Aldehyde dehydrogenase 2 (ALDH2) is a mitochondrial enzyme involved in the detoxification of alcohol-derived acetaldehyde and endogenous aldehydes. The inactivating ALDH2 rs671 polymorphism, present in up to 8% of the global population and in up to 50% of the East Asian population, is associated with increased risk of cardiovascular conditions such as coronary artery disease, alcohol-induced cardiac dysfunction, pulmonary arterial hypertension, heart failure and drug-induced cardiotoxicity.
Although numerous studies have attributed an accumulation of aldehydes (secondary to alcohol consumption, ischaemia or elevated oxidative stress) to an increased risk of cardiovascular disease (CVD), this accumulation alone does not explain the emerging protective role of ALDH2 rs671 against ageing-related cardiac dysfunction and the development of aortic aneurysm or dissection. ALDH2 can also modulate risk factors associated with atherosclerosis, such as cholesterol biosynthesis and HDL biogenesis in hepatocytes and foam cell formation and efferocytosis in macrophages, via non-enzymatic pathways.
In this Review, we summarize the basic biology and the clinical relevance of the enzymatic and non-enzymatic, tissue-specific roles of ALDH2 in CVD, and discuss the future directions in the research and development of therapeutic strategies targeting ALDH2. A thorough understanding of the complex roles of ALDH2 in CVD will improve the diagnosis, management and prognosis of patients with CVD who harbour the ALDH2 rs671 polymorphism.
Alcohol consumption ranging from 1-2 drinks/day associates with a lower risk of coronary heart disease in some studies.
The underlying mechanisms are unclear. The Metabolic Imprints of Alcoholic Beverages (MetAl) trial aimed to explore the short-term effects of moderate alcohol consumption on cardiovascular biomarkers. A 2 x 3-week cross-over single-blinded intervention trial investigating the effect of 1-2 drinks/day (~12-24 g) compared with abstention on (1)H Nuclear Magnetic Resonance-measured main lipoproteins and subfractions was performed in 26 healthy adults.
Volunteers were classified as occasional or habitual drinkers based on their habitual alcohol intakes (/=2 drinks/week).
Compared with abstention, 1-2 drinks/day increased HDL(2a)-C (p = 0.004), HDL(3)-C (p = 0.008), and HDL non-significantly (p = 0.19).
Total apoA1 and apoA1 in HDL and its subfractions increased (p < 0.05). Novel findings were a decreased apoB/apoA1 ratio (p = 0.02), and increased HDL(2a) phospholipid content (p = 0.04). In women alone, the results were similar but attenuated, and LDL-P decreased. Thus, changes in apoA1- and HDL-related biomarkers occur within weeks in moderate drinkers. Compared with abstention, 1-2 drinks/day increased total apoA1 more strongly than HDL-C and increased the cholesterol, apoA1, and phospholipid content of several HDL subfractions.
Whether this provides a cardiovascular benefit requires further study. Clinicaltrials.gov: NCT03384147.
BACKGROUND AND OBJECTIVES: There is uncertainty about the association between alcohol consumption and stroke, particularly for low-moderate intake. We explored these associations in a large international study. METHODS: INTERSTROKE, a case-control study, is the largest international study of risk factors for acute stroke. Alcohol consumption was self-reported and categorized by drinks/week as low (1-7), moderate (7-14 for females and 7-21 for males), or high (>14 for females and >21 for males).
Heavy episodic drinking (HED) was defined as >5 drinks on >/=1 day per month. Multivariable conditional logistic regression was used to determine associations. RESULTS: We included 12,913 cases and 12,935 controls; 25.0% (n = 6,449) were current drinkers, 16.7% (n = 4,318) former drinkers, and 58.3% (n = 15,076) never drinkers. Current drinkers were younger, male, smokers, active, and with higher-paid occupations. Current drinking was associated with all stroke (OR 1.14; 95% CI 1.04-1.26) and intracerebral hemorrhage (ICH) (OR 1.50, 95% CI 1.21-1.84) but not ischemic stroke (OR 1.06; 95% CI 0.95-1.19).
HED pattern was associated with all stroke (OR 1.39; 95% CI 1.21-1.59), ischemic stroke (OR 1.29; 95% CI 1.10-1.51), and ICH (OR 1.76; 95% CI 1.31-2.36). High level of alcohol intake was consistently associated with all stroke, ischemic stroke, and ICH. Moderate intake was associated with all stroke and ICH but not ischemic stroke. Low alcohol intake was not associated with stroke overall, but there were regional differences; low intake was associated with reduced odds of stroke in Western Europe/North America (OR 0.66; 95% CI 0.45-0.96) and increased odds in India (OR 2.18; 95% CI 1.42-3.36) (p-interaction 0.037). Wine consumption was associated with reduced odds of all stroke and ischemic stroke but not ICH. The magnitudes of association were greatest in those without hypertension and current smokers.
DISCUSSION: High and moderate intake were associated with increased odds of stroke, whereas low intake was not associated with stroke. However, there were important regional variations, which may relate to differences in population characteristics of alcohol consumers, types or patterns of consumption.
Alcohol consumption ranging from 1-2 drinks/day associates with a lower risk of coronary heart disease in some studies.
The underlying mechanisms are unclear. The Metabolic Imprints of Alcoholic Beverages (MetAl) trial aimed to explore the short-term effects of moderate alcohol consumption on cardiovascular biomarkers. A 2 x 3-week cross-over single-blinded intervention trial investigating the effect of 1-2 drinks/day (~12-24 g) compared with abstention on (1)H Nuclear Magnetic Resonance-measured main lipoproteins and subfractions was performed in 26 healthy adults. Volunteers were classified as occasional or habitual drinkers based on their habitual alcohol intakes (/=2 drinks/week).
Compared with abstention, 1-2 drinks/day increased HDL(2a)-C (p = 0.004), HDL(3)-C (p = 0.008), and HDL non-significantly (p = 0.19). Total apoA1 and apoA1 in HDL and its subfractions increased (p < 0.05).
Novel findings were a decreased apoB/apoA1 ratio (p = 0.02), and increased HDL(2a) phospholipid content (p = 0.04). In women alone, the results were similar but attenuated, and LDL-P decreased.
Thus, changes in apoA1- and HDL-related biomarkers occur within weeks in moderate drinkers. Compared with abstention, 1-2 drinks/day increased total apoA1 more strongly than HDL-C and increased the cholesterol, apoA1, and phospholipid content of several HDL subfractions. Whether this provides a cardiovascular benefit requires further study. Clinicaltrials.gov: NCT03384147.