Kari Syvänen

endothelial function in a cardiovascular risk population with borderline ankle-brachial index

Introduction: The diagnosis of peripheral arterial disease (PAD) can be made by measuring the ankle–brachial index (ABI). Traditionally ABI values > 1.00–1.40 have been considered normal and ABI ≤ 0.90 defines PAD. Recent studies, however, have shown that individuals with ABI values between 0.90–1.00 are also at risk of cardiovascular events. We studied this cardiovascular risk population subgroup in order to determine their endothelial function using peripheral arterial tonometry (PAT). Methods: We selected 66 individuals with cardiovascular risk and borderline ABI. They all had hypertension, newly diagnosed glucose disorder, metabolic syndrome, obesity, or a ten year risk of cardiovascular disease death of 5% or more according to the Systematic Coronary Risk Evaluation System (SCORE). Subjects with previously diagnosed diabetes or cardiovascular disease were excluded. Endothelial function was assessed by measuring the reactive hyperemia index (RHI) from fingertips using an Endo-PAT device. Results: The mean ABI was 0.95 and mean RHI 2.11. Endothelial dysfunction, defined as RHI < 1.67, was detected in 15/66 (23%) of the subjects. There were no statistically significant differences in RHI values between subjects with different cardiovascular risk factors. The only exception was that subjects with impaired fasting glucose (IFG) had slightly lower RHI values (mean RHI 1.91) than subjects without IFG (mean RHI 2.24) (P = 0.02). Conclusions: In a cardiovascular risk population with borderline ABI nearly every fourth subject had endothelial dysfunction, indicating an elevated risk of cardiovascular events. This might point out a subgroup of individuals in need of more aggressive treatment for their risk factors.

Ankle-brachial index is lower in hypertensive than in normotensive individuals in a cardiovascular risk population.

Background Hypertension is an established risk factor for peripheral arterial disease (PAD), but the prevalence of this condition in hypertensive patients without comorbidities is unknown. Methods In this study, we assess the prevalence and factors associated with PAD, and the usefulness of ankle–brachial index (ABI) in evaluating cardiovascular risk in hypertensive patients without cardiovascular or renal disease or previously known diabetes mellitus. We measured ABI in 972 nonclaudicant patients with hypertension, newly diagnosed glucose disorders, metabolic syndrome, obesity or a 10-year risk of cardiovascular disease death of 5% or more according to the Systematic Coronary Risk Evaluation System. Results The prevalence of PAD (defined as ABI ≤0.90) and borderline PAD (defined as ABI 0.91–1.00) in hypertensive patients was 7.3% (39/532) and 23.7% (126/532), respectively. In a multivariate model, hypertension remained an independent factor associated with PAD (adjusted odds ratio 3.20; 95% confidence interval 1.56–6.58). There was no association between PAD and metabolic risk factors. SBP and pulse pressure increased linearly across subgroups of ABI (normal 0.91–1.00 and ≤0.90) in hypertensive patients (P < 0.001). Conclusion Subclinical PAD is common in hypertensive patients even without comorbidities. The measurement of ABI is an efficient method to identify patients with increased cardiovascular risk and worth performing to hypertensive patients, particularly those with pulse pressure above 65 mmHg. Uniform criterions of defining PAD and borderline PAD would aid physicians in clinical decision-making.

Novel biparametric MRI and targeted biopsy improves risk stratification in men with a clinical suspicion of prostate cancer (IMPROD Trial)

To evaluate the role of a 3T biparametric magnetic resonance imaging (bpMRI), T2‐weighted imaging, and three separate diffusion‐weighted imaging acquisitions combined with targeted biopsy (TB) for improving risk stratification of men with elevated prostate‐specific antigen (PSA).

High-Intensity Physical Activity, Stable Relationship, and High Education Level Associate with Decreasing Risk of Erectile Dysfunction in 1,000 Apparently Healthy Cardiovascular Risk Subjects

INTRODUCTION Erectile dysfunction (ED) is especially common in men with cardiovascular diseases (CVDs). However, the data are scarce concerning populations without manifested CVD. AIM The aim of this study was to describe factors associated with ED, especially those associated with decreasing risk of ED, in men with cardiovascular risk factors but without CVD, diabetes, or chronic renal disease. METHODS In 2004 to 2007, a cross-sectional population-based sample of men 45 to 70 years old in two rural towns in Finland was collected. Men with previously diagnosed CVD, diabetes, or kidney disease were not invited to the study. In total 1,000 eligible men with cardiovascular risk factors, i.e., central obesity, high scores in the Finnish Diabetes Risk Score, high blood pressure, antihypertensive medication, or family history of coronary heart disease, myocardial infarction, or stroke, were included in the analysis. Questionnaires, clinical measurements, and laboratory tests were obtained. The prevalence of ED was studied comparing the means, and risk factors were studied using multivariate logistic regression analysis. MAIN OUTCOME MEASURES The rate of ED was defined by the International Index of Erectile Function short form (IIEF-5) and by two questions (2Q) about the ability to achieve and to maintain an erection. RESULTS The prevalence of ED was 57% or 68% using IIEF-5 or 2Q, respectively. Age (odds ratio [OR]: up to 9.16; 95% confidence interval [CI], 5.00-16.79; P < 0.001), smoking (OR: 1.41; 95% CI, 1.04-1.91; P = 0.028), depressive symptoms (OR: 4.04 for moderate and severe; 95% CI,1.22-13.45; P = 0.001), high-intensity physical activity (OR: 0.50; 95% CI, 0.29-0.86; P = 0.045), high education (OR: 0.52; 95% CI, 0.33-0.83; P = 0.013), and stable relationship (OR: 0.43; 95% CI, 0.21-0.88; P = 0.046) were associated with ED. CONCLUSIONS In apparently healthy men with cardiovascular risk factors, decreasing risk of ED is associated with high-intensity physical activity, stable relationship, and high education level.

Stratification of aggressive prostate cancer from indolent disease—Prospective controlled trial utilizing expression of 11 genes in apparently benign tissue

BACKGROUND The aim of the study was to evaluate the diagnostic power of molecular markers in men with a clinical suspicion of prostate cancer (PCa) using apparently benign areas as targeted by magnetic resonance imaging (MRI). METHODS In the study, 99 consecutive men with clinical suspicion of PCa in a prospective controlled trial (IMPROD, NCT01864135) were included. In addition to 12-core systematic and MRI-targeted biopsies, cores from normal-appearing prostate areas, based on clinical examination, ultrasound, and biparametric prostate MRI, were obtained. The RNA transcript levels of ACSM1, AMACR, CACNA1D, DLX1, KLK3, PCA3, PLA2G7, RHOU, SPINK1, SPON2, TMPRSS2-ERG, and TDRD1 were measured with quantitative reverse-transcription polymerase chain reaction. RESULTS Of the 99 men, 69 were diagnosed with PCa, 31 with primary Gleason pattern 3 and 38 with primary Gleason 4 or 5. TDRD1 messenger RNA (mRNA) levels were 1.3 times higher (P = 0.029) and the presence of TMPRSS2-ERG mRNAs more frequent in biopsies from men diagnosed with PCa (27/69, 39%) than in men without (5/30, 16%) (P = 0.035). The 2 markers identified aggressive PCa defined as Gleason sum≥7 at biopsy: median TDRD1 mRNA level was 1.4 higher (P = 0.005) and TMPRSS2-ERG expression more frequent (P<0.001) in high-grade cancer. A multivariate analysis of mRNA expression of 11 candidate genes combined with KLK3, serum prostate-specific antigen (PSA), percentage-free PSA, and prostate volume improved the discrimination between aggressive and nonaggressive PCa (area under the curve = 0.77) compared with the use of the candidate genes or clinical parameters alone. However, serum PSA, percentage-free PSA, and prostate volume resulted in the best discrimination between non-organ-confined PCa (T3) from organ-confined PCa (T2) and healthy prostate (area under the curve = 0.86). CONCLUSIONS Of the 11 studied genes, TDRD1 and TMPRSS2-ERG were able to statistically significantly differentiate men with PCa from men without it as single markers. However, a multivariate analysis using 15 features outperformed each individual marker in identifying aggressive PCa.

High-Sensitivity C-Reactive Protein and Ankle Brachial Index in a Finnish Cardiovascular Risk Population

High-sensitivity C-reactive protein (hsCRP) has been previously linked to different forms of vascular disease. However, some studies have not found any relationship between hsCRP and atherosclerosis. Also, studies investigating correlation between hsCRP and ankle brachial index (ABI) are scarce. We studied hsCRP in a cardiovascular risk population with a special interest in correlation between hsCRP and ABI. All men and women aged 45 to 70 years from a rural town Harjavalta, Finland were invited to participate in a population survey. Diabetics and people with known vascular disease were excluded. Seventy-three percent (n = 2085) of the invited persons participated and 70% of the respondents (n = 1496) had at least one risk factor to cardiovascular diseases. These subjects were invited to further examinations. From them we measured ABI, hsCRP, leukocyte count, glucose tolerance, systemic coronary risk evaluation (SCORE), body mass index (BMI), and waist circumference. Mean hsCRP was 1.9 mg/L. Smokers had higher hsCRP (mean 2.2 mg/L) than nonsmokers (mean 1.8 mL/L). hsCRP in women was higher than in men (mean 2.0 mg/L versus 1.8 mg/L). Mean ABI was 1.10, and the prevalence of peripheral arterial disease was 3.1%. ABI correlated weakly with hsCRP (r = -0.077, p = 0.014), leukocyte count (r = -0.107, p = 0.001), and SCORE (r = -0.116, p = 0.001). It did not have correlation between age, weight, BMI, or waist circumference. hsCRP correlated with BMI (r = 0.208, p < 0.0001) and waist circumference (r = 0.325, p < 0.0001). When we excluded subjects with hsCRP >10 mg/L, ABI no longer correlated with hsCRP. In a cardiovascular risk population, hsCRP has only a weak correlation with ABI, and this correlation disappeared when we excluded subject with hsCRP >10 mg/L. Instead, hsCRP was correlated to the measures of obesity (waist circumference and BMI), indicating its role as a marker of adipose tissue-driven inflammation. hsCRP does not seem to be a suitable screening method for peripheral arterial disease.

Role of ultrasensitive prostate-specific antigen in the follow-up of prostate cancer after radical prostatectomy

OBJECTIVE Prostate-specific antigen (PSA) is an important tool in the follow-up of prostate cancer after radical prostatectomy (RP). However, the relevance of ultrasensitive PSA (uPSA) after RP is not well defined. The aim of this study was to investigate the value of uPSA in follow-up after RP and to determine whether ultrasensitive PSA doubling time (uDT) correlates with traditional PSA doubling time (tDT). PATIENTS AND METHODS In total, 604 consecutive patients undergoing open RP and pelvic lymphadenectomy between 2004 and 2008 (minimum 5y of follow-up) were studied. To evaluate the postsurgical uPSA level, scatter plot statistics were used. To correlate uDT and tDT in patients with a biochemical recurrence (PSA ≥0.2ng/ml), at least 2 uPSA and 2 PSA measurements without salvage treatment were required and a weighted Cohen kappa statistic and receiver operating characteristic curve were used to test agreement across the categories. RESULTS There were 229 patients without biochemical recurrence who did not have 3 rising PSA values after nadir within ultrasensitive area. Their highest uPSA value was between 0.003 and 0.1ng/ml. In 97.4% of patients, the highest uPSA value was less than 0.03ng/ml, and in 89% of these patients, the values were less than 0.02ng/ml. The median uDT and tDT were 10.2 and 11.4 months, respectively. The weighted Cohen kappa statistic between these 2 groups was 0.30 (95% CI:-0.09 to 0.50), demonstrating a poor agreement of PSA doubling time across categories. The predictive capability of uDT was tested with tDT <9 months. A receiver operating characteristic curve area under the curve value was 0.737 (95% CI:-0.577 to 0.897) demonstrating a fair agreement between the groups. CONCLUSIONS uPSA values>0.03ng/ml seems to be valid and can be used in a clinical setting. There was a poor to fair agreement between tDT and uDT. The accuracy of uDT improves when it approaches the traditional PSA threshold of 0.1ng/ml. Also according to our results, there is no prognostic benefit of uDT calculation.

Surrogates of Large Artery versus Small Artery Stiffness and Ankle-Brachial Index

Peripheral artery tonometry (PAT) is a novel method for assessing arterial stiffness of small digital arteries. Pulse pressure can be regarded as a surrogate of large artery stiffness. When ankle-brachial index (ABI) is calculated using the higher of the two ankle systolic pressures as denominator (ABI-higher), leg perfusion can be reliably estimated. However, using the lower of the ankle pressures to calculate ABI (ABI-lower) identifies more patients with isolated peripheral arterial disease (PAD) in ankle arteries. We aimed to compare the ability of PAT, pulse pressure, and different calculations of ABI to detect atherosclerotic disease in lower extremities. We examined PAT, pulse pressure, and ABI in 66 cardiovascular risk subjects in whom borderline PAD (ABI 0.91 to 1.00) was diagnosed 4 years earlier. Using ABI-lower to diagnose PAD yielded 2-fold higher prevalence of PAD than using ABI-higher. Endothelial dysfunction was diagnosed in 15/66 subjects (23%). In a bivariate correlation analysis, pulse pressure was negatively correlated with ABI-higher (r = -0.347, p = 0.004) and with ABI-lower (r = -0.424, p < 0.001). PAT hyperemic response was not significantly correlated with either ABI-higher (r = -0.148, p = 0.24) or with ABI-lower (r = -0.208, p = 0.095). Measurement of ABI using the lower of the two ankle pressures is an efficient method to identify patients with clinical or subclinical atherosclerosis and worth performing on subjects with pulse pressure above 65 mm Hg. The usefulness of PAT measurement in detecting PAD is vague.

Time trends and occupational variation in the incidence of testicular cancer in the Nordic countries

To describe the trends and occupational variation in the incidence of testicular cancer in the Nordic countries utilising national cancer registries, NORDCAN (NORDCAN project/database presents the incidence, mortality, prevalence and survival from >50 cancers in the Nordic countries) and NOCCA (Nordic Occupational Cancer) databases.

Erectile dysfunction cannot be used in primary screening of pre-diabetes.

We hypothesized that erectile dysfunction is associated with impaired fasting glucose and impaired glucose tolerance and could be used in primary screening of pre-diabetes. Although erectile dysfunction is known to be closely associated with diabetes, we demonstrate that it is not associated with pre-diabetes in 926 apparently healthy men.