Hyperlipidemias: Alrasadi K

Alwaili K, Alrasadi K, Awan Z, Genest J. · Cardiovascular Research Laboratories, McGill University Health Center Research Institute, McGill University, Montreal, Quebec, Canada. · Curr Opin Endocrinol Diabetes Obes. · Pubmed #19306526 No free full text.

Abstract: PURPOSE OF REVIEW: Disorders of lipoprotein metabolism are frequently encountered in clinical practice. Although the severe genetic hyperlipidemias are relatively infrequent, prompt recognition and treatment can prevent complications, such as atherosclerosis and pancreatitis. The secondary dyslipidemias, due to medication or other metabolic disorders (hypothyroidism, renal or hepatic diseases), must be identified and treated. With the growing epidemic of obesity, dyslipidemias are a component of the metabolic syndrome. RECENT FINDINGS: The stratification of cardiovascular risk now includes family history and biomarkers of inflammation, especially high-sensitivity C-reactive protein, which enables sound clinical decision making. Lifelong hypercholesterolemia is strongly associated with increasing risk of atherosclerosis and coronary heart disease death, but the decision to treat pharmacologically depends on the absolute cardiovascular risk over the next 10 years. Clinical trial data support intensive treatment of patients at high cardiovascular risk or for the secondary prevention of recurrent coronary heart disease. The recently published JUPITER trial shows that patients with an elevated C-reactive protein benefit from treatment with a statin (rosuvastatin 20 mg) for primary prevention. SUMMARY: The current guidelines for the prevention of coronary artery disease will continue to focus on the determination of global risk, with intensive treatment aimed at the high-risk group. Family history and high-sensitivity C-reactive protein provide additional risk stratification.

Alrasadi K, Alwaili K, Awan Z, Valenti D, Couture P, Genest J. · McGill University Health Center/Royal Victoria Hospital, Montréal, Québec, Canada. · Am Heart J. · Pubmed #19081415 No free full text.

Abstract: BACKGROUND: We have previously reported premature, extensive aortic calcifications in patients with homozygous familial hypercholesterolemia (hmzFH) due to mutations in the low-density lipoprotein receptor gene (LDL-R). The objective of this study was to measure the degree of aortic calcification in heterozygous FH (htzFH) compared to both hmzFH and controls. We hypothesized that the LDL-R gene may contribute to aortic calcifications in a gene-dosage effect. METHOD: Patients with htzFH due to the French Canadian mutation (Delta15 kb del. null allele) were selected. All patients underwent computed tomographic scan to measure vascular calcification. We used 22 hmzFH patients from our previous study and patients undergoing computed tomographic virtual colonoscopy as controls. RESULTS: Mean age for htzFH was 50 +/- 15 years; initial cholesterol level before treatment was 10.45 +/- 1.73 mmol/L. Major cardiovascular events occurred in 9 of 17 patients. A strong correlation between age and calcium score was found (r = 0.72, P = .0016). There was a strong correlation between the cholesterol-year score (an index of lifelong cholesterol burden) and the aortic calcium score (r = 0.62, P = .0105). Aortic calcifications in htzFH subjects occurred later than in hmzFH patients, but much earlier than in controls, suggesting a gene-dosage effect of LDL-R mutations and aortic calcium deposition. CONCLUSION: Aortic calcification was observed in patients with htzFH but presented at a later time and were less extensive than in hmzFH (34 vs 14 years, respectively). Because aortic calcifications may be partly independent of serum cholesterol levels in patients with familial hypercholesterolemia, implications for screening and the timing of treatment initiation may need reassessment.

Awan Z, Alrasadi K, Francis GA, Hegele RA, McPherson R, Frohlich J, Valenti D, de Varennes B, Marcil M, Gagne C, Genest J, Couture P. · McGill University Health Center/Royal Victoria Hospital, 687 Pine avenue West, Montréal, QC H3A 1A1, Canada. · Arterioscler Thromb Vasc Biol. · Pubmed #18239150 links to  free full text

Abstract: BACKGROUND: Patients with homozygous familial hypercholesterolemia (hmzFH) attributable to LDL receptor gene mutations have shown a remarkable increase in survival over the last 20 years. Early onset coronary heart disease (CHD) and calcific aortic valve stenosis are the major complications of this disorder. We now report extensive premature calcification of the aorta in patients with hmzFH. METHODS AND RESULTS: We examined 25 hmzFH patients from Canada; mean age was 32 years (range 5 to 54), and mean baseline cholesterol before treatment was 19+/-5 mmol/L (737+/-206 mg/dL). Aortic calcification was quantified using computed tomography (CT). An elevated mean calcium score was found in patients by age 20 and correlated with age (r(2)=0.53, P=0.001). One quarter (24%) of patients underwent aortic valve surgery. CONCLUSIONS: We document premature severe aortic calcifications in all adult hmzFH patients studied. These presented considerable surgical management challenges. Strategies to identify and monitor aortic calcification in hmzFH by noninvasive techniques are required, as are clinical trials to determine whether additional or more intensive therapies will prevent the progression of such calcifications. Whether vascular calcifications in hmzFH subjects are related to sustained increases in LDL-C levels or to other mechanisms, such as abnormal osteoblast activity, remains to be determined.