Cinzia Sarti

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...

International Trends in Mortality From Stroke, 1968 to 1994

BACKGROUND AND PURPOSE The World Health Organization data bank is an invaluable source of information for international comparison of mortality trends. We present rates and trends in mortality from stroke up to 1994, with a particular emphasis on the last 10-year period. Data are presented for men and women in 51 industrialized and developing countries from different parts of the world. METHODS We included all deaths from cerebrovascular disease for the population aged 35 to 84 years from all the countries in which death certificates were estimated to be available for at least 80% for the period from 1968 to 1994. Age-standardized mortality rates from stroke were calculated for each country for the last available 5 years. Time trends were calculated by using ordinary linear regression and are presented for the entire study period and for 3 separate time periods: 1968 to 1974, 1975 to 1984, and 1985 to 1994. The last 10-year period was further subdivided into 2 parts of 5 years each. We analyzed data separately for men and women and for groups aged 35 to 74 years and 75 to 84 years. RESULTS The highest rates at the end of the study period for the population aged 35 to 74 years were observed in eastern Europe and previous Soviet Union countries (309 to 156/100 000 per year among men and 222 to 101/100 000 per year among women), Mauritius (268/100 000 per year among men and 138/100 000 per year among women), and Trinidad and Tobago (185/100 000 per year among men and 134/100 000 per year among women). Relatively low to average rates (<100/100 000 per year among men and <70/100 000 per year among women) were reported for Western Europe, with an exception of Portugal (162/100 000 per year among men and 95/100 000 per year among women). The countries with lowest stroke mortality rates at the end of the study period, such as the United States, Canada, Switzerland, France, and Australia, experienced steep declining trends. However, the slope of the decline was substantially reduced during the last 5 years in these countries. Mortality from stroke increased most in the eastern European countries, especially during the last 5 years. Among other high-risk populations, no change in stroke mortality trends was observed in Mauritius, whereas somewhat declining trends were seen in Trinidad and Tobago. CONCLUSIONS We observed large differences in mortality rates from stroke around the world together with a wide variation in mortality trends. A widening gap was observed between 2 groups of nations, those with low and declining stroke mortality rates and those with high and increasing mortality, in particular, between western and eastern Europe. Eastern European countries should initiate actions aiming at the reduction of stroke risk, perhaps by looking at the examples of Japan and Finland and the other countries that have been the most successful in reducing previously very high mortality from stroke.

A Prospective Community-Based Study of Stroke in Germany—The Erlangen Stroke Project (ESPro) Incidence and Case Fatality at 1, 3, and 12 Months

BACKGROUND AND PURPOSE In Germany, basic data on stroke morbidity are lacking. If a population-based register in former East Germany is excluded, only routine mortality statistics have thus far provided information on epidemiology of stroke. Therefore, a population-based register of stroke was set up in Southern Germany to determine incidence and case fatality in a defined German population. METHODS The Erlangen Stroke Project (ESPro) is a prospective community-based study among the 101 450 residents of the city of Erlangen, Bavaria, Germany. Standard definitions and overlapping case-finding methods were used to identify all cases of first-ever stroke in all age-groups, occurring in the 2 years of registration (April 1, 1994, to March 31, 1996). All identified cases of first-ever strokes were followed up at 3 and 12 months from onset. RESULTS During 2 years of registration, 354 first-ever-in-a-lifetime strokes (FELS) were registered. The diagnosis and stroke type were confirmed by CT scan in 95% of cases. Fifty-one percent of all FELS occurred in the age group >/=75 years of age. The crude annual incidence rate was 1.74 per 1000 (1.47 for men and 2.01 for women). After age-adjustment to the European population, the incidence rate was 1.34 per 1000 (1.48 for men and 1. 25 for women). The annual crude incidence rate of cerebral infarction was 1.37/1000, intracerebral hemorrhage 0.24/1000, subarachnoid hemorrhage 0.06/1000, and unspecified stroke 0.08/1000. Overall case fatality at 28 days was 19.4%, at 3 months it was 28.5%, and at 1 year 37.3%. CONCLUSIONS The first prospective community-based stroke register including all age groups in Germany revealed incidence rates of stroke similar to those reported from other population-based studies in western industrialized countries, but lower than that observed in former East Germany.

Diabetes Mellitus as a Risk Factor for Death From Stroke: Prospective Study of the Middle-aged Finnish Population

BACKGROUND AND PURPOSE High blood pressure is the most important risk factor for stroke. It is also known that diabetic patients are at increased risk of both hypertension and stroke. The aim of this study was to assess the independent effect of diabetes as a risk factor for stroke. Results from the previous studies of this question have been somewhat inconclusive. METHODS We performed a prospective study (average follow-up, 16.4 years) of 8077 men and 8572 women who had participated in risk factor surveys in Eastern Finland in 1972 (20 years of follow-up) and 1977 (15 years of follow-up). Risk factors included in the current analyses were smoking, blood pressure, antihypertensive drug treatment, serum total cholesterol, and diabetes either at baseline or developed during the follow-up. Age- and risk factor-adjusted relative risks for death of stroke were determined with the Cox proportional hazards model. RESULTS Diabetes mellitus was the strongest risk factor for death from stroke among both men and women in univariate and multivariate analyses. In addition, smoking and systolic blood pressure appeared to be independent risk factors among both sexes, as did serum total cholesterol among men. Men with diabetes at baseline appeared to be at a sixfold increased risk of death from stroke, while relative risk for men who developed diabetes during the follow-up was 1.7. In women, those who were diabetic at baseline were at higher risk of stroke than women who developed diabetes later (relative risks, 8.2 and 3.7, respectively). Of stroke deaths, 16% in men and 33% in women were attributed to diabetes. CONCLUSIONS Diabetic subjects have a very high risk of death from stroke, particularly women. Our data also suggest that the duration of diabetes is an important factor contributing to the risk of stroke.

Leisure Time, Occupational, and Commuting Physical Activity and the Risk of Stroke

Background and Purpose— The role of physical activity, especially that of occupational and commuting physical activity, in the prediction of stroke risk is not properly established. We assessed the relationship of different types of physical activity with total and type-specific stroke risk. Methods— We prospectively followed 47 721 Finnish subjects 25 to 64 years of age without a history of coronary heart disease, stroke, or cancer at baseline. Hazard ratios (HRs) for incident stroke were estimated for different levels of leisure time, occupational, and commuting physical activity. Results— During a mean follow-up of 19.0 years, 2863 incident stroke events were ascertained. The multivariate-adjusted (age, sex, area, study year, body mass index, systolic blood pressure, cholesterol, education, smoking, alcohol consumption, diabetes, and other 2 types of physical activity) HRs associated with low, moderate, and high leisure time physical activity were 1.00, 0.86, and 0.74 (Ptrend<0.001) for total stroke, 1.00, 0.87, and 0.46 (Ptrend=0.011) for subarachnoid hemorrhage, 1.00, 0.77, and 0.63 (Ptrend=0.024) for intracerebral hemorrhage, and 1.00, 0.87, and 0.80 (Ptrend=0.001) for ischemic stroke, respectively. The multivariate-adjusted HRs associated with none, 1 to 29, and ≥30 minutes of active commuting were 1.00, 0.92, and 0.89 (Ptrend=0.043) for total stroke, and 1.00, 0.93, and 0.86 (Ptrend=0.028) for ischemic stroke, respectively. Occupational activity had a modest association with ischemic stroke in the multivariate analysis (Ptrend=0.046). Conclusion— A high level of leisure time physical activity reduces the risk of all subtypes of stroke. Daily active commuting also reduces the risk of ischemic stroke.

Incidence of cardiovascular disease in Type 1 (insulin-dependent) diabetic subjects with and without diabetic nephropathy in Finland

Summary This study evaluates the impact of diabetic nephropathy on the incidence of coronary heart disease, stroke and any cardiovascular disease in the Finnish population, which has a high risk of Type 1 (insulin-dependent) diabetes mellitus and cardiovascular disease. We performed a prospective analysis of the incidence of coronary heart disease, stroke and cardiovascular disease in all Type 1 subjects in the Finnish Type I diabetes mellitus register diagnosed before the age of 18 years between 1 January 1965 and 31 December 1979 nationwide. The effect of age at onset of diabetes, attained age at the end of follow-up, sex, diabetes duration and of the presence of diabetic nephropathy on the risk for cardiovascular disease was evaluated. Cases of nephropathy, coronary heart disease, stroke and all cardiovascular diseases were ascertained from the nationwide Finnish Hospital Discharge Register and National Death Register using computer linkage with the Type I diabetes mellitus register. Of the 5148 Type 1 diabetic patients followed up, 159 had a cardiovascular event of which 58 were coronary heart diseases, 57 stroke events and 44 other heart diseases. There were virtually no cases of cardiovascular disease before 12 years diabetes duration. The cumulative incidence of cardiovascular disease by the age of 40 years was 43 % in Type 1 diabetic patients with diabetic nephropathy, compared with 7 % in patients without diabetic nephropathy, similarly in men and women. The relative risk for Type 1 diabetic patients with diabetic nephropathy compared with patients without diabetic nephropathy was 10.3 for coronary heart disease, 10.9 for stroke and 10.0 for any cardiovascular disease, similarly in men and women. The presence of nephropathy in Type I diabetic subjects increases not only the risk of coronary heart disease, but also of stroke by tenfold. [Diabetologia (1998) 41: 784–790]

Stroke Trends in the WHO MONICA Project

BACKGROUND AND PURPOSE Stroke registers were established as part of the international collaborative World Health Organization Monitoring of Trends and Determinants in Cardiovascular Disease (WHO MONICA) Project in 17 centers in 10 countries. The aim of the present analyses was to estimate and compare temporal stroke trends across the MONICA populations. METHODS All stroke events in defined populations were ascertained and validated according to a common protocol and uniform criteria. Almost 25,000 stroke events in more than 15 million person-years were analyzed. Age-standardized rates for fatal stroke and for all stroke events were calculated for whole calendar years for each of the populations. Temporal stroke trends were estimated using annual rates for 5 to 6 years. RESULTS Annual stroke attack rates decreased among men in 13 populations and among women in 15 of the 17 MONICA populations. Stroke mortality rates declined among men in 11 populations and among women in 14 of the populations studied. The estimated trends reached the level of statistical significance at the 5% level in only a small number of populations. The trends in official cerebrovascular death rates were in agreement with those estimated on the basis of MONICA data in the majority of the populations studied. CONCLUSIONS Decreasing stroke mortality and attack rates in a large proportion of populations studied can be interpreted as an indication of declining stroke rates in most of the populations studied. The numbers of populations with statistically significant trends were small, and it is therefore not possible to determine with certainty in which of the populations were the changes real.

Epidemiology of subarachnoid hemorrhage in Finland from 1983 to 1985.

The age-standardized incidence of subarachnoid hemorrhage was 33/100,000/yr among Finnish men and 25/100,000/yr among Finnish women. Subarachnoid hemorrhage represented 11% of all strokes detected during 1983-1985 in the community-based stroke register in three areas of Finland. Age-standardized mortality from subarachnoid hemorrhage was 18/100,000/yr among men and 12/100,000/yr among women aged 25-74 years, representing in men 22% and in women 23% of all deaths from stroke in the register. The case-fatality rate of subarachnoid hemorrhage was high: 35% among men and 33% among women within 2 days after the onset of the stroke attack and 48% in men and 46% in women at 1 month. Our findings suggest that the incidence and mortality of subarachnoid hemorrhage in Finland are among the highest worldwide, although differences in criteria, study methods, and classification procedures reduce the comparability of studies from different countries. The occurrence of subarachnoid hemorrhage in our present study is also higher than that previously reported in this country. We believe that this is more likely due to changes in diagnostic classification and improvements in detection of the disease than to a real increase in the morbidity and mortality of subarachnoid hemorrhage.

Incidence of Stroke in Europe at the Beginning of the 21st Century: The European Registers of Stroke (EROS) Investigators

BACKGROUND AND PURPOSE Comparable data on stroke incidence across European countries are lacking because previous studies have used different methods of case ascertainment, different periods of observation, and different age restrictions. METHODS Population-based stroke registers were established in 6 European countries: France (Dijon); Italy (Sesto Fiorentino); Lithuania (Kaunas); the United Kingdom (London); Spain (Menorca); and Poland (Warsaw). Standardized criteria were used among these register including overlapping sources of notification. Overall, a source population of 1087048 inhabitants was observed, ranging from 47236 in Sesto Fiorentino to 365191 in Kaunas. All patients with first-ever stroke of all age groups from the source populations were included. Data collection took part between 2004 and 2006; 4 centers collected data for a 24-month and 2 for a 12-month time period. Crude annual incidence rates were age-adjusted to the European population. RESULTS A total of 2129 patients with first stroke were registered. Median age was 73 years and 51% were female. Annual stroke incidence adjusted to the European population was found in men to be higher in Kaunas and lower in Sesto Fiorentino and Menorca and in women to be higher in Kaunas and Warsaw and lower in Sesto Fiorentino and Menorca compared with mean incidence rates. Total stroke incidence ranged in men from 101.2 per 100000 (95% CI, 82.5 to 123.0) in Sesto Fiorentino to 239.3 per 100000 (95% CI, 209.9 to 271.6) in Kaunas and in women from 63.0 per 100000 (95% CI, 48.5 to 80.7) in Sesto Fiorentino to 158.7 per 100000 (95% CI, 135.0 to 185.4) in Kaunas. Differences in prior-to-stroke risk factors were found among the populations with prevalence of hypertension highest in Warsaw and Kaunas (76% and 67%, respectively) and lowest in Menorca and Sesto Fiorentino (54% and 62%, respectively). CONCLUSIONS The risk of stroke among European populations in our study varied more than 2-fold in men and women. On average, higher rates of stroke were observed in eastern and lower rates in southern European countries.

Prognostic Significance of Renal Function in Elderly Patients with Isolated Systolic Hypertension: Results from the Syst-Eur Trial

Several reports suggest that markers of renal function such as serum creatinine, serum uric acid, and urinary excretion of protein may be related to cardiovascular complications and mortality. This study analyzed the data from the Syst-Eur trial, which was a randomized, placebo-controlled, double-blind intervention trial in elderly patients with isolated systolic hypertension. The purpose was to evaluate whether serum levels of creatinine and uric acid and urinary protein excretion at entry are related to subsequent morbidity and mortality. Incidence rates of total mortality, cardiovascular mortality, stroke (fatal as well as nonfatal), coronary events, and all cardiovascular endpoints were calculated for each quintile of serum creatinine or serum uric acid or for each category of protein excretion (none, trace, and overt). Crude and adjusted relative hazard rates were also determined for each 20 micro M increase in serum creatinine, each 50 micro M increase in serum uric acid, and for each protein excretion category. Even when adjusted for age, gender, and various other covariates, serum creatinine was significantly associated with a worse prognosis. There was an U-shaped relationship between serum uric acid and total mortality, but otherwise no obvious relationships were detected between serum uric acid levels and complications when appropriate adjustments were made for confounding variables. Proteinuria at entry was a significant predictor of total mortality and all cardiovascular endpoints. It is concluded that higher levels of serum creatinine and trace or overt proteinuria are associated with an increased number of cardiovascular events and with a higher mortality in patients with isolated systolic hypertension.