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Papers by Sergio D'Addato

Journal of Clinical Medicine

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Convegno S.IS.A. sezione Emilia Romagna, 2009

The Lancet, 2022

Background: Homozygous familial hypercholesterolaemia (HoFH) is a rare inherited disorder resulti... more Background: Homozygous familial hypercholesterolaemia (HoFH) is a rare inherited disorder resulting in extremely elevated low-density lipoprotein cholesterol (LDL-C) levels and premature atherosclerotic cardiovascular disease (ASCVD). Current guidance about its management and prognosis stems from relatively small studies, mostly from western countries. The objective of this study was to assess the clinical and genetic characteristics as well as the impact of current practice on health outcomes of HoFH patients globally. Methods: The HoFH International Clinical Collaborators (HICC) registry collected data on patients with a clinical and/or genetic diagnosis of HoFH using a retrospective cohort study design. Findings: Overall, 751 patients (52% female) from 38 countries were included, with 75% reporting biallelic pathogenic variants. Median age of diagnosis was 12•0 (IQR 5•5-27•0) years, with major manifestations of ASCVD or aortic stenosis already present in 9% at diagnosis of HoFH. Globally, pretreatment LDL-C levels were 14•7 (IQR 11•6-18•4) mmol/L, with 92% of patients subsequently receiving statins, 64% ezetimibe and 39% lipoprotein apheresis. On-treatment LDL-C levels were lower in highincome versus non-high-income countries (3•93 [IQR 2•6-5•8] versus 9•3 [IQR 6•7-12•7] mmol/L), with greater use of three or more lipid-lowering therapies (LLT) (66% versus 24%) and consequently more patients attaining guideline-recommended LDL-C goals (21% versus 3% respectively). A first major adverse cardiovascular event occurred a decade earlier in non-high-income countries, at a median age of 24•5 (IQR 17•0-34•5) versus 37•0 (IQR 29•0-49•0) years in high-income countries (adjusted hazard ratio: 1•64 [95%CI 1•13-2•38]). Interpretation: Worldwide, patients with HoFH are diagnosed too late, undertreated and at high premature ASCVD risk. Greater use of multi-LLT regimens associates with lower LDL-C levels and better outcomes. Significant global disparities exist in treatment regimens, control of LDL-C levels and cardiovascular event-free survival, which demands a critical re-evaluation of global health policy to reduce inequalities and improve outcomes for all patients with HoFH.

Journal of Hypertension, 2019

This is a PDF file of an article that has undergone enhancements after acceptance, such as the ad... more This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

Polish Archives of Internal Medicine, 2014

INTROduCTION Cardiovascular diseases are still the most common cause of death in developed countr... more INTROduCTION Cardiovascular diseases are still the most common cause of death in developed countries. 1 The atherosclerotic process involves several oxidative reactions such as the development of oxygen and peroxyl radicals and oxidation of low-density lipoprotein (LDL) cholesterol, which is an important target of free radicals in blood. 2 Oxidative burst is an innate immune response to infection, the latter being also associated with marked changes in lipid and lipoprotein metabolism, aimed at neutralizing the

European Journal of Internal Medicine, 2017

Background: High lipoprotein(a) [Lp(a)] levels have been re-evaluated as an independent risk fact... more Background: High lipoprotein(a) [Lp(a)] levels have been re-evaluated as an independent risk factor for atherosclerotic vascular diseases. Methods: We assessed whether serum Lp(a) levels can significantly influence long-term survival in subjects with an equal general cardiovascular (CV) risk profile. We prospectively evaluated a sample of 1215 adult subjects from the Brisighella Heart Study cohort (M: 608; F: 607; aged 40-69) who had no cardiovascular disease at enrolment. According to the CUORE project risk-charts (Italian-specific risk-charts), individuals were stratified into a low-(n = 865), an intermediate-(n = 275) and a high-(n = 75) cardiovascular risk groups. Kaplan-Meier 25-year survival analysis was carried out examining apart each class of risk and the log-rank statistic was used to estimate, when statistically possible, the survival time of the subjects stratified into quartiles of Lp(a). Results: Subjects at high and intermediate CV risk aged 56-69 years (regardless of gender) and women aged 40-55 years with a low CV risk profile who had lower Lp(a) levels showed a significant benefit on CV mortality (P b 0.05 always) and, indicatively, on the estimated survival time (even P b 0.05). The ROC curves constructing for each CV risk group using Lp(a) as test-variable and death as state-variable identified serum Lp(a) as an independent long-term CV mortality prognosticator for subjects at high CV risk (AUC = 0.63, 95%CI [0.50-0.76], P = 0.049) and women with an intermediate CV risk profile (AUC = 0.7, 95%CI [0.52-0.79], P = 0.034). Conclusions: In the light of our finding and at the best of the previous knowledge, dosing Lp(a) is confirmed as important in subjects at high or medium risk (even if in primary prevention for CV diseases), especially in women.

Annals of Medicine, 2016

Background: Serum uric acid (SUA) is an emerging risk factor for incident hypertension and type 2... more Background: Serum uric acid (SUA) is an emerging risk factor for incident hypertension and type 2 diabetes. It is less clear if changes in SUA are associated to different incidence in these main cardiovascular risk factors. Methods: From the cohort of the Brisighella Heart Study, we selected non diabetic subjects that in 2008 were untreated with SUA lowering drugs nor antihypertensive ones. Then we divided the subjects in four main groups: the ones that mantained their SUA level unchanged during the next 4 years, the ones that increased it >1 mg/dL without treatment, the ones that reduced it >1 mg/dL without drug treatment and the ones that reduced it >1 mg/dL with the continuous use of allopurinol. Results: Compared to 2008, SBP significantly increased in subjects with worsened (and untreated) SUA level, while improved in subjects treated with allopurinol (p<0.05). In 2012, subjects with worsened (and untreated) SUA level had a significantly higher SBP compared with subjects with unchanged SUA and those with SUA improved after allopurinol treatment (p<0.05). An identical trend has been observed as it regards FPG. Conclusion: It seems that SUA improvement could positively influence the age-related worsening of SBP and FPG in general population.

Mediterranean Journal of Nutrition and Metabolism, 2009

The aim of our study was to directly compare the metabolic effect of monounsaturated fatty acid r... more The aim of our study was to directly compare the metabolic effect of monounsaturated fatty acid rich oils and polyunsaturated fatty acid rich oils on the plasma lipid pattern of moderately hypercholesterolaemic subjects under controlled isocaloric condition. After a 30-day run-in diet, 44 healthy Caucasian subjects with moderate hypercholesterolaemia were randomly assigned to one of four different isocaloric diets, differing only regarding the oil used (corn oil, corn oil supplemented with vitamin E, extra-virgin olive oil or different self-selected oils), for 45 days. At the end of the study, when compared to the baseline value, low-density lipoprotein (LDL)-cholesterolaemia was significantly lower only in patients taking corn oil (-13.9%; 95%CI-5.9 to-20.1; p = 0.02) or corn oil with added vitamin E (-19.1%; 95%CI-6.9 to-24.1; p = 0.03). Differences in plasma high-density lipoprotein (HDL)-cholesterol and triglyceride levels from baseline levels and between the four diets did not reach statistical significance.

Advances in Clinical and Experimental Medicine, 2014

Background. Recent preclinical evidence and data from adult subjects suggests that statins could ... more Background. Recent preclinical evidence and data from adult subjects suggests that statins could improve the proinflammatory profile of hypercholesterolemic subjects. Objectives. We aim to compare the serum levels of a set of proinflammatory chemokines in elderly statistical twins taking or not taking statins. Material and Methods. Among the historical cohort of the Brisighella Heart Study, we chose 40 healthy elderly subjects continuously treated with statins for at least 1 year and 40 cross-matched subjects not treated with statins (M : F = 1 : 1) characterized by similar age, body mass index (BMI), leisure-time and working activity, smoking habits, history of cardiovascular disease, systolic and diastolic blood pressure, fasting plasma glucose, plasma lipids, uric acid, and creatinine. Results. The proinflammatory chemokine serum level is similar in statin untreated and treated statistical twins. The OR to have a serum level of monocyte chemoattractant protein (MCP-1) lower than the 50 th percentile of the distribution in statin-treated subjects compared to the statin untreated subjects is 0.669 (95% CI 0.193; 2.327), the OR for interleukin-8 (IL-8) = 0.818 (95% CI 0.236; 2.835), the OR for γ-interferon inducible protein-10 (IP-10) = 1.361 (95% CI 0.358; 5.175), and for interleukin-18 (IL-18) = 0.545 (95% CI 0.155; 1.914). Conclusions. In relatively healthy, elderly subjects selected from a randomized general population sample, we did not observe differences in the serum levels of the selected set of proinflammatory chemokines in statin treated and untreated subjects with similar LDL-C level, suggesting that cholesterol reduction per se could be a main determinant of statin anti-inflammatory effects (Adv Clin Exp Med 2014, 23, 5, 723-728).

High Blood Pressure & Cardiovascular Prevention, 2014

Serum uric acid (SUA) may contribute to the increased cardiovascular damage through direct injury... more Serum uric acid (SUA) may contribute to the increased cardiovascular damage through direct injury to the endothelium and alteration of cardiovascular function. To evaluate the association of SUA with the presence of the most recurrent electrographic alterations and with the length of the main ECG intervals in a large sample of general population. For this study, on the database of the Brisighella Heart Study, we evaluated the available data of 790 men and 849 women, excluding subjects affected by gout or taking antihyperuricemic agents, those taking drug increasing the QT interval and those using beta-blockers or non-dihydropyridine calcium channel blockers at the moment of the ECG registration. Multiple ascending stepwise regression analyses were carried out to determine the independent predictors of the predefined ECG alterations. The prevalence of predefined ECG alterations was comparable between genders, with the exception of sinus bradicardia, left-anterior fascicular block, atrio-ventricular blocks and left ventricular hypertrophy (LVH), which appeared to be more frequent in men. The multivariate analysis revealed that SUA was associated to ischaemic alterations, LVH, sinus tachycardia and tachyarrhytmias. Age was associated to all evaluated ECG alterations beyond sinus tachycardia and LVH. Male sex was associated to sinus bradicardia, atrio-ventricular blocks, anterior-left fascicular block and LVH. Blood pressure was associated to different ECG alterations, but with clinically relevant OR with ischaemic alterations and LVH. SUA level is related the prevalence of both organic and rhythm ECG alterations in a wide sample of general population.

Internal and Emergency Medicine, 2012

Metabolic Syndrome and Related Disorders, 2013

Background: Nonalcoholic fatty liver disease (NAFLD) and metabolic syndrome are strongly related ... more Background: Nonalcoholic fatty liver disease (NAFLD) and metabolic syndrome are strongly related from both an epidemiological and a pathological point of view. The main aim of our study was to evaluate if two validated indexes of NAFLD are able to predict the 4-year metabolic syndrome incidence in a large population sample of pharmacologically untreated subjects without metabolic syndrome, type 2 diabetes, history of alcohol abuse, or known liver diseases at the baseline. Methods: From the database of the Brisighella Heart Study, we selected a subsample of 824 pharmacologically untreated subjects (male, 401; female, 423) without metabolic syndrome, type 2 diabetes, alcohol abuse, or known liver diseases at the 2004 survey and revisited in 2008. The Hepatic Steatosis Index (HSI) and Lipid Accumulation Product (LAP) values were calculated for everyone to evaluate their predictive role for metabolic syndrome through a Cox-regression analysis adjusted by metabolic syndrome components. Results: We observed 46 new cases of metabolic syndrome (male, 25; female, 21) with a cumulative incidence of 5.6% (1.4% per year): 6.2% in men (1.5% per year), 4.9% in women (1.2% per year). In women, the 4-year metabolic syndrome predictors (R 2 = 0.680) were age [odds ratio (

European Journal of Clinical Investigation, 2014

Serum cholesterol has been demonstrated to correlate with blood pressure values; therefore, abnor... more Serum cholesterol has been demonstrated to correlate with blood pressure values; therefore, abnormal levels of serum cholesterol might contribute to the development of hypertension. The aim of this study was to assess the new onset of hypertension over a period of 8 years in a pharmacologically untreated population sample in normo- and hypercholesterolemic individuals. 1864 Caucasian subjects with baseline blood pressure values &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;140/90 mmHg were subdivided into two different groups, according to LDL cholesterol changes observed over a period of 8 years. Group 1 included subjects whose LDL cholesterol levels remained or decreased within the normal range, while Group 2 included those whose LDL cholesterol levels were persistently increased above the normal range. The 8-year incidence of new-onset hypertension was 7·1% in Group 1 and 13·8% in Group 2 (P = 0·02), after adjustment for the main confounding risk factors. The difference between Groups 1 and 2 was confirmed in men (8·2 vs. 13·1%, P = 0·04) and women (6·1. vs. 14·5%, P = 006), as well as in subjects younger than 65 years (5·7 vs. 10·9%; P = 0·011), but not in older ones. Baseline serum LDL cholesterol levels are related to the rate of new-onset hypertension in patients with normal or marginally elevated blood pressure values.

Internal and Emergency Medicine, 2013

Serum uric acid is representative for xanthine-oxidase, the key enzyme involved in the production... more Serum uric acid is representative for xanthine-oxidase, the key enzyme involved in the production of uric acid, which is up-regulated in the failing heart, and may play an important role in the pathophysiologic process that leads to heart failure. In our study, we investigated the relation between stroke volume, cardiac output and serum uric acid in a large sample of overall healthy pharmacologically untreated subjects. The Brisighella Heart Study included 2,939 men and women between the ages of 14-84 without prior coronary heart disease or cerebrovascular disease who were not taking antihypertensive therapy at baseline. For this study, we selected 734 adult subjects enrolled in the last Brisighella population survey not taking antihypertensive, antidiabetic, lipid-lowering and uric acid-lowering drugs, and who were also not affected by chronic heart failure or by gout. The main predictors of cardiac functionality parameters were mean arterial pressure (MAP), HR, SUA and age (all p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001), while gender, BMI, LDL-cholesterol, HDL-cholesterol, triglycerides, fasting plasma glucose, creatinine, estimated glomerular filtration rate, physical activity and smoking habit were not significantly associated (all p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; 0.05). In particular, there is a strong relation between estimated cardiac output and serum uric acid (B = -0.219, p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001) and between stroke volume and serum uric acid (B = -3.684, p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001). These observations might have an impact on future considerations about serum uric acid as an early inexpensive marker of heart function decline in the general population.

High Blood Pressure & Cardiovascular Prevention, 2013

A large number of epidemiological trials clearly show the impact of the main cardiovascular disea... more A large number of epidemiological trials clearly show the impact of the main cardiovascular disease risk factors in term of hospitalization and related cost, but relatively less frequently if this reflect the health needs of a given population. To develop a model for the health needs-assessment that will be applied to verify if and how the prevalence of some classical risk factors for cardiovascular disease predicts mortality and hospitalisation episodes at 3 years, and if it could express the health need of that population. The long-life clinical record of 1,704 subjects, recruited during the 2004 Brisighella Heart Study survey, has been monitored. We defined the health profile of these subjects at 2004 (based on clinical history, smoking and dietary habits, physical activity, drug use, anthropometric data, blood pressure, and hematological data) and then sampled data relative to their hospitalisations, mortality, and general medical assistance. Our results shows that age over 65 years (OR 4.08; 95 % CI 2.74-6.08), hypertension (OR 3.44; 95 % CI 2.36-5.01) and hypercholesterolemia (OR 1.33; 95 % CI 0.92-1.94) increase the probability to get hospitalised. Furthermore, the burden of care was defined and computed for our sample. Vascular and respiratory diseases [Burden of health care (Bc) = 24.5 and 36.5, respectively] are the most costly DRGs which means that the biggest part of our resources directed to cardiovascular patients were provided for these diagnoses. The application of the proposed model could help policy makers and researchers in directing resources and workforce in the treatment of cardiovascular diseases.

Nutrition Research, 2013

Despite a recent health claim by the European Agency on Food Safety, the effect of high doses of ... more Despite a recent health claim by the European Agency on Food Safety, the effect of high doses of dietary monacolin supplements from red yeast rice on cholesterolemia has not been tested in Italian subjects. Our aim via a crossover, double-blind, placebo-controlled randomized clinical trial was to test if a short-term treatment with 10 mg monacolins could improve lipid pattern, high-sensitivity C-reactive protein (hs-CRP), and vascular remodeling biomarkers in a small cohort of Mediterranean subjects. Thus, 25 healthy, mildly hypercholesterolemic subjects were enrolled, and after 4 weeks of a stabilization diet, subjects were randomized to the sequence placebo-washout-monacolins or monacolinswashout-placebo, with each period being 4 weeks long. At each study step, a complete lipid pattern, safety parameters, hs-CRP, and matrix metalloproteinases 2 and 9 levels were measured. When compared to the placebo group, monacolins-treated patients experienced a more favorable percent change in total cholesterol (-12.45%, 95% CI −16.19 to −8.71), low-density lipoprotein cholesterol (−21.99%, 95% CI −26.63 to −17.36), non-highdensity lipoprotein cholesterol (−14.67%, 95% CI −19.22 to −10.11), matrix metalloproteinase 2 (−28.05%, 95% CI −35.18 to −20.93), matrix metalloproteinase 9 (−27.19%, 95% CI −36.21 to − 18.15), and hs-CRP (−23.77%, 95% CI −30.54 to −17.01). No significant differences were observed in regards to triglycerides, high-density lipoprotein cholesterol, and safety parameters. On the basis of our data, we demonstrate that a 10-mg monacolin nutraceutical appears to safely reduce cholesterolemia, hs-CRP, and markers of vascular remodeling in Italian subjects. These results have to be confirmed in larger patient samples and longer studies.

Journal of Women's Health, 2010

Objective: To evaluate whether a nutritional education intervention on a general population cohor... more Objective: To evaluate whether a nutritional education intervention on a general population cohort is able to balance the metabolic effects of incident menopause in a large sample of perimenopausal women. Methods: We measured body mass index (BMI), blood pressure, plasma lipids, fasting plasma glucose, and prevalence of metabolic syndrome in two groups of perimenopausal nondiabetic women involved in the Brisighella Heart Study, a longitudinal epidemiological study, before (sample size 301) and after (sample size 262) a nutritional education program aimed at improving the cardiovascular disease (CVD) risk profile in a whole village population. Results: Before the interventional period, women undergoing menopause experienced a significant increase in BMI, systolic blood pressure, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (LDL-C), and triglycerides (all parameters exhibited p < 0.01). After the nutritional intervention, women undergoing menopause experienced a significant reduction only in triglyceride plasma level (p < 0.001). Metabolic syndrome prevalence was 73 in 301 and 99 in 301 (p ¼ 0.018), respectively, before and after menopause in the preintervention group, and it was 66 in 262 and 68 in 262 (p ¼ 0.871), respectively, in the postintervention group. Conclusions: In our study, a nutritional education program aimed at improving the CVD risk profile of a whole village population is associated with the prevention of increase in systolic blood pressure, BMI, cholesterolemia, and metabolic syndrome prevalence linked to menopause.

Journal of Hypertension, 2012

, for the Brisighella Heart Study Group Objective: The objective is to evaluate the relationship ... more , for the Brisighella Heart Study Group Objective: The objective is to evaluate the relationship between cholesterolemia, serum apolipoprotein B (apoB) level and blood pressure in a large sample of general population.

Journal of Hypertension, 2014

Serum uric acid (SUA) levels correlate with many recognized cardiovascular risk factors, includin... more Serum uric acid (SUA) levels correlate with many recognized cardiovascular risk factors, including age, male sex, hypertension, diabetes mellitus, hypertriglyceridemia, obesity, and insulin resistance. The aim of our study was to verify in a large well characterized population sample the relationship between SUA values, hypertension, arterial stiffness and subclinical atherosclerosis. For this study, we selected 248 men and 371 women adult patients enrolled in the last Brisighella Heart Study population survey for which a full set of data were available and not consuming antihypertensive, antidiabetic, lipid-lowering and uric acid-lowering drugs. SUA and other available variables were related to blood pressure level, carotid-femoral pulse wave velocity (cfPWV) and carotid intima-media thickness (cIMT). Hypertension prevalence was strongly related to SUA quartiles: we found significant differences between the 2nd (23.0%) and the 3rd quartiles (36.4%; P vs. 2nd &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05), and between the 3rd and the 4th quartile (56.3%; P vs. 3rd &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05). Similarly, the metabolic syndrome prevalence increased significantly at 39.5% in the 3rd SUA quartile (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05 vs. 2nd) and at 58.9% in the 4th quartile (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05 vs. 3rd). Intima-media thickness gradually and significantly rose along quartiles of SUA (P for trend &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.0001), in particular, it was 0.86 mm in the 1st quartile, 0.90 in the 2nd, 0.94 in the 3rd, and 0.97 in the last quartile, with significant differences between each quartiles (all P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05). In multivariate regression analyses, SUA resulted to be significantly associated to hypertension and metabolic syndrome prevalence, and IMT. Even if a significant association between SUA and cfPWV was found in univariate analysis (P = 0.002), when adjusting for age, the trend became nonsignificant (0.20). In the studied population sample, after adjustment for a large number of parameters, SUA appears to be significantly correlated to hypertension and IMT, but not to aortic stiffness.