Kimmo Ronkainen

Cardiorespiratory Fitness Is Related to the Risk of Sudden Cardiac Death : A Population-Based Follow-Up Study

OBJECTIVES Our aim was to examine the relation of cardiorespiratory fitness with sudden cardiac death (SCD) in a population-based sample of men. BACKGROUND Very limited information is available about the role of cardiorespiratory fitness in the prediction of SCD. METHODS This population study was based on 2,368 men 42 to 60 years of age. Cardiorespiratory fitness was defined by using respiratory gas exchange analyzer and maximal workload during cycle ergometer exercise test. RESULTS During the 17-year follow-up, there were 146 SCDs. As a continuous variable, 1 metabolic equivalent (MET) increment in cardiorespiratory fitness was related to a decrease of 22% in the risk of SCD (relative risk: 0.78, 95% confidence interval: 0.71 to 0.84, p<0.001). In addition to cardiorespiratory fitness, ischemic ST-segment depression during exercise testing, smoking, systolic blood pressure, prevalent coronary heart disease, family history of coronary heart disease, and type 2 diabetes mellitus were related to the risk of SCD. The Harrell C-index for the total model discrimination was 0.767, while cardiorespiratory fitness provides modest improvement (from 0.760 to 0.767) in the risk prediction when added with all other risk factors. The integrated discrimination improvement was 0.0087 (p=0.018, relative integrated discrimination improvement 0.11) when cardiorespiratory fitness was added in the model. However, the net reclassification index (-0.018) was not statistically significantly improved (p=0.703). CONCLUSIONS Cardiorespiratory fitness is a predictor of SCD in addition to that predicted by conventional risk factors. There was a slight improvement in the level of discrimination, although the net reclassification index did not change while using cardiorespiratory fitness with conventional risk factors.

Serum lycopene decreases the risk of stroke in men A population-based follow-up study

Objective: Intake of fruits and vegetables and levels of serum carotenoids have been associated with decreased risk of stroke, but the results have been inconsistent. The aim of the present study was to examine whether serum concentrations of major carotenoids, α-tocopherol and retinol, are related to any stroke and ischemic stroke in men. Methods: The study population consisted of 1,031 Finnish men aged 46−65 years in the Kuopio Ischaemic Heart Disease Risk Factor cohort. Serum concentrations of carotenoids retinol and α-tocopherol were measured by high-performance liquid chromatography. The association between the serum concentrations of lycopene α-carotene, β-carotene, α-tocopherol, and retinol and the risk of strokes was studied by using Cox proportional hazards models. Results: A total of 67 strokes occurred, and 50 of these were ischemic strokes during a median of 12.1 follow-up years. After adjustment for age, examination year, BMI, systolic blood pressure, smoking, serum low-density lipoprotein cholesterol, diabetes, and history of stroke, men in the highest quartile of serum lycopene concentrations had 59% and 55% lower risks of ischemic stroke and any stroke, compared with men in the lowest quartile (hazard ratio [HR] = 0.45, 95% confidence interval [CI] 0.25−0.95, p = 0.036 for any stroke and HR = 0.41; 95% CI 0.17−0.97, p = 0.042 for ischemic stroke). α-Carotene, β-carotene, α-tocopherol, and retinol were not related to the risk of strokes. Conclusions: This prospective study shows that high serum concentrations of lycopene, as a marker of intake of tomatoes and tomato-based products, decrease the risk of any stroke and ischemic stroke in men.

Serum β-carotene concentrations and the risk of congestive heart failure in men: A population-based study

BACKGROUND Fruit and vegetable intake has been associated with lower risk for cardiovascular diseases, but data on congestive heart failure (CHF) are inconsistent. The association of serum carotenoids, biomarkers reflecting fruit and vegetable intake, with the risk of CHF has not been well documented in previous studies. We therefore examined the association between carotenoid levels and the risk of CHF. METHODS Data were available for 1031 males aged 46 to 65 years participating in the Kuopio Ischaemic Heart Disease Risk Factor Study (Finland). Baseline data for the present study were collected between 1991 and 1993. The association between serum concentrations of carotenoids and the risk of CHF was examined by using Cox proportional hazard models. RESULTS During the median of 17.8 follow-up years, CHF occurred in 72 patients. Age and examination year adjusted risk (hazard ratio, HR) for CHF among men within the lowest quartile of serum β-carotene was 4.08 (95% CI, 1.90-8.78, p<0.001) as compared to men in the highest quartile of serum β-carotene. After further adjustment for many potential confounders, men with the lowest quartile of β-carotene had almost 3-fold increased risk of CHF (HR=2.78, 95% CI, 1.23-6.25, p=0.014). However, serum concentrations of lycopene and α-carotene were not related to the risk of CHF. CONCLUSIONS The present study suggests that low concentrations of serum β-carotene may be associated with an increased risk of CHF.

Impaired Fasting Plasma Glucose and Type 2 Diabetes Are Related to the Risk of Out-of-Hospital Sudden Cardiac Death and All-Cause Mortality

OBJECTIVE The aim of the study was to determine whether impaired fasting plasma glucose (FPG) and type 2 diabetes may be risk factors for sudden cardiac death (SCD). RESEARCH DESIGN AND METHODS This prospective study was based on 2,641 middle-aged men 42–60 years of age at baseline. Impaired FPG level (≥5.6 mmol/L) among nondiabetic subjects (501 men) was defined according to the established guidelines, and the group with type 2 diabetes included subjects (159 men) who were treated with oral hypoglycemic agents, insulin therapy, and/or diet. RESULTS During the 19-year follow-up, a total of 190 SCDs occurred. The relative risk (RR) for SCD was 1.51-fold (95% CI 1.07–2.14, P = 0.020) for nondiabetic men with impaired FPG and 2.86-fold (1.87–4.38, P < 0.001) for men with type 2 diabetes as compared with men with normal FPG levels, after adjustment for age, BMI, systolic blood pressure, serum LDL cholesterol, smoking, prevalent coronary heart disease (CHD), and family history of CHD. The respective RRs for out-of-hospital SCDs (157 deaths) were 1.79-fold (1.24–2.58, P = 0.001) for nondiabetic men with impaired FPG and 2.26-fold (1.34–3.77, P < 0.001) for men with type 2 diabetes. Impaired FPG and type 2 diabetes were associated with the risk of all-cause death. As a continuous variable, a 1 mmol/L increment in FPG was related to an increase of 10% in the risk of SCD (1.10 [1.04–1.20], P = 0.001). CONCLUSIONS Impaired FPG and type 2 diabetes represent risk factors for SCD.

Serum β-carotene and the risk of sudden cardiac death in men: A population-based follow-up study

OBJECTIVES To examine whether serum concentrations of carotenoids are related to the risk of sudden cardiac death (SCD) in middle-aged men. METHODS The study population consisted of 1031 Finnish men aged 46-65 years of the Kuopio Ischemic Heart Disease Risk Factor (KIHD) cohort. Serum concentrations of carotenoids were measured by high-performance liquid chromatography. The hazard ratios (HR) of serum β-carotene, lycopene and α-carotene were estimated by using the Cox proportional hazard model after adjusting for age and other potential confounding factors. RESULTS During a median follow-up of 15.9 years a total of 59 incidents of SCD occurred. After controlling for age, systolic blood pressure, waist circumference, smoking, alcohol consumption, years of education, serum LDL cholesterol, serum hs-CRP, diabetes, prevalent coronary heart disease (CHD) and congestive heart failure (CHF), men in the lowest tertile of serum concentrations of β-carotene had a 2-fold increased risk of SCD (HR=2.15, 95% CI: 1.02-4.51; p=0.044) as compared to those in the highest tertile. The risk of SCD was borderline significant for lycopene. In addition, low serum β-carotene concentrations increased the risk of cardiovascular disease (CVD) and total mortality. Lycopene and α-carotene were not related to the risk of SCD. CONCLUSIONS Our findings suggest that low serum β-carotene concentrations may increase the risk of SCD in middle-aged Finnish men. Furthermore, low serum β-carotene concentrations may be related to the risk of CVD and total mortality.

Inflammatory markers and extent and progression of early atherosclerosis: Meta-analysis of individual-participant-data from 20 prospective studies of the PROG-IMT collaboration

Background Large-scale epidemiological evidence on the role of inflammation in early atherosclerosis, assessed by carotid ultrasound, is lacking. We aimed to quantify cross-sectional and longitudinal associations of inflammatory markers with common-carotid-artery intima-media thickness (CCA-IMT) in the general population. Methods Information on high-sensitivity C-reactive protein, fibrinogen, leucocyte count and CCA-IMT was available in 20 prospective cohort studies of the PROG-IMT collaboration involving 49,097 participants free of pre-existing cardiovascular disease. Estimates of associations were calculated within each study and then combined using random-effects meta-analyses. Results Mean baseline CCA-IMT amounted to 0.74 mm (SD = 0.18) and mean CCA-IMT progression over a mean of 3.9 years to 0.011 mm/year (SD = 0.039). Cross-sectional analyses showed positive linear associations between inflammatory markers and baseline CCA-IMT. After adjustment for traditional cardiovascular risk factors, mean differences in baseline CCA-IMT per one-SD higher inflammatory marker were: 0.0082 mm for high-sensitivity C-reactive protein (p < 0.001); 0.0072 mm for fibrinogen (p < 0.001); and 0.0025 mm for leucocyte count (p = 0.033). ‘Inflammatory load’, defined as the number of elevated inflammatory markers (i.e. in upper two quintiles), showed a positive linear association with baseline CCA-IMT (p < 0.001). Longitudinal associations of baseline inflammatory markers and changes therein with CCA-IMT progression were null or at most weak. Participants with the highest ‘inflammatory load’ had a greater CCA-IMT progression (p = 0.015). Conclusion Inflammation was independently associated with CCA-IMT cross-sectionally. The lack of clear associations with CCA-IMT progression may be explained by imprecision in its assessment within a limited time period. Our findings for ‘inflammatory load’ suggest important combined effects of the three inflammatory markers on early atherosclerosis.

Sociodemographic Characteristics and Drug Abuse Patterns of Treatment-Seeking Illicit Drug Abusers in Finland, 1997–2008: The Huuti Study

The epidemiological part of the Huume tietokanta (HUUTI) consortium research project is the first large-scale longitudinal study of treatment-seeking illicit drug abusers in Finland. The objective of this report was to describe the sociodemographic characteristics and drug abuse patterns of treatment-seeking clients at their first visit. This study analysed baseline data of 4817 clients (3365 men and 1452 women) aged 11–65 years who sought treatment for drug abuse between 1997 and 2008 at Helsinki Deaconess Institute. Data were collected using a structured questionnaire. The majority (56%) of clients were between 15 and 24 years, educated at elementary school level (75%), and unemployed (57%). Opiates (30%) were the primary drugs of abuse. The primary drugs were mostly injected (45%) and were abused daily during the past month (44%). Cannabis was the most common secondary drug of abuse (34%). The secondary drugs were predominantly smoked (39%) or taken orally (38%) and were abused once per week or less frequently during the past month (33%). Age at initiation of illicit drug abuse ranged from 5 to 49 years. Polydrug abuse was common, with a mean consumption of 3.5 concurrent polydrug use, which were combined from 3 or more drug classes. The prevalence of lifetime/ever intravenous drug abuse was 64% and past month intravenous drug abuse was 64%, respectively, and 13% reported sharing injecting equipment during the past month. Early initiation, polydrug abuse, and risky consumption of illicit drugs were major areas of concern among the study population. Injecting drug use could place considerable burden on health services in view of complications and transmission of infectious diseases.

Prediagnostic circulating markers of inflammation and risk of prostate cancer

Accruing evidence suggests that inflammation plays a role in prostate carcinogenesis. However, studies evaluating this association using C‐reactive protein (CRP) and interleukin‐6 as markers of inflammation have reported conflicting results. We investigated the associations of three common markers of inflammation (CRP, fibrinogen and leukocyte count) with the risk of prostate cancer in a prospective cohort of 2,571 men from Finland. During an average follow‐up period of 24 years (21–26 years), 203 men from the cohort who developed prostate cancer were identified via linkage to the nationwide Finnish Cancer Registry. We investigated the associations between the markers and the risk of prostate cancer using Cox proportional hazards model, adjusting for potential confounders. Elevated prediagnostic leukocyte count was associated with an increased risk of prostate cancer. In multivariable adjusted model, the relative risk of prostate cancer among men in the highest tertile of leukocyte count compared to men in the lowest tertile was 1.60 (95% confidence interval [CI] = 1.10–2.29, p‐trend = 0.01). Circulating CRP and fibrinogen were not associated with increased risk. The corresponding relative risks for elevated CRP and fibrinogen concentrations were 1.08 (95% CI: 0.74–1.60, p‐trend = 0.56) and 1.25 (95% CI: 0.87–1.81, p‐trend = 0.14), respectively. Men with elevated leukocyte counts had a 2.57‐fold (95% CI: 0.99–6.79) increased risk of prostate cancer mortality. The increased risk associated with elevated leukocyte counts warrants confirmation in other studies. Larger studies should consider combining at least two markers or using an inflammation score derived from many inflammatory markers to evaluate prostate cancer risk.

Serum carotenoids reduce progression of early atherosclerosis in the carotid artery wall among Eastern Finnish men.

Background Several previous epidemiologic studies have shown that high blood levels of carotenoids may be protective against early atherosclerosis, but results have been inconsistent. We assessed the association between atherosclerotic progression, measured by intima-media thickness of the common carotid artery wall, and serum levels of carotenoids. Methods We studied the effect of carotenoids on progression of early atherosclerosis in a population-based study. The association between concentrations of serum carotenoids, and intima-media thickness of the common carotid artery wall was explored in 840 middle-aged men (aged 46–65 years) from Eastern Finland. Ultrasonography of the common carotid arteries were performed at baseline and 7-year follow-up. Serum levels of carotenoids were analyzed at baseline. Changes in mean and maximum intima media thickness of carotid artery wall were related to baseline serum carotenoid levels in covariance analyses adjusted for covariates. Results In a covariance analysis with adjustment for age, ultrasound sonographer, maximum intima media thickness, examination year, body mass index, systolic blood pressure, smoking, physical activity, serum LDL cholesterol, family history of coronary heart disease, antihypertensive medication and serum high sensitivity C-reactive protein, 7-year change in maximum intima media thickness was inversely associated with lycopene (p = 0.005), α-carotene (p = 0.002) and β-carotene (p = 0.019), respectively. Conclusions The present study shows that high serum concentrations of carotenoids may be protective against early atherosclerosis.

T-Wave Inversion, QRS Duration, and QRS/T Angle as Electrocardiographic Predictors of the Risk for Sudden Cardiac Death

The aim of this study was to investigate the prognostic utility of isolated T-wave inversion (TWI), QRS duration, and QRS/T angle on electrocardiogram at rest as predictors for sudden cardiac death (SCD) and death from all causes. The assessment of electrocardiographic findings was based on a population-based cohort of 1,951 men (age 42 to 61 years) with a follow-up period of 20 years. Isolated TWI in the absence of ST depression, bundle branch block or major arrhythmias, prolonged QRS duration from 110 to 119 ms, and a wide QRS/T angle of >67° were identified from the 12-lead electrocardiograms. SCD was observed in 171 men (8.3%) during the follow-up. As a single electrocardiographic parameter, TWI (prevalence 2.4%) was associated with an increased risk of SCD (hazard ratio [HR] 3.30, 95% confidence interval [CI] 1.91 to 5.71, p<0.001) after adjustment for age and clinical factors. Similarly, prolonged QRS duration and wide QRS/T angle were significantly related to the risk of SCD, with HR 1.50 (95% CI 1.08 to 2.19, p=0.017) for QRS duration and HR 3.03 (95% CI 2.23 to 4.14, p<0.001) for QRS/T angle. The integrated discrimination improvement was significant when TWI (0.014, p=0.036) or QRS/T angle (0.015, p=0.002) was added to the model with age and clinical factors. In conclusion, TWI, QRS duration, and QRS/T angle are significantly associated with the risk of SCD and death from all causes beyond conventional cardiovascular risk predictors in the general population.