Riitta Antikainen

Treatment of Hypertension in Patients 80 Years of Age or Older

BACKGROUND Whether the treatment of patients with hypertension who are 80 years of age or older is beneficial is unclear. It has been suggested that antihypertensive therapy may reduce the risk of stroke, despite possibly increasing the risk of death. METHODS We randomly assigned 3845 patients from Europe, China, Australasia, and Tunisia who were 80 years of age or older and had a sustained systolic blood pressure of 160 mm Hg or more to receive either the diuretic indapamide (sustained release, 1.5 mg) or matching placebo. The angiotensin-converting-enzyme inhibitor perindopril (2 or 4 mg), or matching placebo, was added if necessary to achieve the target blood pressure of 150/80 mm Hg. The primary end point was fatal or nonfatal stroke. RESULTS The active-treatment group (1933 patients) and the placebo group (1912 patients) were well matched (mean age, 83.6 years; mean blood pressure while sitting, 173.0/90.8 mm Hg); 11.8% had a history of cardiovascular disease. Median follow-up was 1.8 years. At 2 years, the mean blood pressure while sitting was 15.0/6.1 mm Hg lower in the active-treatment group than in the placebo group. In an intention-to-treat analysis, active treatment was associated with a 30% reduction in the rate of fatal or nonfatal stroke (95% confidence interval [CI], -1 to 51; P=0.06), a 39% reduction in the rate of death from stroke (95% CI, 1 to 62; P=0.05), a 21% reduction in the rate of death from any cause (95% CI, 4 to 35; P=0.02), a 23% reduction in the rate of death from cardiovascular causes (95% CI, -1 to 40; P=0.06), and a 64% reduction in the rate of heart failure (95% CI, 42 to 78; P<0.001). Fewer serious adverse events were reported in the active-treatment group (358, vs. 448 in the placebo group; P=0.001). CONCLUSIONS The results provide evidence that antihypertensive treatment with indapamide (sustained release), with or without perindopril, in persons 80 years of age or older is beneficial. (ClinicalTrials.gov number, NCT00122811 [ClinicalTrials.gov].).

Effects of Calcium-Channel Blockade in Older Patients with Diabetes and Systolic Hypertension

Background Recent reports suggest that calcium-channel blockers may be harmful in patients with diabetes and hypertension. We previously reported that antihypertensive treatment with the calcium-channel blocker nitrendipine reduced the risk of cardiovascular events. In this post hoc analysis, we compared the outcome of treatment with nitrendipine in diabetic and nondiabetic patients. Methods After stratification according to center, sex, and presence or absence of previous cardiovascular complications, 4695 patients (age, ≥60 years) with systolic blood pressure of 160 to 219 mm Hg and diastolic pressure below 95 mm Hg were randomly assigned to receive active treatment or placebo. Active treatment consisted of nitrendipine (10 to 40 mg per day) with the possible addition or substitution of enalapril (5 to 20 mg per day) or hydrochlorothiazide (12.5 to 25 mg per day) or both, titrated to reduce the systolic blood pressure by at least 20 mm Hg and to less than 150 mm Hg. In the control group, matching placeb...

A 2 year multidomain intervention of diet, exercise, cognitive training, and vascular risk monitoring versus control to prevent cognitive decline in at-risk elderly people (FINGER): a randomised controlled trial

BACKGROUND Modifiable vascular and lifestyle-related risk factors have been associated with dementia risk in observational studies. In the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER), a proof-of-concept randomised controlled trial, we aimed to assess a multidomain approach to prevent cognitive decline in at-risk elderly people from the general population. METHODS In a double-blind randomised controlled trial we enrolled individuals aged 60-77 years recruited from previous national surveys. Inclusion criteria were CAIDE (Cardiovascular Risk Factors, Aging and Dementia) Dementia Risk Score of at least 6 points and cognition at mean level or slightly lower than expected for age. We randomly assigned participants in a 1:1 ratio to a 2 year multidomain intervention (diet, exercise, cognitive training, vascular risk monitoring), or a control group (general health advice). Computer-generated allocation was done in blocks of four (two individuals randomly allocated to each group) at each site. Group allocation was not actively disclosed to participants and outcome assessors were masked to group allocation. The primary outcome was change in cognition as measured through comprehensive neuropsychological test battery (NTB) Z score. Analysis was by modified intention to treat (all participants with at least one post-baseline observation). This trial is registered at ClinicalTrials.gov, number NCT01041989. FINDINGS Between Sept 7, 2009, and Nov 24, 2011, we screened 2654 individuals and randomly assigned 1260 to the intervention group (n=631) or control group (n=629). 591 (94%) participants in the intervention group and 599 (95%) in the control group had at least one post-baseline assessment and were included in the modified intention-to-treat analysis. Estimated mean change in NTB total Z score at 2 years was 0·20 (SE 0·02, SD 0·51) in the intervention group and 0·16 (0·01, 0·51) in the control group. Between-group difference in the change of NTB total score per year was 0·022 (95% CI 0·002-0·042, p=0·030). 153 (12%) individuals dropped out overall. Adverse events occurred in 46 (7%) participants in the intervention group compared with six (1%) participants in the control group; the most common adverse event was musculoskeletal pain (32 [5%] individuals for intervention vs no individuals for control). INTERPRETATION Findings from this large, long-term, randomised controlled trial suggest that a multidomain intervention could improve or maintain cognitive functioning in at-risk elderly people from the general population. FUNDING Academy of Finland, La Carita Foundation, Alzheimer Association, Alzheimers Research and Prevention Foundation, Juho Vainio Foundation, Novo Nordisk Foundation, Finnish Social Insurance Institution, Ministry of Education and Culture, Salama bint Hamdan Al Nahyan Foundation, Axa Research Fund, EVO funding for University Hospitals of Kuopio, Oulu, and Turku and for Seinäjoki Central Hospital and Oulu City Hospital, Swedish Research Council, Swedish Research Council for Health, Working Life and Welfare, and af Jochnick Foundation.

Coffee and Tea Consumption and the Risk of Parkinson's Disease

Several prospective studies have assessed the association between coffee consumption and Parkinsons disease (PD) risk, but the results are inconsistent. We examined the association of coffee and tea consumption with the risk of incident PD among 29,335 Finnish subjects aged 25 to 74 years without a history of PD at baseline. During a mean follow‐up of 12.9 years, 102 men and 98 women developed an incident PD. The multivariate‐adjusted (age, body mass index, systolic blood pressure, total cholesterol, education, leisure‐time physical activity, smoking, alcohol and tea consumption, and history of diabetes) hazard ratios (HRs) of PD associated with the amount of coffee consumed daily (0, 1–4, and ≥5 cups) were 1.00, 0.55, and 0.41 (P for trend = 0.063) in men, 1.00, 0.50, and 0.39 (P for trend = 0.073) in women, and 1.00, 0.53, and 0.40 (P for trend = 0.005) in men and women combined (adjusted also for sex), respectively. In both sexes combined, the multivariate‐adjusted HRs of PD for subjects drinking ≥3 cups of tea daily compared with tea nondrinkers was 0.41 (95% CI 0.20–0.83). These results suggest that coffee drinking is associated with a lower risk of PD. More tea drinking is associated with a lower risk of PD.

Joint Effects of Physical Activity, Body Mass Index, Waist Circumference, and Waist-to-Hip Ratio on the Risk of Heart Failure

Background— Obesity increases heart failure (HF) risk; however, the independent effect of physical activity and the joint effect of physical activity and adiposity on HF risk are not established. We evaluated the single and joint associations of physical activity and different indicators of adiposity (body mass index, waist circumference, and waist-to-hip ratio) with HF risk. Methods and Results— Study cohorts included 59178 Finnish participants who were 25 to 74 years of age and free of HF at baseline. During a mean follow-up of 18.4 years, 1921 men and 1693 women developed HF. The multivariable-adjusted hazard ratios of HF associated with low, moderate, and high physical activity were 1.00, 0.79, and 0.69 (Ptrend<0.001) for men and 1.00, 0.86, and 0.68 (Ptrend<0.001) for women, respectively. The multivariable-adjusted hazard ratios of HF at different levels of body mass index (<25, 25 to 29.9, and ≥30 kg/m2) were 1.00, 1.25, and 1.99 (Ptrend<0.001) for men and 1.00, 1.33, and 2.06 (Ptrend<0.001) for women, respectively. Abdominal adiposity, measured by waist circumference or waist-to-hip ratio, was associated with a greater risk of HF among both men and women (all Ptrend<0.01). In joint analyses, the protective effect of physical activity was consistent in subjects at all levels of body mass index. Conclusions— General overweight and general and abdominal obesity are independently associated with an increased risk of HF, whereas moderate or high levels of physical activity are associated with a reduced risk of HF. The protective effect of physical activity on HF risk is observed at all levels of body mass index.

Body mass index and the risk of Parkinson disease.

Objective: To examine the association between body mass index (BMI) and the risk of Parkinson disease (PD). Methods: Study cohorts included 22,367 Finnish men and 23,439 women 25 to 59 years of age without a history of PD at baseline. Hazards ratios (HRs) of incident PD were estimated for different levels of BMI. Results: During a mean follow-up period of 18.8 years, 272 men and 254 women developed incident PD. After adjustment for confounding factors (age, study years, systolic blood pressure, total cholesterol, education, leisure-time physical activity, smoking, and alcohol, coffee, and tea consumption), the HRs of PD at different levels of BMI (<23, 23 to 24.9, 25 to 26.9, 27 to 29.9, and ≥30 kg/m2) were 1.00, 1.97 (95% CI: 1.21 to 3.22), 1.83 (95% CI: 1.12 to 2.99), 2.34 (95% CI: 1.45 to 3.78), and 2.44 (95% CI: 1.44 to 4.15) in men, and 1.00, 1.50 (95% CI: 0.95 to 2.37), 1.65 (95% CI: 1.05 to 2.59), 1.79 (95% CI: 1.15 to 2.80), and 1.77 (95% CI: 1.12 to 2.78) in women, and 1.00, 1.70 (95% CI: 1.23 to 2.37), 1.70 (95% CI: 1.23 to 2.37), 2.02 (95% CI: 1.46 to 2.79), and 2.03 (95% CI: 1.44 to 2.85) in men and women combined (adjusted also for sex). In both sexes combined, the multivariate-adjusted direct association between BMI and the risk of PD was present both in subjects aged 25 to 49 years and 50 to 59 years, in never smokers and smokers and in participants diagnosed PD before and after 65 years of age. Conclusion: Body mass index is associated with a risk of Parkinson disease. The effect is graded and independent of other risk factors.

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.

The Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER): Study design and progress

Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) is a multi‐center, randomized, controlled trial ongoing in Finland.

The Impact of History of Hypertension and Type 2 Diabetes at Baseline on the Incidence of Stroke and Stroke Mortality

Background and Purpose— Both hypertension and diabetes are strong predictors of stroke, but very few studies have assessed their joint effect on stroke risk. We evaluated prospectively the joint association of history of hypertension and type 2 diabetes on the incidence of stroke and stroke mortality. Methods— We prospectively followed 49 582 Finnish subjects aged 25 to 74 years without a history of stroke and coronary heart disease at baseline. Hazards ratios (HRs) for stroke risk were estimated by the hypertension and diabetes status. Results— During a mean follow-up of 19.1 years, 2978 incident stroke events were recorded, of which 924 were fatal. Age-, sex-, and study year-adjusted HRs of stroke incidence were 1.35 (95% CI, 1.21 to 1.51), 1.98 (95% CI, 1.79 to 2.19), 2.54 (95% CI, 1.61 to 4.01), 3.51 (95% CI, 2.40 to 5.14), and 4.50 (95% CI, 3.60 to 5.61), respectively, among subjects with hypertension I (blood pressure 140 to 159/90 to 94 mm Hg) only, with hypertension II (blood pressure ≥160/95 mm Hg, or using antihypertensive drugs) only, with diabetes only, with both hypertension I and diabetes, and with both hypertension II and diabetes compared with the subjects without either of the diseases. The corresponding HRs of stroke mortality were 1.47, 2.62, 3.06, 5.59, and 9.27, respectively. Additional adjustments for body mass index, cholesterol, education, smoking, alcohol consumption, and physical activity did not appreciably change these risk estimates. Blood pressure affected the risk of stroke similarly in diabetic and nondiabetic subjects. Conclusions— Hypertension and type 2 diabetes increase stroke risk independently, and their combination increases the risk drastically. A significant proportion of the risk of stroke assumed to be related to hypertension may be attributable to concomitant diabetes.

Systolic blood pressure, isolated systolic hypertension and risk of coronary heart disease, strokes, cardiovascular disease and all-cause mortality in the middle-aged population

Objective To determine the risk of death from coronary heart disease, stroke, all cardiovascular disease and all-cause mortality associated with systolic blood pressure and in particular with isolated systolic hypertension among the middle-aged population. Methods and design A prospective 15-year cohort study of two independent cross-sectional random samples of subjects participating in baseline surveys in 1972 and 1977. Each survey included a self-administered questionnaire, measurements of height, weight and blood pressure and the determination of the serum cholesterol concentration. Setting North Karelia and Kuopio provinces in eastern Finland. Mortality follow-up complete with the personal identification number. Participants Participants were 10 333 men and 11 160 women aged 25–64 years without histories of myocardial infarction and stroke incidence at the time of the baseline survey. Isolated systolic hypertension in these analyses was defined as systolic blood pressure ≥ 160 mmHg and diastolic blood pressure < 95 mmHg. Subjects with blood pressure < 160/90 mmHg were considered normotensive. Results Coronary heart disease, stroke, cardiovascular disease and all-cause mortality among men and women aged 45–64 years increased with the increasing systolic blood pressure. Among women aged 45–64 years, isolated systolic hypertension increased the relative risk of these fatal events. Among men aged 45–64 years, only coronary heart disease mortality was significantly associated with isolated systolic hypertension. Conclusion Isolated systolic hypertension is an important predictor of death from coronary heart disease, stroke, cardiovascular disease and all causes for women. For men aged 45–64 years, the risk of death from coronary heart disease was associated with isolated systolic hypertension, but the risk of stroke, cardiovascular disease and all-cause mortality associated with increasing systolic blood pressure was evident already at the systolic blood pressure levels < 160 mmHg, independently of the level of diastolic blood pressure. J Hypertens 16:577–583