Ischemic Heart Disease Prospective Cohort Research Articles

Association between Serum Testosterone and Aortic Valve Stenosis: A Prospective Cohort Study.

Serum testosterone is associated with atherosclerotic cardiovascular disease, which shares risk factors with aortic stenosis (AS). The association between serum testosterone and AS has not been previously investigated. We aimed to assess the prospective association between serum testosterone and risk of AS. Serum testosterone was determined at baseline using a radioimmunoassay kit in 2577 men aged 42-61 years recruited into the Kuopio Ischemic Heart Disease prospective cohort study. Hazard ratios (HRs) with 95% confidence intervals (Cis) were estimated for AS. After a median follow-up of 27.2 years, 119 cases of AS were recorded. The risk of AS increased continuously with increasing serum testosterone across the range 25-39 nmol/L (p-value for nonlinearity = 0.49). In an analysis adjusted for age, body mass index, systolic blood pressure, total cholesterol, high-density lipoprotein cholesterol, smoking status, history of type 2 diabetes, history of coronary heart disease, and alcohol consumption, the HR (95% CI) for AS was 1.39 (1.10-1.76) per 10 nmol/L increase in serum testosterone. When alcohol consumption was replaced with physical activity, the HR (95% CI) was 1.38 (1.09-1.74). Comparing the bottom versus top third of serum testosterone, the corresponding (adjusted) risk estimates were 1.76 (1.11-2.81) and 1.76 (1.10-2.80), respectively. In middle-aged and older Finnish men, elevated levels of serum testosterone were associated with an increased risk of AS. Further research is needed to replicate these findings and assess any potential relevance of serum testosterone in AS prevention.

Cardiorespiratory Fitness and Risk of Aortic Stenosis (from a Prospective Cohort Analysis)

Cardiorespiratory fitness (CRF) is a major risk factor and predictor of atherosclerotic cardiovascular disease. However, the relationship between CRF and risk of aortic stenosis (AS) has not been previously investigated. Thus, we aimed to assess the prospective association between CRF and risk of AS. CRF, as measured by maximal oxygen uptake, was assessed using a respiratory gas exchange analyzer during cardiopulmonary exercise testing in 2,308 men aged 42 to 61 years recruited into the Kuopio Ischemic Heart Disease prospective cohort study. Hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated for AS. During a median follow-up of 27 years, 101 cases of AS occurred. Dose-response analysis suggested there might be a nonlinear relation between CRF levels and AS risk. In an analysis adjusted for age, body mass index, systolic blood pressure, total cholesterol, high-density lipoprotein cholesterol, smoking, history of type 2 diabetes mellitus, and coronary heart disease, the HRs 95% (CIs) of AS were 0.57 (0.34 to 0.96) and 0.91 (0.53 to 1.57) for participants in the middle and upper third of CRF levels, respectively, compared with participants in the bottom third. After further adjustment for alcohol consumption, the corresponding HRs (95% CIs) were 0.58 (0.34 to 0.97) and 0.91 (0.53 to 1.56), respectively. In conclusion, higher CRF levels may be associated with a lower incidence of AS in middle-aged and older Finnish men. Given the likely limitations of low statistical power, further research is needed to provide insights into the dose-response nature of any relationship between CRF and AS.

Serum copper-to-zinc ratio and risk of incident pneumonia in caucasian men: a prospective cohort study

Serum copper (Cu) and zinc (Zn), essential micronutrients that have important immunomodulatory and antimicrobial properties, are biomarkers of ageing. Serum Cu/Zn-ratio may be a more reliable marker for age-related degenerative conditions compared with serum Cu or Zn alone. We aimed to assess the association between Cu/Zn-ratio and the risk of incident pneumonia in a prospective cohort study. Serum levels of Cu and Zn were measured at baseline using atomic absorption spectrometry in 2503 men aged 42–61 years in the Kuopio Ischemic Heart Disease prospective cohort study. Hazard ratios (HRs) with confidence intervals (CIs) were calculated for incident pneumonia using Cox regression models. A total of 599 cases of pneumonia occurred during a median follow-up of 26.1 years. Serum Cu/Zn-ratio and Cu were each linearly associated with incident pneumonia. A unit increase in Cu/Zn-ratio was associated with an increased risk of pneumonia in analysis adjusted for potential confounders including C-reactive protein (HR 1.65; 95% CI 1.17–2.33). The corresponding adjusted HR (95% CI) was 2.04 (1.22–3.40) for serum Cu. The association between serum Zn and pneumonia was curvilinear. Compared to the bottom tertile of Zn, the multivariable adjusted HRs (95% CIs) for incident pneumonia were 0.68 (0.55–0.83) and 0.96 (0.79–1.16) for the middle and top tertiles of Zn, respectively. Further analysis in the same participants showed that Cu/Zn-ratio might be a stronger risk indicator for pneumonia than serum C-reactive protein. In middle-aged and older Finnish men, increased serum Cu/Zn-ratio and Cu concentrations are each linearly associated with an increased risk of incident pneumonia.

Exercise heart rate reserve and recovery as risk factors for sudden cardiac death

BackgroundLittle is known if heart rate responses during and after exercise test may be associated with the risk of sudden cardiac death (SCD). Our aim was to determine if exercise heart rate reserve and recovery, providing non-invasive indices, may predict SCD risk in general male population. MethodsWe evaluated the impact of delayed heart rate reserve and slow heart rate recovery and the risk of SCD in the Kuopio Ischemic Heart Disease prospective cohort study of randomly selected 1967 men aged 42–61 years at recruitment. Heart rate reserve was calculated as the difference between the maximal attained heart rate and resting heart rate, whereas heart rate recovery was defined as maximal heart rate minus the heart rate measured at 2 min of recovery, on a symptom-limited cardiopulmonary exercise testing. ResultsDuring a median follow-up interval of 25 years, 209 events of SCD occurred. The age and examination adjusted relative hazards of SCD were in the lowest third of heart rate reserve 3.86 (95% confidence interval (CI) 2.56–5.80, p < 0.001) and the lowest third of heart rate recovery 2.86 (95% CI 1.95–4.20, p < 0.001) as compared to men in the highest third of heart rate reserve and heart rate recovery, respectively. After adjusting for potential confounders, the respective relative hazards were 1.96 (95% CI 1.24–3.12) and 1.75 (95% CI 1.16–2.64). Each unit increment (1 beat/min) in heart rate reserve and heart rate recovery decreased the incidence of SCD by 1–2%. ConclusionsDelayed exercise heart rate reserve and slow heart rate recovery predicted the risk of SCD, suggesting that heart rate responses may be associated with an increased risk for SCD in general population.

The combined effect of blood pressure and C-reactive protein with the risk of mortality from coronary heart and cardiovascular diseases

Background and aimsBoth blood pressure and C-reactive protein (CRP) are individually associated with cardiovascular mortality risk. However, the combined effect of systolic blood pressure (SBP) and CRP on coronary heart disease (CHD) and cardiovascular disease (CVD) mortality risk, has not been studied. Methods and resultsWe evaluated the joint impact of SBP and CRP and the risk of mortality in the Kuopio Ischemic Heart Disease prospective cohort study of 1622 men aged 42–61 years at recruitment with no history of CVD. SBP and CRP were measured. SBP was categorized as low and high (cut-off 135 mmHg) and CRP as low and high (cut-off 1.54 mg/L) based on ROC curves. Multivariable adjusted hazard ratios (HRs) with confidence intervals (CI) were calculated.During a median follow-up of 28 years, 196 cases of CHD and 320 cases of CVD deaths occurred. Elevated SBP (>135 mmHg) combined with elevated (CRP >1.54 mg/L) were associated with CHD and CVD mortality (HR 3.41, 95% CI, 2.20–5.28, p < 0.001) and (HR 2.93, 95% CI, 2.11–4.06, p < 0.001) respectively after adjustment for age, examination year, smoking, alcohol consumption, BMI, Type 2 diabetes, energy expenditure, total cholesterol, serum HDL cholesterol, antihypertensive medication and use of aspirin. ConclusionThe combined effect of both high systolic blood pressure and high CRP is associated with increased risk of future CHD and CVD mortality as compared with both low SBP and low CRP levels in general male Caucasian population.

Circulating Serum Copper Is Associated with Atherosclerotic Cardiovascular Disease, but Not Venous Thromboembolism: A Prospective Cohort Study

Background and Objective: Serum copper has been linked to the risk of atherosclerotic cardiovascular disease (CVD). However, the potential association between serum copper and venous thromboembolism (VTE) is not known. The principal aim was to evaluate the potential prospective association between serum copper and VTE risk. A secondary aim was to confirm or refute previously reported associations between serum copper and atherosclerotic CVD. Methods: Serum copper was measured at baseline using atomic absorption spectrometry in 2,492 men aged 42–61 years without a history of VTE in the Kuopio Ischemic Heart Disease prospective cohort study. Cox regression models were used to calculate hazard ratios (HRs) with 95% confidence interval (CI) for VTE. Results: During a median follow-up of 27.0 years, 166 VTE events occurred. The risk of VTE per 1 standard deviation increase in serum copper in age-adjusted analysis was HR: 1.02; 95% CI: 0.88–1.20, which was attenuated to HR: 0.99; 95% CI: 0.82–1.19, following further adjustment for several established and emerging risk factors. Comparing the top versus bottom tertiles of serum copper, the corresponding adjusted HRs were 1.16 (95% CI: 0.80–1.66) and 1.11 (95% CI: 0.74–1.68), respectively. In 1,901 men without a history of coronary heart disease (CHD), the multivariable-adjusted HR for CHD was 1.32 (95% CI: 1.10–1.59) comparing extreme tertiles of serum copper. Conclusion: In middle-aged Finnish men, we confirmed previously reported associations between high serum copper levels and increased risk of atherosclerotic CVD, but serum copper was not associated with future VTE risk. Other large-scale prospective studies conducted in women, other age-groups, and other populations are needed to confirm or refute these findings.

Joint effect of blood pressure and C-reactive protein and the risk of sudden cardiac death: A prospective cohort study

BackgroundBoth blood pressure and C-reactive protein (CRP) are each independently related to mortality risk. However, the combined effect of systolic blood pressure (SBP) and CRP on sudden cardiac death (SCD) risk has not been studied. Patients and methodsWe studied the joint impact of SBP and CRP and the risk of SCD in the Kuopio Ischemic Heart Disease prospective cohort study of 1953 men aged 42–61 years with no history of ischemic heart disease. Baseline investigations were conducted between March 1984 and December 1989. SBP and CRP were measured. SBP was divided based on median values to low and high (median cutoffs 132 mmHg) and CRP as low and high (median cut-off 1.30 mg/L). Hazard ratios (HRs) with confidence intervals (CIs) were calculated after multivariate adjustment. ResultsSubjects were followed-up for 23.2 years, and 137 SCDs occurred. In this study, elevated SBP (>132 mmHg) combined with elevated (CRP >1.30 mg/L) were associated with SCD risk. Adjustment for age, examination year, alcohol consumption, BMI, energy expenditure during exercise, total cholesterol, HDL-cholesterol, type 2 diabetes, smoking, antihypertension medication and aspirin use, the risk of SCD remained statistically significant (HR, 2,73, 95% CI, 1.62–4.60, p < .001). Further adjustment for socio-economic status, years of education and history of cardiovascular disease in a family the results were only slightly changed (HR, 2.65, 95% CI, 1.57–4.49, p < .001). ConclusionsIn our male cohort study, the joint effect of high SBP together with increased CRP levels is a risk predictor of SCD compared with low SBP and CRP.

Handgrip strength\u2014a risk indicator for future fractures in the general population: findings from a prospective study and meta-analysis of 19 prospective cohort studies

Evolving debate suggests that handgrip strength, a measure of muscular strength, might be associated with the risk of fractures; however, the evidence is conflicting. We aimed to assess the association of handgrip strength with the risk of fracture in the general population. Handgrip strength, measured using a dynamometer, was assessed at baseline in a population-based sample of 853 men and women aged 61–73 years in the Kuopio Ischemic Heart Disease prospective cohort. Hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated for incident fractures. Incident fractures (hip, humeral, or wrist) (n = 159) occurred during a median follow-up of 16.7 years. Comparing extreme tertiles of handgrip strength, the age- and sex-adjusted hazard ratio (95% CI) for fractures was 0.80 (0.55–1.18). The association remained similar on further adjustment for other potential confounders: HR (95% CI) of 0.82 (0.55–1.21). In a meta-analysis of 19 population-based prospective cohort studies (including the current study) comprising 220,757 participants and 9199 fractures (including 1302 hip fractures), the fully adjusted relative risk (RR) (95% confidence interval, CI) for incident fractures was 0.70 (0.61–0.80) comparing the top versus bottom thirds of handgrip strength. The association remained significant after trim-and-fill correction for publication bias. The corresponding RR (95% CI) for hip fractures (9 studies) was 0.61 (0.54–0.70). Handgrip was only modestly associated with fracture risk in the primary analysis, which may be driven by the low event rate. Pooled prospective cohort evidence suggests that elevated handgrip strength is associated with reduced future fracture risk.

Handgrip strength is not associated with risk of venous thromboembolism: a prospective cohort study

Objectives. Consistent evidence suggests an inverse and independent association between handgrip strength and arterial thrombotic disease. However, whether handgrip strength is related to future risk of venous thromboembolism (VTE) is uncertain. We sought to assess the prospective association between handgrip strength and VTE risk. Design. Handgrip strength was assessed using a hand dynamometer in a population-based sample of 864 men and women aged 61–74 years without a history of VTE at baseline in the Kuopio Ischemic Heart Disease prospective cohort study. Handgrip strength was allometrically scaled to account for the effect of body weight (handgrip strength/body weight2/3) and to normalize the data. Hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated for VTE. Results. During a median (interquartile range) follow-up of 17.2 (12.1–18.3) years, 58 VTE events were recorded. The risk of VTE did not significantly decrease per 1 standard deviation increase in normalized handgrip strength in age- and sex-adjusted analysis (HR 0.89; 95% CI 0.65–1.22). The association remained similar in analyses adjusted for several established and emerging risk factors (HR 0.90; 95% CI 0.65–1.25). The corresponding adjusted HRs were 1.10 (95% CI: 0.56–2.18) and 1.15 (95% CI: 0.57–2.34), respectively, when comparing the extreme tertiles of normalized handgrip strength values. Conclusions. Normalized handgrip strength is not associated with future VTE risk in an older Caucasian population. Large-scale studies in other populations and age-groups are warranted to generalize these findings.

Circulating Serum Magnesium and the Risk of Venous Thromboembolism in Men: A Long-Term Prospective Cohort Study

Background and Objective: Serum magnesium, an essential trace element involved in processes that regulate cardiovascular function, has been linked to the risk of atherosclerotic cardiovascular disease. However, the potential association between serum magnesium and venous thromboembolism (VTE) has not been previously investigated. We aimed to assess the prospective association of serum magnesium with the risk of VTE. Methods: Serum magnesium was measured using atomic absorption spectrometry in 2,361 men aged 42–61 years with no history of VTE at baseline in the Kuopio Ischemic Heart Disease prospective cohort. Cox regression models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for VTE. Results: A total of 159 incident VTE events were recorded during a median follow-up of 27.1 years. The risk of VTE per 1 SD increase in serum magnesium in the age-adjusted analysis was (HR 1.30; 95% CI 0.46–3.69). The association remained consistent in analyses adjusted for systolic blood pressure, body mass index, total cholesterol, triglycerides, smoking status, a history of type 2 diabetes, a history of coronary heart disease, medication for dyslipidemia, alcohol consumption, physical activity, socioeconomic status, serum active calcium, high-sensitivity C-reactive protein, and a history of cancer (HR 1.38; 95% CI 0.48–3.96). Comparing the extreme tertiles of serum magnesium, the corresponding adjusted HRs were 1.17 (95% CI 0.81–1.70) and 1.17 (95% CI 0.81–1.70), respectively. Conclusion: In a middle-aged Caucasian male population, serum-circulating magnesium was not associated with a future risk of VTE. Further studies in women, other age groups, and other populations are required to generalize these findings.

Finnish sauna bathing does not increase or decrease the risk of cancer in men: A prospective cohort study

IntroductionEvidence suggests that heat therapy can be used to prevent and treat cancer; anecdotal reports suggest passive heat therapies may increase cancer risk. Finnish sauna bathing has been linked to a reduced risk of chronic diseases, but its association with cancer risk is unknown. We aimed to assess the prospective association between frequency of sauna bathing and the risk of all-cause and site-specific cancers using the Kuopio Ischemic Heart Disease prospective cohort. MethodsBaseline sauna bathing habits were assessed in 2173 men aged 42–61 years with no history of cancer. Hazard ratios (HRs) with 95% confidence intervals (CIs) for cancer were calculated using Cox proportional hazard models. We corrected for within-person variability in sauna bathing habits using data from repeat assessments taken 11 years apart. ResultsDuring a median follow-up of 24.3 years, 588 (27.1%) all-cause cancer cases were recorded. The age-adjusted regression dilution ratio of sauna bathing frequency was 0.69 (0.62–0.76). In multivariable-adjusted analyses, the HRs (95% CIs) of all-cause cancer were 0.92 (0.76–1.11) and 0.92 (0.66–1.27) for men who had 2-3 and ≥4 sauna sessions per week, respectively, compared with men who had ≤1 sauna session per week. The non-significant findings were consistent for prostate, gastrointestinal and lung cancers on multivariate adjustment. ConclusionFrequent Finnish sauna bathing is not associated with the risk of cancer in a middle-aged male Caucasian population. Further studies are required to confirm or refute these findings, particularly in women and other age groups.

Cardiorespiratory fitness is not associated with risk of venous thromboembolism: a cohort study

Objectives. The inverse and independent association between cardiorespiratory fitness (CRF) and arterial thrombotic disease is well established. However, the potential association between CRF and venous thromboembolism (VTE) is not well known. We aimed to assess the prospective association of CRF with the risk of VTE. Design. Cardiorespiratory fitness, as measured by maximal oxygen uptake (VO2max), was assessed using a respiratory gas exchange analyser in 2,249 men aged 42–61 years without a history of VTE at baseline in the Kuopio Ischemic Heart Disease prospective cohort. Cox-regression models were used to calculate hazard ratios (HR) with 95% confidence interval (CI) for VTE. We corrected for within-person variability in CRF levels using data from repeat measurements taken several years apart. Results. There were 144 (6.4%) incident VTE events recorded during a median follow-up of 25.2 years. The age-adjusted regression dilution ratio of CRF was 0.58 (95% CI: 0.53–0.64). The risk of VTE did not significantly decrease per 1 standard deviation increase in CRF in age-adjusted analysis (HR 0.90; 95% CI 0.75–1.08). The association remained consistent in analyses adjusted for several established and emerging risk factors (HR 0.90; 95% CI 0.73–1.12). The corresponding adjusted HRs were 0.80 (95% CI: 0.52–1.23) and 0.82 (95% CI: 0.51–1.32) respectively, when comparing the extreme tertiles of CRF levels. Conclusions. In a middle-aged Caucasian male population, CRF was not associated with future risk of VTE. Further studies are required to confirm and to generalize these findings, particulary in women and other age groups.

Cardiorespiratory Fitness and the Risk of Serious Ventricular Arrhythmias: A Prospective Cohort Study

Cardiorespiratory fitness (CRF) is an established risk factor for cardiovascular disease outcomes. However, the relationship of CRF with risk of ventricular arrhythmias (VAs) is unknown. We aimed to assess the prospective association of CRF with the risk of serious VAs. Cardiorespiratory fitness, as measured by maximal oxygen uptake, was assessed using a respiratory gas exchange analyzer in 2299 middle-aged men in the Kuopio Ischemic Heart Disease prospective cohort. We corrected for within-person variability in CRF levels using data from repeated measurements 11 years apart. During median follow-up of 25.3 years (interquartile range, 18.7-27.2 years), 73 serious VAs were recorded. The age-adjusted regression dilution ratio of CRF was 0.58 (95% CI, 0.53-0.64). In analysis adjusted for age, the hazard ratio (HR) for serious VAs per 1-SD increase in CRF was 0.64 (95% CI, 0.49-0.84). The association persisted on additional adjustment for body mass index, systolic blood pressure, history of hypertension, prevalent coronary heart disease, smoking, history of diabetes, cholesterol level, alcohol consumption, and physical activity (HR, 0.67; 95% CI, 0.51-0.88). The corresponding adjusted HRs (95% CIs) were 0.29 (0.14-0.59) and 0.32 (0.15-0.65), respectively, comparing the top vs bottom tertiles. The associations were stronger on correction for regression dilution bias, remained consistent on exclusion of men with a history of coronary heart disease, and did not vary importantly in several relevant clinical subgroups. Cardiorespiratory fitness is inversely associated with future risk of serious VAs, independently of several cardiovascular disease risk factors. Further research is needed to assess the causal relevance of these findings.

Editors' note: Sauna bathing reduces the risk of stroke in Finnish men and women: A prospective cohort study

In the article “Sauna bathing reduces the risk of stroke in Finnish men and women: A prospective cohort study,” Kunutsor et al. reported a reduced risk of stroke in sauna bathers over a median follow-up of 14.9 years in middle-aged to elderly participants in the Finnish Kuopio Ischemic Heart Disease prospective cohort study. In response, Yu et al. suggest that the status of intracranial vasculature be included in the analysis as it may influence hemodynamic responses to sauna exposure. Dippel et al. highlight the risk of healthy volunteer bias and the absence of a sauna-naive reference group, and also note the lack of an adequate biological explanation for protective effects seen not only in stroke but also in other diseases. Replying to these comments, Kunutsor et al. note that they did not have vascular imaging data but contend that their Caucasian cohort was less likely to have significant asymptomatic intracranial atherosclerosis. While acknowledging potential limitations of selection bias, they emphasize relevant strengths of their study, and cite evidence on beneficial effects of sauna exposure on factors like blood pressure and inflammation that are implicated in stroke, Alzheimer disease, and respiratory conditions. In the article “Sauna bathing reduces the risk of stroke in Finnish men and women: A prospective cohort study,” Kunutsor et al. reported a reduced risk of stroke in sauna bathers over a median follow-up of 14.9 years in middle-aged to elderly participants in the Finnish Kuopio Ischemic Heart Disease prospective cohort study. In response, Yu et al. suggest that the status of intracranial vasculature be included in the analysis as it may influence hemodynamic responses to sauna exposure.

Renin-angiotensin system inhibitors and risk of fractures: a prospective cohort study and meta-analysis of published observational cohort studies

The renin-angiotensin system (RAS) represents an important target of antihypertensive medications. Angiotensin-converting enzyme inhibitors (ACEI) and angiotensin II receptor blockers (ARB), which are widely-used RAS inhibiting drugs, have been suggested to have beneficial effects on bone tissue. We aimed to assess the associations of use of ACEIs and/or ARBs with the risk of fractures using a population-based prospective cohort and a meta-analysis of published prospective cohort studies. Information on antihypertensive medication use (including both ACEIs and ARBs) were assessed in 1743 men and women of the Kuopio Ischemic Heart Disease prospective cohort study. Hazard ratios (HRs) [95% confidence intervals (CI)] of ACEIs or ARBs use with incident fractures were calculated. A total of 203 composite (hip, humeral, and wrist) fractures occurred during a median follow-up of 14.8 years. In multivariate adjusted analysis, the HR for composite fractures comparing users of ACEIs or ARBs with non-users was 1.00 (0.59–1.69). The corresponding adjusted HR for hip fractures comparing users versus non-users of ACEIs or ARBs was 0.89 (0.32–2.47). Including the current study, a total of 11 observational cohort studies involving 3526,319 participants and >323,355 fractures were included in a meta-analysis. Comparing ACEI users with non-users and ARB users with non-users, the HRs for composite fractures were 1.09 (0.89–1.33) and 0.87 (0.76–1.01) respectively. The corresponding HRs for hip fractures were 0.91 (0.86–0.95) and 0.80 (0.75–0.85) respectively. Use of RAS inhibitors was not associated with long-term risk of composite fractures in both primary and pooled analyses. Pooled evidence however suggests a beneficial effect of RAS blockers on hip fracture risk.

Low serum magnesium levels are associated with increased risk of fractures: a long-term prospective cohort study

Magnesium, which is an essential trace element that plays a key role in several cellular processes, is a major component of bone; however, its relationship with risk of major bone fractures is uncertain. We aimed to investigate the association of baseline serum magnesium concentrations with risk of incident fractures. We analyzed data on 2245 men aged 42–61 years in the Kuopio Ischemic Heart Disease prospective cohort study, with the assessment of serum magnesium measurements and dietary intakes made at baseline. Hazard ratios [95% confidence intervals (CI)] for incident total (femoral, humeral, and forearm) and femoral fractures were assessed. During a median follow-up of 25.6 years, 123 total fractures were recorded. Serum magnesium was non-linearly associated with risk of total fractures. In age-adjusted Cox regression analysis, the hazard ratio (HR) (95% CIs) for total fractures in a comparison of the bottom quartile versus top quartile of magnesium concentrations was 2.10 (1.30–3.41), which persisted on adjustment for several established risk factors 1.99 (1.23–3.24). The association remained consistent on further adjustment for renal function, socioeconomic status, total energy intake, and several trace elements 1.80 (1.10–2.94). The corresponding adjusted HRs for femoral fractures were 2.56 (1.38–4.76), 2.43 (1.30–4.53) and 2.13 (1.13–3.99) respectively. There was no evidence of an association of dietary magnesium intake with risk of any fractures. In middle-aged Caucasian men, low serum magnesium is strongly and independently associated with an increased risk of fractures. Further research is needed to assess the potential relevance of serum magnesium in the prevention of fractures.

Gamma-glutamyltransferase and risk of prostate cancer: Findings from the KIHD prospective cohort study.

Increased circulating serum gamma-glutamyltransferase (GGT) has been linked with an increased risk of chronic disease outcomes, including overall and several site-specific cancers. However, the relationship of GGT with prostate cancer risk is uncertain. We aimed to assess the prospective association of GGT with risk of prostate cancer. Serum GGT activity was assessed at baseline in the Finnish Kuopio Ischemic Heart Disease prospective cohort of 2,390 men aged 42-61 years without a history of cancer at baseline. We corrected for within-person variability in GGT values using data from repeat measurements taken several years apart. During a median follow-up of 24.6 years, 230 cases of prostate cancer occurred. The age-adjusted regression dilution ratio for loge GGT was 0.69 [95% confidence interval (CI): 0.63-0.74]. Serum GGT was nonlinearly associated with risk of prostate cancer. In age-adjusted Cox regression analysis, the hazard ratio (95% CIs) for prostate cancer in a comparison of the top quartile versus bottom quartiles 1-3 of GGT values was 1.43 (1.07 to 1.93; p = 0.017), which persisted on adjustment for several established cancer risk factors 1.46 (1.06 to 2.02; p = 0.020). The association remained unchanged on further adjustment for total energy intake, socioeconomic status, physical activity and C-reactive protein. The association did not importantly vary across several clinical subgroups. GGT is positively and independently associated with future risk of prostate cancer in a middle-aged Finnish male population over long-term follow-up. Further research is needed to understand the mechanistic pathways involved and if GGT may have potential relevance in prostate cancer prevention.

Is High Serum LDL/HDL Cholesterol Ratio an Emerging Risk Factor for Sudden Cardiac Death? Findings from the KIHD Study.

Aim: Low-density lipoprotein cholesterol (LDL-c) and high-density lipoprotein cholesterol (HDL-c), which are components of total cholesterol, have each been suggested to be linked to the risk of sudden cardiac death (SCD). However, the relationship between LDL-c/HDL-c ratio and the risk of SCD has not been previously investigated. We aimed to assess the associations of LDL-c, HDL-c, and the ratio of LDL-c/HDL-c with the risk of SCD.Methods: Serum lipoprotein concentrations were assessed at baseline in the Finnish Kuopio Ischemic Heart Disease prospective cohort study of 2,616 men aged 42–61 years at recruitment. Hazard ratios (HRs) (95% confidence intervals [CI]) were assessed.Results: During a median follow-up of 23.0 years, a total of 228 SCDs occurred. There was no significant evidence of an association of LDL-c or HDL-c with the risk of SCD. In analyses adjusted for age, examination year, body mass index, systolic blood pressure, smoking, alcohol consumption, physical activity, years of education, diabetes, previous myocardial infarction, family history of coronary heart disease, and serum high sensitivity C-reactive protein, there was approximately a two-fold increase in the risk of SCD (HR 1.94, 95% CI 1.21–3.11; p = 0.006), comparing the top (> 4.22) versus bottom (≤ 2.30) quintile of serum LDL-c/HDL-c ratio.Conclusion: In this middle-aged male population, LDL-c or HDL-c was not associated with the risk of SCD. However, a high serum LDL-c/HDL-c ratio was found to be independently associated with an increased risk of SCD. Further research is warranted to understand the mechanistic pathways underlying this association.

Lipoprotein(a) and risk of sudden cardiac death in middle-aged Finnish men: A new prospective cohort study

BackgroundLipoprotein(a) [Lp(a)] is an established and independent risk factor for cardiovascular outcomes. However, the relationship of Lp(a) with risk of sudden cardiac death (SCD) is unknown. We aimed to assess the association of Lp(a) with risk of SCD in the Kuopio Ischemic Heart Disease prospective cohort study of 1881 men aged 42–61years at recruitment. Methods and resultsPlasma Lp(a) concentration was assessed at baseline and repeat measurements made several years apart. After a median follow-up of 24.7years, 141 SCDs were recorded. Hazard ratios (HRs) (95% confidence intervals [CI]) were assessed and were corrected for within-person variability in Lp(a) levels. The regression dilution ratio of loge Lp(a) adjusted for age was 0.84 (95% CI: 0.81–0.88). Lipoprotein(a) levels were log-linearly associated with risk of SCD. In analyses adjusted for established risk factors, the HR (95% CI) for SCD per 1 standard deviation (3.56-fold) higher baseline loge Lp(a) was 1.24 (1.05–1.47; P=0.013). This remained consistent on further adjustment for alcohol consumption, resting heart rate, lipids, and C-reactive protein 1.23 (1.04–1.46; P=0.018). HRs remained unchanged after accounting for incident coronary events and did not vary importantly in several relevant clinical subgroups. Adding Lp(a) to a SCD risk prediction model did not significantly improve risk discrimination beyond established risk factors, but improved the continuous net reclassification 30.2% (1.1 to 59.2%, P=0.042). ConclusionsAvailable evidence shows a continuous and independent association between Lp(a) levels and risk of SCD. Further research is needed to replicate these findings.

Serum magnesium and risk of new onset heart failure in men: the Kuopio Ischemic Heart Disease Study.

Serum magnesium is an essential intracellular cation involved in processes that regulate cardiovascular function and has been linked to the risk of several cardiovascular disease outcomes. We aimed to investigate the association of serum magnesium concentrations with risk of incident heart failure (HF). We studied 2181 middle-aged men without prevalent HF (aged 42-61years) enrolled in the finnish Kuopio Ischemic Heart Disease prospective cohort study with serum magnesium measurements made at baseline. Hazard ratios (95% confidence intervals [CI]) for HF were assessed. During a median follow-up of 24.8years, 278 HF events occurred. Baseline serum magnesium was weakly and inversely associated with several clinical markers and was continuously associated with risk of HF. The age-adjusted HR (95% CIs) for HF per 1 standard deviation (SD) higher serum magnesium levels was 0.86 (0.76-0.97). The HR (95% CIs) was 0.87 (0.76-0.98) after controlling for measures of adiposity, socio-economic variables, medical history, blood pressure, renal function, alcohol consumption, and lipids. These findings remained consistent in analyses accounting for incident coronary heart disease. The results were comparable across several clinically relevant subgroups and analyses with atrial fibrillation as a competing risk yielded similar results. Serum magnesium was continuously, inversely and independently associated with future risk of HF. Further research is needed to assess any potential relevance of serum magnesium in HF prevention.