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Higher lipoprotein A in hypertensive patients raises adverse cardiovascular event risk

Elevated lipoprotein A levels appear to have an important role in modifying the level of cardiovascular risk among patients with hypertension

Higher lipoprotein A levels in patients with hypertension increases their risk of an adverse cardiovascular event according to the findings of a study by US researchers.

Lipoprotein A is a form of low-density lipoprotein (LDL) and an established, genetically determined risk factor for atherosclerosis, coronary artery disease, stroke, thrombosis, and aortic stenosis. It is synthesised in the liver and its plasma concentration ranges from < 1 mg to > 1,000 mg/dL although concentrations above 50 mg/dL are associated with an increased risk for cardiovascular disease including myocardial infarction, stroke, aortic valve stenosis, heart failure, peripheral arterial disease, and all-cause mortality. Levels are largely determined by genetics with up to 90% of the concentration explained by a single gene, the LPA gene. Moreover, concentrations above 50 mg/dL are observed in roughly 20% of the Caucasian population and in an even higher proportion of African-American and Asian-Indian people. It can therefore be assumed that Lp(a) is one of the most important genetically determined risk factors for cardiovascular disease.

Given this relationship with cardiovascular disease risk, in the current study, US researchers used data from the Multi-Ethnic Study of Atherosclerosis (MESA) trial, to examine the longitudinal relationship of Lipoprotein A and hypertension to cardiovascular outcomes in a large multi-ethnic cohort, who were initially free of cardiovascular disease. MESA was designed to include patients from different ethnicities and aimed to include approximately 38% White, 28% African-American, 23% Hispanic and 11% Asian (of Chinese descent) individuals.

Among risk factors for cardiovascular disease, hypertension is associated with the strongest evidence for causation. As a result, in the current study, researchers categorised participants into four groups based on both lipoprotein A (Lp(a)) and the presence/absence of hypertension, which was defined by a systolic pressure of 140 mmHg or higher and a diastolic of 90 mmHg or the use of antihypertensive medicines. Group 1 had Lp(a) levels below <50 mg/dL and no hypertension; group 2 had Lp(a) levels ≥50 mg/dL but no hypertension; group 3 had Lp(a) <50 mg/dL and hypertension, whereas participants in group 4 had both an elevated Lp(a) (≥50 mg/dL) and hypertension. Individuals were then followed up until an adverse cardiovascular event.

Lipoprotein A levels, hypertension and adverse cardiovascular events

A total of 6,674 individuals with mean age of 62.1 years (52.8% female) and of whom, 38.6% were White, 27.5% Black, 22.1% Hispanic and 11.9% Chinese American, were followed for a mean of 13.9 years. During this time 809 participants experienced a cardiovascular disease event.

Using group 1 as the reference, those with Lp (a) ≥50 mg/dL and no hypertension (group 2) had no significant increased risk for cardiovascular disease events (Hazard ratio, HR = 1.09, 95% CI 0.79 – 1.50). In contrast, participants in group 3 (i.e., Lp(a) <50 mg/dL and hypertension) had a statistically significant increase in risk (HR = 1.66, 95% CI 1.39 – 1.98). The risk was also significantly elevated for those in group 4 (HR = 2.07, 95% CI 1.63 – 2.62).

In further analysis, the researchers identified that those with an elevated Lp(a) and with hypertension had an increased risk of cardiovascular disease events (HR = 1.24, 95% CI 1.01 – 1.53) relative to those with hypertension but lower Lp(a).

The authors concluded that while hypertension was a major contributor to cardiovascular risk, elevated Lp(a) significantly modified the association of hypertension with cardiovascular disease.

Rikhi R et al. Association of Lp(a) (Lipoprotein[a]) and Hypertension in Primary Prevention of Cardiovascular Disease: The MESA. Hypertension 2022

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