Marta Mauri

Aims : Knowledge of the features of patients with familial hypercholesterolaemia (FH) who are protected from atherosclerotic cardiovascular disease (ASCVD) is important for the clinical and prognostic care of this apparently high-risk condition. Our aim was to investigate the determinant and characteristics of patients with FH who are protected from ASCVD and have normal life expectancy, so-called ‘resilient’ FH (R-FH). Methods and results : Spanish Familial Hypercholesterolaemia cohort study (SAFEHEART) is an open, multicentre, nation-wide, long-term prospective cohort study in genetically defined patients with heterozygous FH in Spain. Patients in the registry who at the time of analysis were at least 65 years or those who would have reached that age had they not died from an ASCVD event were analysed as a case–control study. Resilient FH was defined as the presence of a pathogenic mutation causative of FH in a patient aged ≥65 years without clinical ASCVD. Nine hundred and thirty registrants with FH met the study criteria. A defective low-density lipoprotein (LDL)-receptor mutation, higher plasma level of high-density lipoprotein cholesterol (HDL-C), younger age, female gender, absence of hypertension, and lower plasma lipoprotein (a) [Lp(a)] concentration were independently predictive of R-FH. In a second model, higher levels of HDL-C and lower 10-year score in SAFEHEART-RE were also independently predictive of R-FH. Conclusion : Resilient FH may be typified as being female and having a defective LDL-receptor mutation, higher levels of plasma HDL-C, lower levels of Lp(a), and an absence of hypertension. The implications of this type of FH for clinical practice guidelines and the value for service design and optional care of FH remains to be established. Trial registration: ClinicalTrials.gov number NCT02693548.

Some lipoprotein disorders related to the residual risk of premature cardiovascular disease (PCVD) are not detected by the conventional lipid profile. In this case-control study, the predictive power of PCVD of serum sdLDL-C, measured using a lipoprotein precipitation method, and of the physicochemical properties of serum lipoproteins, analyzed by nuclear magnetic resonance (NMR) techniques, were evaluated. We studied a group of patients with a first PCVD event (n = 125) and a group of control subjects (n = 190). Conventional lipid profile, the size and number of Very Low Density Lipoproteins (VLDL), Low Density Lipoproteins (LDL), High Density Lipoproteins (HDL) particles, and the number of particles of their subclasses (large, medium, and small) were measured. Compared to controls, PCVD patients had lower concentrations of all LDL particles, and smaller and larger diameter of LDL and HDL particles, respectively. PCVD patients also showed higher concentrations of small dense LDL-cholesterol (sdLDL), and triglycerides (Tg) in LDL and HDL particles (HDL-Tg), and higher concentrations of large VLDL particles. Multivariate logistic regression showed that sdLDL-C, HDL-Tg, and large concentrations of LDL particles were the most powerful predictors of PCVD. A strong relationship was observed between increased HDL-Tg concentrations and PCVD. This study demonstrates that beyond the conventional lipid profile, PCVD patients have other atherogenic lipoprotein alterations that are detected by magnetic resonance imaging (MRI) analysis.

A low prevalence of type 2 diabetes mellitus has been reported in familial hypercholesterolaemia. Whether a healthier lifestyle could explain it has not been explored. This cross-sectional study determines the prevalence of lifestyle-related cardiovascular risk factors in heterozygous familial hypercholesterolaemia (HeFH) from the Dyslipidaemia Registry of the Spanish Atherosclerosis Society and in the ENRICA study, a representative sample of the adult Spanish general population, weighted to match the age and sex distribution of the HeFH sample. A total of 2185 HeFH patients and 11,856 individuals from ENRICA were included. HeFH had lower body mass index and fewer of them were smokers than in the reference population. A model adjusted for age, sex and body mass index showed that HeFH more frequently had cardiovascular disease (odds ratio (OR) 23.98; 95% confidence interval (CI) 18.40–31.23) and hypertension (OR 1.20; 95% CI 1.07–1.35), and took anti-hypertensive medication (OR 1.36; 95% CI 1.18–1.56) and anti-diabetic medication (OR 1.25; 95% CI 1.00–1.56), but less frequently were smokers (OR 0.79; 95% CI 0.71–0.89). In a HeFH subsample (n = 513) with complete blood glucose information, those patients without cardiovascular disease showed lower prevalence of smoking and type 2 diabetes mellitus, lower body mass index and glucose, and higher diastolic blood pressure than the Spanish population. The differences in type 2 diabetes mellitus were justified mostly by the difference in body mass index. Body mass index adjustment also showed higher prevalence of hypertension and use of anti-hypertensive drugs in HeFH. In summary, HeFH patients had lower body mass index, which may contribute to explaining the lower prevalence of diabetes, and lower current smoking but higher hypertension.

The objective of this study is to evaluate the characteristics and outcome of elderly patients with Mediterranean spotted fever (MSF). This study was a prospective observational cohort study of all adult cases with confirmed MSF treated in a teaching hospital (1984–2015) to compare the characteristics of elderly patients (> 65 years) with younger adults. We identified 263 adult patients with MSF, and 53 (20.2%) were elderly. Severe MSF was more frequent in the elderly (26.4% vs. 10.5%; p = 0.002). Gastrointestinal symptoms, impaired consciousness, lung infiltrate, oedema, acute hearing loss, raised alanine transaminase, hyponatremia, and thrombocytopenia occurred more frequently in elderly patients, and arthromyalgia occurred less frequently. Most patients were treated with a single-day doxycycline regimen (two oral doses of 200 mg for 1 day). All patients recovered uneventfully. Fever disappeared 2.55 ± 1.16 days after treatment initiation in elderly patients, and the remaining symptoms disappeared after 3.65 ± 1.42 days. These figures were similar to non-elderly patients. Severe MSF was more frequent in elderly patients. Some clinical manifestations occurred with different frequencies in the elderly compared with younger patients. Single-day doxycycline therapy is an effective and well-tolerated treatment for MSF in elderly patients.

Background: Although risk factors for atherosclerotic cardiovascular disease (ASCVD) in familial hypercholesterolemia (FH) have been described, models for predicting incident ASCVD have not been reported. Our aim was to use the SAFEHEART registry (Spanish Familial Hypercholesterolemia Cohort Study) to define key risk factors for predicting incident ASCVD in patients with FH. Methods: SAFEHEART is a multicenter, nationwide, long-term prospective cohort study of a molecularly defined population with FH with or without previous ASCVD. Analyses to define risk factors and to build a risk prediction equation were developed, and the risk prediction equation was tested for its ability to discriminate patients who experience incident ASCVD from those who did not over time. Results: We recruited 2404 adult patients with FH who were followed up for a mean of 5.5 years (SD, 3.2 years), during which 12 (0.5%) and 122 (5.1%) suffered fatal and nonfatal incident ASCVD, respectively. Age, male sex, history of previous ASCVD, high blood pressure, increased body mass index, active smoking, and low-density lipoprotein cholesterol and lipoprotein(a) levels were independent predictors of incident ASCVD from which a risk equation with a Harrell C index of 0.85 was derived. The bootstrap resampling (100 randomized samples) of the original set for internal validation showed a degree of overoptimism of 0.003. Individual risk was estimated for each person without an established diagnosis of ASCVD before enrollment in the registry by use of the SAFEHEART risk equation, the modified Framingham risk equation, and the American College of Cardiology/American Heart Association ASCVD Pooled Cohort Risk Equations. The Harrell C index for these models was 0.81, 0.78, and 0.8, respectively, and differences between the SAFEHEART risk equation and the other 2 were significant ( P =0.023 and P =0.045). Conclusions: The risk of incident ASCVD may be estimated in patients with FH with simple clinical predictors. This finding may improve risk stratification and could be used to guide therapy in patients with FH. Clinical Trial Registration: URL: http://clinicaltrials.gov . Unique identifier: NCT02693548.