Comparison of the burden of familial hypercholesterolemia between two cohorts of French Canadians hospitalized 25 years apart for coronary heart disease.

BACKGROUND: Familial hypercholesterolemia (FH) is associated with lifelong elevated plasma concentrations of low-density lipoprotein cholesterol (LDL-C) and high risk of premature coronary heart disease (CHD). Clinical recommendations and treatments have emerged to facilitate the management of FH patients. Their impact on the burden of FH is however not well documented. OBJECTIVE: To compare the burden of FH between patients hospitalized for a CHD event 25 years apart in the French-Canadian founder population. METHODS: Lipid profiles, cardiovascular risk factors, treatments and FH status of 2,029 patients consecutively hospitalized for an acute CHD event between 2017 and 2022 (2022 Cohort) were compared to those of 2,506 patients with angiographically-confirmed CHD who were admitted between 1995 and 1998 (1998 Cohort). RESULTS: At the time of admission, 24.6 % of CHD patients had LDL-C levels >5.0 mmol/L in 1998 compared to 1.4 % in 2022, and FH was diagnosed in 9.6 % of patients in the 1998 cohort compared to 5.5 % in 2022 (p<0.001). FH patients hospitalized for a CHD event were older in 2022 than in 1998 (p <0.001). The prevalence of premature CHD requiring a hospitalization significantly decreased from 1998 to 2022 (64.3% vs. 44.1 %, p<0.001). At the moment of admission, 18.2 % of FH patients had LDL-C concentration <2.0 mmol/L in 2022 vs 0 % in 1998 (p <0.001). CONCLUSIONS: Over 25 years, FH patients tend to be older and contribute to a lower proportion of hospitalizations for CHD in the French-Canadian founder population. Despite significant improvement in diagnosis and treatment, FH management remains however sub-optimal.

Modulation of body fluids and angiotensin II receptors in a rat model of intra-uterine growth restriction.

We previously reported that sodium restriction during pregnancy reduces plasma volume expansion and promotes intra-uterine growth restriction (IUGR) in rats while it activates the renin-angiotensin-aldosterone system (RAAS). In the present study, we proceeded to determine whether expression of the two angiotensin II (ANGII) receptor subtypes (AT(1) and AT(2)) change in relation to maternal water-electrolyte homeostasis and fetal growth. To this end, pregnant (gestation day 15) and non-pregnant Sprague-Dawley rats were randomly assigned to two groups fed either normal, or Na(+)-restricted diets for 7 days. At the end of the treatment period, plasma aldosterone and renin activity as well as plasma and urine electrolytes were measured. Determinations for AT(1) and AT(2) mRNA and protein were made by RNase protection assay and photoaffinity labelling, respectively, using a number of tissues implicated in volume regulation and fetal growth. In non-pregnant rats, Na(+) restriction decreases Na(+) excretion without altering plasma volume, plasma Na(+) concentration or the expression of AT(1) and AT(2) mRNA or protein in the tissues examined. In normally fed pregnant rats when compared to non-pregnant controls, AT(1) mRNA increases in the hypothalamus as well as pituitary and declines in uterine arteries, while AT(1) protein decreases in the kidney and AT(2) mRNA declines in the adrenal cortex. In pregnant rats, Na(+) restriction induces a decrease in plasma Na(+), an increase in plasma urea, as well as a decline in renal urea and creatinine clearance rates. Protein levels for both AT(1) and AT(2) in the pituitary and AT(2) mRNA in the adrenal cortex are lower in the Na(+)-restricted pregnant group when compared to normally fed pregnant animals. Na(+) restriction also induces a decrease in AT(1) protein in the placenta. In conclusion, these results suggest that pregnancy may increase sensitivity to Na(+) depletion by the tissue-specific modulation of ANGII receptors. Finally, these receptors may be implicated in the IUGR response to low Na(+).