A 2016 study into cardiovascular disease (CVD) amongst members of the NASA Apollo missions found that the CVD mortality rate in Apollo lunar astronauts was 4–5 times higher than in non-flight and Low Earth Orbit astronauts.

[…] although deep space radiation seems a likely cause underlying the higher proportional mortality rate due to CVD in Apollo astronauts, it remains unknown what specific factor(s) in the space environment is responsible."

Source : Apollo Lunar Astronauts Show Higher Cardiovascular Disease Mortality Scientific Reports 6, Article number: 29901 (2016)

Space flights are now known to lead to a wide range of potentially serious health challenges, including loss in bone density and muscle mass, spaceflight-associated neuro-ocular syndrome (SANS), perturbed immune function, and spaceflight anemia. For full technical details, see the 2024Space Omics and Medical Atlas.

Also see:
Microgravity Immune Suppressionplugin-autotooltip__plain plugin-autotooltip_bigMicrogravity Immune Suppression

"Spaceflight causes alterations in human immunity, a finding which has been well documented immediately following spaceflight. Limited in-flight studies have also confirmed that to some degree immunity is compromised
Spaceflight-associated neuro-ocular syndrome (SANS)plugin-autotooltip__plain plugin-autotooltip_bigSpaceflight-associated neuro-ocular syndrome (SANS)

Approximately 60% of the crew members of the International Space Station have reported altered visual acuity after long-duration exposure to micro-gravity.

"Astronauts on long-duration spaceflight missions may develop changes in ocular structure and function, which can persist for years after the return to normal gravity.
Spaceflight anemiaplugin-autotooltip__plain plugin-autotooltip_bigSpaceflight anemia

"Anemia in astronauts has been noted since the first space missions, but the mechanisms contributing to anemia in space flight have remained unclear."

Source : Nature Medicine volume 28, pages 59–62 (2022)"

Anomalies in the amount of hemoglobin degradation in astronauts (around 12% higher than normal) was first discovered in the 1980s. The degradation leads to anemia, and tends to take hold in the first 10 days or so of micro-gravity spaceflight. After-effects appear to be…