Peripheral Atherosclerosis in Patients With Erectile Dysfunction: A Population-Based Study.

INTRODUCTION: The presence of erectile dysfunction (ED) could be a warning of vascular disease in different arterial territories. AIM: The aim of this study was to investigate the association between ED and the presence of atherosclerosis in 2 different vascular beds: carotid and lower limbs. METHODS: A total of 614 volunteers between 45 and 74 years of age (mean age 61.0 years) were randomly selected from the general population. ED was assessed using the International Index of Erectile Function (IIEF-5). Ankle-brachial index (ABI) measurement and carotid atherosclerosis were evaluated by echo-Doppler. MAIN OUTCOME MEASURES: Mean carotid intima-media thickness (IMT), prevalence of carotid plaques, mean ABI, and prevalence of ABI < 0.9 were the main outcome measures. RESULTS: ED was present in 373 subjects (59.7%). Mean carotid IMT was significantly higher in men with ED (0.762 ± 0.151 mm vs 0.718 ± 0.114 mm, P < .001). Also the global prevalence of carotid plaques was more frequent in men with ED (63.8% vs 44.8%, P < .001), even after adjusting by age, cardiovascular risk factors, and ongoing treatment (P = .039). Both the IMT and the prevalence of carotid plaques increased significantly with ED severity (P trend .004 and <.001, respectively). There were no significant differences between groups neither in mean ABI nor in the prevalence of subjects with ABI < 0.9. However, there was a trend to a lower ABI and a higher prevalence of ABI < 0.9 with increasing ED severity. CONCLUSION: In the general population, the presence of ED identifies subjects with higher atherosclerosis burden in carotid arteries but not in the lower extremities.

External validation of three diabetes prediction scores in a Spanish cohort: does adding high risk for depression improve the validation of the FINDRISC score (FINDRISC-MOOD)?

OBJECTIVES: To evaluate the external validity of the FINDRISC, DESIR and ADA risk scores for the prediction of diabetes in a Spanish population aged >45 years and to test the possible improvement of FINDRISC by adding a new variable of high risk of depression when Patient Health Questionnaire-9 (PHQ-9) questionnaire score ≥10 (FINDRISC-MOOD). DESIGN: Prospective population-based cohort study. SETTING: 10 primary healthcare centres in the north of the city of Madrid (Spain). PARTICIPANTS: A total of 1242 participants without a history of diabetes and with 2-hour oral glucose tolerance test (OGTT) plasma glucose <200 mg/dL (<11.1 mmol/L) were followed up for 7.3 years (median) using their electronic health records (EHRs) and telephone contact. PRIMARY AND SECONDARY OUTCOME MEASURES: Diabetes risk scores (FINDRISC, DESIR, ADA), PHQ-9 questionnaire and 2-hour-OGTT were measured at baseline. Incident diabetes was defined as treatment for diabetes, fasting plasma glucose ≥126 mg/dL (≥7.0 mmol/L), new EHR diagnosis or self-reported diagnosis. External validation was performed according to optimal cut-off, sensitivity, specificity and Youden Index. Comparison between diabetes risk scores, including FINDRISC-MOOD (original FINDRISC score plus five points if PHQ-9 ≥10), was measured by area under the receiver operating characteristic curve (AUROC). RESULTS: During follow-up, 104 (8.4%; 95% CI, 6.8 to 9.9) participants developed diabetes and 185 had a PHQ-9 score ≥10. The AUROC values were 0.70 (95% CI, 0.67 to 0.72) for FINDRISC-MOOD and 0.68 (95% CI, 0.65 to 0.71) for the original FINDRISC. The AUROCs for DESIR and ADA were 0.66 (95% CI, 0.63 to 0.68) and 0.66 (95% CI, 0.63 to 0.69), respectively. There were no significant differences in AUROC between FINDRISC-MOOD and the other scores. CONCLUSIONS: The results of FINDRISC-MOOD were like those of the other risk scores and do not allow it to be recommended for clinical use.

Differences in the ankle-brachial index in the general population after 4 years of follow-up.

BACKGROUND: Variation in the ankle-brachial index (ABI) is related to the progression of atherosclerosis in the lower extremities and is associated with mid-term cardiovascular morbidity and mortality. The aim of this study was to investigate the changes in ABI after four years of follow-up of individuals in the general population, and the factors associated with relevant variations observed. PATIENTS AND METHODS: The study was performed in 750 volunteers (mean age 69.9 years) men without any evidence of peripheral artery disease, who attended a primary care centre. A complete physical examination, together with standard blood tests and ABI were performed. Four years later a new clinical evaluation was done. Variations in ABI values were considered relevant if > 10 %. RESULTS: Mean ABI in the second visit was 1.07 ± 0.15, which represented 0.02 ± 0.12 points lower than in the first visit (P < 0.001). Of these subjects, 157 (21.6 %) had an ABI decrease > 10 %. Multivariate analysis showed that the change was associated with male gender, cardiovascular history, no intake of blockers of the renin-angiotensin system, and the presence of atherogenic dyslipidaemia. A relevant increase in ABI was observed in 117 subjects (16.1 %), but was not associated with any of the studied factors. CONCLUSIONS: ABI values tend to decrease in the general population, although one sixth of the studied subjects had a relevant increase in this parameter.

Clinical course and prognostic factors of COVID-19 infection in an elderly hospitalized population.

INTRODUCTION: Older subjects have a higher risk of COVID-19 infection and a greater mortality. However, there is a lack of studies evaluating the characteristics of this infection at advanced age. PATIENTS AND METHODS: We studied 404 patients ≥ 75 years (mean age 85.2 ±â€¯5.3 years, 55 % males), with PCR-confirmed COVID-19 infection, attended in two hospitals in Madrid (Spain). Patients were followed-up until they were discharged from the hospital or until death. RESULTS: Symptoms started 2-7 days before admission, and consisted of fever (64 %), cough (59 %), and dyspnea (57 %). A total of 145 patients (35.9 %) died a median of 9 days after hospitalization. In logistic regression analysis, predictive factors of death were age (OR 1.086; 1.015-1.161 per year, p = 0.016), heart rate (1.040; 1.018-1.061 per beat, p < 0.0001), a decline in renal function during hospitalization (OR 7.270; 2.586-20.441, p < 0.0001) and worsening dyspnea during hospitalization (OR 73.616; 30.642-176.857, p < 0.0001). Factors predicting survival were a female sex (OR 0.271; 0.128-0.575, p = 0.001), previous treatment with RAAS inhibitors (OR 0.459; 0.222-0.949, p = 0.036), a higher oxygen saturation at admission (OR 0.901; 0.842-0.963 per percentage point increase, p = 0.002), and a greater platelet count (OR 0.995; 0.991-0.999 per 106/L, p = 0.025). CONCLUSION: Elderly patients with COVID-19 infection have a similar clinical course to younger individuals. Previous treatment with RAAS inhibitors, and demographic, clinical and laboratory data influence prognosis.

Phenotype of haptoglobin and presence of subclinical vascular disease: Population study. / Fenotipo de la haptoglobina y presencia de enfermedad vascular subclínica: estudio poblacional.

INTRODUCTION AND OBJECTIVES: Haptoglobin is a protein involved in the protection against oxidative damage caused by iron in haemoglobin. This protein is polymorphic, with 3 isomorphs prevalent in the population. The carriers of the Hp2-2 isoform have a lower antioxidant capacity and, in the population with diabetes, an increased risk of subclinical vascular disease and cardiovascular complications. The objective of this study was to evaluate whether this isomorphy is associated with an increased risk of carotid arteriosclerosis in subjects with and without diabetes, and free of cardiovascular disease. PATIENTS AND METHODS: A study was conducted in a population between 45 and 74years of age, randomly selected from the northwest area of Madrid. The participants were characterised in terms of their glycaemic status by oral glucose overload and the determination of the concentration of Hb1Ac. The haptoglobin phenotypes in all of them were determined by means of an immunoenzymatic assay, and the presence of carotid arteriosclerosis by ultrasound. RESULTS: Of the 1,256 participants included in the present analysis (mean age 61.6±6years, 41.8% males), the distribution of the isoforms of haptoglobin was as follows: Hp1-1: 13.3%, Hp1-2: 48.5%, and Hp2-2: 38.2%. In comparison with subjects Hp1-1 and Hp1-2, those with the Hp2-2 phenotype had a higher prevalence of dyslipidaemia (53.3% vs 43%; P<.0001) and arterial hypertension (39.2% vs. 32.2%, P=.012), and they more frequently received treatment with statins (31.5% vs 21.6%, P<.0001), and with antihypertensive agents (38.4% vs 30.8%, P=.006). The carriers of the Hp2-2 isoform had a higher prevalence of carotid plaques (OR: 1.35, 95%CI: 1.07-1.69, P=.011), with no differences in that prevalence as regards the glycaemic status. There were no differences in the intima-media thickness between the different phenotypes. The relationship of the Hp2-2 phenotype with the presence of plaques in the carotid was independent of age, gender, presence of risk factors (dyslipidaemia, hypertension and diabetes), the concentration of LDL-cholesterol, C-reactive protein and uric acid, blood pressure, and treatment with statins, and hypertensive drugs (OR: 1.31, 95%CI 1.01-1.70, P=.044). CONCLUSION: Subjects with the Hp2-2 phenotype of haptoglobin have a higher prevalence of carotid arteriosclerosis, which is independent of the presence of other cardiovascular risk factors and their glycaemic status.

Relationship of the Adherence to a Mediterranean Diet and Its Main Components with CRP Levels in the Spanish Population.

Background: Adherence to a Mediterranean diet seems to be inversely associated with C-reactive protein (CRP) concentration. A 14-point Mediterranean Diet Adherence Screener (MEDAS) has been developed to assess dietary compliance. Objective: The aim of this study was to assess whether each of the MEDAS questions as well as their final score were associated with the levels of CRP in general Spanish population. METHODS: Cross-sectional analysis of 1411 subjects (mean age 61 years, 43.0% males) randomly selected from the general population. CRP levels were determined by a commercial ELISA kit. Adherence to the Mediterranean diet was measured by the 14-point MEDAS. Results: There was an inverse correlation between adherence to the Mediterranean diet and the CRP concentration, even after adjusting by age, gender, hypertension, metabolic syndrome, body mass index, statin treatment and hypertension treatment (p = 0.041). Subjects who consume ≥2 servings of vegetables per day (p = 0.003), ≥3 pieces of fruit per day (p = 0.003), ≥1 serving of butter, margarine, or cream per day (p = 0.041) or ≥3 servings of fish/seafood per week (p = 0.058) had significantly lower levels of CRP. Conclusions: Adherence to a Mediterranean-type diet measured by a simple questionnaire is associated with lower CRP concentration. However, this association seems to be particularly related to a higher consumption of vegetables, fruits, dairy products, and fish.

R46L polymorphism in the PCSK9 gene: Relationship to lipid levels, subclinical vascular disease, and erectile dysfunction.

BACKGROUND: The R46L variant of the proprotein convertase subtilisin/kexin type 9 (PCSK9) gene has been related to lipid levels and cardiovascular disease. OBJECTIVE: To evaluate the influence of this polymorphism on subclinical vascular disease and erectile dysfunction (ED). METHODS: We analyzed the association of the PCSK9 rs11591147 single-nucleotide polymorphism with lipid levels, intima-media thickness (IMT), and the ankle-brachial index, in 1188 adults free of cardiovascular disease, randomly selected from the population. In 473 male participants, we also investigated its relationship with ED. The association of the R46L polymorphism with lipid levels was also assessed in 2 cohorts of 1103 prepuberal children and 830 adolescents. RESULTS: The prevalence of the T allele was 2.9% in adults. Low-density lipoprotein cholesterol (LDL-cholesterol) levels did not vary according to this polymorphism (134 ± 32 vs 134 ± 31 mg/dL, for the TT + GT vs GG carriers, respectively, P = .931). Despite equal LDL-cholesterol levels, adults carrying the T allele had a lower mean common carotid IMT (0.685 ± 0.09 vs 0.723 ± 0.127 mm; P = .035), a lower maximum common carotid IMT (0.819 ± 0.11 vs 0.865 ± 0.159 mm; P = .040), and, in males, a lower prevalence of ED (36.8% vs 61%: P = .036), than GG carriers. Prevalence of the T allele was 3.2% in both cohorts of children. They had lower levels of LDL-cholesterol than GG subjects (100 vs 109 mg/dL; P = .060, for prepuberal children, and 85 vs 99 mg/dL; P = .010 for adolescents). CONCLUSION: In our population, an association between the PCSK9 R46L variant and LDL-cholesterol levels is observed in children. In adults, although its association with lipid levels is not evident, there is a significant relationship between the PCSK9 R46L variant and markers of subclinical atherosclerosis, including IMT and ED.

Risk factors associated with the carotid intima-media thickness and plaques: ESPREDIA Study. / Factores de riesgo asociados con el grosor íntima-media y la presencia de placas en arteria carótida: Estudio ESPREDIA.

OBJECTIVE: To evaluate whether there were any differences in the risk factor profile associated with either the intima-media thickness (IMT) or the presence of carotid plaques. METHODS: Cross-sectional study in 1475 subjects between 45 and 75years, randomly selected from the population of the Northwest area of Madrid (Spain). They had a physical exam, blood analysis, and ultrasound measurement of the IMT and of the presence of plaques. RESULTS: Mean IMT was 0.725±0.132mm. Forty seven percent of the participants had carotid plaques. In multivariate analysis, factors directly associated with the IMT were, age (ß0.227, P<.0001), sex (ß0.104, P<.0001), presence of hypertension (ß0.082, P=.002), diabetes (ß0.130, P<.0001) and current smoking (ß0.107, P<.0001), systolic blood pressure (SBP) (ß0.219, P<.0001) and LDL-cholesterol levels (ß0.074, P=.003), and inversely, diastolic blood pressure (DBP) (ß-0.124, P=.001), HDL-cholesterol (ß-0.111, P<.0001) and triglyceride levels (ß-0.060, P=.028). The presence of plaques was directly associated with age (OR1.08; 95%CI: 1.05-1.10), sex (OR1.95; 95%CI: 1.52-2.51), current smoking (OR2.75; 95%CI: 1.92-3.95), history of hypertension (OR1.58; 95%CI: 1.22-2.04) or diabetes (OR1.84; 95%CI: 1.31-2.58), statin treatment (OR1.56; 95%CI: 1.19-2.04) and SBP (OR1.03; 95%CI: 1.02-1.05), and inversely with DBP (OR0.98; 95%CI: 0.96-0.99). CONCLUSION: Factors associated with the IMT and the presence of plaques are similar, a finding that support a continuum between muscular layer hypertrophy and arteriosclerosis development.

Carotid atherosclerosis severity in relation to glycemic status: a cross-sectional population study.

OBJECTIVE: Intima-media thickness (IMT) is increased in subjects with prediabetes or newly diagnosed diabetes. However, no previous studies have evaluated the relationship between the severity of carotid atherosclerosis, assessed by the presence of carotid plaques or stenosis, and the glycemic status, assessed either by fasting glucose, an oral glucose tolerance test (OGTT) or A1C levels. METHODS: Cross-sectional analysis of 1475 subjects (mean age 62 years, 44% males), randomly selected from the population. A fasting blood sample was obtained to determine glucose, lipids, and A1C levels. An OGTT was performed in non-diabetic subjects. Carotid atherosclerosis was evaluated by echo-doppler. RESULTS: A 10.5% of the population had a previous diagnosis of diabetes. Of the 1320 non-diabetic participants, 349 (26.4%) had normal fasting glucose, normal glucose tolerance and A1C < 5.7%, and were considered controls. Prediabetes was diagnosed in 850 subjects (64.4%), and diabetes was newly diagnosed in 121 (9.2%). The prevalence of patients with carotid plaques was 34.2% in controls, 45.1% in prediabetics, 64.2% in newly diagnosed diabetics, and 72.9% in established diabetic patients. These numbers were 0.3%, 1.1%, 5.0% and 7.7% for carotid stenosis, respectively. In multivariate analysis, glycemic status remained significantly associated with the prevalence of carotid plaques after adjusting for age, sex, statin treatment, and cardiovascular risk factors. CONCLUSIONS: Glycemic status is associated with all grades of carotid atherosclerosis, from early signs, as demonstrated by the IMT, to intermediate degrees, as demonstrated by the presence of carotid plaques, to advance atherosclerosis, as established by the presence of carotid stenosis.

Validating prediction scales of type 2 diabetes mellitus in Spain: the SPREDIA-2 population-based prospective cohort study protocol.

INTRODUCTION: The incidence of type 2 diabetes mellitus (T2DM) is increasing worldwide. When diagnosed, many patients already have organ damage or advance subclinical atherosclerosis. An early diagnosis could allow the implementation of lifestyle changes and treatment options aimed at delaying the progression of the disease and to avoid cardiovascular complications. Different scores for identifying undiagnosed diabetes have been reported, however, their performance in populations of southern Europe has not been sufficiently evaluated. The main objectives of our study are: to evaluate the screening performance and cut-off points of the main scores that identify the risk of undiagnosed T2DM and prediabetes in a Spanish population, and to develop and validate our own predictive models of undiagnosed T2DM (screening model), and future T2DM (prediction risk model) after 5-year follow-up. As a secondary objective, we will evaluate the atherosclerotic burden of the population with undiagnosed T2DM. METHODS AND ANALYSIS: Population-based prospective cohort study with baseline screening, to evaluate the performance of the FINDRISC, DANISH, DESIR, ARIC and QDScore, against the gold standard tests: Fasting plasma glucose, oral glucose tolerance and/or HbA1c. The sample size will include 1352 participants between the ages of 45 and 74 years. ANALYSIS: sensitivity, specificity, positive predictive value, negative predictive value, likelihood ratio positive, likelihood ratio negative and receiver operating characteristic curves and area under curve. Binary logistic regression for the first 700 individuals (derivation) and last 652 (validation) will be performed. All analyses will be calculated with their 95% CI; statistical significance will be p<0.05. ETHICS AND DISSEMINATION: The study protocol has been approved by the Research Ethics Committee of the Carlos III Hospital (Madrid). The score performance and predictive model will be presented in medical conferences, workshops, seminars and round table discussions. Furthermore, the predictive model will be published in a peer-reviewed medical journal to further increase the exposure of the scores.

Association of the -250G/A promoter polymorphism of the hepatic lipase gene with the risk of peripheral arterial disease in type 2 diabetic patients.

AIM: This study aimed to investigate the association between a polymorphism in the hepatic lipase (LIPC) gene promoter and the presence of peripheral arterial disease (PAD) in persons with type 2 diabetes. PATIENT AND METHODS: We evaluated 120 type 2 diabetics and identified those with PAD according to the ankle-arm index. The G-250A polymorphisms in the promoter of the LIPC gene were studied by PCR restriction. A logistic regression analysis was performed to determine the association between the rare allele and PAD. RESULTS: The prevalence of PAD was 19%. The frequency of the -250A allele was 0.211 in the group without PAD and 0.395 in the group with PAD (P<.05). Carriers of the -250A allele differed only in the ankle-arm index (0.92+/-0.12 for carriers vs. 1.00+/-0.12 for noncarriers, P<.05), with the difference remaining significant after adjustment for covariates (age; sex; waist-to-hip ratio; body mass index; duration of diabetes; smoking; hypertension; glycated hemoglobin; triglycerides; HDL cholesterol; LDL cholesterol; small, dense LDL cholesterol). Only smoking [odds ratio (OR)=6.93, 95% confidence interval (CI)=2.12-22.69, P=.001] and the -250A allele (OR=2.89, 95% CI=1.07-7.84, P=.036) were significantly associated with vascular disease in the logistic regression analysis. CONCLUSIONS: Patients with type 2 diabetes who are carriers of the rare -250A allele in the promoter of the hepatic lipase gene are susceptible to PAD.

Smoking and postprandial triglycerides are associated with vascular disease in patients with type 2 diabetes.

AIMS: To determine whether postprandial lipid levels are markers of clinical and subclinical macrovascular disease in a select group of patients with type 2 diabetes. METHODS: We recruited 119 local patients with type 2 diabetes and moderate metabolic control (HbA1c <8%). The patients were being treated with dietary measures and/or oral antihyperglycemic therapy. No patient was receiving lipid-lowering therapy. A history of cardiovascular events was recorded and the ankle-arm index was measured to assess subclinical peripheral artery disease. The patients underwent a lipid analysis after a 12-h fast and 4h after a mixed breakfast (50 g of fat, 40 g of carbohydrates). RESULTS: The patients with clinical and subclinical macrovascular disease had a greater history of smoking, a longer disease duration, and higher serum creatinine levels. The groups with macroangiopathy had lower postprandial concentrations of HDL cholesterol (p<0.05) and a trend towards lower fasting levels of HDL cholesterol (p=0.08) and higher fasting and postprandial levels of triglycerides (p=0.07). Multivariate analysis showed the presence of vascular (both clinical and subclinical) disease to be significantly associated with smoking (OR 3.06; 95% CI, 1.15-8.4), disease duration (for each year, OR 1.12; 95% CI, 1.03-1.22) and postprandial levels of triglycerides (for each 50mg, OR 1.73; 95% CI, 1.13-2.65). CONCLUSIONS: In our diabetic patients, the postprandial level of triglycerides 4h after a fatty breakfast, though not fasting lipids, plus smoking and disease duration were independently associated to clinical and subclinical macrovascular disease.