Polygenic risk scores predict diabetes complications and their response to intensive blood pressure and glucose control.

AIMS/HYPOTHESIS: Type 2 diabetes increases the risk of cardiovascular and renal complications, but early risk prediction could lead to timely intervention and better outcomes. Genetic information can be used to enable early detection of risk. METHODS: We developed a multi-polygenic risk score (multiPRS) that combines ten weighted PRSs (10 wPRS) composed of 598 SNPs associated with main risk factors and outcomes of type 2 diabetes, derived from summary statistics data of genome-wide association studies. The 10 wPRS, first principal component of ethnicity, sex, age at onset and diabetes duration were included into one logistic regression model to predict micro- and macrovascular outcomes in 4098 participants in the ADVANCE study and 17,604 individuals with type 2 diabetes in the UK Biobank study. RESULTS: The model showed a similar predictive performance for cardiovascular and renal complications in different cohorts. It identified the top 30% of ADVANCE participants with a mean of 3.1-fold increased risk of major micro- and macrovascular events (p = 6.3 × 10-21 and p = 9.6 × 10-31, respectively) and a 4.4-fold (p = 6.8 × 10-33) higher risk of cardiovascular death. While in ADVANCE overall, combined intensive blood pressure and glucose control decreased cardiovascular death by 24%, the model identified a high-risk group in whom it decreased the mortality rate by 47%, and a low-risk group in whom it had no discernible effect. High-risk individuals had the greatest absolute risk reduction with a number needed to treat of 12 to prevent one cardiovascular death over 5 years. CONCLUSIONS/INTERPRETATION: This novel multiPRS model stratified individuals with type 2 diabetes according to risk of complications and helped to target earlier those who would receive greater benefit from intensive therapy.

Reference values of retinal microcirculation parameters derived from a population random sample.

Retinal microcirculation reflects retinal perfusion abnormalities and retinal arterial structural changes at relatively early stages of various cardiovascular diseases. Our objective has been to establish reference values for major functional and structural parameters of retinal microcirculation in a randomly selected urban population sample. A total of 398 randomly selected individuals from an urban population aged 25 to 65 years, resident in Pilsen, Czech Republic, were screened for major cardiovascular risk factors. Retinal microcirculation was assessed using scanning laser Doppler flowmetry (SLDF), with data evaluable in 343 patients. Of this number, complete data were available for 256 individuals free from manifest cardiovascular disease, diabetes and drug treatment for hypertension and/or dyslipidemia, constituting the reference value population. Juxtapapillary retinal capillary blood flow has increased significantly with age whereas vessel and luminal diameters have decreased. No sex differences in retinal microcirculation parameters have been found. Therefore, reference values for retinal microcirculation parameters have been established by age groups. Unattended automated office systolic BP, after adjusting for age, correlated significantly with wall-to-lumen ratio (WLR) and wall thickness (WT). Moreover, after adjusting for age and mean BP, a positive relationship has been found between carotid femoral pulse wave velocity and WT, WLR and wall cross-sectional area, indicating the interaction between micro- and macro-vasculature. In conclusion, our study is the first to provide reference values of retinal microcirculation parameters in a random Caucasian population sample. Our results have shown that, at the population level, the first structural changes in retinal microcirculation are those in lumen diameters. Of note, a close relationship between BP and vascular remodeling of retinal arterioles and between aortic stiffness and WLR of retinal arterioles suggests an interaction between micro- and macro-vasculature.

Longitudinal trends in the prevalence of hyperuricaemia and chronic kidney disease in hypertensive and normotensive adults.

The purpose: To evaluate longitudinal trends in the prevalence of hyperuricaemia and chronic kidney disease (CKD) in Czech adults with and without arterial hypertension (HT).Materials and methods: Two independent cross-sectional surveys were performed in 2006-2009 and 2015-2018, each screening involving 1% population random sample of the general population of nine districts of the Czech Republic aged 25-64 years, stratified by age and gender. Hyperuricaemia was defined as serum uric acid ≥ 420 µmol/l in men, and ≥ 360 µmol/l in women. CKD was defined as estimated glomerular filtration rate < 60 ml/min/1.73 m2 and/or albumin/creatinine ratio ≥ 3 mg/mmol.Results: Final analyses included 3504 individuals examined in 2006-2009, and 2309 in 2015-2018. The overall prevalence of hyperuricaemia increased from 16.4% to 25.2% in men (p < 0.001), and from 7.6% to 10.9% in women (p < 0.001), whereas the overall prevalence of CKD declined from 6.8% to 3.6% in men (p = 0.001), and from 7.6% to 4.8% in women (p < 0.001). There was no interaction between HT and hyperuricaemia in either gender; the increase in hyperuricaemia prevalence was observed both in hypertensive and normotensive adults and was accompanied by the increased prevalence of abdominal obesity. Contrarily, there was an interaction between HT and CKD in both men (p < 0.001) and women (p = 0.011); the CKD prevalence declined only in hypertensive individuals, specifically in those using antihypertensive medication and was accompanied by the increased use of renin-angiotensin-aldosterone system (RAS) inhibitors and calcium channel blockers (CCBs).Conclusions: Over the period of 10 years, the overall prevalence of hyperuricaemia increased, while the prevalence of CKD decreased. An increase in the prevalence of hyperuricaemia was observed both in hypertensive and normotensive individuals and was accompanied by an increase in the prevalence of abdominal obesity. A decline in the prevalence of CKD was only observed in hypertensive individuals and was accompanied by the increased use of RAS inhibitors and CCBs.

Primary aldosteronism in a general population sample. The Czech post-MONICA study.

Purpose: Primary aldosteronism (PA) is considered the most common form of secondary hypertension, however, its prevalence, particularly in a general population, is still a matter of debate. The aim of our study was to evaluate the prevalence of PA in a randomly selected general population sample.Materials and methods: A total of 1940 individuals (1% population random sample) aged 25-64 years were screened for major cardiovascular risk factors in six districts of the Czech Republic. Hypertension was defined as a mean of two blood pressure readings ≥140/90 mmHg at one visit or taking antihypertensive medication. Within this population, 740 individuals were labelled as hypertensives and 650 of them sampled for the analysis of direct plasma renin and serum aldosterone. The diagnosis of PA was based on elevated serum aldosterone, low plasma renin and high aldosterone/renin (ARR) ratio and was also verified by a confirmatory test with saline infusion.Results: Positive ARR was found in 52 (8%) individuals (64% women, 36% men, however, due to substatntial proportion of reluctatnt participants to undergo a further work-up (27%), we could confirm the diagnosis of PA only in 13 of them (2%). Aldosterone-producing adenoma was found in one case only, seven patients had idiopathic type and five individuals refused potential surgical treatment therefore, adrenal venous sampling was not performed.Conclusion: Elevated serum aldosterone together with low renin and high ARR were found in 52 (8%) of hypertensives selected from a general population sample, however, the diagnosis of PA was confirmed only in 13 of them (2%). This study based on a general population survey highlighted the difficulty of conducting epidemiological studies on primary aldosteronism in a relatively healthy cohort part of whom did not provide the level of collaboration that is necessary to assess the true prevalence of this condition.

Alcohol and cardiovascular disease: Position Paper of the Czech Society of Cardiology.

Epidemiologic studies consistently report a U-shaped curve relationship between the amount of alcohol consumption and cardiovascular disease, with consumption of ≥ three alcoholic drinks being associated with an increased risk. However, the cardioprotective effect of light and moderate alcohol consumption has been recently questioned. In the absence of a randomized trial confirming the cardioprotective effect of light or moderate alcohol consumption, an alternative method to prove the causality is Mendelian randomization using a genetic variant serving as a proxy for alcohol consumption. A Mendelian randomization analysis by Holmes et al. suggests that a reduction in alcohol intake is beneficial for cardiovascular health also in light to moderate drinkers. In a recent analysis of 83 prospective studies, alcohol consumption was roughly linearly associated with a higher risk of stroke, coronary heart disease excluding myocardial infarction, heart failure and risk of death from aortic aneurysm dissection. By contrast, increased alcohol consumption was associated with a lower risk of myocardial infarction. "Low-risk" alcohol consumption recommended by the National Institute of Public Health, Czech Republic, should not exceed 16 g of 100% ethanol/day for women and 24 g/day for men; at least two days a week should be alcohol free, and the dose of ethanol during binge drinking should not exceed 40 g. In practice, this means one standard drink daily for five days at most and two standard drinks at most when binge drinking. These amounts should be considered the highest acceptable limits, but alcohol consumption in general should be discouraged.

[Hypertension and hypercholesterolemia in the Czech population]. / Hypertenze a hypercholesterolemie v ceské populaci.

INTRODUCTION: Hypertension and hypercholesterolemia are inter-related ad mutually potentiating cardiovascular risk factors, which, when occurring together, strongly accelerate atherosclerosis and significantly increase cardiovascular risk.The aim of our study was to assess the prevalence and control of both risk factors in the Czech population. METHODS: A 1 % population random sample aged 40-64 years was examined within the Czech post-MONICA in 2006-2009. Hypertension was defined as systolic blood pressure 140 mm Hg and/or diastolic BP 90 mm Hg or use of antihypertensive medication. Hypercholesterolemia was defined according to cardiovascular risk and LDL-cholesterol levels or use of lipid-lowering drugs. RESULTS: In a group of 2 508 persons (51 % of females), hypertension was found in 52 % and hypercholesterolemia in 40 % of examined individuals. Both risk factors occurred together in 30 % of subjects. While lipid-lowering drugs were used by 39 % of individuals with hypertension and hypercholesterolemia, target LDL-cholesterol were achieved by only 42 % of treated individuals. Only a total of 10 % individuals with both hypertension and hypercholesterolemia achieved target levels for both risk factors. CONCLUSION: Treatment and control of hypercholesterolemia in patients with hypertension remains unsatisfactory in the Czech Republic. Taking into account the high prevalence of hypercholesterolemia and the substantial increase in cardiovascular risk, lipid-lowering drugs should be considered in each patient with hypertension.Key words: antihypertensive drugs - Czech post-MONICA - lipid-lowering drugs - SCORE - target values - total cardiovascular risk.

Dyslipidemia and cardiovascular disease in women.

Cardiovascular disease is the major cause of death in women in developed countries. Dyslipidemia is highly prevalent in women, particularly after the menopause. Elevated low-density lipoprotein cholesterol (LDL-C) has been identified as the key lipid parameter in both genders whereas HDL-cholesterol and triglycerides have been more closely associated, in some studies, with cardiovascular risk in women. Menopause has been shown to be associated with an increase in total and LDL-cholesterol and a decrease in HDL-cholesterol (predominantly in the HDL2 subfraction). Despite its beneficial effects on the lipid profile, hormone replacement therapy is not recommended for primary or secondary prevention of cardiovascular disease in women. The latest meta-analysis of statin trials with gender-specific outcomes showed a similar benefit in women and men. The addition of ezetimibe to simvastatin in patients with acute coronary syndromes showed a further reduction of the primary endpoint in both genders. While there are no gender-related differences in drug treatment of dyslipidemia, current guidelines, to avoid overtreatment, strongly suggest risk estimation before initiating lipid-lowering treatment in women without manifest cardiovascular disease.

The obesity paradox and survivors of ischemic stroke.

BACKGROUND: Although obesity is a risk factor for stroke and achieving normal weight is advocated to decrease stroke risk, the risk associated with obesity and weight loss after stroke has not been well established. The aim of this study was to assess the association of obesity at the time of stroke admission and weight loss after stroke with total mortality. METHODS: We analyzed 736 consecutive patients (mean age, 66 ± 11 years; 58% men) hospitalized for their first ischemic stroke. Body weight at hospital admission and at the outpatient visit during follow-up was used in the analysis. RESULTS: After multivariate adjustment, obesity at admission was associated with lower mortality risk as compared with normal weight (hazard ratio [HR], .50, P = .03). At the outpatient visit, with a median follow-up time of 16 months, 21% of patients had lost more than 3 kg of weight. Stroke severity, heart failure, transient ischemic attack, and depression after stroke were independently associated with significant weight loss. Weight loss of more than 3 kg was associated with increased mortality risk (HR, 5.87; P = .001) independently of other factors. Similar results were seen when weight loss was defined as losing more than 3% of baseline weight (HR, 4.97; P = .004). Weight gain of more than 5% of the baseline weight tended to be associated with better survival when compared with no weight change (log-rank test, P = .07). CONCLUSIONS: Normal weight at hospital admission and weight loss after ischemic stroke are independently associated with increased mortality. Overweight and obesity at baseline do not decrease the risk associated with weight loss.

Early vascular damage in retinal microcirculation in arterial hypertension: the Czech post-MONICA study.

Retinal microcirculation reflects retinal perfusion abnormalities and retinal arterial structural changes at relatively early stages of various cardiovascular diseases. Wall-to-lumen ratio (WLR) may represent the earliest step in hypertension-mediated organ damage.Our objective was to compare functional and structural parameters of retinal microcirculation in a randomly selected urban population sample, in hypertensive and normotensive individuals. DESIGN AND METHOD: A total of 398 randomly selected individuals from an urban population aged 25-65 years, residing in Pilsen, Czech Republic, were screened for major cardiovascular risk factors. Retinal microcirculation was assessed using scanning laser Doppler flowmetry, with data evaluable in 343 patients. Complete data were available for 342 individuals divided into four groups based on blood pressure and control status of hypertension: normotensive individuals ( n  = 213), treated controlled hypertensive individuals ( n  = 30), treated uncontrolled hypertensive individuals ( n  = 26), and newly detected/untreated hypertensive individuals ( n  = 73). RESULTS: There was a tendency to higher wall thickness in treated but uncontrolled hypertensive patients (compared to normotensive and treated controlled hypertensive individuals). WLR was significantly increased in treated but uncontrolled hypertensive patients as well as in individuals with newly detected thus untreated hypertension or in patients with known but untreated hypertension. There was no difference in WLR in treated, controlled hypertensive patients compared with normotensive individuals. CONCLUSION: Our results show that an increased WLR, reflecting early vascular damage, was found in newly detected individuals with hypertension and in untreated hypertensive patients, reflecting early hypertension-mediated vascular damage. Early initiation of hypertension treatment may be warranted.

Longitudinal Trends in Severe Dyslipidemia in the Czech Population: The Czech MONICA and Czech Post-MONICA Study.

Background: Severe hypercholesterolemia is associated with an increase in the risk of developing atherosclerotic cardiovascular disease. The aim of this analysis was to assess longitudinal trends in severe dyslipidemia (defined as total cholesterol > 8 mmol/L or LDL-cholesterol > 5 mmol/L) in a representative population sample of the Czech Republic and to analyze the longitudinal trends in the basic characteristics of individuals with severe dyslipidemia. Methods: Seven independent cross-sectional surveys were organized in the Czech Republic to screen for major cardiovascular risk factors (from 1985 to 2015-2018). A total of 20,443 randomly selected individuals aged 25-64 years were examined. Results: The overall prevalence of severe dyslipidemia was 6.6%, with a significant downward trend from the fifth survey onwards (2000/2001). Over the study period of 30+ years, the individuals with severe dyslipidemia became older, increased in BMI, and did not change their smoking habits. Total cholesterol and non-HDL-cholesterol decreased significantly in both sexes throughout the duration of the study. Conclusions: Despite a significant improvement in lipids in the Czech Republic from 1985, substantially contributing to the decline in cardiovascular mortality, the number of individuals with severe dyslipidemia remained high, and in most cases, they were newly detected during our screening examinations and were thus untreated.

Longitudinal trends in blood pressure, prevalence, awareness, treatment, and control of hypertension in the Czech population. Are there any sex differences?

Background: Hypertension is the most common cardiovascular disease which substantially increases cardiovascular morbidity and mortality. Despite the broad availability of antihypertensive medication, control of hypertension is not satisfactory worldwide. Objective: The study aim was to assess longitudinal trends in blood pressure, prevalence, awareness, treatment, and control of hypertension in a representative population sample of the Czechia from 1985 to 2016/2017, focusing on sex differences. Methods: A total of 7,606 men and 8,050 women aged 25-64 years were screened for major CV risk factors in seven independent cross-sectional surveys run consistently in the same six country districts of the Czechia between 1985 and 2016/2017. The population samples were randomly selected. Results: Over a study period of 31/32 years, there was a significant decline in systolic and diastolic blood pressure in both sexes, whereas the prevalence of hypertension decreased only in women. There was an increase in hypertension awareness in both sexes over the entire study period with consistently higher rates in women. The proportion of individuals treated with antihypertensive drugs increased significantly in both sexes throughout the study, again with consistently higher rates in women. Control of hypertension increased significantly over the study period with consistently higher rates in women. The age-adjusted trends in blood pressure, prevalence, awareness, and treatment of hypertension were significantly different in men and women, always in favor of women. The age-adjusted trends in control of hypertension in treated patients were equally poor in both sexes. Conclusion: There are significant differences in longitudinal trends in blood pressure, prevalence, awareness, treatment, and control of hypertension between men and women, always in favor of women except for the control of hypertension in treated patients, where it is equally poor in both sexes.

A high ankle-brachial index is associated with increased aortic pulse wave velocity: the Czech post-MONICA study.

BACKGROUND: Ankle brachial index (ABI) has been increasingly used in general practice to identify individuals with low ABI at high cardiovascular risk. However, there has been no consensus on the clinical significance of high ABI. The aim of our study was to compare aortic stiffness as a marker of cardiovascular risk in individuals with low (<1.0), normal (1.0-1.4), and high ABI (>1.4). METHODS: A total of 911 individuals from the Czech post-MONICA study (a randomly selected 1% representative population sample, aged 54 ± 13.5 years, 47% of men) were examined. ABI was measured using a handheld Doppler and aortic pulse wave velocity (aPWV) using the Sphygmocor device. RESULTS: Of the 911 individuals, 28 (3.1%) had low ABI and 23 (2.5%) high ABI. There was a U-shaped association between aPWV and ABI. aPWV was significantly higher in individuals with low and high ABI compared with the normal ABI group (11.1 ± 2.8, 8.3 ± 2.3, p < 0.001; 10.8 ± 2.5, 8.3 ± 2.3 m/s, p < 0.001, respectively). In a model adjusted for age, sex, systolic, diastolic, mean blood pressure and examiner, aPWV remained increased in both extreme ABI groups compared with the normal ABI group. In logistic regression analysis, aPWV together with glucose level, male sex, and a history of deep venous thrombosis were independent predictors of high ABI, while cholesterol was not. CONCLUSION: This is the first study showing increased aortic stiffness in individuals with high ABI, presumably responsible for increased left ventricular mass described previously in this group. These findings suggest increased cardiovascular risk of high ABI individuals.

Comparison of three office blood pressure measurement techniques and their effect on hypertension prevalence in the general population.

OBJECTIVES: There is an ongoing controversy about the magnitude of the difference between unattended automated office blood pressure (AOBP) and conventional office blood pressure (BP). The aim of our study was to compare unattended AOBP with both auscultatory BP and oscillometric attended AOBP in an epidemiological setting. METHODS: In 2588 participants of the Czech post-MoNItoring of CArdiovascular Disease study (a randomly selected 1% representative population sample aged 25-64 years, mean age 48 ±â€Š11 years, 47.5% males), BP was measured using an AOBP device unattended, auscultatory mercury sphygmomanometer and an oscillometric attended AOBP device. RESULTS: On average, auscultatory BP was 10.6/5.6 mmHg higher than unattended AOBP. Similarly, oscillometric attended AOBP was 9.9/3.4 mmHg higher than unattended AOBP, while the mean difference between attended oscillometric AOBP and auscultatory BP was 0.8/2.1 mmHg. Unattended systolic AOBP of 127 mmHg corresponded to SBP of 140 mmHg measured by a conventional sphygmomanometer. The prevalence of hypertension varied depending on the measurement technique and ranged from 31.5 to 40.1%. Reasonable agreement in hypertension diagnosis was observed with unattended AOBP cut-off at least 130/85 mmHg when compared with both auscultatory (McNemar P = 0.07, kappa 0.819) and attended oscillometric AOBP (McNemar P = 0.46, kappa 0.852) thresholds of at least 140/90 mmHg. CONCLUSION: Unattended automated office SBP is on average 10 mmHg lower than the office auscultatory or attended AOBP values. In epidemiological settings, a threshold of unattended AOBP at least 130/85 mmHg should make comparison of hypertension prevalence possible with studies using auscultatory techniques and cut-off values of 140/90 mmHg.

30-year trends in major cardiovascular risk factors in the Czech population, Czech MONICA and Czech post-MONICA, 1985 - 2016/17.

BACKGROUND: Compared with Western Europe, the decline in cardiovascular (CV) mortality has been delayed in former communist countries in Europe, including the Czech Republic. We have assessed longitudinal trends in major CV risk factors in the Czech Republic from 1985 to 2016/17, covering the transition from the totalitarian regime to democracy. METHODS: There were 7 independent cross-sectional surveys for major CV risk factors conducted in the Czech Republic in the same 6 country districts within the WHO MONICA Project (1985, 1988, 1992) and the Czech post-MONICA study (1997/98, 2000/01, 2007/08 and 2016/2017), including a total of 7,606 males and 8,050 females. The population samples were randomly selected (1%, aged 25-64 years). RESULTS: Over the period of 31/32 years, there was a significant decrease in the prevalence of smoking in males (from 45.0% to 23.9%; p < 0.001) and no change in females. BMI increased only in males. Systolic and diastolic blood pressure decreased significantly in both genders, while the prevalence of hypertension declined only in females. Awareness of hypertension, the proportion of individuals treated by antihypertensive drugs and consequently hypertension control improved in both genders. A substantial decrease in total cholesterol was seen in both sexes (males: from 6.21 ± 1.29 to 5.30 ± 1.05 mmol/L; p < 0.001; females: from 6.18 ± 1.26 to 5.31 ± 1.00 mmol/L; p < 0.001). CONCLUSIONS: The significant improvement in most CV risk factors between 1985 and 2016/17 substantially contributed to the remarkable decrease in CV mortality in the Czech Republic.

Which serum uric acid levels are associated with increased cardiovascular risk in the general adult population?

Our aim was to determine the serum uric acid (SUA) levels associated with an increased risk of cardiovascular (CV) and all-cause death in the general adult population. We analyzed data obtained in two independent cross-sectional surveys performed in the Czech Republic in 2006-09 and 2015-18, involving 1% population random samples in nine districts, aged 25-64 years, stratified by age and gender. Ten-year mortality data were obtained in a cohort with examination in 2006-09. Final analyses included 3542 individuals (48.2% men) examined in 2006-09, and 2304 (47.4% men) examined in 2015-18. From a cohort examined in 2006-09, 122 men and 60 women were reported dead (33% and 27% from CV disease). In men, there was no association of baseline SUA levels with baseline SCORE category or 10-year mortality rates. In women, each 10 µmol/L increase in baseline SUA levels was associated with an increase in baseline SCORE category (P < .001). Receiver operating characteristic curve analyses in women identified the baseline SUA cutoff values discriminating: 1. between low/intermediate and high/very high SCORE categories (309 µmol/L), 2. CV mortality (325 µmol/L), and 3. all-cause mortality (298 µmol/L). After adjusting for confounders including SCORE, Cox regression analysis confirmed that the baseline SUA cutoffs of 309 µmol/L and 325 µmol/L were associated with 4-times (P = .010) and 6-times (P = .036) greater risk of CV mortality, whereas the cutoff of 298 µmol/L was associated with 87% greater risk of all-cause mortality (P = .025). In conclusion, the SUA cutoff value of 309 µmol/L identified women at high/very high SCORE category and was associated with 4-times greater risk of observed CV mortality over 10 years.

Systematic COronary Risk Evaluation (SCORE) and 20-year risk of cardiovascular mortality and cancer.

BACKGROUND: Cardiovascular disease (CVD) followed by cancer are the two leading causes of death worldwide. SCORE charts have been recommended in Europe to identify individuals at increased CVD risk. However, the SCORE ability to identify individuals at increased risk of cancer has not yet been evaluated. The aim of this study was to determine the SCORE chart calibration in a country with changing CVD epidemiology, and its discrimination ability to identify individuals at increased risk of cancer over 20-years. METHODS: The present analysis includes data from two cross-sectional independent surveys within the Czech post-MONICA study (randomly selected representative population samples of the Czech Republic, aged 25-64 years); 3209 individuals in 1997/98 and 3612 in 2006-2009. RESULTS: The SCORE had reasonable discrimination to predict 10-year CVD mortality, but significantly overestimated the risk across all risk categories. During the 20-year follow up, high and very high-risk categories were associated with an increased risk of cancer morbidity (in particular colorectal, other gastrointestinal, lung and malignant skin) and cancer mortality, as compared to low risk category. CONCLUSIONS: The present study shows that periodical calibration testing of SCORE charts is needed in countries with changing CVD epidemiology. Furthermore, we show that in middle-aged individuals, identified by SCORE charts as being at high or very high risk for CVD, cancer morbidity and cancer mortality is increased. Rigorous cancer screening may be appropriate in this group, especially in countries with falling CVD mortality, where relative proportion of cancer mortality is increasing.

Is the impact of conventional risk factors the same in men and women? Plea for a more gender-specific approach.

Cardiovascular disease (CVD) is the leading cause of death in women in developed countries. The traditional modifiable risk factors are able to explain the majority of CVD mortality. The aim of this review is to analyze gender-specific aspects of major conventional cardiovascular risk factors and to assess whether they have the same impact on CVD in women. Cigarette smoking remains the single largest preventable cause of cardiovascular morbidity and premature death worldwide. Women smoke less than men; however, smoking seems to be more harmful in women, particularly in oral contraceptive users. Obesity in the general population is more prevalent in women. Visceral adiposity is associated with insulin resistance and a higher risk of developing cardiovascular disease. Life expectancy in female diabetic patients is shorter than in men with diabetes; women with diabetes are also at higher risk of developing cardiovascular events. Changes of main lipid parameters in women are frequently associated with their hormonal status and/or hormonal treatment. Hypertension is highly prevalent in post-menopausal women and carries a higher risk of developing left ventricular hypertrophy, which, together with a greater increase in vascular and myocardial stiffness, results in a higher incidence of heart failure with preserved ejection fraction and a higher risk of developing stroke. The risk of abdominal aortic rupture is substantially higher in women. In conclusion, smoking, diabetes and hypertension seem to be more harmful in women. Therefore, the question is whether there should not be lower thresholds for initiating drug treatment in women with diabetes and hypertension.

Uromodulin in a Pathway Between Decreased Renal Urate Excretion and Albuminuria.

BACKGROUND: The mechanism explaining the inverse association between renal urate and albumin excretion remains unclear. First, we evaluated the impact of candidate variants in the main urate transporter genes (i.e., SLC2A9, SLC22A12, ABCG2) on the association between fractional excretion of uric acid (FEUA) and urinary albumin/creatinine ratio (uACR). Second, we examined uromodulin and sodium excretion as mediators of the association between FEUA and uACR. METHODS: We performed cross-sectional analysis of 737 French Canadians from the CARTaGENE cohort, a random sample of the Quebec population aged 40-69 years (a total of 20,004 individuals). Individuals with available genotyping and urinary data were obtained from a sub-study including gender-matched pairs with high and low Framingham Risk Score and vascular rigidity index. We further excluded individuals with an estimated glomerular filtration rate <60 ml/min/1.73 m2, glycosuria, and use of confounding medication. A spot urine sample was analyzed. Genotyping was performed using the Illumina Omni2.5-8 BeadChips. Genetic variants were analyzed using an additive model. RESULTS: Final analyses included 593 individuals (45.5% of men; mean age 54.3 ± 8.6). We observed an antagonistic interaction between rs13129697 variant of the SLC2A9 gene and FEUA tertiles on uACR (P = 0.002). Using the mediation analysis, uromodulin explained 32%, fractional excretion of sodium (FENa) 44%, and uromodulin together with FENa explained 70% of the inverse relationship between FEUA and uACR. Bootstrapping process confirmed the role of both mediators. CONCLUSIONS: Our data suggest that the association of albuminuria with decreased renal urate excretion may be modified by the transporter SLC2A9, and mediated by uromodulin and sodium handling.

The Impact of Blood Pressure and Visceral Adiposity on the Association of Serum Uric Acid With Albuminuria in Adults Without Full Metabolic Syndrome.

BACKGROUND: The impact of metabolic phenotypes on the association of uricemia with urinary albumin/creatinine ratio (uACR) remains unresolved. We evaluated the association between serum uric acid and uACR in persons with 0, and 1-2 metabolic syndrome (MetS) components and determined the modification effects of visceral adiposity index (VAI), mean arterial pressure (MAP), and fasting glucose on this association. METHODS: Using data from a cross-sectional survey of a representative Czech population aged 25-64 years (n = 3612), we analyzed 1,832 persons without decreased glomerular filtration rate <60ml/min/1.73 m2, diabetes, and MetS. MetS components were defined using the joint statement of the leading societies. RESULTS: Of the 1,832 selected participants, 64.1% (n = 1174) presented with 1-2 MetS components (age 46.3±11.2; men 51.7%), whereas 35.9% (n = 658) were free of any component (age 39.4±10.0; men 34.2 %). In fully adjusted multiple linear regression models for uricemia, uACR was an independent factor for increase in uric acid levels only in persons with 1-2 MetS components (standardized beta (Sß) 0.048; P = 0.024); however, not in those without any component (Sß 0.030; P = 0.264). Uric acid levels increased by the interaction of uACR with VAI (Sß 0.06; P = 0.012), and of uACR with MAP (Sß 0.05; P = 0.009). Finally, the association of uACR with uricemia was confined to persons whose VAI together with MAP were ≥the median of 1.35 and 98mm Hg, respectively (Sß 0.190; P < 0.001). CONCLUSIONS: We demonstrated a strong modification effect of VAI and MAP on the association between uACR and uricemia, which suggests obesity-related hypertension as the underlying mechanism.