High Lipoprotein(a) May Explain One-Quarter of Clinical Familial Hypercholesterolemia Diagnoses in Danish Lipid Clinics.

CONTEXT: Cholesterol carried in lipoprotein(a) adds to measured low-density lipoprotein cholesterol (LDL-C) and may therefore drive some diagnoses of clinical familial hypercholesterolemia (FH). OBJECTIVE: We investigated plasma lipoprotein(a) in individuals referred to Danish lipid clinics and evaluated the effect of plasma lipoprotein(a) on a diagnosis of FH. METHODS: Individuals referred to 15 Danish lipid clinics who were suspected of having FH according to nationwide referral criteria were recruited between September 1, 2020 and November 30, 2021. All individuals were classified according to the Dutch Lipid Clinical Network criteria for FH before and after LDL-C was adjusted for 30% cholesterol content in lipoprotein(a). We calculated the fraction of individuals fulfilling a clinical diagnosis of FH partly due to elevated lipoprotein(a). RESULTS: We included a total of 1166 individuals for analysis, of whom 206 fulfilled a clinical diagnosis of FH. Median lipoprotein(a) was 15 mg/dL (29 nmol/L) in those referred and 28% had lipoprotein(a) greater than or equal to 50 mg/dL (105 nmol/L), while 2% had levels greater than or equal to 180 mg/dL (389 nmol/L). We found that in 27% (55/206) of those fulfilling a clinical diagnosis of FH, this was partly due to high lipoprotein(a). CONCLUSION: Elevated lipoprotein(a) was common in individuals referred to Danish lipid clinics and in one-quarter of individuals who fulfilled a clinical diagnosis of FH, this was partly due to elevated lipoprotein(a). These findings support the notion that the LPA gene should be considered an important causative gene in patients with clinical FH and further support the importance of measuring lipoprotein(a) when diagnosing FH as well as for stratification of cardiovascular risk.

Prognostic value of multi-detector computed tomography in asymptomatic aortic valve stenosis.

BACKGROUND: Multi-Detector Computed Tomography (MDCT) is a high-resolution imaging technique with potential additive value in the evaluation of patients with aortic valve stenosis (AS). We aimed to assess the prognostic value of MDCT in asymptomatic patients with AS compared to conventional transthoracic echocardiography (TTE). METHODS: 116 patients with asymptomatic AS (Vmax>2.5m/s assessed by clinical screening TTE, LVEF>50%) were examined with TTE (Vivid e9) and MDCT (Aquilion 320) on the same day. The treating physician was blinded for research protocol defined imaging results. Outcome was defined as indication for aortic valve replacement (AVR) determined by the treating physician or sudden cardiac death. RESULTS: The mean age was 72 (8) years, 27% were women, mean AVA by TTE was 1.01 (0.30) cm(2). Median follow up time was 27 (IQR 19-44) months. Forty seven patients (41%) developed indication for AVR. No patients suffered a sudden cardiac death. AVA and aortic valve calcification were significant univariable predictors of AVR when measured by both TTE and MDCT, whereas left ventricular mass was only significant measured by MDCT. Significant coronary artery disease by MDCT tended to predict future indication for AVR, but this did not reach statistical significance (HR: 1.79 (95% CI 0.96-3.44), p=0.08). CONCLUSION: MDCT derived AVA can be of use as an alternative to TTE derived AVA in patients with asymptomatic AS to predict future clinical indication for AVR.

Aortic root, not valve, calcification correlates with coronary artery calcification in patients with severe aortic stenosis: A two-center study.

BACKGROUND: The underlying pathology in aortic stenosis (AS) and coronary artery stenosis (CAS) is similar including atherosclerosis and calcification. We hypothesize that coronary artery calcification (CAC) is likely to correlate with aortic root calcification (ARC) rather than with aortic valve calcification (AVC), due to tissue similarity between the two types of vessel rather than with the valve leaflet tissue. MATERIAL AND METHODS: We studied 212 consecutive patients (age 72.5 ± 7.9 years, 91 females) with AS requiring aortic valve replacement (AVR) in two Heart Centers, who underwent multidetector cardiac CT preoperatively. CAC, AVC and ARC were quantified using Agatston scoring. Correlations were tested by Spearman's test and Mann-Whitney U-test was used for comparing different subgroups; bicuspid (BAV) vs tricuspid (TAV) aortic valve. RESULTS: CAC was present in 92%, AVC in 100% and ARC in 82% of patients. CAC correlated with ARC (rho = 0.51, p < 0.001) but not with AVC. The number of calcified coronary arteries correlated with ARC (rho = 0.45, p < 0.001) but not with AVC. 29/152 patients had echocardiographic evidence of BAV and 123 TAV, who were older (p < 0.001) but CAC was associated with TAV even after adjusting for age (p = 0.01). AVC score was associated with BAV after adjusting for age (p = 0.03) but ARC was not. Of the total cohort, 82 patients (39%) had significant coronary stenosis (>50%), but these were not different in the pattern of calcification from those without CAS. CAC was consistently higher in patients with risk factors for atherosclerosis compared to those without. CONCLUSION: The observed relationship between coronary and aortic root calcification suggests a diffuse arterial disease. The lack of relationship between coronary and aortic valve calcification suggests a different pathology.

Aortic valve area assessed with 320-detector computed tomography: comparison with transthoracic echocardiography.

To evaluate the diagnostic accuracy of aortic valve area (AVA) assessment with 320-detector Computed Tomography (MDCT) compared to transthoracic echocardiography (TTE) in a population with mild to severe aortic valve stenosis. AVA was estimated in 169 patients by planimetry on MDCT images (AVA(MDCT)) and by the continuity equation with TTE (AVA(TTE)). To generate a reference AVA (AVA(REF)) we used the stroke volume from MDCT divided by the velocity time integral from CW Doppler by TTE (according to the continuity equation: stroke volume in LVOT = stroke volume passing the aortic valve). AVA(REF) was used as the reference to compare both measures against, since it bypasses the assumption of LVOT being circular in the continuity equation and the potential placement error of PW Doppler in the LVOT. The mean (±SD) age of the patients was 71 (±9) years, 113 (67%) were males. Mean AVA(TTE) was 0.93 (±0.33) cm(2), mean AVA(MDCT) was 0.99 (±0.36) cm(2) and mean AVA(REF) was 1.00 (±0.39) cm(2). The mean difference between AVA(TTE) and AVA(MDCT) was -0.06 cm(2), p = 0.001, mean difference between AVA(TTE) and AVA(REF) was -0.06 cm(2), p < 0.001, and mean difference between AVA(MDCT) and AVA(REF) was -0.01 cm(2), p = 0.60. Calcification of the aortic valve quantified by Agatston score, significantly decreased the correlation between AVA(MDCT) and AVA(REF), (r low Agatston = 0.90, r high Agatston = 0.57). MDCT measured AVA is slightly larger than AVA measured by TTE (0.06 cm(2)). The accuracy and precision errors on AVA measurements are comparable for MDCT and TTE. Valvular calcification may primarily affect the accuracy of AVA(MDCT).