definitions of hypertension were used: 160/95 mmHg or above and 140/90 mmHg or above for systolic or diastolic blood pressure. Subjects on antihypertensive drug treatment were considered to be hypertensive regardless of their blood pressure. Treated subjects whose measured blood pressure level was less than 160/95 or 140/90 mmHg according to the two definitions, respectively, were considered to be adequately treated. RESULTS: The age-adjusted prevalence of hypertension decreased in most and increased in only a few populations. For both definitions of hypertension, the proportion of hypertensive subjects who were aware of their condition increased in three-quarters of the male populations and in two-thirds of the female populations. Furthermore, the proportion of hypertensive individuals on antihypertensive drug treatment increased in three-quarters of the populations. In the final survey, hypertension tended to be better treated and controlled in women than in men. Nevertheless, a large proportion of patients receiving antihypertensive drug therapy still had inadequately controlled blood pressure levels. CONCLUSION: Although awareness and treatment of hypertension according to the data obtained during the late 1980s to the mid-1990s increased in several populations, the effectiveness of antihypertensive treatment showed the continuing need for improvements.

Return to work after first myocardial infarction in 1991-1996 in Finland.

BACKGROUND: A substantial number of myocardial infarctions (MI) occur at working age. It is, however, insufficiently well known how many of these patients return to work after their MI. METHODS: Sources of information were the Hospital Discharge Register, the Causes of Death Register and the registers for social security benefits. Availability for the labour market was used as the return to work criterion. Altogether 10,244 persons (8,733 men, 1,511 women) aged 35-59 years had their first MI or coronary death during 1991-1994 in Finland. Persons who survived for 28 days and were not on pension at the time of MI were included in a two-year follow-up. RESULTS: Twenty-nine per cent of patients were already pensioned at the time of their first MI. Of the patients not pensioned at the time of their MI, 4,929 were alive two years after the event. Of them, 38% of men and 40% of women received disability pension, 3% of both genders were on sick leave and 1% of both genders were on unemployment pension. The remainder, 58% of men and 56% of women, did not receive any of these benefits, thus, being available to the labour force. CONCLUSIONS: Nearly one-third of persons having their first MI at working age were already out of the labour force at the time of their MI. Of those who were not pensioned and who survived the event, slightly more than half were available to the labour market two years later.

Trends in fatal and non-fatal coronary heart disease events in Finland during 1991-2001.

OBJECTIVE: To analyse the trends in fatal and non-fatal coronary heart disease (CHD) events in Finland during an 11-year period 1991-2001. DESIGN: Data on hospitalizations due to CHD in the Hospital Discharge Register were linked to the National Causes of Death Register in order to produce a Cardiovascular Disease Register including data on 271,771 events in 234,244 individuals. RESULTS: The annual average decline in the age-standardized CHD mortality rate was 5.2% (95% CI, -5.6, -4.8%) among men and 6.1% (-6.6, -5.6%) among women. The incidence of first myocardial infarction declined annually on average by 5.5% (-5.9, -5.1%) from 1991 to 1997 and by 2.4% (-3.0, -1.7%) from 1998 to 2001 among men. The respective changes among women were -5.9% (-6.5, -5.2%) and -1.7% (-2.7, -0.6%). The number of hospitalizations due to unstable angina pectoris increased between 1991 and 1996 (p = 0.0002) and remained stable for the rest of the study period. CONCLUSIONS: The Cardiovascular Disease Register is a powerful tool for epidemiological monitoring of cardiovascular diseases in Finland.

Prevention of diabetes mellitus in subjects with impaired glucose tolerance in the Finnish Diabetes Prevention Study: results from a randomized clinical trial.

Type 2 diabetes mellitus is increasing worldwide largely as a result from increasing obesity and sedentary lifestyle. The Finnish Diabetes Prevention Study (DPS) is the first individually randomized controlled clinical trial to test the feasibility and efficacy of lifestyle modification in high-risk subjects. We randomly assigned 522 (172 men, 350 women) middle-aged (mean age 55 yr), overweight (mean body mass index 31 kg/m(2)) subjects with impaired glucose tolerance either to the lifestyle intervention or control group. Each subject in the intervention group received individualized counseling aimed at reducing weight and intake of total and saturated fat, and increasing intake of fiber and physical activity. An oral glucose tolerance test was performed annually to detect incident cases of diabetes and to measure changes in metabolic parameters. The mean (+/- SD) weight reduction from baseline to year 1 and to year 2, respectively, was 4.2 +/- 5.1 kg and 3.5 +/- 5.5 in the intervention group and 0.8 +/- 3.7 kg and 0.8 +/- 4.4 in the control group (P < 0.001 between the groups). At the time of first analysis of the outcome data the mean duration of follow-up was 3.2 yr. The risk of diabetes was reduced by 58% (P < 0.001) in the intervention group compared with the control group. The reduction in the incidence of diabetes was directly associated with number and magnitude of lifestyle changes made. In conclusion, the DPS is the first controlled trial demonstrating that type 2 diabetes can be prevented by changes in lifestyle in high-risk subjects.